| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator. | The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Count of Participants | | Participants | | Study Day 1 to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). | | OG003 | Domagrozumab 40 mg/kg | Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses). |
| | Units | Counts |
|---|
| Participants | - OG00040
- OG00180
- OG00278
- OG003
|
| | Title | Denominators | Categories |
|---|
| All-causalities TEAE | | | Title | Measurements |
|---|
| - OG00038
- OG00166
- OG00257
- OG003
|
|
| |
| Primary | Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. | The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Count of Participants | | Participants | | Study Day 1 to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). |
|
| Primary | Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. | The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Count of Participants | | Participants | | Study Day 1 to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). |
|
| Primary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology | Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils, absolute monocytes and absolute myelocytes. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). |
|
| Primary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation | Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT). | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). | | OG003 | Domagrozumab 40 mg/kg | |
|
| Primary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function | Liver function evaluation included: total/direct/indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). |
|
| Primary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function | Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). | | OG003 | Domagrozumab 40 mg/kg | |
|
| Primary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes | Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate, bicarbonate, ferritin, transferrin saturation, iron, iron binding capacity and unsaturated iron binding capacity. Number of participants with iron abnormalities was reported in different age groups. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). |
|
| Primary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones | Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). |
|
| Primary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry | Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, and amylase. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). | | OG003 |
|
| Primary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis | Urinalysis included: urine pH, qualitative urine glucose, qualitative urine ketones, qualitative urine protein, qualitative blood/hemoglobin, urine nitrite, urine leukocytes, urine RBC, urine WBC, urine granular casts, urine hyaline casts, urine urate (uric acid) acidic crystal, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). |
|
| Primary | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal | Number of participants with blood detected in fecal samples is presented. | This analysis population included all participants who received at least 1 dose of investigational drug and had at least 1 fecal evaluation. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). | | OG003 | Domagrozumab 40 mg/kg | Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses). |
|
| Primary | Categorical Summary of Liver Iron Accumulation by Week 49 | Magnetic resonance imaging (MRI) of Liver was obtained to quantify liver iron accumulation for safety monitoring. MRIs were sent to an independent central radiology imaging facility for calculation of the average transverse relaxation rate (R2*) value which was used to monitor for iron accumulation in the liver. Number of participants meeting the following criteria is presented as follows: 1) normal: R2*<=75Hz at 1.5T or <=139 Hz at 3.0T; 2) above normal: R2*>75Hz and <=190Hz at 1.5T or R2* >139Hz and <=369Hz at 3.0T; 3) mild overload: R2*>190Hz at 1.5T or R2*>360Hz at 3.0T. | This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Count of Participants | | Participants | | Screening, Weeks 13, 29 and 45 | | | | ID | Title | Description |
|---|
| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
|
| Primary | Number of Participants With Physical Examination Findings Reported as SAEs by Week 49 | Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A targeted nose and throat mucosal exam were also performed to monitor for any signs of mucosal telangiectasias. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which physical examination findings were reported as SAEs. | This analysis population included all participants who received at least 1 dose of investigational drug. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
|
| Primary | Summary of Tanner Stage Rating by Week 49 | Tanner staging was performed before the first dose of each dose escalation to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Count of Participants | | Participants | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
| |
| Primary | Number of Participants With Vital Signs Findings Reported as SAEs by Week 49 | Vital signs evaluation included supine systolic and diastolic blood pressure (BP), pulse rate, and respiratory rate. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which vital signs findings were reported as SAEs. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
| |
| Primary | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 | Number of participants with ECG data meeting the following criteria are presented: 1) corrected QT interval using Fridericia's formula (QTcF interval) <450msec; 2) QTcF interval >=450 and <480msec; 3) QTcF interval >=480 and <500msec; 4) QTcF interval>=500msec; 5) QTcF interval increase from baseline<30msec; 6) QTcF interval increase from baseline >=30 and <60msec; 7) QTcF interval increase from baseline >=60msec. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG002 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). |
|
| Primary | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49 | The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance image (MRI) or echocardiogram. The same method of cardiac imaging was used consistently within a single participant. Cardiac MRIs were read by a central imaging vendor and echocardiograms were read locally at each site. The LVEF values measured by cardiac MRI and echocardiogram are combined in the following presentation. The analysis of covariance (ANCOVA) model was used to analyze the change from baseline for domagrozumab compared to placebo on LVEF. The baseline result, age, use of angiotensin receptor blocker (ARB)/beta blocker/angiotensin converting enzyme (ACE) inhibitor and treatment were included as fixed effects in the model. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Ratio of blood | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
|
| Primary | Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49 | Bone mineral density (BMD) was evaluated by Dual energy X-ray Absorptiometry (DXA). The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was "below the expected range for age". If the Z-score was above -2 standard deviations, the result was "within the expected range for age". | This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to number of participants evaluable for specified rows of timepoints. | Posted | | Mean | Standard Deviation | Standard deviations | | Screening and Week 49 | | | | ID | Title | Description |
|---|
| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
|
