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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02310763
Registration number
NCT02310763
Ethics application status
Date submitted
4/11/2014
Date registered
8/12/2014
Date last updated
7/12/2020
Titles & IDs
Public title
A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Duchenne Muscular Dystrophy
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Scientific title
A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTIPLE ASCENDING DOSE STUDY TO EVALUATE THE SAFETY, EFFICACY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-06252616 IN AMBULATORY BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
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Secondary ID [1]
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2014-002072-92
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Secondary ID [2]
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B5161002
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Duchenne Muscular Dystrophy
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Condition category
Condition code
Musculoskeletal
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Other muscular and skeletal disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Neurological
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Other neurological disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - PF-06252616
Treatment: Drugs - Placebo
Experimental: PF-06252616 - 3 dose levels (5mg/kg, 20mg/kg and 40 mg/kg) of IV infused PF-06252616 will be investigated within each subject
Placebo Comparator: Placebo - Matching Placebo
Other interventions: PF-06252616
PF-06252616 IV Infusion, 3 dose levels (5mg/kg, 20 mg/kg and 40 mg/kg) will be investigated within each subject
Treatment: Drugs: Placebo
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Intervention code [1]
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Other interventions
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49
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Assessment method [1]
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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.
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Timepoint [1]
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Study Day 1 to Week 49 visit
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Primary outcome [2]
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Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49
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Assessment method [2]
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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.
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Timepoint [2]
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Study Day 1 to Week 49 visit
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Primary outcome [3]
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Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49
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Assessment method [3]
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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.
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Timepoint [3]
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Study Day 1 to Week 49 visit
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Primary outcome [4]
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Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology
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Assessment method [4]
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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.
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Timepoint [4]
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Baseline to Week 49 visit
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Primary outcome [5]
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Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation
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Assessment method [5]
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Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT).
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Timepoint [5]
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Baseline to Week 49 visit
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Primary outcome [6]
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Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function
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Assessment method [6]
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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.
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Timepoint [6]
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Baseline to Week 49 visit
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Primary outcome [7]
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Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function
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Assessment method [7]
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Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid.
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Timepoint [7]
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Baseline to Week 49 visit
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Primary outcome [8]
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Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes
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Assessment method [8]
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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.
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Timepoint [8]
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Baseline to Week 49 visit
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Primary outcome [9]
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Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones
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Assessment method [9]
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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.
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Timepoint [9]
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Baseline to Week 49 visit
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Primary outcome [10]
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Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry
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Assessment method [10]
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Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, and amylase.
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Timepoint [10]
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Baseline to Week 49 visit
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Primary outcome [11]
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Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis
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Assessment method [11]
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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.
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Timepoint [11]
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Baseline to Week 49 visit
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Primary outcome [12]
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Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal
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Assessment method [12]
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Number of participants with blood detected in fecal samples is presented.
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Timepoint [12]
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Baseline to Week 49 visit
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Primary outcome [13]
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Categorical Summary of Liver Iron Accumulation by Week 49
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Assessment method [13]
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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.
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Timepoint [13]
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Screening, Weeks 13, 29 and 45
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Primary outcome [14]
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Number of Participants With Physical Examination Findings Reported as SAEs by Week 49
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Assessment method [14]
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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.
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Timepoint [14]
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Baseline to Week 49 visit
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Primary outcome [15]
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Summary of Tanner Stage Rating by Week 49
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Assessment method [15]
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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.
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Timepoint [15]
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Baseline, Weeks 17, 33 and 49
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Primary outcome [16]
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Number of Participants With Vital Signs Findings Reported as SAEs by Week 49
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Assessment method [16]
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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.
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Timepoint [16]
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Baseline to Week 49 visit
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Primary outcome [17]
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Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49
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Assessment method [17]
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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.
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Timepoint [17]
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Baseline to Week 49 visit
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Primary outcome [18]
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Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49
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Assessment method [18]
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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.
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Timepoint [18]
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Baseline to Week 49 visit
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Primary outcome [19]
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Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49
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Assessment method [19]
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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".
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Timepoint [19]
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Screening and Week 49
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Primary outcome [20]
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Bone Age to Chronological Age Ratio by Week 49
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Assessment method [20]
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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.
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Timepoint [20]
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Screening, Weeks 17, 33 and 49
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Primary outcome [21]
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Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49
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Assessment method [21]
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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.
