Achondroplasia
Conditions
Keywords
Skeletal Dysplasia
Brief summary
Approximately 63 participants will be randomized to one of three doses to receive Recifercept either * Low Dose * Medium Dose * High Dose Participants will will attend the clinic at baseline and at Day 1, 4, 8, 15, 29 & then Month 2, 3 6, 9 & 12. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements & patient/caregiver quality of life questionnaires Participants will received treatment with Recifercept for 12 months. All participants who complete the study and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll into an open-label extension (OLE) study. A PK cohort will include 12 participants who will randomly receive a single dose of 3 mg/kg of Phase 2 study (process 1c) formulation and a single dose of 3 mg/kg of the proposed Phase 3 (process 2) study formulation in a cross over study. Dose of the cohort could be changed due to emerging safety and efficacy data in the study.
Detailed description
This is a phase 2 randomized, 3 arm (3 active doses of Recifercept), parallel group dose finding study of safety, tolerability, PK and efficacy The total number of participants is 63 in 2 age straified cohorts of 0-2 years and 6-10 years old. The study will enroll approximately 54 children with achondroplasia aged 2-10 years (inclusive) who will be enrolled and randomized to receive one of three doses of recifercept * Low Dose * Medium Dose * High Dose A total of 18 participants will be enrolled per dose 18 per dosesuch that at least 15 participants per dose are evaluable. An interim analysis is planned when at least 15 participants per dose aged ≥2 to \<11 years have received 6 months of treatment with recifercept. eDMC will review safety, PK and efficacy data to confirm ongoing positive benefit:risk in participants. Additionally, an exploratory cohort of approximately 9 children with achondroplasia, ages 0-2 years, will be enrolled later in the study (n=3 per dose). Enrollment will follow an age and dose-staggered approach (descending age and ascending dose) with review of safety and PK data by the study team before progression to the next enrollment block If certain pre-defined safety signals occur then a meeting of the eDMC will be convened to make a decision on progression of enrollment. The PK data collected in block A will be used in the PopPK model (developed using healthy adult data) to confirm the dosing for younger children (ie, ≥2 to \<6 years and 0-\<2 years). Participants will will attend the clinic at baseline and at Day 1, 4, 8, 15, 29 & then Month 2, 3 6, 9 & 12. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements & patient/caregiver quality of life questionnaires All participants will receive recifercept for 12 months. All participants who complete the study and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll into an open-label extension (OLE) study. PK Cohort: Multiple changes have been made in the manufacturing process of the drug product (process 2) which will be used in Phase 3. Therefore, an additional PK cohort (at selected sites only) has been added, to evaluate the PK of Phase 2 formulation (process 1c) and Phase 3 formulation (process 2). PK Cohort: At selected sites only, an additional PK cohort has been added to evaluate the PK of two recifercept formulations. A total of 12 children with achondroplasia aged 2- \<11 years will be enrolled in the PK cohort (6 in each treatment sequence). Each participant will receive 2 treatments (3 mg/kg Phase 2 formulation \[process 1c\] and 3 mg/kg Phase 3 formulation \[process 2\]) in a randomized manner. Dose of the cohort could be changed due to emerging safety and efficacy data in the study. PK samples collected following each dose will be analyzed to evaluate the exposures of two formulations.
Interventions
BIOLOGICALRecifercept
Recifercept
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
Anthropometric Measurements Assessor
Eligibility
Sex/Gender
ALL
Age
3 Months to 10 Years
Healthy volunteers
No
Inclusion criteria
* Main cohort: Aged ≥2 years to \<11 years (up to the day before 11th birthday inclusive) at time of enrollment; or exploratory cohort: aged ≥3 months to \<2 years (up to the day before 2nd birthday inclusive) at time of enrollment * Documented, confirmed genetic diagnosis of achondroplasia from historical medical records prior to entry into this trial (test must have been performed at a laboratory fully accredited for genetic testing under local regulations). * Completed the C4181001 natural history study with at least 2 valid height/length measurements (at least 3 months apart) prior to enrollment in this study. One of these measurement timepoints must be within the 3 months prior to enrollment in C4181005. * Tanner stage 1 based on investigator assessment during physical examination (must include assessment of breast development for females, testicular stage for males). * Able to stand independently for height measurements (if ≥2 years of age at enrollment). * If aged \<2 years at enrollment, has a documented historical MRI brain/cervical spine performed in the previous 12 months.
Exclusion criteria
* Presence of co-morbid conditions or circumstances that, in the opinion of the investigator, would affect interpretation of growth data or ability to complete the trial procedures. * Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. * Presence of severe obesity (BMI \>95th percentile on Hoover-Fong BMI charts) \[Hoover-Fong et al, 2008\].14 * Known closure of long bone growth plates (cessation of height growth). * Body weight \<7 kg or \>30 kg. * Moderate or severe renal impairment CrCL GFR \<60 mL/min/1.73m2 (Calculated GFR based on updated bedside Schwartz formula for pediatric patients (CrCL (mL/min/1.73 m2) = 0.413 \* Height (cms)/ Serum cr (mg/dL) or hepatic impairment (AST/ALT \>1.5 ULN). * History of hypersensitivity to study intervention or any excipients. * History of any prior treatment with human growth hormone or related products (including insulin-like growth factor 1 \[IGF-1\]). * History of receipt of any treatment that are known to potentially affect growth (including oral steroids \>5 days in the last 6 months, high dose inhaled corticosteroids (\>800 mcg/day beclametasone equivalent) and medication for attention deficit hyperactivity disorder). * History of limb lengthening surgery (defined as distraction osteogenesis/Ilizarov/callostasis technique following submetaphyseal osteotomy to extend bone length). * Any limb lengthening/corrective orthopaedic surgery planned at any point during the trial period. * Less than 6 months since fracture or surgical procedure of any bone determined from the screening visit date. * Presence of any internal guided growth plates/devices. * History of removal of internal guided growth plates/devices within less than 6 months. * History of receipt of any investigational product for achondroplasia or that may affect growth/interpretation of growth parameters. * History of receipt of an investigational product (not for achondroplasia/growth affecting) within the last 30 days or 5 half-lives (whichever is longer).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | The first dose up to 28 to 35 days after the last dose of study intervention (13 months) | Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AE is defined as an AE with onset date occurring during the on-treatment period. Relatedness to recifercept was assessed by the investigator (Yes/No). |
| Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Height growth was defined as the ratio of observed change from baseline in standing height to the expected change from baseline in the reference population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Blood pressure measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (eg, television, cell phones) where possible (with consideration of the age of the child). Supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) were summarized by treatment in accordance with the sponsor reporting standards. |
| Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Temperature was obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Temperature measurements were summarized by treatment in accordance with the sponsor reporting standards. |
| Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Month 3, Month 6, Month 9, and Month 12 | A physical examination included, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal systems and skin. Physical examination assessments were summarized by treatment in accordance with the sponsor reporting standards. |
| Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Baseline to Month 12 | Participants with laboratory abnormalities that met pre-specified criteria included following parameters: hematology (corpuscular volume, corpuscular hemoglobin, corpuscular hemoglobin concentration, platelet, leukocytes, lymphocytes, neutrophils, eosinophils, and monocytes), and chemistry (bilirubin, alkaline phosphatase, albumin, urea nitrogen, urate, potassium, phosphate, bicarbonate). |
