Achondroplasia
Conditions
Keywords
Dwarfism, Bone Diseases, Bone Diseases, Developmental, ACH, Natriuretic Peptide, C-Type, Musculoskeletal Diseases, Natriuretic Agents, Physiological Effect of Drugs, Skeletal Dysplasias, Genetic Diseases, Inborn, Osteochondrodysplasias
Brief summary
Study 111-206 is a Phase 2 randomized, double-blind, placebo-controlled clinical trial of BMN 111 in infants and young children with a diagnosis of achondroplasia.
Interventions
DRUGBMN 111
Subcutaneous injection of 15 μg/kg/day and/or 30 μg/kg/day of BMN 111 daily, subject to adjustment per protocol
DRUGPlacebo
Subcutaneous injection of 15 μg/kg of placebo daily, Subject to adjustment per protocol
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 59 Months
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of achondroplasia (ACH), confirmed by genetic testing. If subjects had previous genetic testing, subjects must have a lab report from a certified laboratory with the study specific mutation documented. 2. Age 0 to \< 60 months, at study entry (Day 1) 3. Cohort 1 and 2 subjects must have at least a 6-month period of pretreatment growth assessment in Study 111 901 immediately before screening, and have one documented measurement of height/body length a minimum of 6 months prior to the screening visit for 111-206. Cohort 3 subjects must have a minimum of 3 months of observation prior to treatment. This observational period can be obtained either (1) via prior enrollment in Study 111-901 or (2) via enrollment in this Study 111 206 for a minimum of 3 months of non-treatment observation prior to commencement of treatment. 4. Parent(s) or guardian(s) (and the subjects themselves, if required by local regulations or ethics committee) are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any research-related procedure 5. Willing and able to perform all study procedures as physically possible 6. Parent(s) or caregiver(s) are willing to administer daily injections to the subjects and complete the required training
Exclusion criteria
1. Have hypochondroplasia or short-stature condition other than achondroplasia (e.g., trisomy 21, pseudoachondroplasia, etc.) 2. Subject weighs \< 5.0 kg (Cohort 1 and 2) or \< 4.0 kg (Cohort 3) 3. Have any of the following: * Hypothyroidism or hyperthyroidism * Insulin-requiring diabetes mellitus * Autoimmune inflammatory disease (including celiac disease, systemic lupus erythematosus, juvenile dermatomyositis, scleroderma, etc.) * Inflammatory bowel disease * Autonomic neuropathy 4. Have a history of any of the following: * Renal insufficiency defined as serum creatinine \> 2 mg/dL * Chronic anemia or Hgb \<10.0 g/dL (based on screening clinical laboratory testing) * Baseline systolic blood pressure (BP) below age and gender specified normal range or recurrent symptomatic hypotension (defined as episodes of low BP generally accompanied by symptoms e.g., dizziness, fainting) or recurrent symptomatic orthostatic hypotension * Cardiac or vascular disease, including the following * Cardiac dysfunction (abnormal echocardiogram determined to be clinically significant by principal investigator PI and medical monitor) at Screening Visit * Hypertrophic cardiomyopathy * Pulmonary hypertension * Congenital heart disease with ongoing cardiac dysfunction * Cerebrovascular disease * Aortic insufficiency or other clinically significant valvular dysfunction * Clinically significant atrial or ventricular arrhythmias 5. Have a clinically significant finding or arrhythmia that indicates abnormal cardiac function or conduction or Fridericia's corrected QT interval (QTc-F) \>450 msec on screening ECG 6. Have evidence of cervicomedullary compression (CMC) likely to require surgical intervention within 60 days of Screening as determined by the Investigator based on the following assessments * Physical exam (e.g., neurologic findings of clonus, opisthotonus, exaggerated reflexes, dilated facial veins) * Polysomnography (e.g., severe central sleep apnea) * MRI indicating presence of severe CMC or spinal cord damage 7. Have an unstable medical condition likely to require surgical intervention in the next 6 months, or planned spine or long-bone surgery (i.e., surgery involving significant disruption of bone cortex) during the study period 8. Have documented uncorrected Vitamin D deficiency: 25(OH)D \<=15 ng/mL (37.5 nmol/L) 9. Require any other investigational product prior to completion of the study period 10. Have received another investigational product or investigational medical device within 30 days prior to the Screening visit 11. Have used any other investigational product or investigational medical device for the treatment of achondroplasia or short stature at any time 12. Require current chronic therapy with antihypertensive medication or any medication that, in the investigator's judgment, may compromise the safety or ability of the subject to participate in this clinical study (Table 9.3.5.1) 13. Have been treated with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic steroids in the 6 months prior to screening, or long-term treatment (\>3 months) at any time 14. Have had regular long-term treatment (\> 1 month) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma, or intranasal steroids, are acceptable) in the 12 months prior to screening 15. Have ever had cervicomedullary decompression surgery (Cohorts 2 and 3 only), spine or long-bone surgery (i.e., surgery involving disruption of bone cortex) or have ever had bone-related surgery with chronic complications NOTE: Subjects with prior cervicomedullary decompression may be allowed into Cohort 1 only after discussion and agreement with Medical Monitor. 16. Have ever had limb-lengthening surgery or plan to have limb-lengthening surgery during the study period 17. Have had a fracture of the long bones or spine within 6 months prior to screening 18. Have aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or total bilirubin greater than upper limit of normal (ULN) at screening (except for subjects with a known history of Gilberts or newborns entering screening in Cohort 3) 19. Have evidence of severe untreated sleep apnea; or have newly initiated sleep apnea treatment (eg, Continuous positive airway pressure (CPAP) or sleep apnea-mitigating surgery) in the 2 months prior to screening 20. Have current malignancy, history of malignancy, or currently under work-up for suspected malignancy 21. Have known hypersensitivity to BMN 111 or its excipients 22. Have a history of hip surgery or severe hip dysplasia 23. Have a history of clinically significant hip injury in the 30 days prior to screening 24. Have a history of slipped capital femoral epiphysis or avascular necrosis of the femoral head 25. Have abnormal findings on baseline clinical hip exam or imaging assessments that are determined to be clinically significant as determined by the Investigator 26. Have a condition or circumstance that, in the view of the Investigator, places the subject at high risk for poor treatment compliance or for not completing the study 27. Have any concurrent disease or condition that, in the view of the Investigator, would interfere with study participation or safety evaluations, for any reason Inclusion Criteria for Cohort 3 Observation Period 1. Parent(s) or guardian(s) willing and able to provide signed informed consent after the nature of the study has been explained and prior to performance of any research-related procedure. Also, willing and able to provide written assent (if applicable) after the nature of the study has been explained and prior to performance of any research-related procedure. 2. Birth to \<= 3 months of age at study entry. 3. Have ACH, documented by genetic testing 4. Are willing and able to perform all study procedures as physically possible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Up to Week 56 (Safety Follow-Up +/-7d) | A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. A severity grade was defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE. Safety Population includes all sentinel and randomized participants in the FAS who received at least one dose of vosoritide or placebo in this study. Serious adverse event (SAE) |
| Change From Baseline in Height Z-score at Week 52. | Baseline to Week 52 | Z-Scores were derived using age-sex specific reference data (means and SDS) for average stature children per the Centers for Disease Control and Prevention. A height Z score of 0 would indicate that the subject's height is equal to the mean height for the average stature population of the same sex and age. A positive height Z score indicates that the subjects height is above the mean height for the average stature population of the same sex and age, whilst a negative height Z score indicates that the subjects height is below the mean height for the average stature population of the same sex and age. To conclude if the height Z score increases then this means the height deficit has decreased. standard deviation score (SDS). The primary efficacy analysis population was the subset of randomized participants in the FAS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Height at Week 52 | Baseline to Week 52 | As a general rule, standing height/sitting height was used if participants were aged \>= 24 months at baseline. Body length/crown to rump was used if participants were aged \< 24 months at baseline. If body length was not measured and standing height was available, standing height was used. |
| Change From Baseline in Annualized Growth Velocity (AGV) at Week 52 | Baseline to Week 52 | AGV was derived over 12-month intervals starting from the baseline visit. Annualized growth velocity (AGV) = Standing Height at Date 2 - Standing Height at Date 1/Interval Length (Days) x 365.25. Difference in LS means were obtained from an analysis of covariance model. |
| Change From Baseline in Upper to Lower Body Segment Ratio at Week 52 | Baseline to Week 52 | Upper to Lower Body ratio=Sitting Height / (Standing Height - Sitting Height). |
| Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Baseline to Week 52 | Change from baseline in other growth measures (upper body length, head circumference, arm span, upper arm length, lower arm (Forearm) length, Lower Body Length, Upper Leg Length (Thigh), knee to heel length, and tibial length) at Week 52. Participants aged \<24 months, body length and crown to rump length take precedence over standing height and sitting height. Participants aged \<24 months at baseline and \>=24 months at Week 52, body length and crown to rump length take precedence. |
| Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Baseline to Week 52 | For Height: subjects aged \< 24 months, body length takes precedence over standing height. Subjects aged \< 24 months at baseline and \>= 24 months at Week 52, body length takes precedence. |
| Change From Baseline in Body Mass Index (BMI) at Week 52 | Baseline to Week 52 | Body Mass Index (BMI): For height used for BMI calculation, participants aged \< 24 months, body length takes precedence over standing height. Participants aged \< 24 months at baseline and \>= 24 months at Week 52, body length takes precedence. |
| Change From Baseline in BMI Z-score at Week 52 | Baseline to Week 52 | The body mass index (BMI) Z-score represents the participant's BMI converted to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. The weight Z-score of 0 represents the mean BMI for age and sex of the reference population. A positive BMI Z-score means BMI is above the mean BMI for the average stature population of the same sex and age and a negative BMI Z-Score means BMI is below the mean BMI for the average stature population of the same sex and age. BMI Z-scores are derived only for participants aged 24 months or older, the change from baseline to Week 52 in BMI Z-score is summarized for Cohort 1 only as no participants in Cohort 2 or Cohort 3 were 24 months at baseline. |
| Change From Baseline in Weight Z-score at Week 52 | Baseline to Week 52 | The weight Z-score represents the participant's weight converted to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. The weight Z-score of 0 represents the mean weight for age and sex of the reference population. A positive weight Z-score means weight is above the mean weight for the average stature population of the same sex and age and a negative weight Z-Score means weight is below the mean weight for the average stature population of the same sex and age. |
| Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Baseline to Week 52 | 97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). |
| Change From Baseline in ITQoL-Behavior Scores at Week 52 | Baseline to Week 52 | 97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). The number of subjects assessed in Cohort 3 Placebo is 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/ baseline. Hence, Mean and Standard Deviation (SD) are not applicable. Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed. |
| Change From Baseline in ITQoL-Global Behavior Scores at Week 52 | Baseline to Week 52 | 97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). A higher score indicates better global behaviour. The number of subjects assessed in Cohort 3 Placebo is 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/ baseline. Hence, Mean and Standard Deviation (SD) are not applicable. Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed. |
| Change From Baseline in ITQoL-Getting On With Other Score at Week 52 | Baseline to Week 52 | 97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). A higher score indicates better global health perceptions. The number of subjects assessed in Cohort 3 Placebo and Cohort 3 vosoritide are 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/baseline. Hence, Mean and Standard Deviation (SD) are not applicable. Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed. |
| Change From Baseline in ITQoL-Health Score at Week 52 | Baseline to Week 52 | 97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). A higher score indicates better global change in health. The number of subjects assessed in Cohort 3 Placebo is 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/ baseline. Hence, Mean and Standard Deviation (SD) are not applicable. Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed. |
| Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | Baseline to Week 52 | The Pediatric Functional Independence Measure-II (WeeFIM®-II) is designed to measure functional independence of children between the ages of 6 months & 18 yrs who have physical or general developmental limitations. The WeeFIM-II is comprised of 3 domains that are rated by clinicians based on information obtained from parents/caregivers (self-care \[score range 8 to 56\], mobility \[score range 8 to 35\], & cognition \[score range 8 to 35\]) & provides a total score between 18 (worst) & 126 (Best). Higher score reflects higher level of independence. Performance of a child on each of individual items within WeeFIM is assigned to one of seven levels on an ordinal scale that represent function from complete & modified independence (levels 7 & 6) without a helping person to modified & complete dependence (levels 5 to 1) with a helping person. Functional Independence Measure (Wee-FIM-II) is only validated in children ages 6 months to 18 yrs. Therefore results for Cohort 3 is not summarized. |
| Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Baseline to Week 52 | BSID-III is performance-based clinician-reported outcome assessment for use in children from 1 to 42 months (1 month to 3.5 years). individually administered by the trained clinician to the participant/child Scales include Cognitive subscale, Receptive and Expressive subscales, and Gross and Fine Motor subscales. The two language scales make up a composite Language Scale score and the Gross and Fine Motor subscales yield a composite Motor Scale score. In addition, there is a Social-Emotional Scale and Adaptive Behavior Scale, which is a questionnaire read and completed by parent or caregiver. Scores range from 0 to 2, and indicate mastery (2), emerging (1) or zero (not present) Each (sub)scale yields a total raw score, standardized according to the participant's chronological age (scaled scores) |
| Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | Baseline to Week 52 | The CBCL is used as a screening tool for emotional or behavioral problems, measuring initial behavior severity, tracking changes in behavioral problems over the course of treatment, and treatment planning. The CBCL 1.5-5 years old consists of 100 questions, scored on a three-point Likert scale (0=Not True (as far as you know), 1= Somewhat or Sometimes True, 2=Very True or Often True). The scores for each individual question within a domain are summed to give a domain score. The CBCL uses a normative sample to create standard scores, which are scaled so that 50 is average with a standard deviation of 10, where higher scores indicate more emotional or behavioral issues. CBCL was waived for children \< 18 months old. Therefore results for Cohort 3 is not summarized. |
| Change From Baseline in Bilateral X-rays of Left Femur Length (cm) to Tibia Length (cm) Ratio and Right Femur Length (cm) to Tibia Length (cm) Ratio at Week 52 | Baseline to Week 52 End point timeframe: | — |
| Change From Baseline in Bilateral X-rays of Left Tibia Length (cm) to Fibula Length (cm) Ratio & Right Tibia Length (cm) to Fibula Length (cm) Ratio at Week 52 | Baseline to Week 52 | — |
| Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Baseline to Week 52 | — |
| Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Baseline to Week 52 | — |
| Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Baseline to Week 52 | Baseline is defined as Day 1 or screening if a Day 1 assessment is not available. |
| Change From Baseline in X-ray of Lumbar Spine Angles at Week 52 | Baseline to Week 52 | — |
| Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Baseline to Week 52 | Percentages were calculated using the total number of subjects in the safety population (N for each treatment group) as the denominator. All increases are comparing results at Week 52 relative to the baseline assessment. |
| MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Baseline to Week 52 | — |
| MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Baseline to Week 52 | — |
| MRI Parameter: Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level | Baseline to Week 52 | — |
| MRI Parameter: Percentage Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level | Baseline to Week 52 | — |
| MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Baseline to Week 52 | — |
| MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Baseline to Week 52 | — |
| Dual X Ray Absorptiometry (DEXA) Parameter: Change From Baseline to Week 52 for Whole Body Less Head Bone Mineral Content (BMC) | Baseline to Week 52 | — |
