Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne Muscular Dystrophy, myostatin
Brief summary
This is a Phase 2 randomized, 2-period, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, efficacy, PK and PD of PF-06252616 administered to ambulatory boys diagnosed with Duchenne Muscular Dystrophy. Three intravenous (IV) dose levels will be investigated in a within subject dose escalating fashion. Subjects will be randomly assigned to 1 of 3 sequence groups for approximately 96 weeks (2 periods of 48 weeks each). In period 1, two of the sequence groups will receive PF-06252616 and one sequence group will receive placebo. In period 2, the placebo group will switch to PF-06252616 and the two remaining sequence groups will either receive placebo or PF-06252616. Efficacy will be based on an observed mean change from baseline on function (4 stair climb) of PF-06252616 as compared to the placebo at the end of period 1. Period 2 provides an opportunity to evaluate PK. Subjects will receive monthly IV infused doses of either PF-06252616 or placebo and will undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI), functional evaluations (pulmonary function testing, 4 stair climb, range of motion, strength testing, Northstar Ambulatory Assessment, upper limb functional testing and the six minute walk test), pharmacokinetic testing and pharmacodynamic testing to evaluate changes in muscle volume (MRI).
Interventions
BIOLOGICALPF-06252616
PF-06252616 IV Infusion, 3 dose levels (5mg/kg, 20 mg/kg and 40 mg/kg) will be investigated within each subject
DRUGPlacebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
6 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
1. Ambulatory boys age 6 to \<16 years old (at the time of randomization), diagnosed with DMD. Diagnosis must be confirmed in subject's medical history and by genetic testing obtained during routine clinical care for diagnostic purposes as reported from an appropriate regulated laboratory using a clinically validated genetic test (genetic testing is not provided by the sponsor). 2. Subjects who are able to perform the 4 stair climb in \> or = 0.33 but \< or =1.6 stairs/second. 3. Subjects must be receiving glucocorticosteroids for a minimum of 6 months prior to signing informed consent. There should be no significant change (\>0.2 mg/kg) in dosage or dose regimen (not related to body weight change) for at least 3 months immediately prior to signing the informed consent and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study. 4. Adequate hepatic and renal function on screening laboratory assessments. 5. No underlying disposition for iron accumulation on screening laboratory assessments. 6. Iron content estimate on the screening liver MRI is within the normal range.
Exclusion criteria
1. Subjects with known cognitive impairment or behavioral issues that would impede the ability to follow instructions. 2. History of major surgical procedure within 6 weeks of signing the informed consent or planned surgery during the study. 3. Any injury which may impact functional testing. Previous injuries must be fully healed prior to consenting. Prior lower limb fractures must be fully healed and at least 3 months from injury date. 4. Presence or history of other musculoskeletal or neurologic disease or somatic disorder not related to DMD including pulmonary and cardiac disease. 5. Compromised cardiac function (left ventricular ejection fraction \<55% as determined on a screening cardiac MRI or echocardiogram). Subjects may be receiving ACE (angiotensin converting enzyme) inhibitors or beta blockers, ARB (angiotensin II receptor antagonist) or aldosterone blocker/thiazide diuretic; however they must have initiated treatment more than 3 months prior to screening to ensure stable therapy. 6. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including uncontrolled hypertension), hepatic, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). 7. Documented history of iron overload including hemochromatosis, beta thalassemia major, beta thalassemia intermedia or hemolytic anemia. 8. Unwilling or unable (eg, metal implants, requires sedation) to undergo examination with closed MRI without sedation. 9. Participation in other studies involving investigational drug(s) for a minimum of 30 days or within 5 half lives (whichever is longer) prior to signing the informed consent and/or during study participation. 10. Current or prior treatment with anti-myostatin, exon skipping, nonsense mutation targeted therapies ever or more than 30 days of treatment with utrophin modifiers and treatment with utrophin modifiers within 30 days prior ot signing the informed consent and/or during study participation. 11. Current or prior treatment within the past 3 months with androgens or human growth hormone. 12. Current treatment with immunosuppressant therapies (other than glucocorticoid steroids), aminoglycosides (eg, gentamicin), multi vitamins with iron and iron supplements and other investigational therapies (including idebenone).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | The 4SC quantified the time required for a participant to ascend 4 standard steps. Mixed effect model for repeated measures (MMRM) was used to analyze the change from baseline on 4SC for domagrozumab compared to placebo. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Study Day 1 to Week 49 visit | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator. |
| Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 | Study Day 1 to Week 49 visit | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. |
| Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 | Study Day 1 to Week 49 visit | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Baseline to Week 49 visit | Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils, absolute monocytes and absolute myelocytes. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation | Baseline to Week 49 visit | Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT). |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Baseline to Week 49 visit | Liver function evaluation included: total/direct/indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | Baseline to Week 49 visit | Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Baseline to Week 49 visit | Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate, bicarbonate, ferritin, transferrin saturation, iron, iron binding capacity and unsaturated iron binding capacity. Number of participants with iron abnormalities was reported in different age groups. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Baseline to Week 49 visit | Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Baseline to Week 49 visit | Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, and amylase. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Baseline to Week 49 visit | Urinalysis included: urine pH, qualitative urine glucose, qualitative urine ketones, qualitative urine protein, qualitative blood/hemoglobin, urine nitrite, urine leukocytes, urine RBC, urine WBC, urine granular casts, urine hyaline casts, urine urate (uric acid) acidic crystal, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal | Baseline to Week 49 visit | Number of participants with blood detected in fecal samples is presented. |
| Categorical Summary of Liver Iron Accumulation by Week 49 | Screening, Weeks 13, 29 and 45 | Magnetic resonance imaging (MRI) of Liver was obtained to quantify liver iron accumulation for safety monitoring. MRIs were sent to an independent central radiology imaging facility for calculation of the average transverse relaxation rate (R2\*) value which was used to monitor for iron accumulation in the liver. Number of participants meeting the following criteria is presented as follows: 1) normal: R2\*\<=75Hz at 1.5T or \<=139 Hz at 3.0T; 2) above normal: R2\*\>75Hz and \<=190Hz at 1.5T or R2\* \>139Hz and \<=369Hz at 3.0T; 3) mild overload: R2\*\>190Hz at 1.5T or R2\*\>360Hz at 3.0T. |
| Number of Participants With Physical Examination Findings Reported as SAEs by Week 49 | Baseline to Week 49 visit | Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A targeted nose and throat mucosal exam were also performed to monitor for any signs of mucosal telangiectasias. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which physical examination findings were reported as SAEs. |
| Summary of Tanner Stage Rating by Week 49 | Baseline, Weeks 17, 33 and 49 | Tanner staging was performed before the first dose of each dose escalation to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition. |
| Number of Participants With Vital Signs Findings Reported as SAEs by Week 49 | Baseline to Week 49 visit | Vital signs evaluation included supine systolic and diastolic blood pressure (BP), pulse rate, and respiratory rate. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which vital signs findings were reported as SAEs. |
| Bone Age to Chronological Age Ratio by Week 49 | Screening, Weeks 17, 33 and 49 | Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date-date of birth+1)/365.25. |
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | Baseline to Week 49 visit | Number of participants with ECG data meeting the following criteria are presented: 1) corrected QT interval using Fridericia's formula (QTcF interval) \<450msec; 2) QTcF interval \>=450 and \<480msec; 3) QTcF interval \>=480 and \<500msec; 4) QTcF interval\>=500msec; 5) QTcF interval increase from baseline\<30msec; 6) QTcF interval increase from baseline \>=30 and \<60msec; 7) QTcF interval increase from baseline \>=60msec. |
| Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49 | Baseline to Week 49 visit | The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance image (MRI) or echocardiogram. The same method of cardiac imaging was used consistently within a single participant. Cardiac MRIs were read by a central imaging vendor and echocardiograms were read locally at each site. The LVEF values measured by cardiac MRI and echocardiogram are combined in the following presentation. The analysis of covariance (ANCOVA) model was used to analyze the change from baseline for domagrozumab compared to placebo on LVEF. The baseline result, age, use of angiotensin receptor blocker (ARB)/beta blocker/angiotensin converting enzyme (ACE) inhibitor and treatment were included as fixed effects in the model. |
| Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49 | Screening and Week 49 | Bone mineral density (BMD) was evaluated by Dual energy X-ray Absorptiometry (DXA). The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was below the expected range for age. If the Z-score was above -2 standard deviations, the result was within the expected range for age. |
| Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49 | Baseline to Week 49 visit | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. AEs of suicide ideation or behavior were determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets | Baseline, Week 17 | FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets | Baseline, Week 33 | FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets | Baseline, Week 49 | FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets | Baseline, Week 17 | The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Baseline, Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC \<3.5 seconds are presented below. |
| Maximum Serum Concentration (Cmax) of Domagrozumab | Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3 | Cmax was observed directly from data. |
| Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets | Baseline, Week 33 | The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets | Baseline, Week 49 | The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets | Baseline, Week 17 | The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline .The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets | Baseline, Week 33 | The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items).Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline.The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets | Baseline, Week 49 | The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items).Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline.The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets | Baseline, Week 17 | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets | Baseline, Week 33 | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets | Baseline, Week 49 | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Baseline, Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC \>=3.5 seconds and \<=8 seconds are presented below. |
| Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Baseline, Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC \>8 seconds are presented below. |
| Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | The whole thigh muscle volume was measured by the proton density weighted sequence with magnetic resonance imaging (MRI) which was used to segment the entire thigh region into 3 primary regions for volumetric measure including 1) muscle; 2) inter/intra-muscular fat, 3) subcutaneous fat. MMRM was used to analyze the percent change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | The thigh muscle volume index was derived from the thigh muscle volume measurements as the fraction of total thigh tissue that was the lean muscle. MMRM was used to analyze the percent change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Baseline, Weeks 17, 33, 49 and 97 | The whole thigh muscle volume was measured by the proton density weighted sequence with magnetic resonance imaging (MRI) which was used to segment the entire thigh region into 3 primary regions for volumetric measure including 1) muscle; 2) inter/intra-muscular fat, 3) subcutaneous fat. |
| Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Baseline, Weeks 17, 33, 49 and 97 | The thigh muscle volume index was derived from the thigh muscle volume measurements as the fraction of total thigh tissue that was the lean muscle. |
| Concentration of Growth Differentiation Factor 8 (GDF-8) at Time 0 (Pre-dose),(C0(GDF-8) ) | Predose on Day 1 of Week 1 | GDF-8, also called myostatin, is the target of domagrozumab. C0(GDF-8) was observed directly from data. |
| Trough Serum Concentration of GDF-8 (Ctrough,(GDF-8)) for Participants Receiving Domagrozumab in Period 1 | Every 4 weeks on dosing day (at predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 48 | GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data. |
| Ctrough,(GDF-8) for Participants of Sequence 3 in Period 2 | Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 49 to Week 96 | GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data. |
| Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3 | Ctrough was observed directly from data. |
| Terminal Half-life (t1/2) of Domagrozumab for Participants in Sequence 2 After the Last Dose of Domagrozumab | At predose, end of 2-hour infusion and 6 hours since start of infusion at Week 45 | t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Participants in Sequence 2 received the last dose of domagrozumab at Week 45. |
| Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | At predose, end of 2-hour infusion,6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45 | The dosing interval tau was 672 hours (4 weeks). AUCtau was obtained by linear/log trapezoidal method. The AUCtau was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits. |
| Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45 | Cav was calculated by AUCtau/tau. The Cav was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits. |
| Clearance (CL) of Domagrozumab | At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 13, 29 and 45 | CL was calculated by Dose/AUCtau. The CL was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits. |
| Volume of Distribution at Steady State (Vss) of Domagrozumab for Participants in Sequence 2 Required for Additional PK Assessment | At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Week 45 | Vss was calculated by CL\*MRT, where MRT was the mean residence time. Vss was assessed to fully characterize PK data. |
| Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Baseline, every 4 weeks from Week 5 to Week 97 visit or early termination | The criterion for positive result of ADA samples was ADA titer \>=1.88. |
| Time for Cmax (Tmax) of Domagrozumab | Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3 | Tmax was observed directly from the data. |
| Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | ROM was evaluated by using goniometry to evaluate the loss of motion in the ankles. MMRM was used to analyze the change from baseline on ROM for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Baseline, Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline to Week 49 on 4SC for Participants in Sequence 3 Compared to the Natural History Control Group | Baseline, Week 49 | The 4SC quantified the time required for a participant to ascend 4 standard steps. MMRM was used to analyze the change from baseline on 4SC for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG (Cooperative International Neuromuscular Research Group) natural history database. Participants who met the following requirements at baseline and had evaluable 4SC data on Week 49 were included in this group: 1) age: 6 to \<16 years; 2)treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing. |
| Change From Baseline to Week 97 on 4SC for Participants in Sequence 1 Compared to the Natural History Control Group | Baseline, Week 97 | The 4SC quantified the time required for a participant to ascend 4 standard steps. MMRM was used to analyze the change from baseline on 4SC for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 4SC data on Week 97 were included in this group: 1) age: 6 to \<16 years; 2) treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing. |
| Change From Baseline to Week 49 on FVC for Participants in Sequence 3 Compared to the Natural History Control Group | Baseline, Week 49 | FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for the natural history control group compared to placebo group (Sequence 3). MMRM was used to analyze the change from baseline on FVC for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable FVC data on Week 49 were included in this group: 1) age: 6 to \<16 years; 2)treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing. |
| Change From Baseline to Week 97 on FVC for Participants in Sequence 1 Compared to the Natural History Control Group | Baseline, Week 97 | FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable FVC data on Week 97 were included in this group: 1) age: 6 to \<16 years; 2) treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing. |
| Change From Baseline to Week 49 on NSAA for Participants in Sequence 3 Compared to the Natural History Control Group | Baseline, Week 49 | The NSAA is a 17-item test that measured gross motor function. A total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline on NSAA for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on the using natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable NSAA data on Week 49 were included in this group: 1) age: 6 to \<16 years; 2)treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing. |
| Change From Baseline to Week 97 on NSAA for Participants in Sequence 1 Compared to the Natural History Control Group | Baseline, Week 97 | The NSAA is a 17-item test that measured gross motor function. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline on NSAA for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable NSAA data on Week 97 were included in this group: 1) age: 6 to \<16 years; 2) treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing. |
| Change From Baseline to Week 49 on 6MWD for Participants in Sequence 3 Compared to the Natural History Control Group | Baseline, Week 49 | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 6MWD data on Week 49 were included in this group: 1) age: 6 to \<16 years; 2)treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing. |
| Change From Baseline to Week 97 on 6MWD for Participants in Sequence 1 Compared to the Natural History Control Group | Baseline, Week 97 | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 6MWD data on Week 97 were included in this group: 1) age: 6 to \<16 years; 2)treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing. |
| Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets | Baseline, Week 17 | The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets | Baseline, Week 33 | The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds.MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
| Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets | Baseline, Week 49 | The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Last Quantifiable Serum Concentration (AUClast) of Domagrozumab | At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45 | AUClast was calculated by linear/log trapezoidal method. AUCtau was obtained by linear/log trapezoidal method. AUClast was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits. |
Countries
Australia, Bulgaria, Canada, Italy, Japan, Poland, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 162 participants were screened, 121 participants were enrolled in the study and assigned to 1 of 3 sequences. Only 120 participants received the study treatment and 1 participant withdrew prior to dosing.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1 Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | 41 |
| Sequence 2 Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. | 39 |
| Sequence 3 Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). | 40 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 1 (Weeks 1 to 48) | Adverse Event | 1 | 0 | 0 |
| Period 1 (Weeks 1 to 48) | Lost to Follow-up | 1 | 0 | 0 |
| Period 1 (Weeks 1 to 48) | Unable to comply with study procedures | 0 | 1 | 1 |
| Period 1 (Weeks 1 to 48) | Withdrawal by Subject | 1 | 1 | 1 |
| Period 2 (Weeks 49 to 96) | Study terminated by sponsor | 16 | 16 | 16 |
Baseline characteristics
| Characteristic | Sequence 1 | Sequence 2 | Sequence 3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 41 Participants | 39 Participants | 40 Participants | 120 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.3 Years STANDARD_DEVIATION 1.9 | 8.5 Years STANDARD_DEVIATION 1.5 | 9.3 Years STANDARD_DEVIATION 2.3 | 8.7 Years STANDARD_DEVIATION 2 |
| Race/Ethnicity, Customized Asian | 6 Participants | 5 Participants | 4 Participants | 15 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 33 Participants | 33 Participants | 35 Participants | 101 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 41 Participants | 39 Participants | 40 Participants | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 80 | 0 / 78 | 0 / 76 | 0 / 40 | 0 / 38 | 0 / 38 | 0 / 66 | 0 / 37 |
| other Total, other adverse events | 58 / 80 | 43 / 78 | 50 / 76 | 38 / 40 | 29 / 38 | 22 / 38 | 49 / 66 | 29 / 37 |
| serious Total, serious adverse events | 1 / 80 | 1 / 78 | 1 / 76 | 0 / 40 | 1 / 38 | 1 / 38 | 1 / 66 | 0 / 37 |
Outcome results
Primary
Bone Age to Chronological Age Ratio by Week 49
Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date-date of birth+1)/365.25.