| Pre-Dose Serum Concentration (Ctrough) of Recifercept | Pre-dose on Day(s) 4, 8, 15, 29, 61, 91, 183, 273, 365 | Ctrough was defined as pre-dose serum concentration during dosing and observed directly from data. |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept | The first dose up to 28 to 35 days after the last dose of study intervention (13 months) | The immunogenicity was measured by presence of ADA and NAb in participants treated with recifercept and summarized by dose regimen. |
| Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Sitting/standing height ratio was the ratio of sitting height to standing height. |
| Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Arm span to standing height/length difference was the difference between arm span and standing height. |
| Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Knee height : lower segment ratio was the ratio of knee to heel length to the difference between standing height and sitting height. |
| Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Pulse rate measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (eg, television, cell phones) where possible (with consideration of the age of the child). Pulse rate was summarized by treatment in accordance with the sponsor reporting standards. |
| Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Ratio of occipito-frontal distance to occipito-mid-face measurements was summarized for each treatment arm. |
| Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Height Standard Deviation Score (SDS) (z-score) was calculated as the difference between mean observed standing height at each visit and mean value of reference population divided by standard deviation of reference population. SDS indicates how similar the participant was to the reference population. |
| Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Fixed flexion angles at elbow data were presented for each treatment arm. An average of a participant's elbow extension measurements over a visit was computed. |
| Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Body Mass Index (BMI) = Weight (kg)/\[(Standing Height (m))\^2\]. Standing height and weight were averaged over a visit before BMI was computed. |
| Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12 | Baseline, Month 9, and Month 12 | Waist : Chest Ratio = Waist Circumference / Chest Circumference. Waist and chest circumference were averaged over a visit before waist : chest circumference ratio was computed. |
| Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Baseline and Month 12 | The apnea-hypopnea index (AHI) is the average of the apneic and hypopneic episodes per hour of sleep, which is measured to assess obstructive sleep apnea (OSA). An AHI score of 1 to 4.9 events/hour is mild OSA, 5 to 9.9 events/hour is moderate, and more than 9 events/hour is severe in pediatric population. |
| Change From Baseline in Desaturation Index at Month 12 | Baseline and Month 12 | Desaturation index is one of the polysomnography parameters to assess obstructive sleep apnea. It refers to the average number of desaturation episodes occurring per hour, where desaturation episodes are defined as a decrease in the mean oxygen saturation of ≥3% (over the last 120 seconds) that lasts for at least 10 seconds. |
| Change From Baseline in Polysomnography Other Parameters at Month 12 | Baseline and Month 12 | Polysomnography refers to a systematic process used to collect physiologic parameters during sleep. Polysomnography other parameters included total sleep time spent with oxygen saturation (SaO2) \< 90% (T90), total sleep time spent with end-tidal carbon dioxide (EtCO2) \>50 mm Hg. |
| Change From Baseline in SaO2 Nadir at Month 12 | Baseline and Month 12 | SaO2 measures the percentage of oxyhemoglobin (oxygen-bound hemoglobin) in the blood. SaO2 nadir refers to lowest SaO2. |
| Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Head circumference or the occipito-frontal circumference is the greatest of the cranial dimensions which passes around the forehead anteriorly and the external occipital protruberance posteriorly. It is a routine part of the physical examination of a child and is of great importance in detecting abnormal patterns of cranial growth. Occipito-frontal circumference data were summarized for each treatment arm. |
| Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Baseline, Month 3, Month 6, Month 9, and Month 12 | Respiratory rate was obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Respiratory rate was summarized by treatment in accordance with the sponsor reporting standards. |
Countries
Australia, Belgium, Denmark, Italy, Japan, Portugal, Spain, United States
Participant flow
Pre-assignment details
A total of 60 participants were enrolled, of which, 58 participants were assigned to treatment and 2 participants were not randomized, Out of 58 participants, 57 participants were treated. Note: The pharmacokinetics (PK) study cohort was not enrolled due to early study termination,
Participants by arm
| Arm | Count |
|---|---|
| Recifercept 1 mg/kg QW Children participants were enrolled and randomized to receive recifercept 1 mg/kg once weekly (QW) for 12 months. | 20 |
| Recifercept 2 mg/kg BIW Children participants were enrolled and randomized to receive recifercept 2 mg/kg twice weekly (BIW) for 12 months. | 19 |
| Recifercept 1.5 mg/kg QD Children participants were enrolled and randomized to receive recifercept 1.5 mg/kg once daily (QD) for 12 months. | 18 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Study terminated by sponsor | 4 | 2 | 14 |
| Overall Study | Withdrawal by parent/guardian | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Recifercept 1 mg/kg QW | Recifercept 2 mg/kg BIW | Recifercept 1.5 mg/kg QD | Total |
|---|---|---|---|---|
| Age, Continuous | 5.75 years STANDARD_DEVIATION 2.84 | 5.16 years STANDARD_DEVIATION 2.59 | 5.83 years STANDARD_DEVIATION 2.31 | 5.58 years STANDARD_DEVIATION 2.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 19 Participants | 15 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 15 Participants | 19 Participants | 14 Participants | 48 Participants |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 12 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 19 | 0 / 18 |
| other Total, other adverse events | 16 / 20 | 19 / 19 | 16 / 18 |
| serious Total, serious adverse events | 1 / 20 | 0 / 19 | 0 / 18 |
Outcome results
Primary
Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12
Height growth was defined as the ratio of observed change from baseline in standing height to the expected change from baseline in the reference population.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Recifercept 1 mg/kg QW | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 3 | 1.1 Ratio |
| Recifercept 1 mg/kg QW | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 6 | 0.9 Ratio |
| Recifercept 1 mg/kg QW | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 9 | 1.0 Ratio |
| Recifercept 1 mg/kg QW | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 12 | 1.0 Ratio |
| Recifercept 2 mg/kg BIW | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 12 | 1.0 Ratio |
| Recifercept 2 mg/kg BIW | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 3 | 0.9 Ratio |
| Recifercept 2 mg/kg BIW | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 9 | 1.0 Ratio |
| Recifercept 2 mg/kg BIW | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 6 | 1.1 Ratio |
| Recifercept 1.5 mg/kg QD | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 12 | 0.9 Ratio |
| Recifercept 1.5 mg/kg QD | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 6 | 1.0 Ratio |
| Recifercept 1.5 mg/kg QD | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 9 | 1.0 Ratio |
| Recifercept 1.5 mg/kg QD | Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12 | Month 3 | 0.6 Ratio |
Comparison: Results based on Mixed-Effect Repeated Measures (MMRM) analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.2, 0.6]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [0.1, 0.9]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.7, 0.1]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.4, 0.1]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.4, 0.2]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.4, 0.2]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.2, 0.2]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.2, 0.2]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.2, 0.2]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.2, 0.2]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.2, 0.3]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.4, 0.1]
Primary
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AE is defined as an AE with onset date occurring during the on-treatment period. Relatedness to recifercept was assessed by the investigator (Yes/No).