| Primary | Bone Age to Chronological Age Ratio by Week 49 | Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date-date of birth+1)/365.25. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints. | Posted | | Mean | Standard Deviation | Ratio | | Screening, Weeks 17, 33 and 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
| |
| Primary | Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49 | An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. AEs of suicide ideation or behavior were determined by the investigator. | This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Count of Participants | | Participants | | Baseline to Week 49 visit | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
| |
| Primary | Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 | The 4SC quantified the time required for a participant to ascend 4 standard steps. Mixed effect model for repeated measures (MMRM) was used to analyze the change from baseline on 4SC for domagrozumab compared to placebo. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timeponts. | Posted | | Least Squares Mean | Standard Error | Seconds | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
| |
| Secondary | Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 | FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints. | Posted | | Least Squares Mean | Standard Error | Liters | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
| |
| Secondary | Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 | The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints. | Posted | | Least Squares Mean | Standard Error | Units on a scale | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
|
| Secondary | Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 | ROM was evaluated by using goniometry to evaluate the loss of motion in the ankles. MMRM was used to analyze the change from baseline on ROM for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Degrees of passive dorsiflexion | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 | The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints. | Posted | | Least Squares Mean | Standard Error | Units on a scale | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | |
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| Secondary | Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints. | Posted | | Least Squares Mean | Standard Error | Meters | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Kilograms | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Kilograms | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Kilograms | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Kilograms | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Kilograms | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline to Week 49 on 4SC for Participants in Sequence 3 Compared to the Natural History Control Group | The 4SC quantified the time required for a participant to ascend 4 standard steps. MMRM was used to analyze the change from baseline on 4SC for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG (Cooperative International Neuromuscular Research Group) natural history database. Participants who met the following requirements at baseline and had evaluable 4SC data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing. | This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Seconds | | Baseline, Week 49 | | | | ID | Title | Description |
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| OG000 | Sequence 3 | Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline to Week 97 on 4SC for Participants in Sequence 1 Compared to the Natural History Control Group | The 4SC quantified the time required for a participant to ascend 4 standard steps. MMRM was used to analyze the change from baseline on 4SC for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 4SC data on Week 97 were included in this group: 1) age: 6 to <16 years; 2) treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: >=55% or missing. | This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Seconds | | Baseline, Week 97 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. |
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| Secondary | Change From Baseline to Week 49 on FVC for Participants in Sequence 3 Compared to the Natural History Control Group | FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for the natural history control group compared to placebo group (Sequence 3). MMRM was used to analyze the change from baseline on FVC for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable FVC data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing. | This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Liters | | Baseline, Week 49 | | | | ID | Title | Description |
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| OG000 | Sequence 3 | Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline to Week 97 on FVC for Participants in Sequence 1 Compared to the Natural History Control Group | FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable FVC data on Week 97 were included in this group: 1) age: 6 to <16 years; 2) treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: >=55% or missing. | This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Liters | | Baseline, Week 97 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. |
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| Secondary | Change From Baseline to Week 49 on NSAA for Participants in Sequence 3 Compared to the Natural History Control Group | The NSAA is a 17-item test that measured gross motor function. A total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline on NSAA for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on the using natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable NSAA data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing. | This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Units on a scale | | Baseline, Week 49 | | | | ID | Title | Description |
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| OG000 | Sequence 3 | Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline to Week 97 on NSAA for Participants in Sequence 1 Compared to the Natural History Control Group | The NSAA is a 17-item test that measured gross motor function. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline on NSAA for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable NSAA data on Week 97 were included in this group: 1) age: 6 to <16 years; 2) treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: >=55% or missing. | This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Units on a scale | | Baseline, Week 97 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. |
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| Secondary | Change From Baseline to Week 49 on 6MWD for Participants in Sequence 3 Compared to the Natural History Control Group | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 6MWD data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing. | This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Meters | | Baseline, Week 49 | | | | ID | Title | Description |
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| OG000 | Sequence 3 | Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline to Week 97 on 6MWD for Participants in Sequence 1 Compared to the Natural History Control Group | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 6MWD data on Week 97 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing. | This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. | Posted | | Least Squares Mean | Standard Error | Meters | | Baseline, Week 97 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. |