Time frame: Screening, Weeks 17, 33 and 49
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Bone Age to Chronological Age Ratio by Week 49 | Screening | 0.809 Ratio | Standard Deviation 0.1656 |
| Placebo | Bone Age to Chronological Age Ratio by Week 49 | Week 17 | 0.805 Ratio | Standard Deviation 0.1567 |
| Placebo | Bone Age to Chronological Age Ratio by Week 49 | Week 33 | 0.790 Ratio | Standard Deviation 0.1614 |
| Placebo | Bone Age to Chronological Age Ratio by Week 49 | Week 49 | 0.770 Ratio | Standard Deviation 0.1604 |
| Domagrozumab 5 mg/kg | Bone Age to Chronological Age Ratio by Week 49 | Week 49 | 0.761 Ratio | Standard Deviation 0.1778 |
| Domagrozumab 5 mg/kg | Bone Age to Chronological Age Ratio by Week 49 | Screening | 0.762 Ratio | Standard Deviation 0.165 |
| Domagrozumab 5 mg/kg | Bone Age to Chronological Age Ratio by Week 49 | Week 33 | 0.750 Ratio | Standard Deviation 0.1589 |
| Domagrozumab 5 mg/kg | Bone Age to Chronological Age Ratio by Week 49 | Week 17 | 0.749 Ratio | Standard Deviation 0.1654 |
Primary
Categorical Summary of Liver Iron Accumulation by Week 49
Magnetic resonance imaging (MRI) of Liver was obtained to quantify liver iron accumulation for safety monitoring. MRIs were sent to an independent central radiology imaging facility for calculation of the average transverse relaxation rate (R2\*) value which was used to monitor for iron accumulation in the liver. Number of participants meeting the following criteria is presented as follows: 1) normal: R2\*\<=75Hz at 1.5T or \<=139 Hz at 3.0T; 2) above normal: R2\*\>75Hz and \<=190Hz at 1.5T or R2\* \>139Hz and \<=369Hz at 3.0T; 3) mild overload: R2\*\>190Hz at 1.5T or R2\*\>360Hz at 3.0T.
Time frame: Screening, Weeks 13, 29 and 45
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Screening | 41 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Screening | 0 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Screening | 0 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Week 13 | 27 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Week 13 | 0 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Week 13 | 0 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Week 29 | 23 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Week 29 | 0 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Week 29 | 0 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Week 45 | 37 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Week 45 | 0 Participants |
| Placebo | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Week 45 | 0 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Week 45 | 0 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Screening | 39 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Week 29 | 21 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Week 29 | 0 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Screening | 0 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Week 13 | 0 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Week 45 | 0 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Screening | 0 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Week 29 | 0 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Week 13 | 0 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Week 13 | 24 Participants |
| Domagrozumab 5 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Week 45 | 37 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Week 13 | 26 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Week 13 | 0 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Week 45 | 38 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Week 13 | 0 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Week 29 | 21 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Week 29 | 0 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Week 45 | 0 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Normal, Screening | 40 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Above normal, Screening | 0 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Week 29 | 0 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Screening | 0 Participants |
| Domagrozumab 20 mg/kg | Categorical Summary of Liver Iron Accumulation by Week 49 | Mild overload, Week 45 | 0 Participants |
Primary
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance image (MRI) or echocardiogram. The same method of cardiac imaging was used consistently within a single participant. Cardiac MRIs were read by a central imaging vendor and echocardiograms were read locally at each site. The LVEF values measured by cardiac MRI and echocardiogram are combined in the following presentation. The analysis of covariance (ANCOVA) model was used to analyze the change from baseline for domagrozumab compared to placebo on LVEF. The baseline result, age, use of angiotensin receptor blocker (ARB)/beta blocker/angiotensin converting enzyme (ACE) inhibitor and treatment were included as fixed effects in the model.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49 | -0.063 Ratio of blood | Standard Error 0.8464 |
| Domagrozumab 5 mg/kg | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49 | -1.356 Ratio of blood | Standard Error 0.562 |
p-value: 0.208895% CI: [-0.7343, 3.32]ANCOVA
Primary
Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49
The 4SC quantified the time required for a participant to ascend 4 standard steps. Mixed effect model for repeated measures (MMRM) was used to analyze the change from baseline on 4SC for domagrozumab compared to placebo. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timeponts.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 | Week 17 | 1.6896 Seconds | Standard Error 0.6776 |
| Placebo | Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 | Week 33 | 3.6407 Seconds | Standard Error 1.5837 |
| Placebo | Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 | Week 49 | 8.0122 Seconds | Standard Error 3.03 |
| Domagrozumab 5 mg/kg | Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 | Week 17 | 1.6051 Seconds | Standard Error 0.4814 |
| Domagrozumab 5 mg/kg | Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 | Week 33 | 4.2244 Seconds | Standard Error 1.1209 |
| Domagrozumab 5 mg/kg | Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 | Week 49 | 8.2835 Seconds | Standard Error 2.1507 |
Comparison: Week 17p-value: 0.919195% CI: [-1.7354, 1.5663]Mixed Models Analysis
Comparison: Week 33p-value: 0.764295% CI: [-3.2978, 4.4652]Mixed Models Analysis
Comparison: Week 49p-value: 0.942395% CI: [-7.3799, 7.9223]Mixed Models Analysis
Primary
Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49
Bone mineral density (BMD) was evaluated by Dual energy X-ray Absorptiometry (DXA). The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was below the expected range for age. If the Z-score was above -2 standard deviations, the result was within the expected range for age.
Time frame: Screening and Week 49
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49 | Screening | -0.545151 Standard deviations | Standard Deviation 1.284557 |
| Placebo | Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49 | Week 49 | -0.683750 Standard deviations | Standard Deviation 1.067342 |
| Domagrozumab 5 mg/kg | Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49 | Screening | -0.622784 Standard deviations | Standard Deviation 1.0778788 |
| Domagrozumab 5 mg/kg | Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49 | Week 49 | -0.401631 Standard deviations | Standard Deviation 1.0758951 |
| Domagrozumab 20 mg/kg | Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49 | Screening | -0.572650 Standard deviations | Standard Deviation 1.0283031 |
| Domagrozumab 20 mg/kg | Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49 | Week 49 | -0.489513 Standard deviations | Standard Deviation 1.0057285 |
Primary
Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.
Time frame: Study Day 1 to Week 49 visit
Population: The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 | All-causalities TEAE | 0 Participants |
| Placebo | Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 | Treatment-related TEAE | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 | Treatment-related TEAE | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 | All-causalities TEAE | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 | All-causalities TEAE | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 | Treatment-related TEAE | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 | All-causalities TEAE | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 | Treatment-related TEAE | 1 Participants |
Primary
Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.
Time frame: Study Day 1 to Week 49 visit
Population: The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 | All-causalities TEAE | 8 Participants |
| Placebo | Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 | Treatment-related TEAE | 3 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 | Treatment-related TEAE | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 | All-causalities TEAE | 4 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 | All-causalities TEAE | 4 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 | Treatment-related TEAE | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 | All-causalities TEAE | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 | Treatment-related TEAE | 0 Participants |
Primary
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49
Number of participants with ECG data meeting the following criteria are presented: 1) corrected QT interval using Fridericia's formula (QTcF interval) \<450msec; 2) QTcF interval \>=450 and \<480msec; 3) QTcF interval \>=480 and \<500msec; 4) QTcF interval\>=500msec; 5) QTcF interval increase from baseline\<30msec; 6) QTcF interval increase from baseline \>=30 and \<60msec; 7) QTcF interval increase from baseline \>=60msec.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval <450msec | 40 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase >=30 and <60msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase <30msec | 40 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval>=450 and <480msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase >=60msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval >=480 and <500msec | 0 Participants |
| Placebo | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval>=500msec | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase >=30 and <60msec | 4 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval>=500msec | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval >=480 and <500msec | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase <30msec | 66 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase >=60msec | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval>=450 and <480msec | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval <450msec | 70 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval>=500msec | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval <450msec | 67 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval>=450 and <480msec | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval >=480 and <500msec | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase <30msec | 65 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase >=30 and <60msec | 2 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase >=60msec | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval >=480 and <500msec | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase >=60msec | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase >=30 and <60msec | 6 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval>=450 and <480msec | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval <450msec | 68 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval increase <30msec | 63 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | QTcF interval>=500msec | 0 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry
Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, and amylase.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Glucose <0.6*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Glucose >1.5*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | CK >2.0*ULN | 40 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Troponin I >3.0*ULN | 11 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Amylase >1.5*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Glucose >1.5*ULN | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | CK >2.0*ULN | 80 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Troponin I >3.0*ULN | 12 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Glucose <0.6*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Amylase >1.5*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Glucose <0.6*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Glucose >1.5*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Troponin I >3.0*ULN | 10 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Amylase >1.5*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | CK >2.0*ULN | 78 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Glucose <0.6*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | CK >2.0*ULN | 76 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Amylase >1.5*ULN | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Troponin I >3.0*ULN | 13 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Glucose >1.5*ULN | 2 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation
Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT).