Time frame: The first dose up to 28 to 35 days after the last dose of study intervention (13 months)
Population: Analysis population included all participants who received at least 1 dose of recifercept.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Recifercept 1 mg/kg QW | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Treatment-related SAE | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Treatment-related AE | 7 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Treatment-related SAE | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Treatment-related AE | 15 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Treatment-related AE | 14 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) | Treatment-related SAE | 0 Participants |
Secondary
Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12
The apnea-hypopnea index (AHI) is the average of the apneic and hypopneic episodes per hour of sleep, which is measured to assess obstructive sleep apnea (OSA). An AHI score of 1 to 4.9 events/hour is mild OSA, 5 to 9.9 events/hour is moderate, and more than 9 events/hour is severe in pediatric population.
Time frame: Baseline and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept and with a documented current diagnosis of sleep disordered breathing at enrollment. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Baseline (obstructive AHI) | 3.79 events per hour | Standard Deviation 4.72 |
| Recifercept 1 mg/kg QW | Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Change at Month 12 (total AHI) | -1.03 events per hour | Standard Deviation 8.671 |
| Recifercept 1 mg/kg QW | Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Change at Month 12 (obstructive AHI) | 0.31 events per hour | Standard Deviation 9.902 |
| Recifercept 1 mg/kg QW | Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Baseline (total AHI) | 6.34 events per hour | Standard Deviation 5.837 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Change at Month 12 (total AHI) | -2.90 events per hour | — |
| Recifercept 2 mg/kg BIW | Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Baseline (obstructive AHI) | 1.20 events per hour | Standard Deviation 1.08 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Baseline (total AHI) | 2.25 events per hour | Standard Deviation 2.872 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Change at Month 12 (obstructive AHI) | -1.90 events per hour | — |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Baseline (total AHI) | 16.07 events per hour | Standard Deviation 26.299 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12 | Baseline (obstructive AHI) | 6.23 events per hour | Standard Deviation 6.881 |
Secondary
Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12
Blood pressure measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (eg, television, cell phones) where possible (with consideration of the age of the child). Supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) were summarized by treatment in accordance with the sponsor reporting standards.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Baseline (Supine DBP) | 66.55 millimeters of mercury (mm Hg) | Standard Deviation 9.87 |
| Recifercept 1 mg/kg QW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 (Supine DBP) | -0.76 millimeters of mercury (mm Hg) | Standard Deviation 12.179 |
| Recifercept 1 mg/kg QW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 (Supine DBP) | -3.65 millimeters of mercury (mm Hg) | Standard Deviation 14.845 |
| Recifercept 1 mg/kg QW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 (Supine DBP) | -3.14 millimeters of mercury (mm Hg) | Standard Deviation 16.385 |
| Recifercept 1 mg/kg QW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Baseline (Supine SBP) | 105.70 millimeters of mercury (mm Hg) | Standard Deviation 10.732 |
| Recifercept 1 mg/kg QW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 (Supine SBP) | 10.47 millimeters of mercury (mm Hg) | Standard Deviation 14.261 |
| Recifercept 1 mg/kg QW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 (Supine SBP) | 1.88 millimeters of mercury (mm Hg) | Standard Deviation 21.863 |
| Recifercept 1 mg/kg QW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 (Supine SBP) | 2.59 millimeters of mercury (mm Hg) | Standard Deviation 15.732 |
| Recifercept 1 mg/kg QW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 (Supine DBP) | -3.41 millimeters of mercury (mm Hg) | Standard Deviation 12.846 |
| Recifercept 1 mg/kg QW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 (Supine SBP) | 3.57 millimeters of mercury (mm Hg) | Standard Deviation 27.7 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 (Supine DBP) | -1.13 millimeters of mercury (mm Hg) | Standard Deviation 13.953 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Baseline (Supine DBP) | 67.05 millimeters of mercury (mm Hg) | Standard Deviation 9.897 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Baseline (Supine SBP) | 118.37 millimeters of mercury (mm Hg) | Standard Deviation 22.056 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 (Supine SBP) | -5.68 millimeters of mercury (mm Hg) | Standard Deviation 21.445 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 (Supine SBP) | 3.94 millimeters of mercury (mm Hg) | Standard Deviation 17.424 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 (Supine SBP) | -2.94 millimeters of mercury (mm Hg) | Standard Deviation 16.364 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 (Supine DBP) | -4.47 millimeters of mercury (mm Hg) | Standard Deviation 8.618 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 (Supine SBP) | -11.75 millimeters of mercury (mm Hg) | Standard Deviation 31.865 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 (Supine DBP) | -0.83 millimeters of mercury (mm Hg) | Standard Deviation 10.837 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 (Supine DBP) | -2.50 millimeters of mercury (mm Hg) | Standard Deviation 11.408 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 (Supine DBP) | -4.50 millimeters of mercury (mm Hg) | Standard Deviation 21.92 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Baseline (Supine DBP) | 62.11 millimeters of mercury (mm Hg) | Standard Deviation 13.244 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 (Supine SBP) | 2.33 millimeters of mercury (mm Hg) | Standard Deviation 19.371 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Baseline (Supine SBP) | 106.28 millimeters of mercury (mm Hg) | Standard Deviation 14.199 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 (Supine DBP) | 5.27 millimeters of mercury (mm Hg) | Standard Deviation 12.92 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 (Supine SBP) | 4.82 millimeters of mercury (mm Hg) | Standard Deviation 15.134 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 (Supine SBP) | -6.50 millimeters of mercury (mm Hg) | Standard Deviation 4.95 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 (Supine DBP) | -0.29 millimeters of mercury (mm Hg) | Standard Deviation 12.849 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 (Supine SBP) | 5.73 millimeters of mercury (mm Hg) | Standard Deviation 14.587 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 (Supine DBP) | -2.44 millimeters of mercury (mm Hg) | Standard Deviation 13.492 |
Secondary
Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12
Body Mass Index (BMI) = Weight (kg)/\[(Standing Height (m))\^2\]. Standing height and weight were averaged over a visit before BMI was computed.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.12 kg/m^2 | Standard Deviation 0.671 |
| Recifercept 1 mg/kg QW | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Baseline | 19.83 kg/m^2 | Standard Deviation 1.022 |