| DEXA Parameter: Change From Baseline to Week 52 of Whole Body Less Head Bone Mineral Density (BMD) | Baseline to Week 52 | — |
| DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMC | Baseline to Week 52 | — |
| DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMC | Baseline to Week 52 | — |
| DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMD | Baseline to Week 52 | — |
| DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMD | Baseline to Week 52 | — |
| Change From Baseline to Week 52 in Whole Body BMD Z-score | Baseline to Week 52 | Hologic - Discovery Horizon Whole Body BMD Z-Score. Change in whole body bone mineral density (BMD) Z-score from baseline at 52 weeks indicates whether there has been a positive or negative change in BMD using a z-score generated by converting the participants BMD to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. A whole body BMD Z-score \<-2 SD can indicate low bone density in children. The Whole Body BMD (bone mineral density) z-score compares the BMD to the average bone density of people of the same age, and sex as a comparator. A Z-score less than 0 means that the participant has a lower BMD than people in the same age and sex group, and could indicate a risk of osteopenia or osteoporosis. |
| Change From Baseline to Week 52 in Lumbar Spine BMD Z-Score | Baseline to Week 52 | Hologic - Discovery Horizon Lumbar Spine BMD Z-Score Change in lumbar spine bone mineral density (BMD) Z-score from baseline at 52 weeks indicates whether there has been a positive or negative change in BMD using a z-score generated by converting the participants lumbar spine BMD to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. A BMD Z-score \<-2 SD can indicate low bone density in the lumbar spine in children. The Lumbar Spine BMD (bone mineral density) z-score compares the BMD in the lumbar spine to the average spinal bone density of people of the same age, and sex as a comparator. A Z-score less than 0 means that the participant has a lower BMD than people in the same age and sex group, and could indicate a risk of osteopenia or osteoporosis of the spine. |
| Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | At Day 1, Week 3, Week 13, Week 26, Week 52, & Ever Positive. | Number of participants with Incidence of Antibody Positivity at Scheduled Visits for : total antibody (TAb), Neutralizing antibodies (NAb), atrial natriuretic peptide (ANP), B-type Natriuretic Peptide (BNP) & C-type natriuretic peptide (CNP). TAb Titer Positive, NAb Titer Positive, ANP Reactivity Positive, BNP Reactivity Positive & CNP Reactivity Positive. Day 1 is the baseline assessment result taken prior to first dose of study drug. Ever Positive = the number of participants with at least one positive sample result. |
| Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | At Baseline, Day 8, Week 6, Week 20, & Week 39. | — |
| Biomarker: Type II Collagen C-Telopeptides Normalized for Creatinine (CTX-II) | Baseline to Week 52. | — |
| Biomarker: Plasma Cyclic Guanosine Monophosphate (cGMP) Change From Pre-Dose to Maximum Post-Dose at Week 52 | Week 52 Pre-Dose to Week 52 Maximum Post-Dose. | — |
| Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | At Baseline, Day 8, Week 6, Week 20, & Week 39. | Laboratory results up to 30 days after study drug discontinuation were included. Baseline is the last measurement prior to the initiation of study drug. |
| Change in Sleep Study Indices at Week 52 | Baseline to Week 52 | Sleep-testing device was used to assess presence & severity of sleep-disordered breathing by measurement of blood oxygen(O2)saturation,pulse rate,& airflow during overnight monitoring Episodes(Epi) of sleep apnea variables summarized as: Number(No.)of epi of apnea/hr(AI);No.of epi of hypopnea/hr(HI);No.of epi of obstructive apnea hypopneas/hr(AHI);No.of epi of obstructive apneas/hr(Obstructive Apnea Index);No.of epi of central apneas/hr(CAI);No.of desaturations/hr \>=3% AHI is a marker of obstructive sleep apnea (OSA), scored as No.of apnea or hypopnea epi/hr, with AHI \<=1/hr normal, 1\< AHI\<=5 mild,5\< AHI \<=10 moderate,& AHI\>10/hr severe OSA. CAI reflects cervical cord compression at cervical-medullary junction, & is No. of epi of a pause in ventilation with no associated respiratory effort, with\> 5 epi/hr abnormal.O2 desaturation index measures average No. of desaturation epi/hr, defined as decrease in O2 saturation of \>=3% for at least 10sec, with(\<8/hr normal & \>=8/hr abnormal |
| PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | At Day1, Week 13, Week 26, Week 39, & Week 52. | Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics. PK parameters for another participant on Day 1 obtained from extrapolation. AUC0-∞ excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected. |
| PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | At Day 01, Week 13, Week 26, Week 39, & Week 52 | — |
| PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | At Day 01, Week 13, Week 26, Week 39, & Week 52 | — |
| Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Baseline to Week 52 | — |
| PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | At Day 01, Week 13, Week 26, Week 39, & Week 52. | — |
| PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | At Day 01, Week 13, Week 26, Week 39, & Week 52. | Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics. PK parameters for another participant on Day 1 obtained from extrapolation. AUC0-∞, CL/F, V/F and t1/2 excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected. |
| PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | At Day 01, Week 13, Week 26, Week 39, & Week 52. | Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics. PK parameters for another participant on Day 1 obtained from extrapolation. V/F excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected. |
| PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | At Day 01, Week 13, Week 26, Week 39, & Week 52. | Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics. PK parameters for another participant on Day 1 obtained from extrapolation. AUC0-∞, CL/F, V/F and t1/2 excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected. |
| PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | At Day 01, Week 13, Week 26, Week 39, & Week 52 | — |
| Change From Baseline in Bilateral X-rays of Left/Right Tibia Bowing Angle at Week 52 | Baseline to Week 52 | — |
Countries
Australia, Japan, United Kingdom, United States
Participant flow
Recruitment details
This was a multi-center study conducted by 16 principal investigators at 16 study centers in four countries (United States, Australia, United Kingdom and Japan).
Pre-assignment details
A total of 75 participants (full analysis set \[FAS\]) were enrolled into the study, of which 11 participants were enrolled to receive vosoritide (sentinel participants). 64 participants were blinded and randomized to receive vosoritide or placebo (32 randomized for vosoritide and 32 for placebo), which constituted the FAS (randomized).
Participants by arm
| Arm | Count |
|---|---|
| Sentinel Cohort 1 Sentinel: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=4)
Cohort 2 Sentinel: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day & 30 µg/kg/day single daily subcutaneous injection (n=4)
Cohort 3 Sentinel: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=3) | 11 |
| Randomized Vosoritide Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received vosoritide 15 µg/kg/day single daily subcutaneous injection (n=15)
Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received vosoritide 15 µg/kg/day & 30 µg/kg/day single daily subcutaneous injection (n=8)
Cohort 3: Participants stratified by age 0 to \< 6 months, received vosoritide 30 µg/kg/day single daily subcutaneous injection (n=9) | 32 |
| Randomized Placebo Cohort 1: Participants stratified by age \>= 24 to \< 60 months, received placebo single daily subcutaneous injection (n=16)
Cohort 2: Participants stratified by age \>= 6 to \< 24 months, received placebo single daily subcutaneous injection (n=8)
Cohort 3: Participants stratified by age 0 to \< 6 months, received placebo single daily subcutaneous injection (n=8) | 32 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | AE of sudden infant death syndrome, not related | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Randomized Vosoritide | Randomized Placebo | Total | Sentinel |
|---|---|---|---|---|
| Age, Continuous | 23.0 Months STANDARD_DEVIATION 16.9 | 26.5 Months STANDARD_DEVIATION 19.3 | 24.5 Months STANDARD_DEVIATION 18.4 | 24.71 Months STANDARD_DEVIATION 20.79 |
| BMI | 19.48 kg/m^2 STANDARD_DEVIATION 2.45 | 20.14 kg/m^2 STANDARD_DEVIATION 2.39 | 19.85 kg/m^2 STANDARD_DEVIATION 2.34 | 20.06 kg/m^2 STANDARD_DEVIATION 1.87 |
| BMI Z-Score | 2.52 Z-Score STANDARD_DEVIATION 1.15 | 2.77 Z-Score STANDARD_DEVIATION 0.75 | 2.67 Z-Score STANDARD_DEVIATION 0.94 | 2.79 Z-Score STANDARD_DEVIATION 0.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 29 Participants | 69 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian-Japanese | 4 Participants | 4 Participants | 8 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian-Other | 6 Participants | 2 Participants | 9 Participants | 1 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 21 Participants | 25 Participants | 54 Participants | 8 Participants |
| Sex: Female, Male Female | 15 Participants | 19 Participants | 37 Participants | 3 Participants |
| Sex: Female, Male Male | 17 Participants | 13 Participants | 38 Participants | 8 Participants |
| Weight | 10.20 Kg STANDARD_DEVIATION 3.83 | 10.55 Kg STANDARD_DEVIATION 4.31 | 10.34 Kg STANDARD_DEVIATION 3.98 | 10.12 Kg STANDARD_DEVIATION 3.7 |
| Weight Z-Score | -1.49 Z-Score STANDARD_DEVIATION 1.26 | -1.59 Z-Score STANDARD_DEVIATION 1.44 | -1.52 Z-Score STANDARD_DEVIATION 1.27 | -1.41 Z-Score STANDARD_DEVIATION 0.73 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 1 / 43 |
| other Total, other adverse events | 32 / 32 | 43 / 43 |
| serious Total, serious adverse events | 6 / 32 | 3 / 43 |
Outcome results
Primary
Change From Baseline in Height Z-score at Week 52.
Z-Scores were derived using age-sex specific reference data (means and SDS) for average stature children per the Centers for Disease Control and Prevention. A height Z score of 0 would indicate that the subject's height is equal to the mean height for the average stature population of the same sex and age. A positive height Z score indicates that the subjects height is above the mean height for the average stature population of the same sex and age, whilst a negative height Z score indicates that the subjects height is below the mean height for the average stature population of the same sex and age. To conclude if the height Z score increases then this means the height deficit has decreased. standard deviation score (SDS). The primary efficacy analysis population was the subset of randomized participants in the FAS.
Time frame: Baseline to Week 52
Population: FAS \& FAS (randomized) population:The FAS (randomized) was a subset of the FAS, which included 64 participants who were randomized to study treatment (32 participants randomized to vosoritide \& 32 participants randomized to placebo).~This is model-based analysis, it is true that the participants analyzed for placebo FAS \& FAS (randomized) are the same, but participants analyzed for vosoritide arm FAS \& FAS(randomized) are different, that's why the model-based results for placebo are different
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sentinel | Change From Baseline in Height Z-score at Week 52. | -0.06 Z-score |
| Randomized Vosoritide | Change From Baseline in Height Z-score at Week 52. | -0.31 Z-score |
| Randomized Placebo | Change From Baseline in Height Z-score at Week 52. | 0.01 Z-score |
| Placebo | Change From Baseline in Height Z-score at Week 52. | -0.30 Z-score |
Comparison: Z-Scores were derived using age-sex specific reference data (means and SDs) for average stature children per the Centers for Disease Control and Prevention.~Participants aged \< 24 months, body length takes precedence over standing height. Participants aged \< 24 months at baseline and \>= 24 months at Week 52, body length takes precedence.~Difference in least squares (LS) means were obtained from an analysis of covariance model.95% CI: [-0.02, 0.53]
Comparison: Z-Scores were derived using age-sex specific reference data (means and SDs) for average stature children per the Centers for Disease Control and Prevention.~Participants aged \< 24 months, body length takes precedence over standing height. Participants aged \< 24 months at baseline and \>= 24 months at Week 52, body length takes precedence.~Difference in LS means were obtained from an analysis of covariance model.95% CI: [0.07, 0.54]
Primary
Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs)
A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. A severity grade was defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE. Safety Population includes all sentinel and randomized participants in the FAS who received at least one dose of vosoritide or placebo in this study. Serious adverse event (SAE)
Time frame: Up to Week 56 (Safety Follow-Up +/-7d)
Population: Safety Population: The Safety Population was a subset of the FAS who received at least one dose of vosoritide or placebo in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sentinel | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any AE | 11 Participants |
| Sentinel | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any SAE | 0 Participants |
| Sentinel | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any treatment-related AE | 8 Participants |
| Sentinel | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any treatment-related SAEs | 0 Participants |
| Sentinel | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any AE of CTCAE grade >=3 | 0 Participants |
| Sentinel | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants who died | 0 Participants |
| Randomized Vosoritide | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants who died | 1 Participants |
| Randomized Vosoritide | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any AE | 32 Participants |
| Randomized Vosoritide | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any treatment-related SAEs | 0 Participants |
| Randomized Vosoritide | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any AE of CTCAE grade >=3 | 2 Participants |
| Randomized Vosoritide | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any SAE | 3 Participants |
| Randomized Vosoritide | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any treatment-related AE | 29 Participants |
| Randomized Placebo | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any SAE | 6 Participants |
| Randomized Placebo | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any treatment-related AE | 17 Participants |
| Randomized Placebo | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants who died | 0 Participants |
| Randomized Placebo | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any treatment-related SAEs | 0 Participants |
| Randomized Placebo | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any AE | 32 Participants |
| Randomized Placebo | Number of Participants With Adverse Events (AEs) by Severity Grade and Study Drug Treatment-emergent Adverse Events (TEAEs) | Participants with any AE of CTCAE grade >=3 | 3 Participants |
Secondary
Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM
Laboratory results up to 30 days after study drug discontinuation were included. Baseline is the last measurement prior to the initiation of study drug.
Time frame: At Baseline, Day 8, Week 6, Week 20, & Week 39.
Population: Safety Population.~Change from baseline was based on subjects with available measurements at both timepoints.Overall no. of participants analyzed(N) is greater than no. analyzed for All Vosoritide, as different participants missed for different timepoints(Ex:1 of 42 participants who were part of CNP Col X BM:Baseline was not present in 42 participants who participated in CNP Col X BM:Day 8.Therefore, n for CNP Col X BM:Baseline \& CNP Col X BM:Day 8 are 42 however, overall no of subjects,N=43)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Week 39 | 12249.7 pg/mL | Standard Deviation 5056.5 |
| Sentinel | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Week 20 | 12833.3 pg/mL | Standard Deviation 4581.9 |
| Sentinel | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Change from baseline to Week 39 | 2362.8 pg/mL | Standard Deviation 5752.9 |
| Sentinel | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Change from baseline to Week 6 | 3400.3 pg/mL | Standard Deviation 4554.6 |
| Sentinel | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Baseline | 9833.8 pg/mL | Standard Deviation 3444.7 |
| Sentinel | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Change from baseline to Week 20 | 2928.0 pg/mL | Standard Deviation 4385.9 |
| Sentinel | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Day 8 | 12093.8 pg/mL | Standard Deviation 4443.8 |
| Sentinel | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Week 6 | 13456.3 pg/mL | Standard Deviation 4763.3 |
| Sentinel | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Change from baseline to Day 8 | 2139.5 pg/mL | Standard Deviation 3871.9 |
| Randomized Vosoritide | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Week 6 | 9464.8 pg/mL | Standard Deviation 4243.3 |
| Randomized Vosoritide | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Change from baseline to Day 8 | 1391.3 pg/mL | Standard Deviation 3354.2 |
| Randomized Vosoritide | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Change from baseline to Week 6 | 200.3 pg/mL | Standard Deviation 3867.5 |
| Randomized Vosoritide | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Week 20 | 12064.8 pg/mL | Standard Deviation 5277.3 |
| Randomized Vosoritide | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Change from baseline to Week 20 | 2435.5 pg/mL | Standard Deviation 4666.9 |
| Randomized Vosoritide | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Week 39 | 9932.7 pg/mL | Standard Deviation 4004.4 |
| Randomized Vosoritide | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Change from baseline to Week 39 | 946.4 pg/mL | Standard Deviation 3490.1 |
| Randomized Vosoritide | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Baseline | 9555.0 pg/mL | Standard Deviation 4016.7 |
| Randomized Vosoritide | Biomarker: Bone and Collagen Metabolism Biomarker Over Time-CNP Col X BM | CNP Col X BM: Day 8 | 10017.5 pg/mL | Standard Deviation 3831.2 |
Secondary
Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime
Time frame: At Baseline, Day 8, Week 6, Week 20, & Week 39.