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation | PT >1.1*ULN | 13 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation | aPTT >1.1*ULN | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation | PT >1.1*ULN | 6 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation | aPTT >1.1*ULN | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation | aPTT >1.1*ULN | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation | PT >1.1*ULN | 3 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation | PT >1.1*ULN | 7 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation | aPTT >1.1*ULN | 2 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes
Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate, bicarbonate, ferritin, transferrin saturation, iron, iron binding capacity and unsaturated iron binding capacity. Number of participants with iron abnormalities was reported in different age groups.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Sodium <0.95*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Ferritin >140 (ug/L) | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (1 Year<=Age<11 Years) <50 (ug/dL) | 19 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (1 Year<=Age<11 Years) >120 (ug/dL) | 12 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Potassium >1.1*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Ferritin <15 (ug/L) | 20 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (11 Years<=Age<18 Years) <50 (ug/dL) | 2 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (11 Years<=Age<18 Years) >170 (ug/dL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Transferrin saturation <20% | 26 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Chloride <0.9*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Chloride >1.1*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Sodium >1.05*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Unsaturated iron binding capacity >375 (ug/dL) | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Calcium <0.9*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Calcium >1.1*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Unsaturated iron binding capacity<130 (ug/dL) | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Phosphate <0.8*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Transferrin saturation >50% | 4 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Phosphate >1.2*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Potassium <0.9*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron binding capacity <37.6 (ug/dL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Bicarbonate <0.9*LLN | 8 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Bicarbonate >1.1*ULN | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron binding capacity <37.6 (ug/dL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Bicarbonate <0.9*LLN | 2 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Calcium <0.9*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (1 Year<=Age<11 Years) <50 (ug/dL) | 23 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Transferrin saturation <20% | 34 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Ferritin <15 (ug/L) | 32 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Sodium >1.05*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (1 Year<=Age<11 Years) >120 (ug/dL) | 29 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Unsaturated iron binding capacity<130 (ug/dL) | 7 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Phosphate >1.2*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Calcium >1.1*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (11 Years<=Age<18 Years) <50 (ug/dL) | 4 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Potassium >1.1*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (11 Years<=Age<18 Years) >170 (ug/dL) | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Sodium <0.95*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Potassium <0.9*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Ferritin >140 (ug/L) | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Chloride <0.9*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Transferrin saturation >50% | 9 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Unsaturated iron binding capacity >375 (ug/dL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Phosphate <0.8*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Chloride >1.1*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Bicarbonate >1.1*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Bicarbonate >1.1*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Sodium <0.95*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Sodium >1.05*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Potassium <0.9*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Chloride <0.9*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Chloride >1.1*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Calcium <0.9*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Calcium >1.1*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Phosphate <0.8*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Phosphate >1.2*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Bicarbonate <0.9*LLN | 3 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Potassium >1.1*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (1 Year<=Age<11 Years) <50 (ug/dL) | 14 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (1 Year<=Age<11 Years) >120 (ug/dL) | 33 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (11 Years<=Age<18 Years) <50 (ug/dL) | 2 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (11 Years<=Age<18 Years) >170 (ug/dL) | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Ferritin <15 (ug/L) | 38 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Ferritin >140 (ug/L) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron binding capacity <37.6 (ug/dL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Unsaturated iron binding capacity<130 (ug/dL) | 6 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Unsaturated iron binding capacity >375 (ug/dL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Transferrin saturation <20% | 26 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Transferrin saturation >50% | 19 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Bicarbonate <0.9*LLN | 4 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Transferrin saturation >50% | 18 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Ferritin >140 (ug/L) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Phosphate >1.2*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Phosphate <0.8*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Transferrin saturation <20% | 20 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron binding capacity <37.6 (ug/dL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Calcium >1.1*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Calcium <0.9*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Sodium >1.05*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Unsaturated iron binding capacity<130 (ug/dL) | 10 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Chloride >1.1*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Chloride <0.9*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Sodium <0.95*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Unsaturated iron binding capacity >375 (ug/dL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (11 Years<=Age<18 Years) <50 (ug/dL) | 2 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Potassium >1.1*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (11 Years<=Age<18 Years) >170 (ug/dL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (1 Year<=Age<11 Years) >120 (ug/dL) | 39 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Iron (1 Year<=Age<11 Years) <50 (ug/dL) | 11 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Potassium <0.9*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Ferritin <15 (ug/L) | 42 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Bicarbonate >1.1*ULN | 0 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal
Number of participants with blood detected in fecal samples is presented.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug and had at least 1 fecal evaluation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal | 2 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal | 8 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal | 2 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal | 3 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology
Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils, absolute monocytes and absolute myelocytes.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute lymphocytes >1.2*ULN | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute Lymphocytes <0.8*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | RBC Morphology >0 | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute monocytes >1.2*ULN | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | WBC count >1.5*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | WBC count <0.6*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute basophils >1.2*ULN | 2 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute band cells >0.27 (10*3/uL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | RBC count <0.8*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Hemoglobin <0.8*lower limit of normal (LLN) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils count >8.15 (10*3/uL) | 20 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils count <1.35 (10*3/uL) | 2 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Platelets <0.5*LLN | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute eosinophils >1.2*ULN | 6 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils >1.2*ULN | 13 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils <0.8*LLN | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Platelets >1.75*upper limit of normal (ULN) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Hematocrit <0.8*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | RBC count <0.8*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Hemoglobin <0.8*lower limit of normal (LLN) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Hematocrit <0.8*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Platelets <0.5*LLN | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Platelets >1.75*upper limit of normal (ULN) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | RBC Morphology >0 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | WBC count <0.6*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | WBC count >1.5*ULN | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute Lymphocytes <0.8*LLN | 2 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute lymphocytes >1.2*ULN | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute atypical lymphocytes >0 (10*3/uL) | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils <0.8*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils >1.2*ULN | 8 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils count <1.35 (10*3/uL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils count >8.15 (10*3/uL) | 13 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute band cells >0.27 (10*3/uL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute basophils >1.2*ULN | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute eosinophils >1.2*ULN | 2 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute monocytes >1.2*ULN | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Platelets >1.75*upper limit of normal (ULN) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute lymphocytes >1.2*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils <0.8*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Platelets <0.5*LLN | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute eosinophils >1.2*ULN | 6 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils >1.2*ULN | 5 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils count <1.35 (10*3/uL) | 2 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | RBC count <0.8*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Hemoglobin <0.8*lower limit of normal (LLN) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils count >8.15 (10*3/uL) | 12 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute band cells >0.27 (10*3/uL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Hematocrit <0.8*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | WBC count <0.6*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | RBC Morphology >0 | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute monocytes >1.2*ULN | 2 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | WBC count >1.5*ULN | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute basophils >1.2*ULN | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute Lymphocytes <0.8*LLN | 2 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | WBC count <0.6*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Platelets >1.75*upper limit of normal (ULN) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils count >8.15 (10*3/uL) | 9 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Hematocrit <0.8*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute lymphocytes >1.2*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Hemoglobin <0.8*lower limit of normal (LLN) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute atypical lymphocytes >0 (10*3/uL) | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Platelets <0.5*LLN | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute monocytes >1.2*ULN | 2 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute myelocytes >0 (10*3/uL) | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils <0.8*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute Lymphocytes <0.8*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute band cells >0.27 (10*3/uL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | RBC Morphology >0 | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils >1.2*ULN | 5 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | RBC count <0.8*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute eosinophils >1.2*ULN | 6 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute basophils >1.2*ULN | 2 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Absolute total neutrophils count <1.35 (10*3/uL) | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | WBC count >1.5*ULN | 0 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones
Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (9 Years<=Age<11 Years) >4.50 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (9 Years<=Age<11 Years) >2.8 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(7Years<=Age<10Years) >31(ng/dL) | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (7 Years<=Age<9 Years) >4.10 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (4 Years<=Age<7 Years) >6.70 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (11 Years<=Age<12 Years) <0.3 (mIU/mL) | 2 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (7 Years<=Age<10Years)<3(ng/dL) | 5 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (13 Years<=Age<14 Years) >6.0 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (13 Years<=Age<14 Years) <0.3 (mIU/mL) | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (11 Years<=Age<12 Years) >1.8 (mIU/mL) | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | TSH >1.2*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (12 Years<=Age<13 Years) >4.0 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (12 Years<=Age<13 Years) <0.3 (mIU/mL) | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Free T4 >1.2*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (1 Year<=Age<7Years) >50(ng/dL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (1 Year<=Age<7 Years) <8 (ng/dL) | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (15 Days<=Age<7 Years) <0.3 (mIU/mL) | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(12 Years<=Age<14Years)>64 (ng/dL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (13 Years<=Age<14 Years) >10.80 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (15 Days<=Age<7 Years) >2.8 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (10Years<=Age<12Years)>41 (ng/dL) | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (13 Years<=Age<14 Years) <0.70 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (7 Years<=Age<9 Years) <0.3 (mIU/mL) | 6 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(10Years<=Age<12Years) <7(ng/dL) | 13 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (12 Years<=Age<13 Years) >10.50 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (12 Years<=Age<13 Years) <0.50 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (7 Years<=Age<9 Years) >2.8 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | TSH <0.8*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Free T4 <0.8*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (11 Years<=Age<12 Years) >8.90 (mIU/mL) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (9 Years<=Age<11 Years) <0.3 (mIU/mL) | 17 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (12Years<=Age<14Years)<11 (ng/dL) | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (11 Years<=Age<12 Years) <0.40 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (11 Years<=Age<12 Years) >8.90 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Free T4 <0.8*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Free T4 >1.2*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | TSH <0.8*LLN | 2 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | TSH >1.2*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (15 Days<=Age<7 Years) <0.3 (mIU/mL) | 2 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (15 Days<=Age<7 Years) >2.8 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (7 Years<=Age<9 Years) <0.3 (mIU/mL) | 23 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (7 Years<=Age<9 Years) >2.8 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (9 Years<=Age<11 Years) <0.3 (mIU/mL) | 17 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (9 Years<=Age<11 Years) >2.8 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (11 Years<=Age<12 Years) <0.3 (mIU/mL) | 2 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (11 Years<=Age<12 Years) >1.8 (mIU/mL) | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (12 Years<=Age<13 Years) <0.3 (mIU/mL) | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (12 Years<=Age<13 Years) >4.0 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (13 Years<=Age<14 Years) <0.3 (mIU/mL) | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (13 Years<=Age<14 Years) >6.0 (mIU/mL) | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (4 Years<=Age<7 Years) >6.70 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (7 Years<=Age<9 Years) >4.10 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (9 Years<=Age<11 Years) >4.50 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (11 Years<=Age<12 Years) <0.40 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (12 Years<=Age<13 Years) <0.50 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (12 Years<=Age<13 Years) >10.50 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (13 Years<=Age<14 Years) <0.70 (mIU/mL) | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (13 Years<=Age<14 Years) >10.80 (mIU/mL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (1 Year<=Age<7 Years) <8 (ng/dL) | 2 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (1 Year<=Age<7Years) >50(ng/dL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (7 Years<=Age<10Years)<3(ng/dL) | 11 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(7Years<=Age<10Years) >31(ng/dL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(10Years<=Age<12Years) <7(ng/dL) | 8 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (10Years<=Age<12Years)>41 (ng/dL) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (12Years<=Age<14Years)<11 (ng/dL) | 4 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(12 Years<=Age<14Years)>64 (ng/dL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Free T4 <0.8*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (7 Years<=Age<9 Years) >4.10 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (11 Years<=Age<12 Years) <0.40 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (7 Years<=Age<9 Years) >2.8 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (11 Years<=Age<12 Years) >8.90 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Free T4 >1.2*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (12 Years<=Age<13 Years) <0.50 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (7 Years<=Age<9 Years) <0.3 (mIU/mL) | 21 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (12 Years<=Age<13 Years) >10.50 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (15 Days<=Age<7 Years) >2.8 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (10Years<=Age<12Years)>41 (ng/dL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (13 Years<=Age<14 Years) <0.70 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (15 Days<=Age<7 Years) <0.3 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (13 Years<=Age<14 Years) >10.80 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (1 Year<=Age<7 Years) <8 (ng/dL) | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | TSH >1.2*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(12 Years<=Age<14Years)>64 (ng/dL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (1 Year<=Age<7Years) >50(ng/dL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (12Years<=Age<14Years)<11 (ng/dL) | 2 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (7 Years<=Age<10Years)<3(ng/dL) | 10 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | TSH <0.8*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (12 Years<=Age<13 Years) <0.3 (mIU/mL) | 2 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (11 Years<=Age<12 Years) >1.8 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (12 Years<=Age<13 Years) >4.0 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(7Years<=Age<10Years) >31(ng/dL) | 4 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (13 Years<=Age<14 Years) <0.3 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (11 Years<=Age<12 Years) <0.3 (mIU/mL) | 3 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (13 Years<=Age<14 Years) >6.0 (mIU/mL) | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (4 Years<=Age<7 Years) >6.70 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (9 Years<=Age<11 Years) >2.8 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(10Years<=Age<12Years) <7(ng/dL) | 8 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (9 Years<=Age<11 Years) >4.50 (mIU/mL) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (9 Years<=Age<11 Years) <0.3 (mIU/mL) | 23 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (7 Years<=Age<9 Years) >4.10 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (9 Years<=Age<11 Years) <0.3 (mIU/mL) | 27 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (13 Years<=Age<14 Years) >10.80 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | TSH >1.2*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (9 Years<=Age<11 Years) >4.50 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Free T4 <0.8*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(10Years<=Age<12Years) <7(ng/dL) | 10 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (9 Years<=Age<11 Years) >2.8 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (11 Years<=Age<12 Years) <0.40 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (7 Years<=Age<9 Years) >2.8 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (12Years<=Age<14Years)<11 (ng/dL) | 2 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(7Years<=Age<10Years) >31(ng/dL) | 4 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (11 Years<=Age<12 Years) >8.90 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (7 Years<=Age<9 Years) <0.3 (mIU/mL) | 14 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (12 Years<=Age<13 Years) >4.0 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | TSH <0.8*LLN | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (12 Years<=Age<13 Years) <0.50 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (11 Years<=Age<12 Years) <0.3 (mIU/mL) | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione(12 Years<=Age<14Years)>64 (ng/dL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Free T4 >1.2*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (12 Years<=Age<13 Years) >10.50 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (7 Years<=Age<10Years)<3(ng/dL) | 7 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (11 Years<=Age<12 Years) >1.8 (mIU/mL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (13 Years<=Age<14 Years) >6.0 (mIU/mL) | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | FSH (13 Years<=Age<14 Years) <0.70 (mIU/mL) | 2 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (13 Years<=Age<14 Years) <0.3 (mIU/mL) | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Androstenedione (10Years<=Age<12Years)>41 (ng/dL) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | LH (12 Years<=Age<13 Years) <0.3 (mIU/mL) | 2 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function