| Recifercept 1 mg/kg QW | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.25 kg/m^2 | Standard Deviation 0.547 |
| Recifercept 1 mg/kg QW | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.10 kg/m^2 | Standard Deviation 0.376 |
| Recifercept 1 mg/kg QW | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.36 kg/m^2 | Standard Deviation 0.565 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.06 kg/m^2 | Standard Deviation 0.593 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Baseline | 20.18 kg/m^2 | Standard Deviation 1.318 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.28 kg/m^2 | Standard Deviation 0.569 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.04 kg/m^2 | Standard Deviation 0.5 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -0.13 kg/m^2 | Standard Deviation 0.4 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -0.01 kg/m^2 | Standard Deviation 0.635 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.50 kg/m^2 | Standard Deviation 0.735 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.21 kg/m^2 | Standard Deviation 0.843 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.02 kg/m^2 | Standard Deviation 0.996 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12 | Baseline | 21.57 kg/m^2 | Standard Deviation 2.566 |
Secondary
Change From Baseline in Desaturation Index at Month 12
Desaturation index is one of the polysomnography parameters to assess obstructive sleep apnea. It refers to the average number of desaturation episodes occurring per hour, where desaturation episodes are defined as a decrease in the mean oxygen saturation of ≥3% (over the last 120 seconds) that lasts for at least 10 seconds.
Time frame: Baseline and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept and with a documented current diagnosis of sleep disordered breathing at enrollment. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Desaturation Index at Month 12 | Baseline | 4.90 desaturations per hour | Standard Deviation 8.601 |
| Recifercept 1 mg/kg QW | Change From Baseline in Desaturation Index at Month 12 | Change at Month 12 | -4.61 desaturations per hour | Standard Deviation 14.598 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Desaturation Index at Month 12 | Baseline | 2.18 desaturations per hour | Standard Deviation 2.502 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Desaturation Index at Month 12 | Change at Month 12 | 0.20 desaturations per hour | — |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Desaturation Index at Month 12 | Baseline | 13.53 desaturations per hour | Standard Deviation 21.364 |
Secondary
Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12
Fixed flexion angles at elbow data were presented for each treatment arm. An average of a participant's elbow extension measurements over a visit was computed.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.03 degrees (°) | Standard Deviation 16.659 |
| Recifercept 1 mg/kg QW | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 2.23 degrees (°) | Standard Deviation 8.976 |
| Recifercept 1 mg/kg QW | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Baseline | -11.33 degrees (°) | Standard Deviation 20.002 |
| Recifercept 1 mg/kg QW | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.02 degrees (°) | Standard Deviation 16.407 |
| Recifercept 1 mg/kg QW | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 2.78 degrees (°) | Standard Deviation 34.075 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Baseline | -18.31 degrees (°) | Standard Deviation 12.707 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 4.83 degrees (°) | Standard Deviation 7.658 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 1.00 degrees (°) | Standard Deviation 7.016 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 4.29 degrees (°) | Standard Deviation 10.519 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 2.80 degrees (°) | Standard Deviation 6.842 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.83 degrees (°) | Standard Deviation 5.742 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 1.09 degrees (°) | Standard Deviation 5.285 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.77 degrees (°) | Standard Deviation 10.621 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Baseline | -6.45 degrees (°) | Standard Deviation 17.628 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.08 degrees (°) | Standard Deviation 0.825 |
Secondary
Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12
Height Standard Deviation Score (SDS) (z-score) was calculated as the difference between mean observed standing height at each visit and mean value of reference population divided by standard deviation of reference population. SDS indicates how similar the participant was to the reference population.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Overall Number of Participants Analyzed was based on age 2-10 years at baseline. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Baseline | -0.2 SDS | Standard Deviation 0.91 |
| Recifercept 1 mg/kg QW | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.0 SDS | Standard Deviation 0.26 |
| Recifercept 1 mg/kg QW | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.0 SDS | Standard Deviation 0.13 |
| Recifercept 1 mg/kg QW | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.0 SDS | Standard Deviation 0.21 |
| Recifercept 1 mg/kg QW | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.0 SDS | Standard Deviation 0.33 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Baseline | 0.1 SDS | Standard Deviation 0.91 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -0.0 SDS | Standard Deviation 0.17 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.0 SDS | Standard Deviation 0.21 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.0 SDS | Standard Deviation 0.21 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.1 SDS | Standard Deviation 0.26 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.0 SDS | Standard Deviation 0.2 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Baseline | 0.2 SDS | Standard Deviation 1.26 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.0 SDS | Standard Deviation 0.24 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.0 SDS | Standard Deviation 0.26 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.2 SDS | Standard Deviation 0.17 |
Secondary
Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12
Knee height : lower segment ratio was the ratio of knee to heel length to the difference between standing height and sitting height.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.00 Ratio | Standard Deviation 0.028 |
| Recifercept 1 mg/kg QW | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -0.00 Ratio | Standard Deviation 0.02 |
| Recifercept 1 mg/kg QW | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline | 0.81 Ratio | Standard Deviation 0.052 |
| Recifercept 1 mg/kg QW | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.00 Ratio | Standard Deviation 0.027 |
| Recifercept 1 mg/kg QW | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.00 Ratio | Standard Deviation 0.028 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline | 0.84 Ratio | Standard Deviation 0.058 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -0.01 Ratio | Standard Deviation 0.052 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.02 Ratio | Standard Deviation 0.081 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.02 Ratio | Standard Deviation 0.062 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.02 Ratio | Standard Deviation 0.065 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.01 Ratio | Standard Deviation 0.026 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline | 0.80 Ratio | Standard Deviation 0.035 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.00 Ratio | Standard Deviation 0.026 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.02 Ratio | Standard Deviation 0.023 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.02 Ratio | Standard Deviation 0.035 |