Population: Safety population~Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is the last measurement prior to the initiation of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Week 6 | 130.38 U/L | Standard Deviation 140.08 |
| Sentinel | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Week 20 | 109.67 U/L | Standard Deviation 30.88 |
| Sentinel | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Change from baseline to Day 8 | -19.39 U/L | Standard Deviation 202.9 |
| Sentinel | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Change from baseline to Week 20 | -7.21 U/L | Standard Deviation 96.94 |
| Sentinel | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Baseline | 140.28 U/L | Standard Deviation 183.23 |
| Sentinel | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Week 39 | 108.49 U/L | Standard Deviation 32.02 |
| Sentinel | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Day 8 | 122.32 U/L | Standard Deviation 99.09 |
| Sentinel | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Change from baseline to Week 39 | -12.21 U/L | Standard Deviation 105.04 |
| Sentinel | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Change from baseline to Week 6 | 2.63 U/L | Standard Deviation 218.6 |
| Randomized Vosoritide | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Change from baseline to Week 39 | 95.41 U/L | Standard Deviation 352.78 |
| Randomized Vosoritide | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Day 8 | 104.12 U/L | Standard Deviation 29.12 |
| Randomized Vosoritide | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Change from baseline to Day 8 | -7.67 U/L | Standard Deviation 17.53 |
| Randomized Vosoritide | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Week 6 | 109.46 U/L | Standard Deviation 29.04 |
| Randomized Vosoritide | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Baseline | 113.43 U/L | Standard Deviation 33.56 |
| Randomized Vosoritide | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Change from baseline to Week 6 | -6.17 U/L | Standard Deviation 24.32 |
| Randomized Vosoritide | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Week 20 | 104.46 U/L | Standard Deviation 29.69 |
| Randomized Vosoritide | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Change from baseline to Week 20 | -11.32 U/L | Standard Deviation 18.19 |
| Randomized Vosoritide | Biomarker: Bone Specific Alkaline Phosphatase (BSAP) Overtime | BSAP: Week 39 | 208.13 U/L | Standard Deviation 363.56 |
Secondary
Biomarker: Plasma Cyclic Guanosine Monophosphate (cGMP) Change From Pre-Dose to Maximum Post-Dose at Week 52
Time frame: Week 52 Pre-Dose to Week 52 Maximum Post-Dose.
Population: Safety population. Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is the last measurement prior to the initiation of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Biomarker: Plasma Cyclic Guanosine Monophosphate (cGMP) Change From Pre-Dose to Maximum Post-Dose at Week 52 | 39.079 nM | Standard Deviation 25.706 |
| Randomized Vosoritide | Biomarker: Plasma Cyclic Guanosine Monophosphate (cGMP) Change From Pre-Dose to Maximum Post-Dose at Week 52 | 9.460 nM | Standard Deviation 26.307 |
Secondary
Biomarker: Type II Collagen C-Telopeptides Normalized for Creatinine (CTX-II)
Time frame: Baseline to Week 52.
Population: Safety Population~Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is the last measurement prior to the initiation of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Biomarker: Type II Collagen C-Telopeptides Normalized for Creatinine (CTX-II) | -9364.7 ng/ mmol Cr | Standard Deviation 65244.1 |
| Randomized Vosoritide | Biomarker: Type II Collagen C-Telopeptides Normalized for Creatinine (CTX-II) | -7607.6 ng/ mmol Cr | Standard Deviation 54614.9 |
Secondary
Change From Baseline in Annualized Growth Velocity (AGV) at Week 52
AGV was derived over 12-month intervals starting from the baseline visit. Annualized growth velocity (AGV) = Standing Height at Date 2 - Standing Height at Date 1/Interval Length (Days) x 365.25. Difference in LS means were obtained from an analysis of covariance model.
Time frame: Baseline to Week 52
Population: FAS (randomized) Population and FAS population.~This is model-based analysis, it is true that the participants analyzed for placebo FAS \& FAS (randomized) are the same, but participants analyzed for vosoritide arm FAS \& FAS (randomized) are different, that's why the model-based results for placebo are different.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sentinel | Change From Baseline in Annualized Growth Velocity (AGV) at Week 52 | -2.17 cm/year |
| Randomized Vosoritide | Change From Baseline in Annualized Growth Velocity (AGV) at Week 52 | -2.95 cm/year |
| Randomized Placebo | Change From Baseline in Annualized Growth Velocity (AGV) at Week 52 | -2.41 cm/year |
| Placebo | Change From Baseline in Annualized Growth Velocity (AGV) at Week 52 | -3.32 cm/year |
95% CI: [0.02, 1.54]
Comparison: Difference in LS means were obtained from an analysis of covariance model.95% CI: [0.24, 1.59]
Secondary
Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52
BSID-III is performance-based clinician-reported outcome assessment for use in children from 1 to 42 months (1 month to 3.5 years). individually administered by the trained clinician to the participant/child Scales include Cognitive subscale, Receptive and Expressive subscales, and Gross and Fine Motor subscales. The two language scales make up a composite Language Scale score and the Gross and Fine Motor subscales yield a composite Motor Scale score. In addition, there is a Social-Emotional Scale and Adaptive Behavior Scale, which is a questionnaire read and completed by parent or caregiver. Scores range from 0 to 2, and indicate mastery (2), emerging (1) or zero (not present) Each (sub)scale yields a total raw score, standardized according to the participant's chronological age (scaled scores)
Time frame: Baseline to Week 52
Population: FAS population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language composite score | 4.5 Score on a scale | Standard Deviation 2.1 |
| Sentinel | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Expressive communication language scaled score | 2.5 Score on a scale | Standard Deviation 0.7 |
| Sentinel | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language sum of scaled score | 1.5 Score on a scale | Standard Deviation 0.7 |
| Sentinel | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive scaled score | -1.0 Score on a scale | Standard Deviation 2.8 |
| Sentinel | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Gross motor scaled score | 0.0 Score on a scale | Standard Deviation 5.7 |
| Sentinel | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive composite score | -5.0 Score on a scale | Standard Deviation 14.1 |
| Sentinel | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Fine motor scaled score | -0.5 Score on a scale | Standard Deviation 3.5 |
| Sentinel | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Receptive communication language scaled score | -1.0 Score on a scale | Standard Deviation 0 |
| Sentinel | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Motor Composite Score | -2.0 Score on a scale | Standard Deviation 5.7 |
| Randomized Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Receptive communication language scaled score | -1.8 Score on a scale | Standard Deviation 2.5 |
| Randomized Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Fine motor scaled score | 0.0 Score on a scale | Standard Deviation 2.9 |
| Randomized Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Motor Composite Score | 4.8 Score on a scale | Standard Deviation 11.5 |
| Randomized Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language sum of scaled score | -1.5 Score on a scale | Standard Deviation 3.3 |
| Randomized Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language composite score | -4.5 Score on a scale | Standard Deviation 9.9 |
| Randomized Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Expressive communication language scaled score | 0.3 Score on a scale | Standard Deviation 1.3 |
| Randomized Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive composite score | -2.5 Score on a scale | Standard Deviation 8.7 |
| Randomized Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive scaled score | -0.5 Score on a scale | Standard Deviation 1.7 |
| Randomized Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Gross motor scaled score | 1.0 Score on a scale | Standard Deviation 0.8 |
| Randomized Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Expressive communication language scaled score | 2.8 Score on a scale | Standard Deviation 2.9 |
| Randomized Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Motor Composite Score | 12.0 Score on a scale | Standard Deviation 17.5 |
| Randomized Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language sum of scaled score | 6.0 Score on a scale | Standard Deviation 5.2 |
| Randomized Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Gross motor scaled score | 2.8 Score on a scale | Standard Deviation 3.2 |
| Randomized Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive scaled score | 3.3 Score on a scale | Standard Deviation 4.9 |
| Randomized Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive composite score | 16.7 Score on a scale | Standard Deviation 24.7 |
| Randomized Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Receptive communication language scaled score | 3.3 Score on a scale | Standard Deviation 4 |
| Randomized Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language composite score | 17.8 Score on a scale | Standard Deviation 15.2 |
| Randomized Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Fine motor scaled score | 1.5 Score on a scale | Standard Deviation 3.3 |
| Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive composite score | 3.1 Score on a scale | Standard Deviation 16 |
| Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive scaled score | 0.6 Score on a scale | Standard Deviation 3.2 |
| Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Expressive communication language scaled score | -0.1 Score on a scale | Standard Deviation 2.2 |
| Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Gross motor scaled score | 1.3 Score on a scale | Standard Deviation 2.8 |
| Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Receptive communication language scaled score | 1.0 Score on a scale | Standard Deviation 1.2 |
| Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Motor Composite Score | -2.3 Score on a scale | Standard Deviation 12.3 |
| Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Fine motor scaled score | -2.1 Score on a scale | Standard Deviation 2.5 |
| Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language composite score | 5.3 Score on a scale | Standard Deviation 12.1 |
| Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language sum of scaled score | 1.8 Score on a scale | Standard Deviation 4 |
| Cohort 3: Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Gross motor scaled score | -0.2 Score on a scale | Standard Deviation 3.1 |
| Cohort 3: Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive composite score | 7.5 Score on a scale | Standard Deviation 9.4 |
| Cohort 3: Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language composite score | -13.4 Score on a scale | Standard Deviation 5.8 |
| Cohort 3: Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Fine motor scaled score | 2.2 Score on a scale | Standard Deviation 4.8 |
| Cohort 3: Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive scaled score | 1.5 Score on a scale | Standard Deviation 1.9 |
| Cohort 3: Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Motor Composite Score | 5.4 Score on a scale | Standard Deviation 22.2 |
| Cohort 3: Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Receptive communication language scaled score | -3.0 Score on a scale | Standard Deviation 2.1 |
| Cohort 3: Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Expressive communication language scaled score | -1.8 Score on a scale | Standard Deviation 1.6 |
| Cohort 3: Placebo | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language sum of scaled score | -7.3 Score on a scale | Standard Deviation 6.4 |
| Cohort 3: Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language composite score | -0.9 Score on a scale | Standard Deviation 19.5 |
| Cohort 3: Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Motor Composite Score | 11.1 Score on a scale | Standard Deviation 18.1 |
| Cohort 3: Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Receptive communication language scaled score | 0.7 Score on a scale | Standard Deviation 5.2 |
| Cohort 3: Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive scaled score | 2.1 Score on a scale | Standard Deviation 4.4 |
| Cohort 3: Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Language sum of scaled score | -0.3 Score on a scale | Standard Deviation 6.6 |
| Cohort 3: Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Expressive communication language scaled score | -0.1 Score on a scale | Standard Deviation 3.3 |
| Cohort 3: Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Gross motor scaled score | 0.1 Score on a scale | Standard Deviation 3 |
| Cohort 3: Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Fine motor scaled score | 2.6 Score on a scale | Standard Deviation 2.7 |
| Cohort 3: Vosoritide | Change From Baseline in Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) Scores at Week 52 | Cognitive composite score | 10.6 Score on a scale | Standard Deviation 22.1 |
Secondary
Change From Baseline in Bilateral X-rays of Left Femur Length (cm) to Tibia Length (cm) Ratio and Right Femur Length (cm) to Tibia Length (cm) Ratio at Week 52
Time frame: Baseline to Week 52 End point timeframe:
Population: Safety Population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in Bilateral X-rays of Left Femur Length (cm) to Tibia Length (cm) Ratio and Right Femur Length (cm) to Tibia Length (cm) Ratio at Week 52 | Left Femur Length (cm) to Tibia Length (cm) Ratio | -0.03 Ratio | Standard Deviation 0.06 |
| Sentinel | Change From Baseline in Bilateral X-rays of Left Femur Length (cm) to Tibia Length (cm) Ratio and Right Femur Length (cm) to Tibia Length (cm) Ratio at Week 52 | Right Femur Length (cm) to Tibia Length (cm) Ratio | -0.05 Ratio | Standard Deviation 0.06 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Left Femur Length (cm) to Tibia Length (cm) Ratio and Right Femur Length (cm) to Tibia Length (cm) Ratio at Week 52 | Left Femur Length (cm) to Tibia Length (cm) Ratio | -0.05 Ratio | Standard Deviation 0.05 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Left Femur Length (cm) to Tibia Length (cm) Ratio and Right Femur Length (cm) to Tibia Length (cm) Ratio at Week 52 | Right Femur Length (cm) to Tibia Length (cm) Ratio | -0.02 Ratio | Standard Deviation 0.03 |
Secondary
Change From Baseline in Bilateral X-rays of Left/Right Tibia Bowing Angle at Week 52
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in Bilateral X-rays of Left/Right Tibia Bowing Angle at Week 52 | Left Tibia Bowing Angle | -0.97 Degrees | Standard Deviation 5.88 |
| Sentinel | Change From Baseline in Bilateral X-rays of Left/Right Tibia Bowing Angle at Week 52 | Right Tibia Bowing Angle | -2.34 Degrees | Standard Deviation 5.37 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Left/Right Tibia Bowing Angle at Week 52 | Left Tibia Bowing Angle | 1.07 Degrees | Standard Deviation 5.38 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Left/Right Tibia Bowing Angle at Week 52 | Right Tibia Bowing Angle | -0.93 Degrees | Standard Deviation 5.54 |
Secondary
Change From Baseline in Bilateral X-rays of Left Tibia Length (cm) to Fibula Length (cm) Ratio & Right Tibia Length (cm) to Fibula Length (cm) Ratio at Week 52
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in Bilateral X-rays of Left Tibia Length (cm) to Fibula Length (cm) Ratio & Right Tibia Length (cm) to Fibula Length (cm) Ratio at Week 52 | Left Tibia Length (cm) to Fibula Length (cm) Ratio | -0.02 Ratio | Standard Deviation 0.04 |
| Sentinel | Change From Baseline in Bilateral X-rays of Left Tibia Length (cm) to Fibula Length (cm) Ratio & Right Tibia Length (cm) to Fibula Length (cm) Ratio at Week 52 | Right Tibia Length (cm) to Fibula Length(cm) Ratio | -0.02 Ratio | Standard Deviation 0.05 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Left Tibia Length (cm) to Fibula Length (cm) Ratio & Right Tibia Length (cm) to Fibula Length (cm) Ratio at Week 52 | Left Tibia Length (cm) to Fibula Length (cm) Ratio | -0.04 Ratio | Standard Deviation 0.04 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Left Tibia Length (cm) to Fibula Length (cm) Ratio & Right Tibia Length (cm) to Fibula Length (cm) Ratio at Week 52 | Right Tibia Length (cm) to Fibula Length(cm) Ratio | -0.03 Ratio | Standard Deviation 0.04 |
Secondary
Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Right Tibia Length | 1.96 cm | Standard Deviation 0.57 |
| Sentinel | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Left Fibula Length | 2.00 cm | Standard Deviation 0.61 |
| Sentinel | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Right Fibula Length | 2.00 cm | Standard Deviation 0.64 |
| Sentinel | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Left Tibia Length | 1.92 cm | Standard Deviation 0.55 |
| Sentinel | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Left Distance Between Ankle Joint and Distal Growth Plate of Fibula | -0.02 cm | Standard Deviation 0.23 |
| Sentinel | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Right Distance Between Ankle Joint and Distal Growth Plate of Fibula | -0.05 cm | Standard Deviation 0.23 |
| Sentinel | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Left Lower Extremity | 6.02 cm | Standard Deviation 6.67 |
| Sentinel | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Right Lower Extremity | 6.08 cm | Standard Deviation 6.54 |
| Sentinel | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Left Femur Length | 2.29 cm | Standard Deviation 0.58 |
| Sentinel | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Right Femur Length | 2.35 cm | Standard Deviation 0.49 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Right Lower Extremity | 4.26 cm | Standard Deviation 1.85 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Right Tibia Length | 1.68 cm | Standard Deviation 0.77 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Right Distance Between Ankle Joint and Distal Growth Plate of Fibula | 0.05 cm | Standard Deviation 0.22 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Left Fibula Length | 1.97 cm | Standard Deviation 0.69 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Right Femur Length | 2.20 cm | Standard Deviation 0.73 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Right Fibula Length | 1.89 cm | Standard Deviation 0.75 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Left Lower Extremity | 3.87 cm | Standard Deviation 1.56 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Left Tibia Length | 1.69 cm | Standard Deviation 0.7 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Left Femur Length | 2.01 cm | Standard Deviation 0.62 |
| Randomized Vosoritide | Change From Baseline in Bilateral X-rays of Lower Extremities at Week 52 | Left Distance Between Ankle Joint and Distal Growth Plate of Fibula | 0.07 cm | Standard Deviation 0.23 |
Secondary
Change From Baseline in BMI Z-score at Week 52
The body mass index (BMI) Z-score represents the participant's BMI converted to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. The weight Z-score of 0 represents the mean BMI for age and sex of the reference population. A positive BMI Z-score means BMI is above the mean BMI for the average stature population of the same sex and age and a negative BMI Z-Score means BMI is below the mean BMI for the average stature population of the same sex and age. BMI Z-scores are derived only for participants aged 24 months or older, the change from baseline to Week 52 in BMI Z-score is summarized for Cohort 1 only as no participants in Cohort 2 or Cohort 3 were 24 months at baseline.