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Timepoint [21]
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Baseline to Week 49 visit
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Primary outcome [22]
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Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49
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Assessment method [22]
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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.
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Timepoint [22]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [1]
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Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [2]
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Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49
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Assessment method [2]
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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.
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Timepoint [2]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [3]
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Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49
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Assessment method [3]
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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.
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Timepoint [3]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [4]
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Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49
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Assessment method [4]
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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.
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Timepoint [4]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [5]
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Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49
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Assessment method [5]
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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.
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Timepoint [5]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [6]
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Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49
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Assessment method [6]
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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.
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Timepoint [6]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [7]
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Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49
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Assessment method [7]
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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.
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Timepoint [7]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [8]
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Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49
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Assessment method [8]
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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.
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Timepoint [8]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [9]
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Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49
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Assessment method [9]
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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.
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Timepoint [9]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [10]
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Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49
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Assessment method [10]
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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.
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Timepoint [10]
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Baseline, Weeks 17, 33 and 49
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Secondary outcome [11]
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Change From Baseline to Week 49 on 4SC for Participants in Sequence 3 Compared to the Natural History Control Group
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Assessment method [11]
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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.
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Timepoint [11]
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Baseline, Week 49
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Secondary outcome [12]
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Change From Baseline to Week 97 on 4SC for Participants in Sequence 1 Compared to the Natural History Control Group
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Assessment method [12]
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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.
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Timepoint [12]
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0
Baseline, Week 97
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Secondary outcome [13]
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Change From Baseline to Week 49 on FVC for Participants in Sequence 3 Compared to the Natural History Control Group
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Assessment method [13]
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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.
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Timepoint [13]
0
0
Baseline, Week 49
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Secondary outcome [14]
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Change From Baseline to Week 97 on FVC for Participants in Sequence 1 Compared to the Natural History Control Group
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Assessment method [14]
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0
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.
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Timepoint [14]
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0
Baseline, Week 97
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Secondary outcome [15]
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Change From Baseline to Week 49 on NSAA for Participants in Sequence 3 Compared to the Natural History Control Group
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Assessment method [15]
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0
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.
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Timepoint [15]
0
0
Baseline, Week 49
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Secondary outcome [16]
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0
Change From Baseline to Week 97 on NSAA for Participants in Sequence 1 Compared to the Natural History Control Group
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Assessment method [16]
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0
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.
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Timepoint [16]
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0
Baseline, Week 97
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Secondary outcome [17]
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0
Change From Baseline to Week 49 on 6MWD for Participants in Sequence 3 Compared to the Natural History Control Group
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Assessment method [17]
0
0
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.
Query!
Timepoint [17]
0
0
Baseline, Week 49
Query!
Secondary outcome [18]
0
0
Change From Baseline to Week 97 on 6MWD for Participants in Sequence 1 Compared to the Natural History Control Group
Query!
Assessment method [18]
0
0
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.
Query!
Timepoint [18]
0
0
Baseline, Week 97
Query!
Secondary outcome [19]
0
0
Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets
Query!
Assessment method [19]
0
0
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.
Query!
Timepoint [19]
0
0
Baseline, Week 17
Query!
Secondary outcome [20]
0
0
Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets
Query!
Assessment method [20]
0
0
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.
Query!
Timepoint [20]
0
0
Baseline, Week 33
Query!
Secondary outcome [21]
0
0
Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets
Query!
Assessment method [21]
0
0
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.
Query!
Timepoint [21]
0
0
Baseline, Week 49
Query!
Secondary outcome [22]
0
0
Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets
Query!
Assessment method [22]
0
0
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.
Query!
Timepoint [22]
0
0
Baseline, Week 17
Query!
Secondary outcome [23]
0
0
Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets
Query!
Assessment method [23]
0
0
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.
Query!
Timepoint [23]
0
0
Baseline, Week 33
Query!
Secondary outcome [24]
0
0
Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets
Query!
Assessment method [24]
0
0
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.
Query!
Timepoint [24]
0
0
Baseline, Week 49
Query!
Secondary outcome [25]
0
0
Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets
Query!
Assessment method [25]
0
0
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.
Query!
Timepoint [25]
0
0
Baseline, Week 17
Query!
Secondary outcome [26]
0
0
Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets
Query!
Assessment method [26]
0
0
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.
Query!
Timepoint [26]
0
0
Baseline, Week 33
Query!
Secondary outcome [27]
0
0
Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets
Query!