Secondary
Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12
Head circumference or the occipito-frontal circumference is the greatest of the cranial dimensions which passes around the forehead anteriorly and the external occipital protruberance posteriorly. It is a routine part of the physical examination of a child and is of great importance in detecting abnormal patterns of cranial growth. Occipito-frontal circumference data were summarized for each treatment arm.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Baseline | 54.56 cm | Standard Deviation 2.877 |
| Recifercept 1 mg/kg QW | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.46 cm | Standard Deviation 0.619 |
| Recifercept 1 mg/kg QW | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.87 cm | Standard Deviation 1.106 |
| Recifercept 1 mg/kg QW | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.19 cm | Standard Deviation 0.345 |
| Recifercept 1 mg/kg QW | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.33 cm | Standard Deviation 0.396 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.35 cm | Standard Deviation 0.597 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.53 cm | Standard Deviation 0.557 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.19 cm | Standard Deviation 0.382 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Baseline | 55.00 cm | Standard Deviation 2.179 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.35 cm | Standard Deviation 0.506 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.30 cm | Standard Deviation 0.515 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | 0.54 cm | Standard Deviation 0.588 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.00 cm | Standard Deviation 0.424 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Baseline | 56.13 cm | Standard Deviation 1.949 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.30 cm | Standard Deviation 0.437 |
Secondary
Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12
Ratio of occipito-frontal distance to occipito-mid-face measurements was summarized for each treatment arm.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.01 Ratio | Standard Deviation 0.024 |
| Recifercept 1 mg/kg QW | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.01 Ratio | Standard Deviation 0.042 |
| Recifercept 1 mg/kg QW | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline | 1.00 Ratio | Standard Deviation 0.053 |
| Recifercept 1 mg/kg QW | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.01 Ratio | Standard Deviation 0.056 |
| Recifercept 1 mg/kg QW | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.04 Ratio | Standard Deviation 0.034 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.01 Ratio | Standard Deviation 0.028 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.00 Ratio | Standard Deviation 0.039 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.00 Ratio | Standard Deviation 0.027 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline | 1.00 Ratio | Standard Deviation 0.055 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.01 Ratio | Standard Deviation 0.034 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline | 1.00 Ratio | Standard Deviation 0.058 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.00 Ratio | Standard Deviation 0.018 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.02 Ratio | Standard Deviation 0.031 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -0.01 Ratio | Standard Deviation 0.034 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.02 Ratio | Standard Deviation 0.039 |
Secondary
Change From Baseline in Polysomnography Other Parameters at Month 12
Polysomnography refers to a systematic process used to collect physiologic parameters during sleep. Polysomnography other parameters included total sleep time spent with oxygen saturation (SaO2) \< 90% (T90), total sleep time spent with end-tidal carbon dioxide (EtCO2) \>50 mm Hg.
Time frame: Baseline and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept and with a documented diagnosis of sleep-disordered breathing at enrollment. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Polysomnography Other Parameters at Month 12 | Change at Month 12 (T90) | -48.95 percentage (%) of total sleep time | Standard Deviation 69.933 |
| Recifercept 1 mg/kg QW | Change From Baseline in Polysomnography Other Parameters at Month 12 | Baseline (EtCO2) | 7.02 percentage (%) of total sleep time | Standard Deviation 14.03 |
| Recifercept 1 mg/kg QW | Change From Baseline in Polysomnography Other Parameters at Month 12 | Change at Month 12 (EtCO2) | -14.03 percentage (%) of total sleep time | Standard Deviation 19.841 |
| Recifercept 1 mg/kg QW | Change From Baseline in Polysomnography Other Parameters at Month 12 | Baseline (T90) | 16.43 percentage (%) of total sleep time | Standard Deviation 40.155 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Polysomnography Other Parameters at Month 12 | Baseline (T90) | 24.79 percentage (%) of total sleep time | Standard Deviation 49.472 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Polysomnography Other Parameters at Month 12 | Change at Month 12 (EtCO2) | -38.00 percentage (%) of total sleep time | — |
| Recifercept 2 mg/kg BIW | Change From Baseline in Polysomnography Other Parameters at Month 12 | Change at Month 12 (T90) | -99.00 percentage (%) of total sleep time | — |
| Recifercept 2 mg/kg BIW | Change From Baseline in Polysomnography Other Parameters at Month 12 | Baseline (EtCO2) | 9.50 percentage (%) of total sleep time | Standard Deviation 19 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Polysomnography Other Parameters at Month 12 | Baseline (EtCO2) | 7.37 percentage (%) of total sleep time | Standard Deviation 17.355 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Polysomnography Other Parameters at Month 12 | Baseline (T90) | 0.72 percentage (%) of total sleep time | Standard Deviation 0.758 |
Secondary
Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12
Pulse rate measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (eg, television, cell phones) where possible (with consideration of the age of the child). Pulse rate was summarized by treatment in accordance with the sponsor reporting standards.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -2.65 beats per minute (BPM) | Standard Deviation 8.76 |
| Recifercept 1 mg/kg QW | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -1.47 beats per minute (BPM) | Standard Deviation 13.639 |
| Recifercept 1 mg/kg QW | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Baseline | 96.40 beats per minute (BPM) | Standard Deviation 16.583 |
| Recifercept 1 mg/kg QW | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -4.35 beats per minute (BPM) | Standard Deviation 16.035 |