Time frame: Baseline to Week 52
Population: FAS population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Change From Baseline in BMI Z-score at Week 52 | -0.12 Z-Score | Standard Deviation 0.48 |
| Randomized Vosoritide | Change From Baseline in BMI Z-score at Week 52 | -0.18 Z-Score | Standard Deviation 0.65 |
Secondary
Change From Baseline in Body Mass Index (BMI) at Week 52
Body Mass Index (BMI): For height used for BMI calculation, participants aged \< 24 months, body length takes precedence over standing height. Participants aged \< 24 months at baseline and \>= 24 months at Week 52, body length takes precedence.
Time frame: Baseline to Week 52
Population: FAS population.~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 measurement is not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Change From Baseline in Body Mass Index (BMI) at Week 52 | 0.20 kg/m^2 | Standard Deviation 1.34 |
| Randomized Vosoritide | Change From Baseline in Body Mass Index (BMI) at Week 52 | -0.45 kg/m^2 | Standard Deviation 0.94 |
| Randomized Placebo | Change From Baseline in Body Mass Index (BMI) at Week 52 | 0.55 kg/m^2 | Standard Deviation 1.17 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at Week 52 | 0.08 kg/m^2 | Standard Deviation 0.75 |
| Cohort 3: Placebo | Change From Baseline in Body Mass Index (BMI) at Week 52 | 0.74 kg/m^2 | Standard Deviation 1.7 |
| Cohort 3: Vosoritide | Change From Baseline in Body Mass Index (BMI) at Week 52 | 0.94 kg/m^2 | Standard Deviation 1.42 |
Secondary
Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52
The CBCL is used as a screening tool for emotional or behavioral problems, measuring initial behavior severity, tracking changes in behavioral problems over the course of treatment, and treatment planning. The CBCL 1.5-5 years old consists of 100 questions, scored on a three-point Likert scale (0=Not True (as far as you know), 1= Somewhat or Sometimes True, 2=Very True or Often True). The scores for each individual question within a domain are summed to give a domain score. The CBCL uses a normative sample to create standard scores, which are scaled so that 50 is average with a standard deviation of 10, where higher scores indicate more emotional or behavioral issues. CBCL was waived for children \< 18 months old. Therefore results for Cohort 3 is not summarized.
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Total Problems Total | -3.0 Score on a scale | Standard Deviation 13 |
| Sentinel | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Sleep Problems Total | -0.3 Score on a scale | Standard Deviation 3.2 |
| Sentinel | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Somatic Complaints Total | 0.1 Score on a scale | Standard Deviation 1.7 |
| Sentinel | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Anxious/Depressed Total | 0.3 Score on a scale | Standard Deviation 1.7 |
| Sentinel | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Emotionally Reactive Total | -0.2 Score on a scale | Standard Deviation 1.5 |
| Sentinel | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Aggressive Behavior Total | -1.1 Score on a scale | Standard Deviation 2.4 |
| Sentinel | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Attention Problems Total | -0.1 Score on a scale | Standard Deviation 1.9 |
| Sentinel | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Withdrawn Total | -0.6 Score on a scale | Standard Deviation 1.7 |
| Randomized Vosoritide | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Emotionally Reactive Total | 0.1 Score on a scale | Standard Deviation 1.4 |
| Randomized Vosoritide | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Anxious/Depressed Total | 0.2 Score on a scale | Standard Deviation 1.4 |
| Randomized Vosoritide | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Withdrawn Total | 0.6 Score on a scale | Standard Deviation 1.5 |
| Randomized Vosoritide | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Somatic Complaints Total | 0.3 Score on a scale | Standard Deviation 1 |
| Randomized Vosoritide | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Sleep Problems Total | 0.1 Score on a scale | Standard Deviation 1.9 |
| Randomized Vosoritide | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Attention Problems Total | -0.1 Score on a scale | Standard Deviation 1.6 |
| Randomized Vosoritide | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Aggressive Behavior Total | 0.3 Score on a scale | Standard Deviation 4.1 |
| Randomized Vosoritide | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Total Problems Total | 2.8 Score on a scale | Standard Deviation 11.7 |
| Randomized Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Withdrawn Total | 0.8 Score on a scale | Standard Deviation 2.2 |
| Randomized Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Sleep Problems Total | -0.3 Score on a scale | Standard Deviation 1.7 |
| Randomized Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Emotionally Reactive Total | 1.0 Score on a scale | Standard Deviation 2 |
| Randomized Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Attention Problems Total | -0.3 Score on a scale | Standard Deviation 1 |
| Randomized Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Anxious/Depressed Total | 0.0 Score on a scale | Standard Deviation 2.2 |
| Randomized Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Aggressive Behavior Total | -0.8 Score on a scale | Standard Deviation 1.5 |
| Randomized Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Somatic Complaints Total | 0.5 Score on a scale | Standard Deviation 1 |
| Randomized Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Total Problems Total | -2.3 Score on a scale | Standard Deviation 6 |
| Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Somatic Complaints Total | 1.8 Score on a scale | Standard Deviation 4.1 |
| Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Aggressive Behavior Total | -0.4 Score on a scale | Standard Deviation 2.7 |
| Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Sleep Problems Total | 1.4 Score on a scale | Standard Deviation 4.3 |
| Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Anxious/Depressed Total | 0.8 Score on a scale | Standard Deviation 3.1 |
| Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Emotionally Reactive Total | 1.0 Score on a scale | Standard Deviation 3.9 |
| Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Withdrawn Total | -0.2 Score on a scale | Standard Deviation 1.6 |
| Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Total Problems Total | 3.6 Score on a scale | Standard Deviation 23.2 |
| Placebo | Change From Baseline in Child Behaviour Checklist (CBCL) at Week 52 | CBCL Pre-School : Attention Problems Total | -0.2 Score on a scale | Standard Deviation 2 |
Secondary
Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52
The Pediatric Functional Independence Measure-II (WeeFIM®-II) is designed to measure functional independence of children between the ages of 6 months & 18 yrs who have physical or general developmental limitations. The WeeFIM-II is comprised of 3 domains that are rated by clinicians based on information obtained from parents/caregivers (self-care \[score range 8 to 56\], mobility \[score range 8 to 35\], & cognition \[score range 8 to 35\]) & provides a total score between 18 (worst) & 126 (Best). Higher score reflects higher level of independence. Performance of a child on each of individual items within WeeFIM is assigned to one of seven levels on an ordinal scale that represent function from complete & modified independence (levels 7 & 6) without a helping person to modified & complete dependence (levels 5 to 1) with a helping person. Functional Independence Measure (Wee-FIM-II) is only validated in children ages 6 months to 18 yrs. Therefore results for Cohort 3 is not summarized.
Time frame: Baseline to Week 52
Population: FAS population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM: Cognitive Score | 2.6 Score on a scale | Standard Deviation 4 |
| Sentinel | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM-II Total Score | 11.2 Score on a scale | Standard Deviation 11.1 |
| Sentinel | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM: Mobility Score | 2.2 Score on a scale | Standard Deviation 3.4 |
| Sentinel | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM : Self-Care Score | 6.4 Score on a scale | Standard Deviation 6 |
| Randomized Vosoritide | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM: Mobility Score | 4.5 Score on a scale | Standard Deviation 5.6 |
| Randomized Vosoritide | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM-II Total Score | 14.7 Score on a scale | Standard Deviation 17.3 |
| Randomized Vosoritide | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM : Self-Care Score | 6.6 Score on a scale | Standard Deviation 7.2 |
| Randomized Vosoritide | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM: Cognitive Score | 3.6 Score on a scale | Standard Deviation 6 |
| Randomized Placebo | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM : Self-Care Score | 3.7 Score on a scale | Standard Deviation 2.3 |
| Randomized Placebo | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM: Mobility Score | 7.0 Score on a scale | Standard Deviation 7.5 |
| Randomized Placebo | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM-II Total Score | 16.2 Score on a scale | Standard Deviation 14.6 |
| Randomized Placebo | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM: Cognitive Score | 5.5 Score on a scale | Standard Deviation 7.6 |
| Placebo | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM: Cognitive Score | 4.2 Score on a scale | Standard Deviation 8.4 |
| Placebo | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM : Self-Care Score | 5.6 Score on a scale | Standard Deviation 14.1 |
| Placebo | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM: Mobility Score | 6.7 Score on a scale | Standard Deviation 9.4 |
| Placebo | Change From Baseline in Functional Independence Measure for Children (WeeFIM-II) Score at Week 52 | WeeFIM-II Total Score | 16.5 Score on a scale | Standard Deviation 28.1 |
Secondary
Change From Baseline in Height at Week 52
As a general rule, standing height/sitting height was used if participants were aged \>= 24 months at baseline. Body length/crown to rump was used if participants were aged \< 24 months at baseline. If body length was not measured and standing height was available, standing height was used.
Time frame: Baseline to Week 52
Population: FAS (randomized) Population and FAS population.~This is model-based analysis, it is true that the participants analyzed for placebo FAS \& FAS (randomized) are the same, but participants analyzed for vosoritide arm FAS \& FAS (randomized) are different, that's why the model-based results for placebo are different.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sentinel | Change From Baseline in Height at Week 52 | 8.15 cm |
| Randomized Vosoritide | Change From Baseline in Height at Week 52 | 7.38 cm |
| Randomized Placebo | Change From Baseline in Height at Week 52 | 8.41 cm |
| Placebo | Change From Baseline in Height at Week 52 | 7.45 cm |
Comparison: Difference in LS means were obtained from an analysis of covariance model.95% CI: [-0.02, 1.56]
Comparison: Difference in LS means were obtained from an analysis of covariance model.95% CI: [0.26, 1.66]
Secondary
Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52
97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health).
Time frame: Baseline to Week 52
Population: FAS population.~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Global health perceptions score | -1.07 Score on a scale | Standard Deviation 15.43 |
| Sentinel | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Temperament and mood Score | 4.79 Score on a scale | Standard Deviation 9.6 |
| Sentinel | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Family Cohesion Score | 1.79 Score on a scale | Standard Deviation 13.53 |
| Sentinel | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental impact emotional score | 2.04 Score on a scale | Standard Deviation 23.13 |
| Sentinel | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Growth and Development Scores | 4.82 Score on a scale | Standard Deviation 11.62 |
| Sentinel | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Overall Health Score | 3.75 Score on a scale | Standard Deviation 17.6 |
| Sentinel | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Physical Abilities Score | -6.01 Score on a scale | Standard Deviation 9.83 |
| Sentinel | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental Impact Time Score | 9.52 Score on a scale | Standard Deviation 29.06 |
| Sentinel | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Pain Score | -1.19 Score on a scale | Standard Deviation 20.37 |
| Randomized Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Pain Score | -1.47 Score on a scale | Standard Deviation 18.22 |
| Randomized Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Growth and Development Scores | 4.34 Score on a scale | Standard Deviation 9.4 |
| Randomized Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Physical Abilities Score | 8.82 Score on a scale | Standard Deviation 23.06 |
| Randomized Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Global health perceptions score | 2.24 Score on a scale | Standard Deviation 12.37 |
| Randomized Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental impact emotional score | -0.84 Score on a scale | Standard Deviation 8.89 |
| Randomized Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Family Cohesion Score | -1.25 Score on a scale | Standard Deviation 10.72 |
| Randomized Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental Impact Time Score | 4.76 Score on a scale | Standard Deviation 10.78 |
| Randomized Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Temperament and mood Score | 0.54 Score on a scale | Standard Deviation 5.4 |
| Randomized Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Overall Health Score | 4.33 Score on a scale | Standard Deviation 15.1 |
| Randomized Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Family Cohesion Score | 0.00 Score on a scale | Standard Deviation 15 |
| Randomized Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Overall Health Score | -5.00 Score on a scale | Standard Deviation 15.41 |
| Randomized Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Growth and Development Scores | -0.71 Score on a scale | Standard Deviation 8.75 |
| Randomized Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental Impact Time Score | -8.05 Score on a scale | Standard Deviation 19.7 |
| Randomized Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Physical Abilities Score | 3.36 Score on a scale | Standard Deviation 8.62 |
| Randomized Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental impact emotional score | 0.51 Score on a scale | Standard Deviation 14.64 |
| Randomized Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Temperament and mood Score | 0.66 Score on a scale | Standard Deviation 7.18 |
| Randomized Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Global health perceptions score | -2.73 Score on a scale | Standard Deviation 11.29 |
| Randomized Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Pain Score | -1.19 Score on a scale | Standard Deviation 18.9 |
| Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Overall Health Score | -3.50 Score on a scale | Standard Deviation 14.15 |
| Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Physical Abilities Score | 1.30 Score on a scale | Standard Deviation 16.05 |
| Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Family Cohesion Score | -7.08 Score on a scale | Standard Deviation 28.08 |
| Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Pain Score | -7.64 Score on a scale | Standard Deviation 27.63 |
| Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Growth and Development Scores | 1.46 Score on a scale | Standard Deviation 26.01 |
| Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Temperament and mood Score | -0.49 Score on a scale | Standard Deviation 9.78 |
| Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Global health perceptions score | -4.55 Score on a scale | Standard Deviation 12.18 |
| Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental impact emotional score | -6.85 Score on a scale | Standard Deviation 11.94 |
| Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental Impact Time Score | -2.38 Score on a scale | Standard Deviation 35.61 |
| Cohort 3: Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Pain Score | -4.69 Score on a scale | Standard Deviation 27.77 |
| Cohort 3: Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Temperament and mood Score | -2.43 Score on a scale | Standard Deviation 6.76 |
| Cohort 3: Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Overall Health Score | -5.00 Score on a scale | Standard Deviation 7.75 |
| Cohort 3: Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental Impact Time Score | -10.7 Score on a scale | Standard Deviation 17.59 |
| Cohort 3: Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Global health perceptions score | -2.84 Score on a scale | Standard Deviation 13.62 |
| Cohort 3: Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Family Cohesion Score | -3.13 Score on a scale | Standard Deviation 8.84 |
| Cohort 3: Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental impact emotional score | 9.82 Score on a scale | Standard Deviation 20.89 |
| Cohort 3: Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Growth and Development Scores | 3.57 Score on a scale | Standard Deviation 6.35 |
| Cohort 3: Placebo | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Physical Abilities Score | 2.35 Score on a scale | Standard Deviation 29.29 |
| Cohort 3: Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Growth and Development Scores | -3.50 Score on a scale | Standard Deviation 13.19 |
| Cohort 3: Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Family Cohesion Score | -4.50 Score on a scale | Standard Deviation 15.54 |
| Cohort 3: Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental Impact Time Score | 2.38 Score on a scale | Standard Deviation 14.93 |
| Cohort 3: Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Overall Health Score | 0.50 Score on a scale | Standard Deviation 13.01 |
| Cohort 3: Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Pain Score | 2.50 Score on a scale | Standard Deviation 22.58 |
| Cohort 3: Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Temperament and mood Score | 4.62 Score on a scale | Standard Deviation 10.48 |
| Cohort 3: Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Physical Abilities Score | -15.91 Score on a scale | Standard Deviation 22.74 |
| Cohort 3: Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Parental impact emotional score | -2.50 Score on a scale | Standard Deviation 19.05 |
| Cohort 3: Vosoritide | Change From Baseline in Infant Toddler Quality of Life (ITQoL) Scores at Week 52 | Global health perceptions score | 0.50 Score on a scale | Standard Deviation 17.11 |
Secondary
Change From Baseline in ITQoL-Behavior Scores at Week 52
97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). The number of subjects assessed in Cohort 3 Placebo is 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/ baseline. Hence, Mean and Standard Deviation (SD) are not applicable. Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed.