Liver function evaluation included: total/direct/indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | ALT >3*ULN | 40 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total protein >1.2*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total bilirubin >1.5*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Albumin >1.2*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | GGT >3*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | AST >3*ULN | 39 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Direct bilirubin >1.5*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Albumin <0.8*LLN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Alkaline phosphatase >3*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Glutamate dehydrogenase >1.0*ULN | 8 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Indirect bilirubin >1.5*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total protein <0.8*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Alkaline phosphatase >3*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total protein <0.8*LLN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total protein >1.2*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | AST >3*ULN | 80 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total bilirubin >1.5*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Albumin >1.2*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | ALT >3*ULN | 80 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Glutamate dehydrogenase >1.0*ULN | 8 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | GGT >3*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Albumin <0.8*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Albumin >1.2*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total bilirubin >1.5*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | AST >3*ULN | 76 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | ALT >3*ULN | 78 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | GGT >3*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Alkaline phosphatase >3*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total protein <0.8*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total protein >1.2*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Albumin <0.8*LLN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Glutamate dehydrogenase >1.0*ULN | 6 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Alkaline phosphatase >3*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | GGT >3*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Glutamate dehydrogenase >1.0*ULN | 5 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Albumin <0.8*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | ALT >3*ULN | 75 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | AST >3*ULN | 74 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Indirect bilirubin >1.5*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Albumin >1.2*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Direct bilirubin >1.5*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total protein <0.8*LLN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total bilirubin >1.5*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Total protein >1.2*ULN | 0 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function
Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | BUN >1.3*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | Uric acid >1.2*ULN | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | Creatinine >1.3*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | BUN >1.3*ULN | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | Uric acid >1.2*ULN | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | Creatinine >1.3*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | Creatinine >1.3*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | BUN >1.3*ULN | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | Uric acid >1.2*ULN | 3 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | BUN >1.3*ULN | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | Uric acid >1.2*ULN | 3 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | Creatinine >1.3*ULN | 0 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis
Urinalysis included: urine pH, qualitative urine glucose, qualitative urine ketones, qualitative urine protein, qualitative blood/hemoglobin, urine nitrite, urine leukocytes, urine RBC, urine WBC, urine granular casts, urine hyaline casts, urine urate (uric acid) acidic crystal, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine pH (dipstick) >8 | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine hyaline casts >1 (/LPF) | 2 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine granular casts >1 (/low power field [LPF]) | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine leukocytes (dipstick): +1 | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine microscopic exam: Positive | 31 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine WBC >=20 (/HPF) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine RBC >=20 (/high power field[HPF]) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine glucose (dipstick) >=1 | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine protein (dipstick) >=1 | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine pH (dipstick) <4.5 | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine bacteria >20 (/HPF) | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine amorphous crystals: Present | 7 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine blood/hemoglobin (dipstick) >=1 | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine ketones(dipstick) >=1 | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine calcium oxalate crystals: Present | 19 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine urate (uric acid) acidic crystal: Present | 4 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine nitrite (dipstick) >=1 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine bacteria >20 (/HPF) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine glucose (dipstick) >=1 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine ketones(dipstick) >=1 | 3 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine protein (dipstick) >=1 | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine blood/hemoglobin (dipstick) >=1 | 2 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine nitrite (dipstick) >=1 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine leukocytes (dipstick): +1 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine RBC >=20 (/high power field[HPF]) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine WBC >=20 (/HPF) | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine urate (uric acid) acidic crystal: Present | 2 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine calcium oxalate crystals: Present | 24 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine amorphous crystals: Present | 7 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine microscopic exam: Positive | 50 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine pH (dipstick) <4.5 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine pH (dipstick) >8 | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine glucose (dipstick) >=1 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine bacteria >20 (/HPF) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine calcium oxalate crystals: Present | 23 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine ketones(dipstick) >=1 | 5 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine pH (dipstick) >8 | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine microscopic exam: Positive | 49 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine pH (dipstick) <4.5 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine urate (uric acid) acidic crystal: Present | 2 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine nitrite (dipstick) >=1 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine RBC >=20 (/high power field[HPF]) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine amorphous crystals: Present | 6 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine leukocytes (dipstick): +1 | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine blood/hemoglobin (dipstick) >=1 | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine WBC >=20 (/HPF) | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine protein (dipstick) >=1 | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine WBC >=20 (/HPF) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine blood/hemoglobin (dipstick) >=1 | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine urate (uric acid) acidic crystal: Present | 2 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine calcium oxalate crystals: Present | 24 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine protein (dipstick) >=1 | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine pH (dipstick) <4.5 | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine amorphous crystals: Present | 11 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine ketones(dipstick) >=1 | 6 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine bacteria >20 (/HPF) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine microscopic exam: Positive | 45 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine leukocytes (dipstick): +1 | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Qualitative urine glucose (dipstick) >=1 | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine RBC >=20 (/high power field[HPF]) | 0 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine pH (dipstick) >8 | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urine nitrite (dipstick) >=1 | 0 Participants |
Primary
Number of Participants With Physical Examination Findings Reported as SAEs by Week 49
Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A targeted nose and throat mucosal exam were also performed to monitor for any signs of mucosal telangiectasias. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which physical examination findings were reported as SAEs.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Physical Examination Findings Reported as SAEs by Week 49 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Physical Examination Findings Reported as SAEs by Week 49 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Physical Examination Findings Reported as SAEs by Week 49 | 0 Participants |
Primary
Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. AEs of suicide ideation or behavior were determined by the investigator.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49 | Suicidal ideation | 0 Participants |
| Placebo | Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49 | Suicidal behavior | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49 | Suicidal ideation | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49 | Suicidal behavior | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator.
Time frame: Study Day 1 to Week 49 visit
Population: The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities TEAE | 38 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related TEAE | 14 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities serious TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related serious TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities severe TEAE | 2 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related severe TEAE | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related severe TEAE | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related serious TEAE | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities TEAE | 66 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities serious TEAE | 1 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related TEAE | 18 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities severe TEAE | 2 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related TEAE | 14 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities serious TEAE | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related serious TEAE | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related severe TEAE | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities severe TEAE | 3 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities TEAE | 57 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities severe TEAE | 2 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related severe TEAE | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related TEAE | 16 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | Treatment-related serious TEAE | 1 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities TEAE | 59 Participants |
| Domagrozumab 40 mg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | All-causalities serious TEAE | 1 Participants |
Primary
Number of Participants With Vital Signs Findings Reported as SAEs by Week 49
Vital signs evaluation included supine systolic and diastolic blood pressure (BP), pulse rate, and respiratory rate. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which vital signs findings were reported as SAEs.
Time frame: Baseline to Week 49 visit
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Vital Signs Findings Reported as SAEs by Week 49 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Vital Signs Findings Reported as SAEs by Week 49 | 0 Participants |
Primary
Summary of Tanner Stage Rating by Week 49
Tanner staging was performed before the first dose of each dose escalation to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 1, Week 33 | 22 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 4, Week 17 | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 2, Week 33 | 11 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 2, Week 49 | 11 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 3, Week 33 | 3 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 2, Baseline | 4 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 4, Week 33 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 3, Week 49 | 3 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 5, Week 33 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 5, Week 17 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 1, Week 49 | 21 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 4, Week 49 | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 2, Week 49 | 9 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 1, Week 17 | 30 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 3, Week 49 | 5 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 5, Week 49 | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 4, Week 49 | 2 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 1, Week 33 | 23 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 5, Week 49 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 1, Baseline | 30 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 1, Baseline | 34 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 4, Baseline | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 2, Baseline | 4 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 2, Baseline | 9 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 3, Baseline | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 2, Week 33 | 11 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 4, Baseline | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 3, Baseline | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 5, Baseline | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 2, Week 17 | 9 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 1, Week 17 | 29 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 4, Baseline | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 2, Week 17 | 10 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 3, Week 33 | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 3, Week 17 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 5, Baseline | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 4, Week 17 | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 3, Baseline | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 5, Week 17 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 1, Week 17 | 29 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 1, Week 33 | 24 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 4, Week 33 | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 2, Week 33 | 9 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 2, Week 17 | 10 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 3, Week 33 | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 3, Week 17 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 4, Week 33 | 2 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 3, Week 17 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 5, Week 33 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 5, Week 33 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 1, Week 49 | 19 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 4, Week 17 | 1 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 2, Week 49 | 11 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 5, Baseline | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 3, Week 49 | 4 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 5, Week 17 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 4, Week 49 | 3 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 1, Week 49 | 21 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 5, Week 49 | 0 Participants |
| Placebo | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 1, Baseline | 35 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 5, Week 49 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 1, Baseline | 70 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 2, Baseline | 7 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 3, Baseline | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 4, Baseline | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 5, Baseline | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 1, Week 17 | 64 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 2, Week 17 | 11 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 3, Week 17 | 2 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 4, Week 17 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 5, Week 17 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 1, Week 33 | 60 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 2, Week 33 | 13 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 3, Week 33 | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 4, Week 33 | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 5, Week 33 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 1, Week 49 | 52 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 2, Week 49 | 15 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 3, Week 49 | 4 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 4, Week 49 | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Pubic hair, Stage 5, Week 49 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 1, Baseline | 70 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 2, Baseline | 7 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 3, Baseline | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 4, Baseline | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 5, Baseline | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 1, Week 17 | 68 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 2, Week 17 | 8 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 3, Week 17 | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 4, Week 17 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 5, Week 17 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 1, Week 33 | 58 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 2, Week 33 | 16 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 3, Week 33 | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 4, Week 33 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 5, Week 33 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 1, Week 49 | 57 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 2, Week 49 | 14 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 3, Week 49 | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 4, Week 49 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Penis, Stage 5, Week 49 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 1, Baseline | 67 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 2, Baseline | 10 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 3, Baseline | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 4, Baseline | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 5, Baseline | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 1, Week 17 | 66 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 2, Week 17 | 10 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 3, Week 17 | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 4, Week 17 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 5, Week 17 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 1, Week 33 | 59 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 2, Week 33 | 15 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 3, Week 33 | 1 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 4, Week 33 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 5, Week 33 | 0 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 1, Week 49 | 53 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 2, Week 49 | 15 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 3, Week 49 | 3 Participants |
| Domagrozumab 5 mg/kg | Summary of Tanner Stage Rating by Week 49 | Testes, Stage 4, Week 49 | 0 Participants |
Secondary
Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab
The dosing interval tau was 672 hours (4 weeks). AUCtau was obtained by linear/log trapezoidal method. The AUCtau was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.
Time frame: At predose, end of 2-hour infusion,6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45
Population: This analysis population included participants who were among the first 12 participants enrolled in the study, had received at least 1 dose of domagrozumab and in whom at least 1 of the PK parameters of interest was calculated. Participants without contributing to the summary statistics are excluded below.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 1 | 26500 Microgram*hour per milliliter (ug*hr/mL) |
| Placebo | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 13 | 34650 Microgram*hour per milliliter (ug*hr/mL) |
| Placebo | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 17 | 120500 Microgram*hour per milliliter (ug*hr/mL) |
| Placebo | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 29 | 152000 Microgram*hour per milliliter (ug*hr/mL) |
| Placebo | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 33 | 244500 Microgram*hour per milliliter (ug*hr/mL) |
| Placebo | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 45 | 333500 Microgram*hour per milliliter (ug*hr/mL) |
| Domagrozumab 5 mg/kg | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 1 | 26300 Microgram*hour per milliliter (ug*hr/mL) |
| Domagrozumab 5 mg/kg | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 33 | 291000 Microgram*hour per milliliter (ug*hr/mL) |
| Domagrozumab 5 mg/kg | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 13 | 40500 Microgram*hour per milliliter (ug*hr/mL) |
| Domagrozumab 5 mg/kg | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 29 | 195500 Microgram*hour per milliliter (ug*hr/mL) |
| Domagrozumab 5 mg/kg | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | Week 17 | 117000 Microgram*hour per milliliter (ug*hr/mL) |
Secondary
Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab
Cav was calculated by AUCtau/tau. The Cav was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.