Assessment method [27]
0
0
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.
Query!
Timepoint [27]
0
0
Baseline, Week 49
Query!
Secondary outcome [28]
0
0
Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets
Query!
Assessment method [28]
0
0
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.
Query!
Timepoint [28]
0
0
Baseline, Week 17
Query!
Secondary outcome [29]
0
0
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets
Query!
Assessment method [29]
0
0
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.
Query!
Timepoint [29]
0
0
Baseline, Week 33
Query!
Secondary outcome [30]
0
0
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets
Query!
Assessment method [30]
0
0
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.
Query!
Timepoint [30]
0
0
Baseline, Week 49
Query!
Secondary outcome [31]
0
0
Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets
Query!
Assessment method [31]
0
0
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.
Query!
Timepoint [31]
0
0
Baseline, Week 17
Query!
Secondary outcome [32]
0
0
Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets
Query!
Assessment method [32]
0
0
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.
Query!
Timepoint [32]
0
0
Baseline, Week 33
Query!
Secondary outcome [33]
0
0
Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets
Query!
Assessment method [33]
0
0
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.
Query!
Timepoint [33]
0
0
Baseline, Week 49
Query!
Secondary outcome [34]
0
0
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds)
Query!
Assessment method [34]
0
0
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.
Query!
Timepoint [34]
0
0
Baseline, Weeks 17, 33 and 49
Query!
Secondary outcome [35]
0
0
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds)
Query!
Assessment method [35]
0
0
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.
Query!
Timepoint [35]
0
0
Baseline, Weeks 17, 33 and 49
Query!
Secondary outcome [36]
0
0
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds)
Query!
Assessment method [36]
0
0
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.
Query!
Timepoint [36]
0
0
Baseline, Weeks 17, 33 and 49
Query!
Secondary outcome [37]
0
0
Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49
Query!
Assessment method [37]
0
0
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.
Query!
Timepoint [37]
0
0
Baseline, Weeks 17, 33 and 49
Query!
Secondary outcome [38]
0
0
Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49
Query!
Assessment method [38]
0
0
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.
Query!
Timepoint [38]
0
0
Baseline, Weeks 17, 33 and 49
Query!
Secondary outcome [39]
0
0
Change From Baseline in Whole Thigh Muscle Volume Through Week 97
Query!
Assessment method [39]
0
0
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.
Query!
Timepoint [39]
0
0
Baseline, Weeks 17, 33, 49 and 97
Query!
Secondary outcome [40]
0
0
Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97
Query!
Assessment method [40]
0
0
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.
Query!
Timepoint [40]
0
0
Baseline, Weeks 17, 33, 49 and 97
Query!
Secondary outcome [41]
0
0
Concentration of Growth Differentiation Factor 8 (GDF-8) at Time 0 (Pre-dose),(C0(GDF-8) )
Query!
Assessment method [41]
0
0
GDF-8, also called myostatin, is the target of domagrozumab. C0(GDF-8) was observed directly from data.
Query!
Timepoint [41]
0
0
Predose on Day 1 of Week 1
Query!
Secondary outcome [42]
0
0
Trough Serum Concentration of GDF-8 (Ctrough,(GDF-8)) for Participants Receiving Domagrozumab in Period 1
Query!
Assessment method [42]
0
0
GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data.
Query!
Timepoint [42]
0
0
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
Query!
Secondary outcome [43]
0
0
Ctrough,(GDF-8) for Participants of Sequence 3 in Period 2
Query!
Assessment method [43]
0
0
GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data.
Query!
Timepoint [43]
0
0
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
Query!
Secondary outcome [44]
0
0
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab
Query!
Assessment method [44]
0
0
Ctrough was observed directly from data.
Query!
Timepoint [44]
0
0
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
Query!
Secondary outcome [45]
0
0
Maximum Serum Concentration (Cmax) of Domagrozumab
Query!
Assessment method [45]
0
0
Cmax was observed directly from data.
Query!
Timepoint [45]
0
0
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
Query!
Secondary outcome [46]
0
0
Time for Cmax (Tmax) of Domagrozumab
Query!
Assessment method [46]
0
0
Tmax was observed directly from the data.
Query!
Timepoint [46]
0
0
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
Query!
Secondary outcome [47]
0
0
Terminal Half-life (t1/2) of Domagrozumab for Participants in Sequence 2 After the Last Dose of Domagrozumab
Query!