Time frame: Baseline to Week 52
Population: Full Analysis Set.~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Change From Baseline in ITQoL-Behavior Scores at Week 52 | 2.73 Score on a scale | Standard Deviation 23.36 |
| Randomized Vosoritide | Change From Baseline in ITQoL-Behavior Scores at Week 52 | 0.37 Score on a scale | Standard Deviation 9.5 |
| Randomized Placebo | Change From Baseline in ITQoL-Behavior Scores at Week 52 | 1.74 Score on a scale | Standard Deviation 13.6 |
| Placebo | Change From Baseline in ITQoL-Behavior Scores at Week 52 | -3.39 Score on a scale | Standard Deviation 7.46 |
| Cohort 3: Placebo | Change From Baseline in ITQoL-Behavior Scores at Week 52 | 0.00 Score on a scale | — |
Secondary
Change From Baseline in ITQoL-Getting On With Other Score at Week 52
97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). A higher score indicates better global health perceptions. The number of subjects assessed in Cohort 3 Placebo and Cohort 3 vosoritide are 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/baseline. Hence, Mean and Standard Deviation (SD) are not applicable. Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed.
Time frame: Baseline to Week 52
Population: FAS population.~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Change From Baseline in ITQoL-Getting On With Other Score at Week 52 | 7.78 Score on a scale | Standard Deviation 17.18 |
| Randomized Vosoritide | Change From Baseline in ITQoL-Getting On With Other Score at Week 52 | 1.74 Score on a scale | Standard Deviation 8.88 |
| Randomized Placebo | Change From Baseline in ITQoL-Getting On With Other Score at Week 52 | 2.33 Score on a scale | Standard Deviation 7.22 |
| Placebo | Change From Baseline in ITQoL-Getting On With Other Score at Week 52 | 0.82 Score on a scale | Standard Deviation 5.35 |
Secondary
Change From Baseline in ITQoL-Global Behavior Scores at Week 52
97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). A higher score indicates better global behaviour. The number of subjects assessed in Cohort 3 Placebo is 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/ baseline. Hence, Mean and Standard Deviation (SD) are not applicable. Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed.
Time frame: Baseline to Week 52
Population: FAS population.~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Change From Baseline in ITQoL-Global Behavior Scores at Week 52 | 1.15 Score on a scale | Standard Deviation 21.42 |
| Randomized Vosoritide | Change From Baseline in ITQoL-Global Behavior Scores at Week 52 | 0.29 Score on a scale | Standard Deviation 18.58 |
| Randomized Placebo | Change From Baseline in ITQoL-Global Behavior Scores at Week 52 | 3.00 Score on a scale | Standard Deviation 12.55 |
| Placebo | Change From Baseline in ITQoL-Global Behavior Scores at Week 52 | -10.56 Score on a scale | Standard Deviation 21.71 |
| Cohort 3: Placebo | Change From Baseline in ITQoL-Global Behavior Scores at Week 52 | -15.00 Score on a scale | — |
Secondary
Change From Baseline in ITQoL-Health Score at Week 52
97(ITQOL) item full-length version was used. For each concept, item responses are scored, summed, & transformed on a scale from 0(worst health) to 100(best health). A higher score indicates better global change in health. The number of subjects assessed in Cohort 3 Placebo is 0 as assessment was not done or overall score could not be derived because no more than half assessments were done at Screening/ baseline. Hence, Mean and Standard Deviation (SD) are not applicable. Note: For each variable, there are different numbers of individual questions. The variable can only be derived if at least half of the questions were completed.
Time frame: Baseline to Week 52
Population: FAS population.~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Change From Baseline in ITQoL-Health Score at Week 52 | 0.08 Score on a scale | Standard Deviation 0.64 |
| Randomized Vosoritide | Change From Baseline in ITQoL-Health Score at Week 52 | 0.13 Score on a scale | Standard Deviation 0.62 |
| Randomized Placebo | Change From Baseline in ITQoL-Health Score at Week 52 | -0.60 Score on a scale | Standard Deviation 1.34 |
| Placebo | Change From Baseline in ITQoL-Health Score at Week 52 | 0.33 Score on a scale | Standard Deviation 0.52 |
| Cohort 3: Placebo | Change From Baseline in ITQoL-Health Score at Week 52 | 0.00 Score on a scale | — |
Secondary
Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52
For Height: subjects aged \< 24 months, body length takes precedence over standing height. Subjects aged \< 24 months at baseline and \>= 24 months at Week 52, body length takes precedence.
Time frame: Baseline to Week 52
Population: FAS population.~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 measurement is not available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Arm Length to Lower Arm(Forearm)Length Ratio | 0.05 Ratio | Standard Deviation 0.15 |
| Sentinel | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length(Thigh)-Knee to Heel Length Ratio | -0.01 Ratio | Standard Deviation 0.08 |
| Sentinel | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length (Thigh) to Tibial Length Ratio | 0.00 Ratio | Standard Deviation 0.12 |
| Sentinel | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Arm Span to Standing Height Ratio | 0.00 Ratio | Standard Deviation 0.02 |
| Randomized Vosoritide | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Arm Span to Standing Height Ratio | 0.00 Ratio | Standard Deviation 0.06 |
| Randomized Vosoritide | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length (Thigh) to Tibial Length Ratio | 0.02 Ratio | Standard Deviation 0.17 |
| Randomized Vosoritide | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Arm Length to Lower Arm(Forearm)Length Ratio | 0.00 Ratio | Standard Deviation 0.12 |
| Randomized Vosoritide | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length(Thigh)-Knee to Heel Length Ratio | 0.01 Ratio | Standard Deviation 0.07 |
| Randomized Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Arm Length to Lower Arm(Forearm)Length Ratio | -0.09 Ratio | Standard Deviation 0.06 |
| Randomized Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Arm Span to Standing Height Ratio | 0.00 Ratio | Standard Deviation 0.02 |
| Randomized Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length (Thigh) to Tibial Length Ratio | -0.16 Ratio | Standard Deviation 0.24 |
| Randomized Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length(Thigh)-Knee to Heel Length Ratio | -0.09 Ratio | Standard Deviation 0.1 |
| Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Arm Length to Lower Arm(Forearm)Length Ratio | 0.01 Ratio | Standard Deviation 0.1 |
| Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length(Thigh)-Knee to Heel Length Ratio | -0.03 Ratio | Standard Deviation 0.08 |
| Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Arm Span to Standing Height Ratio | -0.01 Ratio | Standard Deviation 0.02 |
| Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length (Thigh) to Tibial Length Ratio | -0.10 Ratio | Standard Deviation 0.07 |
| Cohort 3: Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length (Thigh) to Tibial Length Ratio | 0.00 Ratio | Standard Deviation 0.29 |
| Cohort 3: Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Arm Span to Standing Height Ratio | -0.01 Ratio | Standard Deviation 0.04 |
| Cohort 3: Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length(Thigh)-Knee to Heel Length Ratio | 0.01 Ratio | Standard Deviation 0.16 |
| Cohort 3: Placebo | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Arm Length to Lower Arm(Forearm)Length Ratio | 0.02 Ratio | Standard Deviation 0.11 |
| Cohort 3: Vosoritide | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length(Thigh)-Knee to Heel Length Ratio | -0.02 Ratio | Standard Deviation 0.11 |
| Cohort 3: Vosoritide | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Leg Length (Thigh) to Tibial Length Ratio | 0.04 Ratio | Standard Deviation 0.22 |
| Cohort 3: Vosoritide | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Arm Span to Standing Height Ratio | -0.02 Ratio | Standard Deviation 0.07 |
| Cohort 3: Vosoritide | Change From Baseline in Other Body Proportion Ratios (Arm Span to Height Ratio, Upper Arm Length to Lower Arm [Forearm] Length Ratio, Upper Leg Length [Thigh] to Knee to Heel Length Ratio, and Upper Leg Length (Thigh) to Tibial Length Ratio) at Week 52 | Upper Arm Length to Lower Arm(Forearm)Length Ratio | -0.01 Ratio | Standard Deviation 0.12 |
Secondary
Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52
Change from baseline in other growth measures (upper body length, head circumference, arm span, upper arm length, lower arm (Forearm) length, Lower Body Length, Upper Leg Length (Thigh), knee to heel length, and tibial length) at Week 52. Participants aged \<24 months, body length and crown to rump length take precedence over standing height and sitting height. Participants aged \<24 months at baseline and \>=24 months at Week 52, body length and crown to rump length take precedence.
Time frame: Baseline to Week 52
Population: FAS population.~Change from baseline was based on the participants with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 measurement is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Arm Span | 4.86 cm | Standard Deviation 1.99 |
| Sentinel | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Head Circumference | 0.68 cm | Standard Deviation 0.66 |
| Sentinel | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper body length | 3.04 cm | Standard Deviation 1.52 |
| Sentinel | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Arm Length | 1.02 cm | Standard Deviation 1.13 |
| Sentinel | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Arm (Forearm) Length | 0.49 cm | Standard Deviation 0.96 |
| Sentinel | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Body Length | 2.41 cm | Standard Deviation 1.31 |
| Sentinel | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Leg Length (Thigh) | 0.82 cm | Standard Deviation 1.75 |
| Sentinel | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Knee to Heel Length | 1.52 cm | Standard Deviation 0.76 |
| Sentinel | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Tibial Length | 0.85 cm | Standard Deviation 0.69 |
| Randomized Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Arm Length | 0.77 cm | Standard Deviation 0.96 |
| Randomized Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper body length | 3.54 cm | Standard Deviation 1.81 |
| Randomized Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Arm (Forearm) Length | 0.79 cm | Standard Deviation 0.9 |
| Randomized Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Knee to Heel Length | 2.21 cm | Standard Deviation 0.67 |
| Randomized Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Arm Span | 5.82 cm | Standard Deviation 3.65 |
| Randomized Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Head Circumference | 0.74 cm | Standard Deviation 0.49 |
| Randomized Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Leg Length (Thigh) | 1.55 cm | Standard Deviation 1.46 |
| Randomized Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Body Length | 2.89 cm | Standard Deviation 1.99 |
| Randomized Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Tibial Length | 1.16 cm | Standard Deviation 1.35 |
| Randomized Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Knee to Heel Length | 2.70 cm | Standard Deviation 0.75 |
| Randomized Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Arm Span | 7.13 cm | Standard Deviation 1.59 |
| Randomized Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Arm Length | 1.08 cm | Standard Deviation 0.93 |
| Randomized Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Tibial Length | 1.97 cm | Standard Deviation 1.49 |
| Randomized Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Arm (Forearm) Length | 1.78 cm | Standard Deviation 0.44 |
| Randomized Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Body Length | 2.39 cm | Standard Deviation 1.27 |
| Randomized Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Leg Length (Thigh) | 0.38 cm | Standard Deviation 1.71 |
| Randomized Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper body length | 5.45 cm | Standard Deviation 1.75 |
| Randomized Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Head Circumference | 2.29 cm | Standard Deviation 1.28 |
| Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Arm Span | 7.22 cm | Standard Deviation 1.45 |
| Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Head Circumference | 3.10 cm | Standard Deviation 1.45 |
| Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Leg Length (Thigh) | 1.10 cm | Standard Deviation 1.42 |
| Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Arm Length | 1.44 cm | Standard Deviation 1.26 |
| Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper body length | 5.20 cm | Standard Deviation 1.5 |
| Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Body Length | 3.79 cm | Standard Deviation 1.56 |
| Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Arm (Forearm) Length | 1.57 cm | Standard Deviation 0.98 |
| Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Knee to Heel Length | 2.29 cm | Standard Deviation 1.91 |
| Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Tibial Length | 1.99 cm | Standard Deviation 0.8 |
| Cohort 3: Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Arm (Forearm) Length | 1.66 cm | Standard Deviation 0.82 |
| Cohort 3: Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Body Length | 3.86 cm | Standard Deviation 1.55 |
| Cohort 3: Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Tibial Length | 1.83 cm | Standard Deviation 0.88 |
| Cohort 3: Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Leg Length (Thigh) | 1.98 cm | Standard Deviation 2.21 |
| Cohort 3: Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Arm Span | 8.22 cm | Standard Deviation 1.93 |
| Cohort 3: Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Knee to Heel Length | 2.93 cm | Standard Deviation 0.68 |
| Cohort 3: Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Head Circumference | 5.35 cm | Standard Deviation 0.71 |
| Cohort 3: Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Arm Length | 1.95 cm | Standard Deviation 1.23 |
| Cohort 3: Placebo | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper body length | 6.58 cm | Standard Deviation 0.99 |
| Cohort 3: Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper body length | 6.75 cm | Standard Deviation 0.86 |
| Cohort 3: Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Head Circumference | 6.29 cm | Standard Deviation 0.81 |
| Cohort 3: Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Arm Span | 8.99 cm | Standard Deviation 4.77 |
| Cohort 3: Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Arm (Forearm) Length | 1.49 cm | Standard Deviation 0.79 |
| Cohort 3: Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Leg Length (Thigh) | 1.93 cm | Standard Deviation 1.65 |
| Cohort 3: Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Tibial Length | 1.39 cm | Standard Deviation 0.77 |
| Cohort 3: Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Upper Arm Length | 1.44 cm | Standard Deviation 1.33 |
| Cohort 3: Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Knee to Heel Length | 3.12 cm | Standard Deviation 0.85 |
| Cohort 3: Vosoritide | Change From Baseline in Other Growth Measures (Upper Body Length, Head Circumference, Arm Span, Upper Arm Length, Lower Arm Length, Lower Body Length, Upper Leg Length, Knee to Heel Length, and Tibial Length) at Week 52 | Lower Body Length | 4.41 cm | Standard Deviation 1.53 |
Secondary
Change From Baseline in Upper to Lower Body Segment Ratio at Week 52
Upper to Lower Body ratio=Sitting Height / (Standing Height - Sitting Height).