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| Secondary | Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets | The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Seconds | | Baseline, Week 17 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets | The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds.MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Seconds | | Baseline, Week 33 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets | The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Seconds | | Baseline, Week 49 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets | FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Liters | | Baseline, Week 17 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets | FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Liters | | Baseline, Week 33 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets | FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Liters | | Baseline, Week 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets | The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Units on a scale | | Baseline, Week 17 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | |
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| Secondary | Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets | The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Units on a scale | | Baseline, Week 33 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | |
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| Secondary | Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets | The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Units on a scale | | Baseline, Week 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | |
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| Secondary | Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets | The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline .The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Units on a scale | | Baseline, Week 17 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab |
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| Secondary | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets | The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items).Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline.The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Units on a scale | | Baseline, Week 33 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab |
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| Secondary | Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets | The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items).Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline.The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Units on a scale | | Baseline, Week 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab |
|
| Secondary | Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Meters | | Baseline, Week 17 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Meters | | Baseline, Week 33 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets | 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Meters | | Baseline, Week 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC <3.5 seconds are presented below. | This analysis population included all participants (with baseline 4SC <3.5 seconds) randomized and who had received at least 1 dose o f randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Mean | 95% Confidence Interval | Kilograms | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC >=3.5 seconds and <=8 seconds are presented below. | This analysis population included all participants (with baseline 4SC >=3.5 seconds and <=8 seconds ) randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Mean | 95% Confidence Interval | Kilograms | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) | Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC >8 seconds are presented below. | This analysis population included all participants (with baseline 4SC >8 seconds) randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Mean | 95% Confidence Interval | Kilograms | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
|---|
| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 | The whole thigh muscle volume was measured by the proton density weighted sequence with magnetic resonance imaging (MRI) which was used to segment the entire thigh region into 3 primary regions for volumetric measure including 1) muscle; 2) inter/intra-muscular fat, 3) subcutaneous fat. MMRM was used to analyze the percent change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of time points. | Posted | | Least Squares Mean | Standard Error | Percent change of thigh muscle volume | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 | The thigh muscle volume index was derived from the thigh muscle volume measurements as the fraction of total thigh tissue that was the lean muscle. MMRM was used to analyze the percent change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories. | Posted | | Least Squares Mean | Standard Error | Percent change of muscle volume index | | Baseline, Weeks 17, 33 and 49 | | | | ID | Title | Description |
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| OG000 | Placebo | Participants received placebo from Week 1 to Week 48. | | OG001 | Domagrozumab | Participants received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) from Week 1 to Week 48. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). |
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| Secondary | Change From Baseline in Whole Thigh Muscle Volume Through Week 97 | The whole thigh muscle volume was measured by the proton density weighted sequence with magnetic resonance imaging (MRI) which was used to segment the entire thigh region into 3 primary regions for volumetric measure including 1) muscle; 2) inter/intra-muscular fat, 3) subcutaneous fat. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of time points. | Posted | | Mean | 95% Confidence Interval | Cubic centimeters | | Baseline, Weeks 17, 33, 49 and 97 | | | | ID | Title | Description |
|---|
| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
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| Secondary | Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 | The thigh muscle volume index was derived from the thigh muscle volume measurements as the fraction of total thigh tissue that was the lean muscle. | This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of time points. | Posted | | Mean | 95% Confidence Interval | Percent of whole thign volume | | Baseline, Weeks 17, 33, 49 and 97 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
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| Secondary | Concentration of Growth Differentiation Factor 8 (GDF-8) at Time 0 (Pre-dose),(C0(GDF-8) ) | GDF-8, also called myostatin, is the target of domagrozumab. C0(GDF-8) was observed directly from data. | This analysis population included all enrolled participants in whom at least 1 GDF-8 concentration value was reported. Participants without contributing to the summary statistics are excluded below. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter (ng/mL) | | Predose on Day 1 of Week 1 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