Time frame: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45
Population: This analysis population included participants who were among the first 12 participants enrolled in the study, had received at least 1 dose of domagrozumab and in whom at least 1 of the PK parameters of interest was calculated. Participants without contributing to the summary statistics are excluded below.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 1 | 39.45 ug/mL |
| Placebo | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 13 | 51.55 ug/mL |
| Placebo | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 17 | 179 ug/mL |
| Placebo | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 29 | 226.5 ug/mL |
| Placebo | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 33 | 364 ug/mL |
| Placebo | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 45 | 496 ug/mL |
| Domagrozumab 5 mg/kg | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 1 | 39.2 ug/mL |
| Domagrozumab 5 mg/kg | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 33 | 433.5 ug/mL |
| Domagrozumab 5 mg/kg | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 13 | 60.3 ug/mL |
| Domagrozumab 5 mg/kg | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 29 | 291 ug/mL |
| Domagrozumab 5 mg/kg | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Week 17 | 174 ug/mL |
Secondary
Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets
The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 17
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.2329 Seconds | Standard Error 0.1513 |
| Placebo | Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 0.7644 Seconds | Standard Error 0.4108 |
| Placebo | Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets | Baseline 4SC>8 seconds | 7.7149 Seconds | Standard Error 4.8455 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.1637 Seconds | Standard Error 0.092 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 0.9758 Seconds | Standard Error 0.3283 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets | Baseline 4SC>8 seconds | 5.071 Seconds | Standard Error 3.0969 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.703395% CI: [-0.4345, 0.2961]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<= 8 secondsp-value: 0.689395% CI: [-0.8472, 1.27]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.646995% CI: [-14.4292, 9.1414]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets
The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds.MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 33
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.435 Seconds | Standard Error 0.1852 |
| Placebo | Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 2.2085 Seconds | Standard Error 0.8933 |
| Placebo | Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets | Baseline 4SC>8 seconds | 3.7436 Seconds | Standard Error 8.1156 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.1062 Seconds | Standard Error 0.1061 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 2.5542 Seconds | Standard Error 0.7234 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets | Baseline 4SC>8 seconds | 12.0329 Seconds | Standard Error 3.6174 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.135395% CI: [-0.7649, 0.1072]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<=8 secondsp-value: 0.764895% CI: [-1.9614, 2.6528]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.356295% CI: [-9.6409, 26.2194]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets
The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 1.0056 Seconds | Standard Error 0.294 |
| Placebo | Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets | Baseline 4SC>=3.5 and <= 8 seconds | 3.526 Seconds | Standard Error 1.1574 |
| Placebo | Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets | Baseline 4SC>8 seconds | 30.3411 Seconds | Standard Error 9.7373 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.4474 Seconds | Standard Error 0.1816 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets | Baseline 4SC>=3.5 and <= 8 seconds | 3.6204 Seconds | Standard Error 0.9391 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets | Baseline 4SC>8 seconds | 19.053 Seconds | Standard Error 4.1965 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.116395% CI: [-1.2615, 0.1451]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<=8 secondsp-value: 0.950395% CI: [-3.0798, 3.2686]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.294795% CI: [-32.8328, 10.2566]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 17
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -6.9 Meters | Standard Error 15.4 |
| Placebo | Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -21.0 Meters | Standard Error 8.8 |
| Placebo | Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets | Baseline 4SC>8 seconds | -34.0 Meters | Standard Error 28.3 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -12.7 Meters | Standard Error 9.3 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -22.4 Meters | Standard Error 7 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets | Baseline 4SC>8 seconds | -20.9 Meters | Standard Error 16.3 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.748395% CI: [-42.4, 30.7]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<=8 secondsp-value: 0.905395% CI: [-23.9, 21.2]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.689695% CI: [-53.4, 79.7]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 33
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -12.0 Meters | Standard Error 13.2 |
| Placebo | Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -45.7 Meters | Standard Error 10.9 |
| Placebo | Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets | Baseline 4SC>8 seconds | -71.9 Meters | Standard Error 40.6 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -15.7 Meters | Standard Error 7.8 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -38.4 Meters | Standard Error 8.6 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets | Baseline 4SC>8 seconds | -55.6 Meters | Standard Error 17.5 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.811795% CI: [-34.8, 27.5]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<=8 secondsp-value: 0.601895% CI: [-20.6, 35.2]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.715295% CI: [-73.4, 106]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -33.5 Meters | Standard Error 16.4 |
| Placebo | Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -42.0 Meters | Standard Error 16.7 |
| Placebo | Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets | Baseline 4SC>8 seconds | -75.1 Meters | Standard Error 47.6 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -26.5 Meters | Standard Error 10.1 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -57.8 Meters | Standard Error 13.4 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets | Baseline 4SC>8 seconds | -71.2 Meters | Standard Error 18.9 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.71995% CI: [-32.1, 46.1]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<=8 secondsp-value: 0.463495% CI: [-58.9, 27.3]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.9495% CI: [-100.7, 108.5]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49
FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 | Week 17 | 0.0578 Liters | Standard Error 0.0327 |
| Placebo | Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 | Week 33 | 0.1008 Liters | Standard Error 0.0385 |
| Placebo | Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 | Week 49 | 0.1513 Liters | Standard Error 0.0367 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 | Week 17 | 0.0578 Liters | Standard Error 0.025 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 | Week 33 | 0.0749 Liters | Standard Error 0.0286 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 | Week 49 | 0.1092 Liters | Standard Error 0.0278 |
Comparison: Week 17p-value: 0.999395% CI: [-0.0693, 0.0693]Mixed Models Analysis
Comparison: Week 33p-value: 0.546495% CI: [-0.1107, 0.0589]Mixed Models Analysis
Comparison: Week 49p-value: 0.304195% CI: [-0.1227, 0.0386]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets
FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 17
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.0562 Liters | Standard Error 0.0603 |
| Placebo | Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 0.0543 Liters | Standard Error 0.0352 |
| Placebo | Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets | Baseline 4SC>8 seconds | -0.0168 Liters | Standard Error 0.08 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.0722 Liters | Standard Error 0.0368 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 0.0411 Liters | Standard Error 0.0276 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets | Baseline 4SC>8 seconds | 0.0721 Liters | Standard Error 0.0534 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.822995% CI: [-0.127, 0.1588]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<=8 secondsp-value: 0.770995% CI: [-0.1036, 0.0772]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.374695% CI: [-0.1219, 0.2996]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets
FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 33
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.1971 Liters | Standard Error 0.0659 |
| Placebo | Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 0.0585 Liters | Standard Error 0.0476 |
| Placebo | Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets | Baseline 4SC>8 seconds | 0.0332 Liters | Standard Error 0.1053 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.1036 Liters | Standard Error 0.0389 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 0.0468 Liters | Standard Error 0.0376 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets | Baseline 4SC>8 seconds | 0.0895 Liters | Standard Error 0.0703 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.229495% CI: [-0.2481, 0.0613]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<= 8 secondsp-value: 0.848595% CI: [-0.1339, 0.1105]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.664595% CI: [-0.2187, 0.3312]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets
FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.2199 Liters | Standard Error 0.0675 |
| Placebo | Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 0.1364 Liters | Standard Error 0.0376 |
| Placebo | Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets | Baseline 4SC>8 seconds | 0.0052 Liters | Standard Error 0.0936 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.1186 Liters | Standard Error 0.0418 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 0.1006 Liters | Standard Error 0.0297 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets | Baseline 4SC>8 seconds | 0.1091 Liters | Standard Error 0.0634 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.210195% CI: [-0.2622, 0.0597]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<= 8 secondsp-value: 0.460395% CI: [-0.1326, 0.0608]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.373995% CI: [-0.1386, 0.3463]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Left elbow extension, Week 17 | -0.182 Kilograms | Standard Error 0.183 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Left elbow extension, Week 33 | -0.213 Kilograms | Standard Error 0.187 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Left elbow extension, Week 49 | -0.353 Kilograms | Standard Error 0.2 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Right elbow extension, Week 17 | -0.064 Kilograms | Standard Error 0.209 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Right elbow extension, Week 33 | -0.052 Kilograms | Standard Error 0.197 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Right elbow extension, Week 49 | -0.396 Kilograms | Standard Error 0.192 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Right elbow extension, Week 33 | -0.491 Kilograms | Standard Error 0.148 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Left elbow extension, Week 17 | -0.067 Kilograms | Standard Error 0.141 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Right elbow extension, Week 17 | -0.086 Kilograms | Standard Error 0.158 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Left elbow extension, Week 33 | -0.376 Kilograms | Standard Error 0.141 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Right elbow extension, Week 49 | -0.562 Kilograms | Standard Error 0.145 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Left elbow extension, Week 49 | -0.479 Kilograms | Standard Error 0.15 |
Comparison: Left elbow extension, Week 17p-value: 0.572695% CI: [-0.287, 0.517]Mixed Models Analysis
Comparison: Left elbow extension, Week 33p-value: 0.433495% CI: [-0.574, 0.248]Mixed Models Analysis
Comparison: Left elbow extension, Week 49p-value: 0.576795% CI: [-0.573, 0.321]Mixed Models Analysis
Comparison: Right elbow extension, Week 17p-value: 0.927495% CI: [-0.489, 0.446]Mixed Models Analysis
Comparison: Right elbow extension, Week 33p-value: 0.046995% CI: [-0.872, -0.006]Mixed Models Analysis
Comparison: Right elbow extension, Week 49p-value: 0.436295% CI: [-0.587, 0.255]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Left elbow flexion, Week 17 | -0.096 Kilograms | Standard Error 0.237 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Left elbow flexion, Week 33 | -0.194 Kilograms | Standard Error 0.244 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Left elbow flexion, Week 49 | -0.573 Kilograms | Standard Error 0.205 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Right elbow flexion, Week 17 | -0.035 Kilograms | Standard Error 0.22 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Right elbow flexion, Week 33 | -0.057 Kilograms | Standard Error 0.234 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Right elbow flexion, Week 49 | -0.495 Kilograms | Standard Error 0.199 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Right elbow flexion, Week 33 | -0.418 Kilograms | Standard Error 0.175 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Left elbow flexion, Week 17 | -0.252 Kilograms | Standard Error 0.181 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Right elbow flexion, Week 17 | -0.118 Kilograms | Standard Error 0.168 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Left elbow flexion, Week 33 | -0.497 Kilograms | Standard Error 0.183 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Right elbow flexion, Week 49 | -0.684 Kilograms | Standard Error 0.152 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Left elbow flexion, Week 49 | -0.734 Kilograms | Standard Error 0.159 |
Comparison: Left elbow flexion, Week 17p-value: 0.555795% CI: [-0.679, 0.367]Mixed Models Analysis
Comparison: Left elbow flexion, Week 33p-value: 0.266995% CI: [-0.841, 0.235]Mixed Models Analysis
Comparison: Left elbow flexion, Week 49p-value: 0.466595% CI: [-0.598, 0.276]Mixed Models Analysis
Comparison: Right elbow flexion, Week 17p-value: 0.733595% CI: [-0.564, 0.399]Mixed Models Analysis
Comparison: Right elbow flexion, Week 33p-value: 0.169595% CI: [-0.877, 0.156]Mixed Models Analysis
Comparison: Right elbow flexion, Week 49p-value: 0.378395% CI: [-0.612, 0.234]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Left hip abduction, Week 17 | 0.430 Kilograms | Standard Error 0.321 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Left hip abduction, Week 33 | -0.217 Kilograms | Standard Error 0.318 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Left hip abduction, Week 49 | -0.097 Kilograms | Standard Error 0.334 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Right hip abduction, Week 17 | 0.535 Kilograms | Standard Error 0.32 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Right hip abduction, Week 33 | 0.087 Kilograms | Standard Error 0.34 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Right hip abduction, Week 49 | 0.056 Kilograms | Standard Error 0.343 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Right hip abduction, Week 33 | -0.249 Kilograms | Standard Error 0.255 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Left hip abduction, Week 17 | -0.156 Kilograms | Standard Error 0.245 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Right hip abduction, Week 17 | -0.154 Kilograms | Standard Error 0.247 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Left hip abduction, Week 33 | -0.171 Kilograms | Standard Error 0.236 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Right hip abduction, Week 49 | -0.266 Kilograms | Standard Error 0.26 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Left hip abduction, Week 49 | -0.475 Kilograms | Standard Error 0.251 |