Time frame: Baseline to Week 52
Population: FAS (randomized) Population and FAS population.~This is model-based analysis, it is true that the participants analyzed for placebo FAS \& FAS (randomized) are the same, but participants analyzed for vosoritide arm FAS \& FAS (randomized) are different, that's why the model-based results for placebo are different.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sentinel | Change From Baseline in Upper to Lower Body Segment Ratio at Week 52 | -0.20 Ratio |
| Randomized Vosoritide | Change From Baseline in Upper to Lower Body Segment Ratio at Week 52 | -0.13 Ratio |
| Randomized Placebo | Change From Baseline in Upper to Lower Body Segment Ratio at Week 52 | -0.19 Ratio |
| Placebo | Change From Baseline in Upper to Lower Body Segment Ratio at Week 52 | -0.13 Ratio |
Comparison: Difference in LS means were obtained from an analysis of covariance model.95% CI: [-0.17, 0.04]
Comparison: Difference in LS means were obtained from an analysis of covariance model.95% CI: [-0.15, 0.03]
Secondary
Change From Baseline in Weight Z-score at Week 52
The weight Z-score represents the participant's weight converted to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. The weight Z-score of 0 represents the mean weight for age and sex of the reference population. A positive weight Z-score means weight is above the mean weight for the average stature population of the same sex and age and a negative weight Z-Score means weight is below the mean weight for the average stature population of the same sex and age.
Time frame: Baseline to Week 52
Population: FAS population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 measurement is not available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Change From Baseline in Weight Z-score at Week 52 | 0.14 Z-score | Standard Deviation 0.44 |
| Randomized Vosoritide | Change From Baseline in Weight Z-score at Week 52 | 0.14 Z-score | Standard Deviation 0.42 |
| Randomized Placebo | Change From Baseline in Weight Z-score at Week 52 | 0.74 Z-score | Standard Deviation 0.82 |
| Placebo | Change From Baseline in Weight Z-score at Week 52 | 0.70 Z-score | Standard Deviation 0.64 |
| Cohort 3: Placebo | Change From Baseline in Weight Z-score at Week 52 | -0.81 Z-score | Standard Deviation 0.49 |
| Cohort 3: Vosoritide | Change From Baseline in Weight Z-score at Week 52 | -0.66 Z-score | Standard Deviation 0.77 |
Secondary
Change From Baseline in X-ray of Lumbar Spine Angles at Week 52
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Angles at Week 52 | Sacral Tilt | 10.6 Degree | Standard Deviation 13.2 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Angles at Week 52 | Lordosis Angle | 12.5 Degree | Standard Deviation 17.4 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Angles at Week 52 | Kyphosis Angle | -2.2 Degree | Standard Deviation 13.9 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Angles at Week 52 | Sacral Tilt | 5.7 Degree | Standard Deviation 15.9 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Angles at Week 52 | Lordosis Angle | 8.4 Degree | Standard Deviation 14.2 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Angles at Week 52 | Kyphosis Angle | -2.1 Degree | Standard Deviation 10.3 |
Secondary
Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52
Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on subjects with available measurements at both time points. Overall no. of participants analyzed (N) is greater than no. analyzed for Placebo, as different participants missed for different variables (Ex:1 subject missed sagittal width L1,L2,L3, 1 subject missed sagittal width L5 \& 1 subject missed sagittal width L4 \& L5. Therefore, n for sagittal width L1,L2,L3,L4 \& L5 are 26,26,26,26,25 respectively but the overall number of subjects is 27)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Sagittal Width (L2) | 0.05 cm | Standard Deviation 0.18 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Sagittal Width (L4) | 0.16 cm | Standard Deviation 0.24 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Sagittal Width (L3) | 0.08 cm | Standard Deviation 0.2 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Sagittal Width (L5) | 0.13 cm | Standard Deviation 0.34 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Sagittal Width (L1) | 0.07 cm | Standard Deviation 0.26 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Sagittal Width (L5) | 0.06 cm | Standard Deviation 0.26 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Sagittal Width (L1) | 0.00 cm | Standard Deviation 0.22 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Sagittal Width (L2) | 0.01 cm | Standard Deviation 0.18 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Sagittal Width (L3) | 0.04 cm | Standard Deviation 0.19 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Sagittal Width and Week 52 | Sagittal Width (L4) | 0.03 cm | Standard Deviation 0.16 |
Secondary
Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Transverse Diameter (L2) | 0.12 cm | Standard Deviation 0.16 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Transverse Diameter (L4) | 0.09 cm | Standard Deviation 0.13 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Transverse Diameter (L3) | 0.08 cm | Standard Deviation 0.15 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Transverse Diameter (L5) | 0.10 cm | Standard Deviation 0.13 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Transverse Diameter (L1) | 0.12 cm | Standard Deviation 0.17 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Transverse Diameter (L5) | 0.05 cm | Standard Deviation 0.14 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Transverse Diameter (L1) | 0.12 cm | Standard Deviation 0.11 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Transverse Diameter (L2) | 0.09 cm | Standard Deviation 0.13 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Transverse Diameter (L3) | 0.09 cm | Standard Deviation 0.12 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Transverse Diameter at Week 52 | Transverse Diameter (L4) | 0.06 cm | Standard Deviation 0.11 |
Secondary
Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Medial Height Ratio (L5) | -0.02 Ratio | Standard Deviation 0.15 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Posterior Height Ratio (L4) | 0.03 Ratio | Standard Deviation 0.11 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Medial Height Ratio (L2) | -0.06 Ratio | Standard Deviation 0.16 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Posterior Height Ratio (L5) | 0.01 Ratio | Standard Deviation 0.13 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Posterior Height Ratio (L1) | -0.03 Ratio | Standard Deviation 0.13 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Medial Height to Posterior Height Ratio (L1) | -0.01 Ratio | Standard Deviation 0.15 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Medial Height Ratio (L4) | 0.02 Ratio | Standard Deviation 0.12 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Medial Height to Posterior Height Ratio (L2) | 0.05 Ratio | Standard Deviation 0.11 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Posterior Height Ratio (L2) | -0.02 Ratio | Standard Deviation 0.13 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Medial Height to Posterior Height Ratio (L3) | -0.02 Ratio | Standard Deviation 0.1 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Medial Height Ratio (L3) | -0.02 Ratio | Standard Deviation 0.19 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Medial Height to Posterior Height Ratio (L4) | -0.03 Ratio | Standard Deviation 0.13 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Posterior Height Ratio (L3) | -0.01 Ratio | Standard Deviation 0.16 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Medial Height to Posterior Height Ratio (L5) | 0.02 Ratio | Standard Deviation 0.16 |
| Sentinel | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Medial Height Ratio (L1) | -0.04 Ratio | Standard Deviation 0.16 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Medial Height to Posterior Height Ratio (L5) | -0.04 Ratio | Standard Deviation 0.21 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Medial Height Ratio (L1) | -0.04 Ratio | Standard Deviation 0.2 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Medial Height Ratio (L2) | -0.07 Ratio | Standard Deviation 0.16 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Medial Height Ratio (L3) | 0.04 Ratio | Standard Deviation 0.09 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Medial Height Ratio (L4) | -0.01 Ratio | Standard Deviation 0.11 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Medial Height Ratio (L5) | 0.04 Ratio | Standard Deviation 0.17 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Posterior Height Ratio (L1) | -0.08 Ratio | Standard Deviation 0.17 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Posterior Height Ratio (L2) | -0.03 Ratio | Standard Deviation 0.12 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Posterior Height Ratio (L3) | 0.04 Ratio | Standard Deviation 0.12 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Posterior Height Ratio (L4) | 0.02 Ratio | Standard Deviation 0.13 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Anterior Height to Posterior Height Ratio (L5) | 0.02 Ratio | Standard Deviation 0.15 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Medial Height to Posterior Height Ratio (L1) | -0.04 Ratio | Standard Deviation 0.12 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Medial Height to Posterior Height Ratio (L2) | 0.03 Ratio | Standard Deviation 0.09 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Medial Height to Posterior Height Ratio (L3) | -0.02 Ratio | Standard Deviation 0.1 |
| Randomized Vosoritide | Change From Baseline in X-ray of Lumbar Spine Vertebral Ratios at Week 52 | Medial Height to Posterior Height Ratio (L4) | 0.04 Ratio | Standard Deviation 0.1 |
Secondary
Change From Baseline to Week 52 in Lumbar Spine BMD Z-Score
Hologic - Discovery Horizon Lumbar Spine BMD Z-Score Change in lumbar spine bone mineral density (BMD) Z-score from baseline at 52 weeks indicates whether there has been a positive or negative change in BMD using a z-score generated by converting the participants lumbar spine BMD to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. A BMD Z-score \<-2 SD can indicate low bone density in the lumbar spine in children. The Lumbar Spine BMD (bone mineral density) z-score compares the BMD in the lumbar spine to the average spinal bone density of people of the same age, and sex as a comparator. A Z-score less than 0 means that the participant has a lower BMD than people in the same age and sex group, and could indicate a risk of osteopenia or osteoporosis of the spine.
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Change From Baseline to Week 52 in Lumbar Spine BMD Z-Score | 0.17 Z-score | Standard Deviation 0.24 |
| Randomized Vosoritide | Change From Baseline to Week 52 in Lumbar Spine BMD Z-Score | 0.03 Z-score | Standard Deviation 0.45 |
Secondary
Change From Baseline to Week 52 in Whole Body BMD Z-score
Hologic - Discovery Horizon Whole Body BMD Z-Score. Change in whole body bone mineral density (BMD) Z-score from baseline at 52 weeks indicates whether there has been a positive or negative change in BMD using a z-score generated by converting the participants BMD to an age and sex appropriate standard deviation score (SDS) by comparison with an average stature reference population. A whole body BMD Z-score \<-2 SD can indicate low bone density in children. The Whole Body BMD (bone mineral density) z-score compares the BMD to the average bone density of people of the same age, and sex as a comparator. A Z-score less than 0 means that the participant has a lower BMD than people in the same age and sex group, and could indicate a risk of osteopenia or osteoporosis.
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sentinel | Change From Baseline to Week 52 in Whole Body BMD Z-score | -0.20 Z-score | Standard Deviation 0.35 |
| Randomized Vosoritide | Change From Baseline to Week 52 in Whole Body BMD Z-score | 0.30 Z-score | Standard Deviation 0.47 |
Secondary
Change in Sleep Study Indices at Week 52
Sleep-testing device was used to assess presence & severity of sleep-disordered breathing by measurement of blood oxygen(O2)saturation,pulse rate,& airflow during overnight monitoring Episodes(Epi) of sleep apnea variables summarized as: Number(No.)of epi of apnea/hr(AI);No.of epi of hypopnea/hr(HI);No.of epi of obstructive apnea hypopneas/hr(AHI);No.of epi of obstructive apneas/hr(Obstructive Apnea Index);No.of epi of central apneas/hr(CAI);No.of desaturations/hr \>=3% AHI is a marker of obstructive sleep apnea (OSA), scored as No.of apnea or hypopnea epi/hr, with AHI \<=1/hr normal, 1\< AHI\<=5 mild,5\< AHI \<=10 moderate,& AHI\>10/hr severe OSA. CAI reflects cervical cord compression at cervical-medullary junction, & is No. of epi of a pause in ventilation with no associated respiratory effort, with\> 5 epi/hr abnormal.O2 desaturation index measures average No. of desaturation epi/hr, defined as decrease in O2 saturation of \>=3% for at least 10sec, with(\<8/hr normal & \>=8/hr abnormal
Time frame: Baseline to Week 52
Population: FAS population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 measurement is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Change in Sleep Study Indices at Week 52 | Central Apnea Index (CAI) | -1.26 Events per hour | Standard Deviation 2.66 |
| Sentinel | Change in Sleep Study Indices at Week 52 | Apnea Hypopnea Index (AHI) | -0.54 Events per hour | Standard Deviation 2.7 |
| Sentinel | Change in Sleep Study Indices at Week 52 | Obstructive Index | 0.19 Events per hour | Standard Deviation 0.73 |
| Sentinel | Change in Sleep Study Indices at Week 52 | Desaturation per Hour >=3% | -0.41 Events per hour | Standard Deviation 1.51 |
| Sentinel | Change in Sleep Study Indices at Week 52 | Hypopnea Index (HI) | 0.52 Events per hour | Standard Deviation 1.35 |
| Sentinel | Change in Sleep Study Indices at Week 52 | Apnea Index (AI) | -1.07 Events per hour | Standard Deviation 2.12 |
| Randomized Vosoritide | Change in Sleep Study Indices at Week 52 | Apnea Hypopnea Index (AHI) | -1.45 Events per hour | Standard Deviation 4.63 |
| Randomized Vosoritide | Change in Sleep Study Indices at Week 52 | Central Apnea Index (CAI) | -0.74 Events per hour | Standard Deviation 1.86 |
| Randomized Vosoritide | Change in Sleep Study Indices at Week 52 | Hypopnea Index (HI) | -0.61 Events per hour | Standard Deviation 3.63 |
| Randomized Vosoritide | Change in Sleep Study Indices at Week 52 | Desaturation per Hour >=3% | -1.24 Events per hour | Standard Deviation 3.98 |
| Randomized Vosoritide | Change in Sleep Study Indices at Week 52 | Apnea Index (AI) | -0.83 Events per hour | Standard Deviation 1.93 |
| Randomized Vosoritide | Change in Sleep Study Indices at Week 52 | Obstructive Index | -0.09 Events per hour | Standard Deviation 0.45 |
| Randomized Placebo | Change in Sleep Study Indices at Week 52 | Apnea Index (AI) | 0.40 Events per hour | Standard Deviation 2.34 |
| Randomized Placebo | Change in Sleep Study Indices at Week 52 | Obstructive Index | 0.68 Events per hour | Standard Deviation 1.52 |
| Randomized Placebo | Change in Sleep Study Indices at Week 52 | Apnea Hypopnea Index (AHI) | 1.06 Events per hour | Standard Deviation 4.8 |
| Randomized Placebo | Change in Sleep Study Indices at Week 52 | Central Apnea Index (CAI) | -0.28 Events per hour | Standard Deviation 0.89 |
| Randomized Placebo | Change in Sleep Study Indices at Week 52 | Hypopnea Index (HI) | 0.66 Events per hour | Standard Deviation 2.53 |
| Randomized Placebo | Change in Sleep Study Indices at Week 52 | Desaturation per Hour >=3% | 0.98 Events per hour | Standard Deviation 3.6 |
| Placebo | Change in Sleep Study Indices at Week 52 | Desaturation per Hour >=3% | -0.69 Events per hour | Standard Deviation 1.3 |
| Placebo | Change in Sleep Study Indices at Week 52 | Hypopnea Index (HI) | -0.01 Events per hour | Standard Deviation 1.32 |
| Placebo | Change in Sleep Study Indices at Week 52 | Apnea Index (AI) | -0.71 Events per hour | Standard Deviation 1.61 |
| Placebo | Change in Sleep Study Indices at Week 52 | Apnea Hypopnea Index (AHI) | -0.72 Events per hour | Standard Deviation 1.41 |
| Placebo | Change in Sleep Study Indices at Week 52 | Obstructive Index | -0.01 Events per hour | Standard Deviation 0.08 |
| Placebo | Change in Sleep Study Indices at Week 52 | Central Apnea Index (CAI) | -0.71 Events per hour | Standard Deviation 1.61 |
| Cohort 3: Placebo | Change in Sleep Study Indices at Week 52 | Central Apnea Index (CAI) | -1.00 Events per hour | Standard Deviation 0.97 |
| Cohort 3: Placebo | Change in Sleep Study Indices at Week 52 | Hypopnea Index (HI) | 2.97 Events per hour | Standard Deviation 5.45 |
| Cohort 3: Placebo | Change in Sleep Study Indices at Week 52 | Apnea Hypopnea Index (AHI) | 1.89 Events per hour | Standard Deviation 6.31 |
| Cohort 3: Placebo | Change in Sleep Study Indices at Week 52 | Obstructive Index | -0.07 Events per hour | Standard Deviation 0.64 |
| Cohort 3: Placebo | Change in Sleep Study Indices at Week 52 | Desaturation per Hour >=3% | 1.71 Events per hour | Standard Deviation 6.63 |
| Cohort 3: Placebo | Change in Sleep Study Indices at Week 52 | Apnea Index (AI) | -1.09 Events per hour | Standard Deviation 1.22 |
| Cohort 3: Vosoritide | Change in Sleep Study Indices at Week 52 | Apnea Index (AI) | -0.36 Events per hour | Standard Deviation 2.54 |
| Cohort 3: Vosoritide | Change in Sleep Study Indices at Week 52 | Central Apnea Index (CAI) | 0.50 Events per hour | Standard Deviation 0.92 |
| Cohort 3: Vosoritide | Change in Sleep Study Indices at Week 52 | Desaturation per Hour >=3% | -0.93 Events per hour | Standard Deviation 2.6 |
| Cohort 3: Vosoritide | Change in Sleep Study Indices at Week 52 | Hypopnea Index (HI) | -0.56 Events per hour | Standard Deviation 0.54 |
| Cohort 3: Vosoritide | Change in Sleep Study Indices at Week 52 | Apnea Hypopnea Index (AHI) | -0.94 Events per hour | Standard Deviation 2.78 |
| Cohort 3: Vosoritide | Change in Sleep Study Indices at Week 52 | Obstructive Index | -0.86 Events per hour | Standard Deviation 2.08 |
Secondary
Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52
Percentages were calculated using the total number of subjects in the safety population (N for each treatment group) as the denominator. All increases are comparing results at Week 52 relative to the baseline assessment.