| Recifercept 1 mg/kg QW | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 1.17 beats per minute (BPM) | Standard Deviation 15.484 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -2.18 beats per minute (BPM) | Standard Deviation 17.746 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -6.05 beats per minute (BPM) | Standard Deviation 20.871 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -1.44 beats per minute (BPM) | Standard Deviation 15.659 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.75 beats per minute (BPM) | Standard Deviation 34.012 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Baseline | 97.58 beats per minute (BPM) | Standard Deviation 21.823 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Baseline | 94.50 beats per minute (BPM) | Standard Deviation 15.497 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -11.50 beats per minute (BPM) | Standard Deviation 37.477 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -2.20 beats per minute (BPM) | Standard Deviation 15.88 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -15.20 beats per minute (BPM) | Standard Deviation 14.853 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -2.94 beats per minute (BPM) | Standard Deviation 16.913 |
Secondary
Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12
Respiratory rate was obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Respiratory rate was summarized by treatment in accordance with the sponsor reporting standards.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -1.12 breaths/min | Standard Deviation 3.516 |
| Recifercept 1 mg/kg QW | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.47 breaths/min | Standard Deviation 5.691 |
| Recifercept 1 mg/kg QW | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -1.06 breaths/min | Standard Deviation 3.473 |
| Recifercept 1 mg/kg QW | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 2.00 breaths/min | Standard Deviation 5.132 |
| Recifercept 1 mg/kg QW | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Baseline | 23.15 breaths/min | Standard Deviation 4.603 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.94 breaths/min | Standard Deviation 4.507 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Baseline | 24.37 breaths/min | Standard Deviation 3.905 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -1.00 breaths/min | Standard Deviation 2.809 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.94 breaths/min | Standard Deviation 4.221 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -3.75 breaths/min | Standard Deviation 4.979 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 2.00 breaths/min | Standard Deviation 15.556 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -1.53 breaths/min | Standard Deviation 4.939 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.53 breaths/min | Standard Deviation 4.502 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -1.30 breaths/min | Standard Deviation 6.945 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12 | Baseline | 23.39 breaths/min | Standard Deviation 5.863 |
Secondary
Change From Baseline in SaO2 Nadir at Month 12
SaO2 measures the percentage of oxyhemoglobin (oxygen-bound hemoglobin) in the blood. SaO2 nadir refers to lowest SaO2.
Time frame: Baseline and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept and with a documented diagnosis of sleep-disordered breathing at enrollment. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in SaO2 Nadir at Month 12 | Baseline | 92.29 percentage (%) of oxyhemoglobin | Standard Deviation 3.147 |
| Recifercept 1 mg/kg QW | Change From Baseline in SaO2 Nadir at Month 12 | Change at Month 12 | -2.67 percentage (%) of oxyhemoglobin | Standard Deviation 7.095 |
| Recifercept 2 mg/kg BIW | Change From Baseline in SaO2 Nadir at Month 12 | Baseline | 94.25 percentage (%) of oxyhemoglobin | Standard Deviation 6.397 |
| Recifercept 2 mg/kg BIW | Change From Baseline in SaO2 Nadir at Month 12 | Change at Month 12 | 1.00 percentage (%) of oxyhemoglobin | — |
| Recifercept 1.5 mg/kg QD | Change From Baseline in SaO2 Nadir at Month 12 | Baseline | 91.06 percentage (%) of oxyhemoglobin | Standard Deviation 5.882 |
Secondary
Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12
Sitting/standing height ratio was the ratio of sitting height to standing height.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Overall Number of Participants Analyzed was based on age 2-10 years at baseline. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.0 Ratio | Standard Deviation 0.01 |
| Recifercept 1 mg/kg QW | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | 0.0 Ratio | Standard Deviation 0.01 |
| Recifercept 1 mg/kg QW | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline | 0.7 Ratio | Standard Deviation 0.02 |
| Recifercept 1 mg/kg QW | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.0 Ratio | Standard Deviation 0.01 |
| Recifercept 1 mg/kg QW | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.0 Ratio | Standard Deviation 0.01 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.0 Ratio | Standard Deviation 0.01 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -0.0 Ratio | Standard Deviation 0.01 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline | 0.7 Ratio | Standard Deviation 0.02 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.0 Ratio | Standard Deviation 0.01 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.0 Ratio | Standard Deviation 0.01 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.0 Ratio | Standard Deviation 0 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.0 Ratio | Standard Deviation 0.01 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Baseline | 0.7 Ratio | Standard Deviation 0.02 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.0 Ratio | Standard Deviation 0.01 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.0 Ratio | Standard Deviation 0.01 |
Secondary
Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12
Temperature was obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Temperature measurements were summarized by treatment in accordance with the sponsor reporting standards.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.16 Degree Celsius (°C) | Standard Deviation 0.614 |
| Recifercept 1 mg/kg QW | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.08 Degree Celsius (°C) | Standard Deviation 0.493 |
| Recifercept 1 mg/kg QW | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.21 Degree Celsius (°C) | Standard Deviation 0.313 |
| Recifercept 1 mg/kg QW | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Baseline | 36.57 Degree Celsius (°C) | Standard Deviation 0.441 |
| Recifercept 1 mg/kg QW | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -0.06 Degree Celsius (°C) | Standard Deviation 0.362 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | -0.14 Degree Celsius (°C) | Standard Deviation 0.316 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | -0.04 Degree Celsius (°C) | Standard Deviation 0.297 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.02 Degree Celsius (°C) | Standard Deviation 0.298 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.12 Degree Celsius (°C) | Standard Deviation 0.437 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Baseline | 36.43 Degree Celsius (°C) | Standard Deviation 0.519 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 6 | -0.03 Degree Celsius (°C) | Standard Deviation 0.417 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Baseline | 36.58 Degree Celsius (°C) | Standard Deviation 0.466 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 3 | 0.11 Degree Celsius (°C) | Standard Deviation 0.493 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 9 | -0.20 Degree Celsius (°C) | Standard Deviation 0.503 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12 | Change at Month 12 | 0.30 Degree Celsius (°C) | Standard Deviation 0.141 |
Secondary
Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12
Waist : Chest Ratio = Waist Circumference / Chest Circumference. Waist and chest circumference were averaged over a visit before waist : chest circumference ratio was computed.