Comparison: Left hip abduction, Week 17p-value: 0.107895% CI: [-1.303, 0.13]Mixed Models Analysis
Comparison: Left hip abduction, Week 33p-value: 0.896795% CI: [-0.654, 0.746]Mixed Models Analysis
Comparison: Left hip abduction, Week 49p-value: 0.319695% CI: [-1.128, 0.371]Mixed Models Analysis
Comparison: Right hip abduction, Week 17p-value: 0.052695% CI: [-1.386, 0.008]Mixed Models Analysis
Comparison: Right hip abduction, Week 33p-value: 0.373995% CI: [-1.082, 0.41]Mixed Models Analysis
Comparison: Right hip abduction, Week 49p-value: 0.401995% CI: [-1.079, 0.436]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Left knee extension, Week 17 | -0.326 Kilograms | Standard Error 0.336 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Left knee extension, Week 33 | -0.713 Kilograms | Standard Error 0.359 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Left knee extension, Week 49 | -1.223 Kilograms | Standard Error 0.369 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Right knee extension, Week 17 | -0.213 Kilograms | Standard Error 0.328 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Right knee extension, Week 33 | -0.413 Kilograms | Standard Error 0.38 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Right knee extension, Week 49 | -0.976 Kilograms | Standard Error 0.391 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Right knee extension, Week 33 | -0.880 Kilograms | Standard Error 0.283 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Left knee extension, Week 17 | -0.434 Kilograms | Standard Error 0.261 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Right knee extension, Week 17 | -0.450 Kilograms | Standard Error 0.253 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Left knee extension, Week 33 | -1.036 Kilograms | Standard Error 0.272 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Right knee extension, Week 49 | -1.125 Kilograms | Standard Error 0.292 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Left knee extension, Week 49 | -1.110 Kilograms | Standard Error 0.279 |
Comparison: Left knee extension, Week 17p-value: 0.767695% CI: [-0.825, 0.61]Mixed Models Analysis
Comparison: Left knee extension, Week 33p-value: 0.412795% CI: [-1.098, 0.454]Mixed Models Analysis
Comparison: Left knee extension, Week 49p-value: 0.781595% CI: [-0.693, 0.919]Mixed Models Analysis
Comparison: Right knee extension, Week 17p-value: 0.497595% CI: [-0.924, 0.451]Mixed Models Analysis
Comparison: Right knee extension, Week 33p-value: 0.264695% CI: [-1.294, 0.359]Mixed Models Analysis
Comparison: Right knee extension, Week 49p-value: 0.73295% CI: [-1.008, 0.71]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Left shoulder abduction, Week 17 | -0.099 Kilograms | Standard Error 0.213 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Left shoulder abduction, Week 33 | -0.123 Kilograms | Standard Error 0.226 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Left shoulder abduction, Week 49 | -0.296 Kilograms | Standard Error 0.238 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Right shoulder abduction, Week 17 | 0.079 Kilograms | Standard Error 0.217 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Right shoulder abduction, Week 33 | 0.421 Kilograms | Standard Error 0.251 |
| Placebo | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Right shoulder abduction, Week 49 | 0.140 Kilograms | Standard Error 0.313 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Right shoulder abduction, Week 33 | -0.336 Kilograms | Standard Error 0.185 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Left shoulder abduction, Week 17 | -0.143 Kilograms | Standard Error 0.163 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Right shoulder abduction, Week 17 | -0.157 Kilograms | Standard Error 0.165 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Left shoulder abduction, Week 33 | -0.278 Kilograms | Standard Error 0.166 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Right shoulder abduction, Week 49 | -0.300 Kilograms | Standard Error 0.229 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Left shoulder abduction, Week 49 | -0.319 Kilograms | Standard Error 0.177 |
Comparison: Left shoulder abduction, Week 17p-value: 0.856995% CI: [-0.525, 0.437]Mixed Models Analysis
Comparison: Left shoulder abduction, Week 33p-value: 0.549595% CI: [-0.663, 0.355]Mixed Models Analysis
Comparison: Left shoulder abduction, Week 49p-value: 0.93495% CI: [-0.566, 0.521]Mixed Models Analysis
Comparison: Right shoulder abduction, Week 17p-value: 0.327995% CI: [-0.711, 0.239]Mixed Models Analysis
Comparison: Right shoulder abduction, Week 33p-value: 0.008695% CI: [-1.318, -0.196]Mixed Models Analysis
Comparison: Right shoulder abduction, Week 49p-value: 0.232895% CI: [-1.165, 0.286]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets
The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 17
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -0.4 Units on a scale | Standard Error 1.8 |
| Placebo | Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -1.3 Units on a scale | Standard Error 0.8 |
| Placebo | Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets | Baseline 4SC>8 seconds | -3.2 Units on a scale | Standard Error 0.9 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -0.7 Units on a scale | Standard Error 1.1 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -0.1 Units on a scale | Standard Error 0.6 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets | Baseline 4SC>8 seconds | -1.9 Units on a scale | Standard Error 0.6 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.892595% CI: [-4.5, 3.9]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<=8 secondsp-value: 0.210795% CI: [-0.7, 3.2]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.229895% CI: [-0.9, 3.5]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets
The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 33
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -3.9 Units on a scale | Standard Error 1.5 |
| Placebo | Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -3.5 Units on a scale | Standard Error 1 |
| Placebo | Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets | Baseline 4SC>8 seconds | -5.6 Units on a scale | Standard Error 1.3 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -0.4 Units on a scale | Standard Error 0.9 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -2.0 Units on a scale | Standard Error 0.8 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets | Baseline 4SC>8 seconds | -2.7 Units on a scale | Standard Error 0.9 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.055495% CI: [-0.1, 7.1]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<= 8 secondsp-value: 0.202795% CI: [-0.9, 4]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.092695% CI: [-0.5, 6.3]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets
The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) \<3.5 seconds, 2)\>=3.5 seconds and \<=8 seconds, 3) \>8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -3.8 Units on a scale | Standard Error 1.8 |
| Placebo | Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets | Baseline 4SC>=3.5 and <= 8 seconds | -4.2 Units on a scale | Standard Error 1.1 |
| Placebo | Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets | Baseline 4SC>8 seconds | -8.4 Units on a scale | Standard Error 1.4 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -1.8 Units on a scale | Standard Error 1.1 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets | Baseline 4SC>=3.5 and <= 8 seconds | -3.7 Units on a scale | Standard Error 0.9 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets | Baseline 4SC>8 seconds | -4.4 Units on a scale | Standard Error 0.9 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.359795% CI: [-2.4, 6.3]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<=8 secondsp-value: 0.734595% CI: [-2.3, 3.3]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.03295% CI: [0.4, 7.7]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets
The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items).Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline.The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 33
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -6.4 Units on a scale | Standard Error 3.3 |
| Placebo | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets | Baseline 4SC>=3.5 and <= 8 seconds | 0 Units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets | Baseline 4SC>8 seconds | -1.0 Units on a scale | Standard Error 1.9 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.1 Units on a scale | Standard Error 2 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets | Baseline 4SC>=3.5 and <= 8 seconds | -0.3 Units on a scale | Standard Error 0.5 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets | Baseline 4SC>8 seconds | -2.0 Units on a scale | Standard Error 1.2 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.09795% CI: [-1.2, 14.2]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<=8 secondsp-value: 0.691995% CI: [-1.9, 1.3]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.673695% CI: [-5.8, 3.9]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets
The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items).Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline.The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.3 Units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -0.9 Units on a scale | Standard Error 0.7 |
| Placebo | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets | Baseline 4SC>8 seconds | -2.6 Units on a scale | Standard Error 1.7 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.3 Units on a scale | Standard Error 0.4 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -1.0 Units on a scale | Standard Error 0.5 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets | Baseline 4SC>8 seconds | -3.5 Units on a scale | Standard Error 1.1 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.958295% CI: [-1.5, 1.5]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<= 8 secondsp-value: 0.862995% CI: [-1.8, 1.5]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.674695% CI: [-5.5, 3.7]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets
The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline .The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Week 17
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | -1.1 Units on a scale | Standard Error 1.1 |
| Placebo | Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | 0.2 Units on a scale | Standard Error 0.7 |
| Placebo | Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets | Baseline 4SC>8 seconds | 0.4 Units on a scale | Standard Error 1.7 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets | Baseline 4SC<3.5 seconds | 0.2 Units on a scale | Standard Error 0.7 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets | Baseline 4SC>=3.5 and <=8 seconds | -1.0 Units on a scale | Standard Error 0.5 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets | Baseline 4SC>8 seconds | -0.5 Units on a scale | Standard Error 1.2 |
Comparison: Baseline 4SC\<3.5 secondsp-value: 0.334595% CI: [-1.3, 3.8]Mixed Models Analysis
Comparison: Baseline 4SC\>=3.5 and \<= 8 secondsp-value: 0.1495% CI: [-2.9, 0.4]Mixed Models Analysis
Comparison: Baseline 4SC\>8 secondsp-value: 0.676495% CI: [-5.4, 3.6]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49
ROM was evaluated by using goniometry to evaluate the loss of motion in the ankles. MMRM was used to analyze the change from baseline on ROM for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Left ankle, Week 17 | -1.0 Degrees of passive dorsiflexion | Standard Error 1.2 |
| Placebo | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Left ankle, Week 33 | -1.9 Degrees of passive dorsiflexion | Standard Error 1.2 |
| Placebo | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Left ankle, Week 49 | -2.3 Degrees of passive dorsiflexion | Standard Error 1.3 |
| Placebo | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Right ankle, Week 17 | -2.1 Degrees of passive dorsiflexion | Standard Error 1.3 |
| Placebo | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Right ankle, Week 33 | -4.1 Degrees of passive dorsiflexion | Standard Error 1.3 |
| Placebo | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Right ankle, Week 49 | -3.6 Degrees of passive dorsiflexion | Standard Error 1.4 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Right ankle, Week 33 | -1.3 Degrees of passive dorsiflexion | Standard Error 0.9 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Left ankle, Week 17 | -1.4 Degrees of passive dorsiflexion | Standard Error 0.9 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Right ankle, Week 17 | -1.3 Degrees of passive dorsiflexion | Standard Error 1 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Left ankle, Week 33 | -1.7 Degrees of passive dorsiflexion | Standard Error 0.9 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Right ankle, Week 49 | -3.6 Degrees of passive dorsiflexion | Standard Error 1.1 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | Left ankle, Week 49 | -3.7 Degrees of passive dorsiflexion | Standard Error 1 |
Comparison: Left ankle, Week 17p-value: 0.733795% CI: [-2.9, 2.1]Mixed Models Analysis
Comparison: Left ankle, Week 33p-value: 0.889395% CI: [-2.4, 2.7]Mixed Models Analysis
Comparison: Left ankle, Week 49p-value: 0.293995% CI: [-4.3, 1.3]Mixed Models Analysis
Comparison: Right ankle, Week 17p-value: 0.599595% CI: [-2.1, 3.6]Mixed Models Analysis
Comparison: Right ankle, Week 33p-value: 0.038595% CI: [0.2, 5.6]Mixed Models Analysis
Comparison: Right ankle, Week 49p-value: 0.992795% CI: [-3.3, 3.2]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49
The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 | Week 17 | -1.9 Units on a scale | Standard Error 0.8 |
| Placebo | Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 | Week 33 | -4.5 Units on a scale | Standard Error 0.8 |
| Placebo | Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 | Week 49 | -5.2 Units on a scale | Standard Error 0.9 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 | Week 17 | -1.1 Units on a scale | Standard Error 0.6 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 | Week 33 | -2.0 Units on a scale | Standard Error 0.6 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 | Week 49 | -3.6 Units on a scale | Standard Error 0.7 |
Comparison: Week 17p-value: 0.352295% CI: [-0.9, 2.5]Mixed Models Analysis
Comparison: Week 33p-value: 0.006195% CI: [0.7, 4.2]Mixed Models Analysis
p-value: 0.126895% CI: [-0.5, 3.8]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49
The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 | Week 17 | -0.7 Units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 | Week 33 | -2.7 Units on a scale | Standard Error 1.1 |
| Placebo | Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 | Week 49 | -1.3 Units on a scale | Standard Error 0.5 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 | Week 17 | -1.0 Units on a scale | Standard Error 0.4 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 | Week 33 | -0.9 Units on a scale | Standard Error 0.8 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 | Week 49 | -1.4 Units on a scale | Standard Error 0.4 |
Comparison: Week 17p-value: 0.604995% CI: [-1.7, 1]Mixed Models Analysis
Comparison: Week 33p-value: 0.206595% CI: [-1, 4.4]Mixed Models Analysis
Comparison: Week 49p-value: 0.939195% CI: [-1.3, 1.2]Mixed Models Analysis
Secondary
Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 | Week 17 | -32.0 Meters | Standard Error 9.1 |
| Placebo | Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 | Week 33 | -52.3 Meters | Standard Error 9.9 |
| Placebo | Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 | Week 49 | -56.5 Meters | Standard Error 12.7 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 | Week 33 | -43.4 Meters | Standard Error 7.4 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 | Week 49 | -58.0 Meters | Standard Error 9.3 |
| Domagrozumab 5 mg/kg | Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 | Week 17 | -30.2 Meters | Standard Error 6.9 |
Comparison: Week 17p-value: 0.849995% CI: [-16.7, 20.3]Mixed Models Analysis
Comparison: Week 33p-value: 0.400895% CI: [-12, 29.8]Mixed Models Analysis
Comparison: Week 49p-value: 0.91695% CI: [-30, 27]Mixed Models Analysis
Secondary
Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97
The thigh muscle volume index was derived from the thigh muscle volume measurements as the fraction of total thigh tissue that was the lean muscle.