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sentinel | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in lordosis angle (deg) >=10 | 19 Number of participants |
| Sentinel | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in kyphosis angle (deg) >=10 | 9 Number of participants |
| Sentinel | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in lordosis angle (deg) >=5 to <10 | 5 Number of participants |
| Sentinel | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in sacral tilt (deg) >=5 to <10 | 3 Number of participants |
| Sentinel | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in kyphosis angle (deg) >=5 to <10 | 3 Number of participants |
| Sentinel | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in sacral tilt (deg) >=10 | 24 Number of participants |
| Randomized Vosoritide | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in kyphosis angle (deg) >=5 to <10 | 2 Number of participants |
| Randomized Vosoritide | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in lordosis angle (deg) >=5 to <10 | 1 Number of participants |
| Randomized Vosoritide | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in lordosis angle (deg) >=10 | 14 Number of participants |
| Randomized Vosoritide | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in sacral tilt (deg) >=10 | 10 Number of participants |
| Randomized Vosoritide | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in kyphosis angle (deg) >=10 | 4 Number of participants |
| Randomized Vosoritide | Changes From Baseline in X-ray of Lumbar Spine Angle Changes: Number of Participants With an Increase in Lumbar Spine Angle at Week 52 | Increase in sacral tilt (deg) >=5 to <10 | 6 Number of participants |
Secondary
DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMC
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMC | GE - Lunar Prodigy Lumbar Spine BMC | 2.73 gm | Standard Deviation 0.83 |
| Sentinel | DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMC | Hologic - Discovery Horizon Lumbar Spine BMC | 2.19 gm | Standard Deviation 0.68 |
| Randomized Vosoritide | DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMC | GE - Lunar Prodigy Lumbar Spine BMC | 2.09 gm | Standard Deviation 0.97 |
| Randomized Vosoritide | DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMC | Hologic - Discovery Horizon Lumbar Spine BMC | 1.94 gm | Standard Deviation 0.72 |
Secondary
DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMD
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMD | GE - Lunar Prodigy Lumbar Spine BMD | 0.07 g/cm^2 | Standard Deviation 0.04 |
| Sentinel | DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMD | Hologic - Discovery Horizon Lumbar Spine BMD | 0.05 g/cm^2 | Standard Deviation 0.03 |
| Randomized Vosoritide | DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMD | GE - Lunar Prodigy Lumbar Spine BMD | 0.05 g/cm^2 | Standard Deviation 0.03 |
| Randomized Vosoritide | DEXA Parameter: Change From Baseline to Week 52 of Lumbar Spine BMD | Hologic - Discovery Horizon Lumbar Spine BMD | 0.06 g/cm^2 | Standard Deviation 0.04 |
Secondary
DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMC
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMC | GE - Lunar Prodigy Whole Body BMC | 96.85 gm | Standard Deviation 39.82 |
| Sentinel | DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMC | Hologic - Discovery Horizon Whole Body BMC | 87.97 gm | Standard Deviation 32.35 |
| Randomized Vosoritide | DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMC | GE - Lunar Prodigy Whole Body BMC | 98.99 gm | Standard Deviation 32.45 |
| Randomized Vosoritide | DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMC | Hologic - Discovery Horizon Whole Body BMC | 101.33 gm | Standard Deviation 33.34 |
Secondary
DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMD
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMD | GE - Lunar Prodigy Whole Body BMD | 0.06 g/cm^2 | Standard Deviation 0.06 |
| Sentinel | DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMD | Hologic - Discovery Horizon Whole Body BMD | 0.05 g/cm^2 | Standard Deviation 0.02 |
| Randomized Vosoritide | DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMD | Hologic - Discovery Horizon Whole Body BMD | 0.07 g/cm^2 | Standard Deviation 0.03 |
| Randomized Vosoritide | DEXA Parameter: Change From Baseline to Week 52 of Whole Body BMD | GE - Lunar Prodigy Whole Body BMD | 0.07 g/cm^2 | Standard Deviation 0.04 |
Secondary
DEXA Parameter: Change From Baseline to Week 52 of Whole Body Less Head Bone Mineral Density (BMD)
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | DEXA Parameter: Change From Baseline to Week 52 of Whole Body Less Head Bone Mineral Density (BMD) | GE - Lunar Prodigy Whole Body Less Head BMD | 0.04 g/cm^2 | Standard Deviation 0.02 |
| Sentinel | DEXA Parameter: Change From Baseline to Week 52 of Whole Body Less Head Bone Mineral Density (BMD) | Hologic Discovery Horizon Whole Body Less Head BMD | 0.03 g/cm^2 | Standard Deviation 0.01 |
| Randomized Vosoritide | DEXA Parameter: Change From Baseline to Week 52 of Whole Body Less Head Bone Mineral Density (BMD) | GE - Lunar Prodigy Whole Body Less Head BMD | 0.05 g/cm^2 | Standard Deviation 0.03 |
| Randomized Vosoritide | DEXA Parameter: Change From Baseline to Week 52 of Whole Body Less Head Bone Mineral Density (BMD) | Hologic Discovery Horizon Whole Body Less Head BMD | 0.04 g/cm^2 | Standard Deviation 0.02 |
Secondary
Dual X Ray Absorptiometry (DEXA) Parameter: Change From Baseline to Week 52 for Whole Body Less Head Bone Mineral Content (BMC)
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline was based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | Dual X Ray Absorptiometry (DEXA) Parameter: Change From Baseline to Week 52 for Whole Body Less Head Bone Mineral Content (BMC) | GE - Lunar Prodigy: Whole Body Less Head BMC | 55.87 gm | Standard Deviation 14.68 |
| Sentinel | Dual X Ray Absorptiometry (DEXA) Parameter: Change From Baseline to Week 52 for Whole Body Less Head Bone Mineral Content (BMC) | Hologic Discovery Horizon Whole Body Less Head BMC | 44.61 gm | Standard Deviation 12.62 |
| Randomized Vosoritide | Dual X Ray Absorptiometry (DEXA) Parameter: Change From Baseline to Week 52 for Whole Body Less Head Bone Mineral Content (BMC) | GE - Lunar Prodigy: Whole Body Less Head BMC | 50.26 gm | Standard Deviation 17.44 |
| Randomized Vosoritide | Dual X Ray Absorptiometry (DEXA) Parameter: Change From Baseline to Week 52 for Whole Body Less Head Bone Mineral Content (BMC) | Hologic Discovery Horizon Whole Body Less Head BMC | 47.19 gm | Standard Deviation 12.55 |
Secondary
Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits
Number of participants with Incidence of Antibody Positivity at Scheduled Visits for : total antibody (TAb), Neutralizing antibodies (NAb), atrial natriuretic peptide (ANP), B-type Natriuretic Peptide (BNP) & C-type natriuretic peptide (CNP). TAb Titer Positive, NAb Titer Positive, ANP Reactivity Positive, BNP Reactivity Positive & CNP Reactivity Positive. Day 1 is the baseline assessment result taken prior to first dose of study drug. Ever Positive = the number of participants with at least one positive sample result.
Time frame: At Day 1, Week 3, Week 13, Week 26, Week 52, & Ever Positive.
Population: FAS population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Positive: Week 13 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Ever Positive | 8 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Positive: Day 1 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Positive: Week 26 | 2 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Positive: Week 52 | 8 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Positive: Day 1 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Positive: Week 3 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Positive: Week 13 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Positive: Week 26 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Positive: Week 52 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Ever Positive | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Positive: Week 3 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Positive: Week 13 | 1 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Positive: Week 26 | 6 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Ever Positive | 12 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Positive: Day 1 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Positive: Week 3 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Positive: Week 52 | 2 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Ever Positive | 3 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Positive: Day 1 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Positive: Week 13 | 1 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Ever Positive | 4 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Positive: Week 3 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Positive: Day 1 | 3 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Positive: Week 52 | 11 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Positive: Week 13 | 2 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Positive: Week 26 | 3 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Positive: Week 3 | 0 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Positive: Week 26 | 2 participants |
| Sentinel | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Positive: Week 52 | 4 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Ever Positive | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Positive: Week 26 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Ever Positive | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Positive: Day 1 | 3 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Positive: Day 1 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Positive: Week 3 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Positive: Week 13 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Positive: Week 26 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Positive: Week 13 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | TAb Titer Positive: Week 52 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Positive: Week 26 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Positive: Day 1 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Ever Positive | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Positive: Week 3 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Positive: Week 52 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Positive: Day 1 | 5 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Positive: Week 13 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Positive: Week 13 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Positive: Week 26 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Ever Positive | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Positive: Week 52 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Positive: Week 52 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | NAb Titer Ever Positive | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Positive: Day 1 | 1 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Positive: Week 3 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Positive: Week 3 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Positive: Week 13 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | BNP Reactivity Positive: Week 3 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | ANP Reactivity Positive: Week 26 | 0 participants |
| Randomized Vosoritide | Immunogenicity: Number of Participants With Incidence of Antibody Positivity at Scheduled Visits | CNP Reactivity Positive: Week 52 | 0 participants |
Secondary
MRI Parameter: Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | MRI Parameter: Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level | Area of Foramen Magnum | 0.021 cm^2 | Standard Deviation 0.342 |
| Sentinel | MRI Parameter: Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level | Area of Spinal Cord at the Foramen Magnum Level | 0.011 cm^2 | Standard Deviation 0.197 |
| Randomized Vosoritide | MRI Parameter: Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level | Area of Foramen Magnum | 0.060 cm^2 | Standard Deviation 0.203 |
| Randomized Vosoritide | MRI Parameter: Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level | Area of Spinal Cord at the Foramen Magnum Level | 0.072 cm^2 | Standard Deviation 0.163 |
Secondary
MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus
Time frame: Baseline to Week 52
Population: Safety population.~Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of face volume to calvarium | 0.002 Ratio | Standard Deviation 0.031 |
| Sentinel | MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of area of spinal cord to foramen magnum | 0.005 Ratio | Standard Deviation 0.12 |
| Sentinel | MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of face volume to sinus | -6.798 Ratio | Standard Deviation 175.646 |
| Randomized Vosoritide | MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of face volume to calvarium | 0.003 Ratio | Standard Deviation 0.033 |
| Randomized Vosoritide | MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of area of spinal cord to foramen magnum | 0.037 Ratio | Standard Deviation 0.1 |
| Randomized Vosoritide | MRI Parameter: Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of face volume to sinus | 14.505 Ratio | Standard Deviation 284.95 |
Secondary
MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume.
Time frame: Baseline to Week 52
Population: Safety population~Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of Sinus | 2.362 cm^3 | Standard Deviation 3.578 |
| Sentinel | MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Whole Brain Total Volume | 175.399 cm^3 | Standard Deviation 158.088 |
| Sentinel | MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of Calvarium | 213.075 cm^3 | Standard Deviation 202.415 |
| Sentinel | MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Ventricles Total Volume | 11.394 cm^3 | Standard Deviation 20.416 |
| Sentinel | MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of Face | 80.527 cm^3 | Standard Deviation 59.211 |
| Randomized Vosoritide | MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Ventricles Total Volume | 8.515 cm^3 | Standard Deviation 16.325 |
| Randomized Vosoritide | MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of Face | 78.107 cm^3 | Standard Deviation 33.369 |
| Randomized Vosoritide | MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of Sinus | 1.195 cm^3 | Standard Deviation 3.769 |
| Randomized Vosoritide | MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of Calvarium | 183.427 cm^3 | Standard Deviation 183.21 |
| Randomized Vosoritide | MRI Parameter: Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Whole Brain Total Volume | 146.247 cm^3 | Standard Deviation 115.274 |
Secondary
MRI Parameter: Percentage Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level
Time frame: Baseline to Week 52
Population: Safety Population.~Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | MRI Parameter: Percentage Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level | Area of Foramen Magnum | 9.19 Percent change | Standard Deviation 47.36 |
| Sentinel | MRI Parameter: Percentage Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level | Area of spinal cord at the foramen magnum level | 7.51 Percent change | Standard Deviation 33.14 |
| Randomized Vosoritide | MRI Parameter: Percentage Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level | Area of Foramen Magnum | 7.50 Percent change | Standard Deviation 19.88 |
| Randomized Vosoritide | MRI Parameter: Percentage Change From Baseline to Week 52 for Area of Foramen Magnum & Area of Spinal Cord at the Foramen Magnum Level | Area of spinal cord at the foramen magnum level | 19.60 Percent change | Standard Deviation 44.26 |
Secondary
MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus
Time frame: Baseline to Week 52
Population: Safety Population.~Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of face volume to sinus | -5.37 Percent change | Standard Deviation 60.83 |
| Sentinel | MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of Face Volume to Calvarium | 0.78 Percent change | Standard Deviation 9.06 |
| Sentinel | MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of Area of Spinal Cord to Foramen Magnum | 2.86 Percent change | Standard Deviation 23.4 |
| Randomized Vosoritide | MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of Area of Spinal Cord to Foramen Magnum | 9.50 Percent change | Standard Deviation 22.68 |
| Randomized Vosoritide | MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of face volume to sinus | 92.24 Percent change | Standard Deviation 341.33 |
| Randomized Vosoritide | MRI Parameter: Percentage Change From Baseline to Week 52 for Ratio of Face Volume to Calvarium, Ratio of Area of Spinal Cord to Foramen Magnum, Ratio of Face Volume to Sinus | Ratio of Face Volume to Calvarium | 1.31 Percent change | Standard Deviation 10.07 |
Secondary
MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume.