Time frame: Baseline, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12 | Baseline | 0.93 Ratio | Standard Deviation 0.048 |
| Recifercept 1 mg/kg QW | Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12 | Change at Month 12 | 0.05 Ratio | Standard Deviation 0.074 |
| Recifercept 1 mg/kg QW | Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12 | Change at Month 9 | 0.07 Ratio | — |
| Recifercept 2 mg/kg BIW | Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12 | Baseline | 0.94 Ratio | Standard Deviation 0.051 |
| Recifercept 2 mg/kg BIW | Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12 | Change at Month 9 | 0.00 Ratio | — |
| Recifercept 2 mg/kg BIW | Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12 | Change at Month 12 | 0.00 Ratio | Standard Deviation 0.063 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12 | Baseline | 0.97 Ratio | Standard Deviation 0.052 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12 | Change at Month 12 | -0.01 Ratio | Standard Deviation 0.007 |
| Recifercept 1.5 mg/kg QD | Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12 | Change at Month 9 | -0.01 Ratio | — |
Secondary
Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12
Arm span to standing height/length difference was the difference between arm span and standing height.
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Recifercept 1 mg/kg QW | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 12 | 1.0 centimeter (cm) |
| Recifercept 1 mg/kg QW | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 6 | 0.2 centimeter (cm) |
| Recifercept 1 mg/kg QW | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 3 | 0.4 centimeter (cm) |
| Recifercept 1 mg/kg QW | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 9 | 0.7 centimeter (cm) |
| Recifercept 2 mg/kg BIW | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 3 | 0.0 centimeter (cm) |
| Recifercept 2 mg/kg BIW | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 6 | 0.7 centimeter (cm) |
| Recifercept 2 mg/kg BIW | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 12 | 0.9 centimeter (cm) |
| Recifercept 2 mg/kg BIW | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 9 | 0.7 centimeter (cm) |
| Recifercept 1.5 mg/kg QD | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 12 | 0.3 centimeter (cm) |
| Recifercept 1.5 mg/kg QD | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 9 | 0.0 centimeter (cm) |
| Recifercept 1.5 mg/kg QD | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 3 | -0.6 centimeter (cm) |
| Recifercept 1.5 mg/kg QD | Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12 | Month 6 | -0.5 centimeter (cm) |
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.5, 1.2]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [0.2, 1.8]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-1.5, 0.1]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-1.6, 0.6]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.4, 1.9]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-2.3, -0.1]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.8, 0.7]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-0.2, 1.5]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-1.5, 0.2]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-1.3, 1.5]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-1.4, 2.8]
Comparison: Results based on MMRM analysis with gender as a covariate, participant (and/or time) as a random effect; treatment, visit, treatment-by-visit interaction, age and gender as fixed effects using an unstructured covariance matrix.95% CI: [-2.6, 1.4]
Secondary
Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12
A physical examination included, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal systems and skin. Physical examination assessments were summarized by treatment in accordance with the sponsor reporting standards.
Time frame: Month 3, Month 6, Month 9, and Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 3 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 6 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 12 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 6 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 9 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 12 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 3 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 6 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 12 | 1 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 3 | 2 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 6 | 1 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 12 | 2 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 9 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 3 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 9 | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 9 | 3 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 3 | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 6 | 2 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 12 | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 9 | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 3 | 3 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 6 | 4 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 12 | 3 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 6 | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 3 | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 12 | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 3 | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 9 | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 9 | 3 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 9 | 2 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 6 | 1 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 12 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 12 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 3 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 9 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 3 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 6 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 9 | 2 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 6 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 12 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 9 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 12 | 1 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 3 | 1 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Lungs at Month 9 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Gastrointestinal at Month 6 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Skin at Month 6 | 2 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 12 | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12 | Abnormal Cardiovascular at Month 3 | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Participants with laboratory abnormalities that met pre-specified criteria included following parameters: hematology (corpuscular volume, corpuscular hemoglobin, corpuscular hemoglobin concentration, platelet, leukocytes, lymphocytes, neutrophils, eosinophils, and monocytes), and chemistry (bilirubin, alkaline phosphatase, albumin, urea nitrogen, urate, potassium, phosphate, bicarbonate).
Time frame: Baseline to Month 12
Population: Analysis population included all participants who received at least 1 dose of recifercept.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urate (mg/dL) > 1.2 x ULN | 2 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Potassium (mEq/L) > 1.1 x ULN | 2 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Phosphate (mg/dL) < 0.8 x LLN | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bicarbonate (mEq/L) < 0.9 x LLN | 2 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Lymphocytes (10^9/L) < 0.8 x LLN | 5 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin (pg/cell) < 0.9 x LLN | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Leukocytes (10^9/L) < 0.6 x LLN | 1 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Neutrophils (10^9/L) < 0.8x LLN | 1 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (fL) < 0.9 x lower limit of normal (LLN) | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Neutrophils (10^9/L) > 1.2 x ULN | 1 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (fL) > 1.1 x upper limit of normal (ULN) | 1 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Eosinophils (10^9/L) > 1.2 x ULN | 1 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Monocytes (10^9/L) > 1.2 x ULN | 4 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin Concentration (g/dL) < 0.9x LLN | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bilirubin (mg/dL) > 1.5 x ULN | 0 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Alkaline Phosphatase (U/L) > 3.0 x ULN | 1 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Albumin (g/dL) > 1.2 x ULN | 2 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urea Nitrogen (mg/dL) > 1.3 x ULN | 2 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Platelets (10^9/L) > 1.75 x ULN | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bilirubin (mg/dL) > 1.5 x ULN | 1 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Platelets (10^9/L) > 1.75 x ULN | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Neutrophils (10^9/L) > 1.2 x ULN | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Potassium (mEq/L) > 1.1 x ULN | 4 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Leukocytes (10^9/L) < 0.6 x LLN | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin Concentration (g/dL) < 0.9x LLN | 1 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Phosphate (mg/dL) < 0.8 x LLN | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (fL) < 0.9 x lower limit of normal (LLN) | 1 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urate (mg/dL) > 1.2 x ULN | 1 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bicarbonate (mEq/L) < 0.9 x LLN | 2 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Eosinophils (10^9/L) > 1.2 x ULN | 4 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Lymphocytes (10^9/L) < 0.8 x LLN | 9 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urea Nitrogen (mg/dL) > 1.3 x ULN | 5 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Monocytes (10^9/L) > 1.2 x ULN | 1 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Albumin (g/dL) > 1.2 x ULN | 3 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Neutrophils (10^9/L) < 0.8x LLN | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin (pg/cell) < 0.9 x LLN | 1 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Alkaline Phosphatase (U/L) > 3.0 x ULN | 0 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (fL) > 1.1 x upper limit of normal (ULN) | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Alkaline Phosphatase (U/L) > 3.0 x ULN | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (fL) > 1.1 x upper limit of normal (ULN) | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin (pg/cell) < 0.9 x LLN | 2 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Hemoglobin Concentration (g/dL) < 0.9x LLN | 1 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Leukocytes (10^9/L) < 0.6 x LLN | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Lymphocytes (10^9/L) < 0.8 x LLN | 4 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Neutrophils (10^9/L) < 0.8x LLN | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Neutrophils (10^9/L) > 1.2 x ULN | 1 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Monocytes (10^9/L) > 1.2 x ULN | 1 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bilirubin (mg/dL) > 1.5 x ULN | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Albumin (g/dL) > 1.2 x ULN | 1 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urea Nitrogen (mg/dL) > 1.3 x ULN | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urate (mg/dL) > 1.2 x ULN | 0 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Potassium (mEq/L) > 1.1 x ULN | 4 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Phosphate (mg/dL) < 0.8 x LLN | 1 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bicarbonate (mEq/L) < 0.9 x LLN | 4 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Ery. Mean Corpuscular Volume (fL) < 0.9 x lower limit of normal (LLN) | 2 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Platelets (10^9/L) > 1.75 x ULN | 1 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Eosinophils (10^9/L) > 1.2 x ULN | 3 Participants |
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept
The immunogenicity was measured by presence of ADA and NAb in participants treated with recifercept and summarized by dose regimen.