Time frame: Baseline, Weeks 17, 33, 49 and 97
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of time points.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 17 | -1.866 Percent of whole thign volume |
| Placebo | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 33 | -4.151 Percent of whole thign volume |
| Placebo | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 49 | -5.750 Percent of whole thign volume |
| Placebo | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 97 | -12.130 Percent of whole thign volume |
| Domagrozumab 5 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 97 | -14.861 Percent of whole thign volume |
| Domagrozumab 5 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 17 | -2.302 Percent of whole thign volume |
| Domagrozumab 5 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 49 | -6.529 Percent of whole thign volume |
| Domagrozumab 5 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 33 | -3.706 Percent of whole thign volume |
| Domagrozumab 20 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 97 | -14.906 Percent of whole thign volume |
| Domagrozumab 20 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 33 | -5.582 Percent of whole thign volume |
| Domagrozumab 20 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 49 | -7.818 Percent of whole thign volume |
| Domagrozumab 20 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | Week 17 | -3.049 Percent of whole thign volume |
Secondary
Change From Baseline in Whole Thigh Muscle Volume Through Week 97
The whole thigh muscle volume was measured by the proton density weighted sequence with magnetic resonance imaging (MRI) which was used to segment the entire thigh region into 3 primary regions for volumetric measure including 1) muscle; 2) inter/intra-muscular fat, 3) subcutaneous fat.
Time frame: Baseline, Weeks 17, 33, 49 and 97
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of time points.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 17 | 36292.279 Cubic centimeters |
| Placebo | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 33 | 37646.693 Cubic centimeters |
| Placebo | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 49 | 37184.268 Cubic centimeters |
| Placebo | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 97 | 22715.921 Cubic centimeters |
| Domagrozumab 5 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 97 | -42588.405 Cubic centimeters |
| Domagrozumab 5 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 17 | 26292.475 Cubic centimeters |
| Domagrozumab 5 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 49 | 25360.797 Cubic centimeters |
| Domagrozumab 5 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 33 | 37037.651 Cubic centimeters |
| Domagrozumab 20 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 97 | -13903.138 Cubic centimeters |
| Domagrozumab 20 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 33 | 12682.521 Cubic centimeters |
| Domagrozumab 20 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 49 | -13438.274 Cubic centimeters |
| Domagrozumab 20 mg/kg | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | Muscle volume, Week 17 | 5624.962 Cubic centimeters |
Secondary
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds)
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC \<3.5 seconds are presented below.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants (with baseline 4SC \<3.5 seconds) randomized and who had received at least 1 dose o f randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right hip abduction, Week 17 | 1.47 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow flexion, Week 49 | -0.88 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right hip abduction, Week 33 | 0.40 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow extension, Week 33 | -0.30 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right hip abduction, Week 49 | -0.75 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow flexion, Week 17 | 1.29 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left knee extension, Week 17 | 0.99 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow extension, Week 49 | -0.74 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left knee extension, Week 33 | 0.11 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow flexion, Week 33 | 1.38 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left knee extension, Week 49 | -1.54 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow extension, Week 17 | 0.35 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right knee extension, Week 17 | 1.01 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow flexion, Week 49 | -0.33 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right knee extension, Week 33 | 0.26 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow flexion, Week 17 | 0.65 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right knee extension, Week 49 | -1.79 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left hip abduction, Week 17 | 0.62 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left shoulder abduction, Week 17 | 0.66 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow extension, Week 49 | -1.13 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left shoulder abduction, Week 33 | 0.48 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left hip abduction, Week 33 | -0.51 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left shoulder abduction, Week 49 | -0.32 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow flexion, Week 33 | 0.95 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right shoulder abduction, Week 17 | 1.16 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left hip abduction, Week 49 | -1.18 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right shoulder abduction, Week 33 | 1.06 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow extension, Week 33 | 0.46 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right shoulder abduction, Week 49 | 0.17 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow extension, Week 17 | -0.08 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right shoulder abduction, Week 49 | -0.20 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow extension, Week 17 | -0.33 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow extension, Week 33 | -0.61 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow extension, Week 49 | -0.60 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow extension, Week 17 | -0.50 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow extension, Week 33 | -0.88 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow extension, Week 49 | -0.78 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow flexion, Week 17 | -0.61 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow flexion, Week 33 | -0.77 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left elbow flexion, Week 49 | -0.96 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow flexion, Week 17 | -0.21 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow flexion, Week 33 | -0.35 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right elbow flexion, Week 49 | -0.69 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left hip abduction, Week 17 | -0.18 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left hip abduction, Week 33 | -0.02 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left hip abduction, Week 49 | -0.30 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right hip abduction, Week 17 | -0.26 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right hip abduction, Week 33 | -0.34 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right hip abduction, Week 49 | -0.14 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left knee extension, Week 17 | -1.12 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left knee extension, Week 33 | -1.31 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left knee extension, Week 49 | -1.33 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right knee extension, Week 17 | -0.97 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right knee extension, Week 33 | -1.31 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right knee extension, Week 49 | -1.47 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left shoulder abduction, Week 17 | -0.33 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left shoulder abduction, Week 33 | -0.32 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Left shoulder abduction, Week 49 | -0.16 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right shoulder abduction, Week 17 | -0.40 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Right shoulder abduction, Week 33 | -0.50 Kilograms |
Secondary
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds)
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC \>=3.5 seconds and \<=8 seconds are presented below.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants (with baseline 4SC \>=3.5 seconds and \<=8 seconds ) randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right hip abduction, Week 17 | 0.30 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow flexion, Week 49 | -0.22 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right hip abduction, Week 33 | 0 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow extension, Week 33 | -0.02 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right hip abduction, Week 49 | 0.32 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow flexion,Week 17 | -0.20 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left knee extension, Week 17 | -0.51 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow extension, Week 49 | -0.02 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left knee extension, Week 33 | -0.59 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow flexion,Week 33 | -0.15 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left knee extension, Week 49 | -0.80 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow extension, Week 17 | 0 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right knee extension, Week 17 | -0.41 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow flexion,Week 49 | -0.21 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right knee extension, Week 33 | -0.35 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow flexion, Week 17 | -0.10 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right knee extension, Week 49 | -0.33 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left hip abduction, Week 17 | 0.65 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left shoulder abduction, Week 17 | -0.24 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow extension, Week 49 | 0.15 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left shoulder abduction, Week 33 | -0.19 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left hip abduction, Week 33 | -0.04 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left shoulder abduction, Week 49 | -0.20 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow flexion, Week 33 | -0.26 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Rightshoulder abduction, Week 17 | -0.18 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left hip abduction, Week 49 | 0.48 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right shoulder abduction, Week 33 | 0.38 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow extension, Week 33 | 0.02 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right shoulder abduction, Week 49 | 0.31 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow extension, Week 17 | -0.05 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right shoulder abduction, Week 49 | -0.19 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow extension, Week 17 | 0.31 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow extension, Week 33 | -0.09 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow extension, Week 49 | -0.26 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow extension, Week 17 | 0.31 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow extension, Week 33 | -0.17 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow extension, Week 49 | -0.29 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow flexion, Week 17 | 0.31 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow flexion, Week 33 | -0.13 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left elbow flexion, Week 49 | -0.31 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow flexion,Week 17 | 0.19 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow flexion,Week 33 | -0.23 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right elbow flexion,Week 49 | -0.43 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left hip abduction, Week 17 | 0.34 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left hip abduction, Week 33 | -0.02 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left hip abduction, Week 49 | -0.09 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right hip abduction, Week 17 | 0.29 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right hip abduction, Week 33 | -0.05 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right hip abduction, Week 49 | 0.20 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left knee extension, Week 17 | 0.50 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left knee extension, Week 33 | -0.67 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left knee extension, Week 49 | -0.59 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right knee extension, Week 17 | 0.14 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right knee extension, Week 33 | -0.53 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right knee extension, Week 49 | -0.69 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left shoulder abduction, Week 17 | 0.49 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left shoulder abduction, Week 33 | 0.03 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Left shoulder abduction, Week 49 | -0.01 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Rightshoulder abduction, Week 17 | 0.14 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Right shoulder abduction, Week 33 | -0.18 Kilograms |
Secondary
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds)
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC \>8 seconds are presented below.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants (with baseline 4SC \>8 seconds) randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right hip abduction, Week 17 | 0.22 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow flexion, Week 49 | -0.34 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right hip abduction, Week 33 | 0.32 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow extension, Week 33 | 0.14 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right hip abduction, Week 49 | 0.68 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow flexion, Week 17 | -0.30 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left knee extension, Week 17 | 0.04 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow extension, Week 49 | 0.06 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left knee extension, Week 33 | -0.24 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow flexion, Week 33 | -0.02 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left knee extension, Week 49 | -0.02 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow extension, Week 17 | 0.32 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right knee extension, Week 17 | 0.32 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow flexion, Week 49 | -0.14 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right knee extension, Week 33 | -0.02 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow flexion, Week 17 | -0.12 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right knee extension, Week 49 | 0.06 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left hip abduction, Week 17 | 0.12 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left shoulder abduction, Week 17 | 0.02 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow extension, Week 49 | 0.08 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left shoulder abduction, Week 33 | -0.12 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left hip abduction, Week 33 | 0.36 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left shoulder abduction, Week 49 | 0.06 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow flexion, Week 33 | -0.36 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right shoulder abduction, Week 17 | 0.14 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left hip abduction, Week 49 | 0.16 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right shoulder abduction, Week 33 | 0.36 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow extension, Week 33 | 0.10 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right shoulder abduction, Week 49 | 0.32 Kilograms |
| Placebo | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow extension, Week 17 | 0.10 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right shoulder abduction, Week 49 | -0.17 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow extension, Week 17 | 0.14 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow extension, Week 33 | 0.06 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow extension, Week 49 | -0.15 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow extension, Week 17 | 0.41 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow extension, Week 33 | 0.23 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow extension, Week 49 | -0.13 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow flexion, Week 17 | 0.10 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow flexion, Week 33 | 0.33 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left elbow flexion, Week 49 | -0.27 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow flexion, Week 17 | 0.20 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow flexion, Week 33 | 0.12 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right elbow flexion, Week 49 | -0.34 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left hip abduction, Week 17 | -0.18 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left hip abduction, Week 33 | 0.65 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left hip abduction, Week 49 | -0.68 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right hip abduction, Week 17 | 0.09 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right hip abduction, Week 33 | 0.80 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right hip abduction, Week 49 | -0.55 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left knee extension, Week 17 | 0.22 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left knee extension, Week 33 | 0.32 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left knee extension, Week 49 | -0.33 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right knee extension, Week 17 | 0.17 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right knee extension, Week 33 | 0.35 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right knee extension, Week 49 | -0.20 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left shoulder abduction, Week 17 | -0.39 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left shoulder abduction, Week 33 | 0.29 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Left shoulder abduction, Week 49 | -0.39 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right shoulder abduction, Week 17 | 0 Kilograms |
| Domagrozumab 5 mg/kg | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Right shoulder abduction, Week 33 | 0.28 Kilograms |
Secondary
Change From Baseline to Week 49 on 4SC for Participants in Sequence 3 Compared to the Natural History Control Group
The 4SC quantified the time required for a participant to ascend 4 standard steps. MMRM was used to analyze the change from baseline on 4SC for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG (Cooperative International Neuromuscular Research Group) natural history database. Participants who met the following requirements at baseline and had evaluable 4SC data on Week 49 were included in this group: 1) age: 6 to \<16 years; 2)treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing.
Time frame: Baseline, Week 49
Population: This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 49 on 4SC for Participants in Sequence 3 Compared to the Natural History Control Group | 3.464 Seconds | Standard Error 1.232 |
p-value: 0.890895% CI: [-2.8353, 3.2573]Mixed Models Analysis
Secondary
Change From Baseline to Week 49 on 6MWD for Participants in Sequence 3 Compared to the Natural History Control Group
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 6MWD data on Week 49 were included in this group: 1) age: 6 to \<16 years; 2)treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing.
Time frame: Baseline, Week 49
Population: This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 49 on 6MWD for Participants in Sequence 3 Compared to the Natural History Control Group | -80.8 Meters | Standard Error 19.3 |
p-value: 0.166995% CI: [-76.9, 13.6]Mixed Models Analysis
Secondary
Change From Baseline to Week 49 on FVC for Participants in Sequence 3 Compared to the Natural History Control Group
FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for the natural history control group compared to placebo group (Sequence 3). MMRM was used to analyze the change from baseline on FVC for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable FVC data on Week 49 were included in this group: 1) age: 6 to \<16 years; 2)treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing.
Time frame: Baseline, Week 49
Population: This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 49 on FVC for Participants in Sequence 3 Compared to the Natural History Control Group | 0.1358 Liters | Standard Error 0.0328 |
p-value: 0.80795% CI: [-0.0692, 0.0887]Mixed Models Analysis
Secondary
Change From Baseline to Week 49 on NSAA for Participants in Sequence 3 Compared to the Natural History Control Group
The NSAA is a 17-item test that measured gross motor function. A total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline on NSAA for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on the using natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable NSAA data on Week 49 were included in this group: 1) age: 6 to \<16 years; 2)treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing.
Time frame: Baseline, Week 49
Population: This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 49 on NSAA for Participants in Sequence 3 Compared to the Natural History Control Group | -4.8 Units on a scale | Standard Error 1.2 |
p-value: 0.048395% CI: [-5.7, 0]Mixed Models Analysis
Secondary
Change From Baseline to Week 97 on 4SC for Participants in Sequence 1 Compared to the Natural History Control Group
The 4SC quantified the time required for a participant to ascend 4 standard steps. MMRM was used to analyze the change from baseline on 4SC for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 4SC data on Week 97 were included in this group: 1) age: 6 to \<16 years; 2) treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing.