Time frame: Baseline to Week 52
Population: Safety Population~Change from baseline and percent change from baseline are based on the subjects with available measurements at both time points. Baseline is defined as Day 1 or screening if a Day 1 assessment is not available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of Face | 20.79 percent change | Standard Deviation 18.46 |
| Sentinel | MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of sinus | 72.33 percent change | Standard Deviation 100.93 |
| Sentinel | MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of Calvarium | 19.41 percent change | Standard Deviation 21.73 |
| Sentinel | MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Whole Brain Total Volume | 20.58 percent change | Standard Deviation 21.29 |
| Sentinel | MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Ventricles Total Volume | 33.44 percent change | Standard Deviation 52.69 |
| Randomized Vosoritide | MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Ventricles Total Volume | 30.85 percent change | Standard Deviation 50.65 |
| Randomized Vosoritide | MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Whole Brain Total Volume | 16.89 percent change | Standard Deviation 17.22 |
| Randomized Vosoritide | MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of sinus | 81.97 percent change | Standard Deviation 169.74 |
| Randomized Vosoritide | MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of Face | 19.18 percent change | Standard Deviation 12.22 |
| Randomized Vosoritide | MRI Parameter: Percentage Change From Baseline to Week 52 for Volume of Face, Sinus, Calvarium, Whole Brain Total Volume, Ventricles Total Volume. | Volume of Calvarium | 16.50 percent change | Standard Deviation 19.82 |
Secondary
PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52
Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics. PK parameters for another participant on Day 1 obtained from extrapolation. AUC0-∞, CL/F, V/F and t1/2 excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected.
Time frame: At Day 01, Week 13, Week 26, Week 39, & Week 52.
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Day 01 | 134 ml/min/kg | Standard Deviation 59.8 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 13 | 111 ml/min/kg | Standard Deviation 58.5 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 26 | 79.8 ml/min/kg | Standard Deviation 48.3 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 13 | 201 ml/min/kg | — |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Day 01 | 65.9 ml/min/kg | Standard Deviation 31.6 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 13 | 58.7 ml/min/kg | Standard Deviation 40.4 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 26 | 79.4 ml/min/kg | Standard Deviation 37.7 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 39 | 78.3 ml/min/kg | Standard Deviation 10.9 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 52 | 49.7 ml/min/kg | Standard Deviation 32 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Day 01 | 95.9 ml/min/kg | Standard Deviation 34 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 13 | 115 ml/min/kg | Standard Deviation 78.1 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 26 | 104 ml/min/kg | Standard Deviation 23.2 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 39 | 73.6 ml/min/kg | Standard Deviation 41.6 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 39 | 65.3 ml/min/kg | Standard Deviation 32.7 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 52 | 69 ml/min/kg | Standard Deviation 41.2 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Day 1 | 147 ml/min/kg | — |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 26 | 79.5 ml/min/kg | Standard Deviation 38.4 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 39 | 75.5 ml/min/kg | Standard Deviation 14.8 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 52 | 122 ml/min/kg | Standard Deviation 52.5 |
| Sentinel | PK Parameter: Apparent Clearance (CL/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 52 | 76.5 ml/min/kg | Standard Deviation 49.8 |
Secondary
PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52
Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics. PK parameters for another participant on Day 1 obtained from extrapolation. V/F excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected.
Time frame: At Day 01, Week 13, Week 26, Week 39, & Week 52.
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 39 | 2250 ml/kg | Standard Deviation 284 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Day 01 | 4070 ml/kg | Standard Deviation 2310 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 13 | 3990 ml/kg | Standard Deviation 2960 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 26 | 3400 ml/kg | Standard Deviation 2520 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 39 | 2330 ml/kg | Standard Deviation 1150 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 52 | 2660 ml/kg | Standard Deviation 1420 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Day 01 | 5550 ml/kg | — |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 13 | 7810 ml/kg | — |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 26 | 3890 ml/kg | Standard Deviation 2880 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 13 | 2090 ml/kg | Standard Deviation 1360 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 26 | 1960 ml/kg | Standard Deviation 829 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 39 | 2920 ml/kg | Standard Deviation 205 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 52 | 3040 ml/kg | Standard Deviation 2630 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Day 01 | 5240 ml/kg | Standard Deviation 1890 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 26 | 2750 ml/kg | Standard Deviation 710 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 39 | 2200 ml/kg | Standard Deviation 951 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 52 | 2620 ml/kg | Standard Deviation 1950 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 52 | 3770 ml/kg | Standard Deviation 1410 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Day 01 | 3190 ml/kg | Standard Deviation 1790 |
| Sentinel | PK Parameter: Apparent Volume of Distribution (Vz/F) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 13 | 4260 ml/kg | Standard Deviation 2960 |
Secondary
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52
Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics. PK parameters for another participant on Day 1 obtained from extrapolation. AUC0-∞ excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected.
Time frame: At Day1, Week 13, Week 26, Week 39, & Week 52.
Population: Pharmacokinetics (PK) Population includes all sentinel and randomized participants in the safety population who have at least one evaluable PK concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 13 | 197000 min*pg/ml | Standard Deviation 144000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 26 | 306000 min*pg/ml | Standard Deviation 252000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 13 | 74500 min*pg/ml | — |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 26 | 233000 min*pg/ml | Standard Deviation 132000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 39 | 204000 min*pg/ml | Standard Deviation 39700 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 26 | 429000 min*pg/ml | Standard Deviation 163000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 39 | 387000 min*pg/ml | Standard Deviation 53800 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 52 | 768000 min*pg/ml | Standard Deviation 391000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Day 01 | 353000 min*pg/ml | Standard Deviation 133000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 13 | 382000 min*pg/ml | Standard Deviation 268000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 26 | 305000 min*pg/ml | Standard Deviation 82100 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 39 | 575000 min*pg/ml | Standard Deviation 455000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 52 | 622000 min*pg/ml | Standard Deviation 455000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Day 01 | 149000 min*pg/ml | Standard Deviation 98000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 39 | 284000 min*pg/ml | Standard Deviation 137000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 52 | 303000 min*pg/ml | Standard Deviation 208000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Day 01 | 102000 min*pg/ml | — |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 52 | 137000 min*pg/ml | Standard Deviation 48900 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Day 01 | 557000 min*pg/ml | Standard Deviation 278000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) at Day1, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 13 | 670000 min*pg/ml | Standard Deviation 312000 |
Secondary
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52
Time frame: At Day 01, Week 13, Week 26, Week 39, & Week 52
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Day 01 | 134000 min*pg/ml | Standard Deviation 96500 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 13 | 183000 min*pg/ml | Standard Deviation 126000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 26 | 283000 min*pg/ml | Standard Deviation 222000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 39 | 257000 min*pg/ml | Standard Deviation 132000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 52 | 260000 min*pg/ml | Standard Deviation 172000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Day 01 | 83100 min*pg/ml | Standard Deviation 48300 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 13 | 115000 min*pg/ml | Standard Deviation 59300 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 26 | 197000 min*pg/ml | Standard Deviation 121000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 39 | 166000 min*pg/ml | Standard Deviation 81000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 52 | 125000 min*pg/ml | Standard Deviation 76700 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Day 01 | 525000 min*pg/ml | Standard Deviation 251000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 13 | 642000 min*pg/ml | Standard Deviation 353000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 26 | 408000 min*pg/ml | Standard Deviation 148000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 39 | 365000 min*pg/ml | Standard Deviation 44700 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 26 | 300000 min*pg/ml | Standard Deviation 79100 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 39 | 591000 min*pg/ml | Standard Deviation 359000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 52 | 558000 min*pg/ml | Standard Deviation 400000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 52 | 670000 min*pg/ml | Standard Deviation 335000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Day 01 | 312000 min*pg/ml | Standard Deviation 119000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to Nominal 120 Minutes Postdose (AUC 0- 120 Min) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 13 | 342000 min*pg/ml | Standard Deviation 245000 |
Secondary
PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52
Time frame: At Day 01, Week 13, Week 26, Week 39, & Week 52
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Day 01 | 132000 min*pg/ml | Standard Deviation 97300 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 13 | 182000 min*pg/ml | Standard Deviation 127000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 26 | 282000 min*pg/ml | Standard Deviation 222000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 39 | 256000 min*pg/ml | Standard Deviation 132000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 52 | 258000 min*pg/ml | Standard Deviation 169000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Day 01 | 65900 min*pg/ml | Standard Deviation 33600 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 13 | 112000 min*pg/ml | Standard Deviation 62900 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 26 | 196000 min*pg/ml | Standard Deviation 121000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 39 | 165000 min*pg/ml | Standard Deviation 82400 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 52 | 122000 min*pg/ml | Standard Deviation 75700 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Day 01 | 547000 min*pg/ml | Standard Deviation 279000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 13 | 645000 min*pg/ml | Standard Deviation 357000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 26 | 407000 min*pg/ml | Standard Deviation 148000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 39 | 567000 min*pg/ml | Standard Deviation 361000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 52 | 557000 min*pg/ml | Standard Deviation 401000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 39 | 365000 min*pg/ml | Standard Deviation 44300 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 52 | 672000 min*pg/ml | Standard Deviation 334000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Day 01 | 323000 min*pg/ml | Standard Deviation 129000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 13 | 340000 min*pg/ml | Standard Deviation 244000 |
| Sentinel | PK Parameter: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Measurable Concentration (AUC0-t) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 26 | 297000 min*pg/ml | Standard Deviation 80700 |
Secondary
PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52
Vosoritide concentrations at 5-, 15- and 30-minute post-dose for one participant on Day 1 were not available, hence PK parameters for this participant were excluded from summary statistics. PK parameters for another participant on Day 1 obtained from extrapolation. AUC0-∞, CL/F, V/F and t1/2 excluded from summary statistics. PK parameters are not available for this participant at Week 13 due to unsuccessful venipuncture, and Week 26 as post-dose PK samples were not collected.
Time frame: At Day 01, Week 13, Week 26, Week 39, & Week 52.
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Day 01 | 21.7 min | Standard Deviation 7.99 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 13 | 25.4 min | Standard Deviation 10.7 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 26 | 29.2 min | Standard Deviation 7.06 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 39 | 25.7 min | Standard Deviation 7.82 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 52 | 29 min | Standard Deviation 9.12 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Day 01 | 26.1 min | — |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 13 | 26.9 min | — |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 26 | 32.7 min | Standard Deviation 9.62 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 39 | 20.9 min | Standard Deviation 2.18 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 52 | 24 min | Standard Deviation 12.8 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Day 01 | 33.3 min | Standard Deviation 8.41 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 13 | 25.6 min | Standard Deviation 3.59 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 26 | 21 min | Standard Deviation 13.1 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 39 | 26.2 min | Standard Deviation 5.46 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Day 01 | 41.1 min | Standard Deviation 18.8 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 13 | 26.2 min | Standard Deviation 7.1 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 26 | 19.2 min | Standard Deviation 6.14 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 39 | 22.7 min | Standard Deviation 5.36 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 52 | 24.3 min | Standard Deviation 6.58 |
| Sentinel | PK Parameter: Elimination Half-life (t1/2) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 52 | 40.1 min | Standard Deviation 15.2 |
Secondary
PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52
Time frame: At Day 01, Week 13, Week 26, Week 39, & Week 52
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Day 01 | 2840 pg/ml | Standard Deviation 1230 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 13 | 5970 pg/ml | Standard Deviation 2390 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 26 | 6800 pg/ml | Standard Deviation 3360 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 39 | 4600 pg/ml | Standard Deviation 2150 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 52 | 3870 pg/ml | Standard Deviation 2120 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Day 01 | 14500 pg/ml | Standard Deviation 5950 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 13 | 13400 pg/ml | Standard Deviation 6070 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 26 | 10100 pg/ml | Standard Deviation 2970 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 39 | 6980 pg/ml | Standard Deviation 1140 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 52 | 12900 pg/ml | Standard Deviation 6260 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Day 01 | 13400 pg/ml | Standard Deviation 5710 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 13 | 10500 pg/ml | Standard Deviation 6850 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 26 | 11500 pg/ml | Standard Deviation 4290 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Day 01 | 4430 pg/ml | Standard Deviation 3670 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 13 | 4350 pg/ml | Standard Deviation 1670 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 26 | 5850 pg/ml | Standard Deviation 3260 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 39 | 5600 pg/ml | Standard Deviation 2200 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 52 | 5640 pg/ml | Standard Deviation 2740 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 39 | 18400 pg/ml | Standard Deviation 11900 |
| Sentinel | PK Parameter: Maximum Observed Plasma Concentration (Cmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 52 | 13500 pg/ml | Standard Deviation 6770 |
Secondary
PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52
Time frame: At Day 01, Week 13, Week 26, Week 39, & Week 52.
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 13 | 14.3 min | Standard Deviation 5.5 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 26 | 16.1 min | Standard Deviation 8.69 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 39 | 17.4 min | Standard Deviation 11.9 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Week 52 | 16.1 min | Standard Deviation 6.27 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Day 01 | 11.3 min | Standard Deviation 6.35 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 13 | 6 min | Standard Deviation 1.41 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 26 | 10.8 min | Standard Deviation 5.5 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 39 | 15.4 min | Standard Deviation 11.6 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 15 μg/kg/day: Week 52 | 14.2 min | Standard Deviation 5.76 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Day 01 | 12.9 min | Standard Deviation 9.1 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 13 | 14 min | Standard Deviation 8.42 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 26 | 12 min | Standard Deviation 5.2 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 39 | 15 min | Standard Deviation 0 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 2 30 μg/kg/day: Week 52 | 14.3 min | Standard Deviation 1.53 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Day 01 | 7.36 min | Standard Deviation 3.53 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 13 | 9.43 min | Standard Deviation 5.22 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 26 | 9 min | Standard Deviation 4.69 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 39 | 11.3 min | Standard Deviation 3.59 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 3 30 μg/kg/day: Week 52 | 14.5 min | Standard Deviation 3.51 |
| Sentinel | PK Parameter: Time to Reach Maximum Concentration (Tmax) at Day 01, Week 13, Week 26, Week 39, & Week 52 | Cohort 1 15 μg/kg/day: Day 01 | 13.1 min | Standard Deviation 6.33 |