Time frame: The first dose up to 28 to 35 days after the last dose of study intervention (13 months)
Population: Analysis population included all participants who received at least 1 dose of recifercept.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Recifercept 1 mg/kg QW | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept | Overall incidence of positive ADA | 16 Participants |
| Recifercept 1 mg/kg QW | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept | Overall incidence of positive NAb | 13 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept | Overall incidence of positive ADA | 18 Participants |
| Recifercept 2 mg/kg BIW | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept | Overall incidence of positive NAb | 16 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept | Overall incidence of positive ADA | 17 Participants |
| Recifercept 1.5 mg/kg QD | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept | Overall incidence of positive NAb | 16 Participants |
Secondary
Pre-Dose Serum Concentration (Ctrough) of Recifercept
Ctrough was defined as pre-dose serum concentration during dosing and observed directly from data.
Time frame: Pre-dose on Day(s) 4, 8, 15, 29, 61, 91, 183, 273, 365
Population: Analysis population included all participants who received at least 1 dose of recifercept and had at least one evaluable concentration. The Number Analyzed in a row was based on actual analyzed participants at each visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Recifercept 1 mg/kg QW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 61 | 183.8 nanograms per millilitre (ng/mL) | Standard Deviation 75.76 |
| Recifercept 1 mg/kg QW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 8 | 95.3 nanograms per millilitre (ng/mL) | Standard Deviation 23.35 |
| Recifercept 1 mg/kg QW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 91 | 225.5 nanograms per millilitre (ng/mL) | Standard Deviation 90.91 |
| Recifercept 1 mg/kg QW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 183 | 370.9 nanograms per millilitre (ng/mL) | Standard Deviation 424.8 |
| Recifercept 1 mg/kg QW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 273 | 278.2 nanograms per millilitre (ng/mL) | Standard Deviation 140.41 |
| Recifercept 1 mg/kg QW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 365 | 249.5 nanograms per millilitre (ng/mL) | Standard Deviation 174.54 |
| Recifercept 1 mg/kg QW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 15 | 137.1 nanograms per millilitre (ng/mL) | Standard Deviation 39.26 |
| Recifercept 1 mg/kg QW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 29 | 154.3 nanograms per millilitre (ng/mL) | Standard Deviation 46.91 |
| Recifercept 1 mg/kg QW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 4 | 215.8 nanograms per millilitre (ng/mL) | Standard Deviation 63.28 |
| Recifercept 2 mg/kg BIW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 273 | 1340.8 nanograms per millilitre (ng/mL) | Standard Deviation 695.1 |
| Recifercept 2 mg/kg BIW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 4 | 517.3 nanograms per millilitre (ng/mL) | Standard Deviation 174.18 |
| Recifercept 2 mg/kg BIW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 15 | 868.1 nanograms per millilitre (ng/mL) | Standard Deviation 341.98 |
| Recifercept 2 mg/kg BIW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 183 | 1078.9 nanograms per millilitre (ng/mL) | Standard Deviation 563.83 |
| Recifercept 2 mg/kg BIW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 8 | 614.6 nanograms per millilitre (ng/mL) | Standard Deviation 228.35 |
| Recifercept 2 mg/kg BIW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 61 | 974.8 nanograms per millilitre (ng/mL) | Standard Deviation 604.47 |
| Recifercept 2 mg/kg BIW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 365 | 1320.4 nanograms per millilitre (ng/mL) | Standard Deviation 662.18 |
| Recifercept 2 mg/kg BIW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 29 | 940.8 nanograms per millilitre (ng/mL) | Standard Deviation 415.45 |
| Recifercept 2 mg/kg BIW | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 91 | 944.8 nanograms per millilitre (ng/mL) | Standard Deviation 466.38 |
| Recifercept 1.5 mg/kg QD | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 365 | 6766.7 nanograms per millilitre (ng/mL) | Standard Deviation 3145.18 |
| Recifercept 1.5 mg/kg QD | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 183 | 5185.5 nanograms per millilitre (ng/mL) | Standard Deviation 3190.3 |
| Recifercept 1.5 mg/kg QD | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 15 | 3199.4 nanograms per millilitre (ng/mL) | Standard Deviation 1311.65 |
| Recifercept 1.5 mg/kg QD | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 273 | 3879.6 nanograms per millilitre (ng/mL) | Standard Deviation 3027.59 |
| Recifercept 1.5 mg/kg QD | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 29 | 3804.4 nanograms per millilitre (ng/mL) | Standard Deviation 1573.91 |
| Recifercept 1.5 mg/kg QD | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 91 | 3702.3 nanograms per millilitre (ng/mL) | Standard Deviation 2074.64 |
| Recifercept 1.5 mg/kg QD | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 4 | 1785.2 nanograms per millilitre (ng/mL) | Standard Deviation 651.92 |
| Recifercept 1.5 mg/kg QD | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 8 | 2682.6 nanograms per millilitre (ng/mL) | Standard Deviation 912.79 |
| Recifercept 1.5 mg/kg QD | Pre-Dose Serum Concentration (Ctrough) of Recifercept | Day 61 | 3431.4 nanograms per millilitre (ng/mL) | Standard Deviation 1477.48 |