Time frame: Baseline, Week 97
Population: This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 97 on 4SC for Participants in Sequence 1 Compared to the Natural History Control Group | 4.205 Seconds | Standard Error 1.011 |
p-value: 0.474895% CI: [-1.4514, 3.0895]Mixed Models Analysis
Secondary
Change From Baseline to Week 97 on 6MWD for Participants in Sequence 1 Compared to the Natural History Control Group
6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 6MWD data on Week 97 were included in this group: 1) age: 6 to \<16 years; 2)treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing.
Time frame: Baseline, Week 97
Population: This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 97 on 6MWD for Participants in Sequence 1 Compared to the Natural History Control Group | -97.6 Meters | Standard Error 20.7 |
p-value: 0.026795% CI: [-124.5, -8.1]Mixed Models Analysis
Secondary
Change From Baseline to Week 97 on FVC for Participants in Sequence 1 Compared to the Natural History Control Group
FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable FVC data on Week 97 were included in this group: 1) age: 6 to \<16 years; 2) treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing.
Time frame: Baseline, Week 97
Population: This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 97 on FVC for Participants in Sequence 1 Compared to the Natural History Control Group | 0.2528 Liters | Standard Error 0.0508 |
p-value: 0.364395% CI: [-0.0594, 0.1607]Mixed Models Analysis
Secondary
Change From Baseline to Week 97 on NSAA for Participants in Sequence 1 Compared to the Natural History Control Group
The NSAA is a 17-item test that measured gross motor function. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline on NSAA for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable NSAA data on Week 97 were included in this group: 1) age: 6 to \<16 years; 2) treatment of glucocorticoid steroids \>=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: \>=55% or missing.
Time frame: Baseline, Week 97
Population: This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 97 on NSAA for Participants in Sequence 1 Compared to the Natural History Control Group | -4.5 Units on a scale | Standard Error 1.2 |
p-value: 0.014695% CI: [-7, -0.8]Mixed Models Analysis
Secondary
Clearance (CL) of Domagrozumab
CL was calculated by Dose/AUCtau. The CL was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.
Time frame: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 13, 29 and 45
Population: This analysis population included participants who were among the first 12 participants enrolled in the study, had received at least 1 dose of domagrozumab and in whom at least 1 of the PK parameters of interest was calculated. Participants without contributing to the summary statistics are excluded below.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Clearance (CL) of Domagrozumab | Week 45 | 0.1225 Milliliter/hr/kilogram(mL/hr/kg) |
| Placebo | Clearance (CL) of Domagrozumab | Week 13 | 0.148 Milliliter/hr/kilogram(mL/hr/kg) |
| Placebo | Clearance (CL) of Domagrozumab | Week 29 | 0.1345 Milliliter/hr/kilogram(mL/hr/kg) |
| Domagrozumab 5 mg/kg | Clearance (CL) of Domagrozumab | Week 29 | 0.102 Milliliter/hr/kilogram(mL/hr/kg) |
| Domagrozumab 5 mg/kg | Clearance (CL) of Domagrozumab | Week 13 | 0.123 Milliliter/hr/kilogram(mL/hr/kg) |
Secondary
Concentration of Growth Differentiation Factor 8 (GDF-8) at Time 0 (Pre-dose),(C0(GDF-8) )
GDF-8, also called myostatin, is the target of domagrozumab. C0(GDF-8) was observed directly from data.
Time frame: Predose on Day 1 of Week 1
Population: This analysis population included all enrolled participants in whom at least 1 GDF-8 concentration value was reported. Participants without contributing to the summary statistics are excluded below.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Concentration of Growth Differentiation Factor 8 (GDF-8) at Time 0 (Pre-dose),(C0(GDF-8) ) | 0.3187 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38773 |
| Domagrozumab 5 mg/kg | Concentration of Growth Differentiation Factor 8 (GDF-8) at Time 0 (Pre-dose),(C0(GDF-8) ) | 0.4557 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 6787 |
| Domagrozumab 20 mg/kg | Concentration of Growth Differentiation Factor 8 (GDF-8) at Time 0 (Pre-dose),(C0(GDF-8) ) | 0.5052 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 7405 |
Secondary
Ctrough,(GDF-8) for Participants of Sequence 3 in Period 2
GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data.
Time frame: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 49 to Week 96
Population: This analysis population included all enrolled participants in Sequence 3 and in whom at least 1 GDF-8 concentration value was reported. Participants without contributing to the summary statistics are excluded below.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Ctrough,(GDF-8) for Participants of Sequence 3 in Period 2 | 5.572 ng/mL | Geometric Coefficient of Variation 36 |
| Domagrozumab 5 mg/kg | Ctrough,(GDF-8) for Participants of Sequence 3 in Period 2 | 7.776 ng/mL | Geometric Coefficient of Variation 45 |
| Domagrozumab 20 mg/kg | Ctrough,(GDF-8) for Participants of Sequence 3 in Period 2 | 8.383 ng/mL | Geometric Coefficient of Variation 53 |
Secondary
Maximum Serum Concentration (Cmax) of Domagrozumab
Cmax was observed directly from data.
Time frame: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3
Population: Data were not collected and analyzed due to study early termination.
Secondary
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97
The criterion for positive result of ADA samples was ADA titer \>=1.88.
Time frame: Baseline, every 4 weeks from Week 5 to Week 97 visit or early termination
Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to the number of participants evaluable for specified rows of time points.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 25 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 5 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 9 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 13 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 17 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 21 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Baseline | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 29 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 33 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 37 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 41 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 45 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 49 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 53 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 57 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 61 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 65 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 69 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 73 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 77 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 81 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 85 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 89 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 93 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 97 | 0 Participants |
| Placebo | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Early termination | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 49 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 97 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Baseline | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 5 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 9 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 13 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 17 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 21 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 25 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 29 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 33 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 37 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 41 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 45 | 0 Participants |
| Domagrozumab 5 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Early termination | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 81 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 53 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 89 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 77 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 57 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 69 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 85 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 93 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 61 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Early termination | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 97 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 49 | 0 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 65 | 1 Participants |
| Domagrozumab 20 mg/kg | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | Week 73 | 0 Participants |
Secondary
Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49
The thigh muscle volume index was derived from the thigh muscle volume measurements as the fraction of total thigh tissue that was the lean muscle. MMRM was used to analyze the percent change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 | Week 17 | -5.434 Percent change of muscle volume index | Standard Error 0.844 |
| Placebo | Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 | Week 33 | -9.408 Percent change of muscle volume index | Standard Error 1.121 |
| Placebo | Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 | Week 49 | -13.357 Percent change of muscle volume index | Standard Error 1.358 |
| Domagrozumab 5 mg/kg | Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 | Week 17 | -3.859 Percent change of muscle volume index | Standard Error 0.657 |
| Domagrozumab 5 mg/kg | Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 | Week 33 | -6.797 Percent change of muscle volume index | Standard Error 0.836 |
| Domagrozumab 5 mg/kg | Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 | Week 49 | -10.149 Percent change of muscle volume index | Standard Error 0.992 |
Comparison: Week 17p-value: 0.068495% CI: [-0.1213, 3.2715]Mixed Models Analysis
Comparison: Week 33p-value: 0.037695% CI: [0.1521, 5.0711]Mixed Models Analysis
Comparison: Week 49p-value: 0.041195% CI: [0.1318, 6.2844]Mixed Models Analysis
Secondary
Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49
The whole thigh muscle volume was measured by the proton density weighted sequence with magnetic resonance imaging (MRI) which was used to segment the entire thigh region into 3 primary regions for volumetric measure including 1) muscle; 2) inter/intra-muscular fat, 3) subcutaneous fat. MMRM was used to analyze the percent change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.
Time frame: Baseline, Weeks 17, 33 and 49
Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of time points.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 | Week 17 | 0.979 Percent change of thigh muscle volume | Standard Error 1.062 |
| Placebo | Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 | Week 33 | 1.380 Percent change of thigh muscle volume | Standard Error 1.349 |
| Placebo | Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 | Week 49 | -0.802 Percent change of thigh muscle volume | Standard Error 1.623 |
| Domagrozumab 5 mg/kg | Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 | Week 17 | 3.924 Percent change of thigh muscle volume | Standard Error 0.871 |
| Domagrozumab 5 mg/kg | Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 | Week 33 | 4.298 Percent change of thigh muscle volume | Standard Error 1.043 |
| Domagrozumab 5 mg/kg | Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 | Week 49 | 3.285 Percent change of thigh muscle volume | Standard Error 1.22 |
Comparison: Week 17p-value: 0.008795% CI: [0.7597, 5.1309]Mixed Models Analysis
Comparison: Week 33p-value: 0.053695% CI: [-0.0461, 5.8811]Mixed Models Analysis
Comparison: Week 49p-value: 0.029895% CI: [0.4069, 7.7677]Mixed Models Analysis
Secondary
Terminal Half-life (t1/2) of Domagrozumab for Participants in Sequence 2 After the Last Dose of Domagrozumab
t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Participants in Sequence 2 received the last dose of domagrozumab at Week 45.
Time frame: At predose, end of 2-hour infusion and 6 hours since start of infusion at Week 45
Population: Data were not collected and analyzed due to study early termination.
Secondary
Time for Cmax (Tmax) of Domagrozumab
Tmax was observed directly from the data.
Time frame: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3
Population: Data were not collected and analyzed due to study early termination.
Secondary
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab
Ctrough was observed directly from data.
Time frame: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3
Population: This analysis population included all participants who received at least 1 dose of domagrozumab and in whom at least 1 concentration value was reported. Participants without contributing to the summary statistics are excluded below. Number analyzed refers to number of participants evaluable for specified rows of timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 49 | 289.1 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 31 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 53 | 307.3 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 29 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 93 | 380.2 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 17 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 57 | 331.3 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 29 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 89 | 352.9 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 26 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 61 | 327.6 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 34 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 65 | 315.4 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 39 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 85 | 367 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 27 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 69 | 315.7 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 28 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 81 | 340.5 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 26 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 73 | 333.8 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 34 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 77 | 309.6 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 51 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 9 | 25.11 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 32 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 29 | 131.4 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 26 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 17 | 31.36 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 30 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 33 | 130.9 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 36 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 5 | 18.66 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 28 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 37 | 227.5 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 33 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 21 | 89.57 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 43 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 41 | 260.9 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 31 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 13 | 30.36 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 28 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 45 | 295.7 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 32 |
| Placebo | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 25 | 122.2 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 25 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 21 | 97.5 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 32 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 5 | 19.26 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 48 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 9 | 27.95 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 28 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 13 | 31.98 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 39 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 17 | 35.08 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 33 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 1 | 75.3 Microgram per milliliter (ug/mL) | — |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 25 | 129.4 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 28 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 29 | 140.4 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 31 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 33 | 148.2 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 32 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 37 | 250.7 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 44 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 41 | 284.5 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 29 |
| Domagrozumab 5 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 45 | 323.4 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 22 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 73 | 168.1 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 30 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 77 | 185.9 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 27 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 69 | 139.5 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 47 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 81 | 201.2 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 30 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 65 | 48.39 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 39 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 85 | 314.6 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 32 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 57 | 39.9 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 31 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 89 | 367.4 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 33 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 53 | 25.72 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 36 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 93 | 418.4 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 33 |
| Domagrozumab 20 mg/kg | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Week 61 | 42.62 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 46 |
Secondary
Trough Serum Concentration of GDF-8 (Ctrough,(GDF-8)) for Participants Receiving Domagrozumab in Period 1
GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data.
Time frame: Every 4 weeks on dosing day (at predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 48
Population: This analysis population included all enrolled participants in Sequences 1 and 2 in whom at least 1 GDF-8 concentration value was reported. Participants without contributing to the summary statistics are excluded below.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough Serum Concentration of GDF-8 (Ctrough,(GDF-8)) for Participants Receiving Domagrozumab in Period 1 | 4.540 ng/mL | Geometric Coefficient of Variation 43 |
| Domagrozumab 5 mg/kg | Trough Serum Concentration of GDF-8 (Ctrough,(GDF-8)) for Participants Receiving Domagrozumab in Period 1 | 6.257 ng/mL | Geometric Coefficient of Variation 42 |
| Domagrozumab 20 mg/kg | Trough Serum Concentration of GDF-8 (Ctrough,(GDF-8)) for Participants Receiving Domagrozumab in Period 1 | 7.449 ng/mL | Geometric Coefficient of Variation 40 |
Secondary
Volume of Distribution at Steady State (Vss) of Domagrozumab for Participants in Sequence 2 Required for Additional PK Assessment
Vss was calculated by CL\*MRT, where MRT was the mean residence time. Vss was assessed to fully characterize PK data.
Time frame: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Week 45
Population: Data were not collected and analyzed due to study early termination.
Other Pre-specified
Area Under the Curve From Time Zero to Last Quantifiable Serum Concentration (AUClast) of Domagrozumab
AUClast was calculated by linear/log trapezoidal method. AUCtau was obtained by linear/log trapezoidal method. AUClast was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.
Time frame: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45
Population: Data were not collected and analyzed due to study early termination.