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| Secondary | Trough Serum Concentration of GDF-8 (Ctrough,(GDF-8)) for Participants Receiving Domagrozumab in Period 1 | GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data. | This analysis population included all enrolled participants in Sequences 1 and 2 in whom at least 1 GDF-8 concentration value was reported. Participants without contributing to the summary statistics are excluded below. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Every 4 weeks on dosing day (at predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 48 | | | | ID | Title | Description |
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| OG000 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses). | | OG001 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses). | | OG002 | Domagrozumab 40 mg/kg | Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses). |
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| Secondary | Ctrough,(GDF-8) for Participants of Sequence 3 in Period 2 | GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data. | This analysis population included all enrolled participants in Sequence 3 and in whom at least 1 GDF-8 concentration value was reported. Participants without contributing to the summary statistics are excluded below. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 49 to Week 96 | | | | ID | Title | Description |
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| OG000 | Domagrozumab 5 mg/kg | Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 49 to Week 64 (4 doses). | | OG001 | Domagrozumab 20 mg/kg | Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 65 to Week 80 (4 doses). | | OG002 | Domagrozumab 40 mg/kg | Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 81 to Week 96 (4 doses). |
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| Secondary | Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab | Ctrough was observed directly from data. | This analysis population included all participants who received at least 1 dose of domagrozumab and in whom at least 1 concentration value was reported. Participants without contributing to the summary statistics are excluded below. Number analyzed refers to number of participants evaluable for specified rows of timepoints. | Posted | | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter (ug/mL) | | Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
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| Secondary | Maximum Serum Concentration (Cmax) of Domagrozumab | Cmax was observed directly from data. | Data were not collected and analyzed due to study early termination. | Posted | | | | | | Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. | | OG002 | Sequence 3 |
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| Secondary | Time for Cmax (Tmax) of Domagrozumab | Tmax was observed directly from the data. | Data were not collected and analyzed due to study early termination. | Posted | | | | | | Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. | | OG002 | Sequence 3 |
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| Secondary | Terminal Half-life (t1/2) of Domagrozumab for Participants in Sequence 2 After the Last Dose of Domagrozumab | t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Participants in Sequence 2 received the last dose of domagrozumab at Week 45. | Data were not collected and analyzed due to study early termination. | Posted | | | | | | At predose, end of 2-hour infusion and 6 hours since start of infusion at Week 45 | | | | ID | Title | Description |
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| OG000 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
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| Secondary | Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab | The dosing interval tau was 672 hours (4 weeks). AUCtau was obtained by linear/log trapezoidal method. The AUCtau was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits. | This analysis population included participants who were among the first 12 participants enrolled in the study, had received at least 1 dose of domagrozumab and in whom at least 1 of the PK parameters of interest was calculated. Participants without contributing to the summary statistics are excluded below. | Posted | | Median | Full Range | Microgram*hour per milliliter (ug*hr/mL) | | At predose, end of 2-hour infusion,6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
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| Secondary | Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab | Cav was calculated by AUCtau/tau. The Cav was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits. | This analysis population included participants who were among the first 12 participants enrolled in the study, had received at least 1 dose of domagrozumab and in whom at least 1 of the PK parameters of interest was calculated. Participants without contributing to the summary statistics are excluded below. | Posted | | Median | Full Range | ug/mL | | At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45 | | | | ID | Title | Description |
|---|
| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
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| Secondary | Clearance (CL) of Domagrozumab | CL was calculated by Dose/AUCtau. The CL was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits. | This analysis population included participants who were among the first 12 participants enrolled in the study, had received at least 1 dose of domagrozumab and in whom at least 1 of the PK parameters of interest was calculated. Participants without contributing to the summary statistics are excluded below. | Posted | | Median | Full Range | Milliliter/hr/kilogram(mL/hr/kg) | | At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 13, 29 and 45 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
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| Secondary | Volume of Distribution at Steady State (Vss) of Domagrozumab for Participants in Sequence 2 Required for Additional PK Assessment | Vss was calculated by CL*MRT, where MRT was the mean residence time. Vss was assessed to fully characterize PK data. | Data were not collected and analyzed due to study early termination. | Posted | | | | | | At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Week 45 | | | | ID | Title | Description |
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| OG000 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
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| Secondary | Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 | The criterion for positive result of ADA samples was ADA titer >=1.88. | This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to the number of participants evaluable for specified rows of time points. | Posted | | Count of Participants | | Participants | | Baseline, every 4 weeks from Week 5 to Week 97 visit or early termination | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. | |
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| Other Pre-specified | Area Under the Curve From Time Zero to Last Quantifiable Serum Concentration (AUClast) of Domagrozumab | AUClast was calculated by linear/log trapezoidal method. AUCtau was obtained by linear/log trapezoidal method. AUClast was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits. | Data were not collected and analyzed due to study early termination. | Posted | | | | | | At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45 | | | | ID | Title | Description |
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| OG000 | Sequence 1 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study. | | OG001 | Sequence 2 | Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study. |
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