Assessment method [47]
0
0
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.
Query!
Timepoint [47]
0
0
At predose, end of 2-hour infusion and 6 hours since start of infusion at Week 45
Query!
Secondary outcome [48]
0
0
Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab
Query!
Assessment method [48]
0
0
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.
Query!
Timepoint [48]
0
0
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
Query!
Secondary outcome [49]
0
0
Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab
Query!
Assessment method [49]
0
0
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.
Query!
Timepoint [49]
0
0
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
Query!
Secondary outcome [50]
0
0
Clearance (CL) of Domagrozumab
Query!
Assessment method [50]
0
0
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.
Query!
Timepoint [50]
0
0
At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 13, 29 and 45
Query!
Secondary outcome [51]
0
0
Volume of Distribution at Steady State (Vss) of Domagrozumab for Participants in Sequence 2 Required for Additional PK Assessment
Query!
Assessment method [51]
0
0
Vss was calculated by CL*MRT, where MRT was the mean residence time. Vss was assessed to fully characterize PK data.
Query!
Timepoint [51]
0
0
At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Week 45
Query!
Secondary outcome [52]
0
0
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97
Query!
Assessment method [52]
0
0
The criterion for positive result of ADA samples was ADA titer >=1.88.
Query!
Timepoint [52]
0
0
Baseline, every 4 weeks from Week 5 to Week 97 visit or early termination
Query!
Eligibility
Key inclusion criteria
1. Ambulatory boys age 6 to <16 years old (at the time of randomization), diagnosed with
DMD. Diagnosis must be confirmed in subject's medical history and by genetic testing
obtained during routine clinical care for diagnostic purposes as reported from an
appropriate regulated laboratory using a clinically validated genetic test (genetic
testing is not provided by the sponsor).
2. Subjects who are able to perform the 4 stair climb in > or = 0.33 but < or =1.6
stairs/second.
3. Subjects must be receiving glucocorticosteroids for a minimum of 6 months prior to
signing informed consent. There should be no significant change (>0.2 mg/kg) in dosage
or dose regimen (not related to body weight change) for at least 3 months immediately
prior to signing the informed consent and a reasonable expectation that dosage and
dosing regimen will not change significantly for the duration of the study.
4. Adequate hepatic and renal function on screening laboratory assessments.
5. No underlying disposition for iron accumulation on screening laboratory assessments.
6. Iron content estimate on the screening liver MRI is within the normal range.
Query!
Minimum age
6
Years
Query!
Query!
Maximum age
15
Years
Query!
Query!
Sex
Males
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
1. Subjects with known cognitive impairment or behavioral issues that would impede the
ability to follow instructions.
2. History of major surgical procedure within 6 weeks of signing the informed consent or
planned surgery during the study.
3. Any injury which may impact functional testing. Previous injuries must be fully healed
prior to consenting. Prior lower limb fractures must be fully healed and at least 3
months from injury date.
4. Presence or history of other musculoskeletal or neurologic disease or somatic disorder
not related to DMD including pulmonary and cardiac disease.
5. Compromised cardiac function (left ventricular ejection fraction <55% as determined on
a screening cardiac MRI or echocardiogram). Subjects may be receiving ACE (angiotensin
converting enzyme) inhibitors or beta blockers, ARB (angiotensin II receptor
antagonist) or aldosterone blocker/thiazide diuretic; however they must have initiated
treatment more than 3 months prior to screening to ensure stable therapy.
6. Evidence or history of clinically significant hematological, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular (including uncontrolled hypertension),
hepatic, neurologic, or allergic disease (including drug allergies, but excluding
untreated, asymptomatic, seasonal allergies at time of dosing).
7. Documented history of iron overload including hemochromatosis, beta thalassemia major,
beta thalassemia intermedia or hemolytic anemia.
8. Unwilling or unable (eg, metal implants, requires sedation) to undergo examination
with closed MRI without sedation.
9. Participation in other studies involving investigational drug(s) for a minimum of 30
days or within 5 half lives (whichever is longer) prior to signing the informed
consent and/or during study participation.
10. Current or prior treatment with anti-myostatin, exon skipping, nonsense mutation
targeted therapies ever or more than 30 days of treatment with utrophin modifiers and
treatment with utrophin modifiers within 30 days prior ot signing the informed consent
and/or during study participation.
11. Current or prior treatment within the past 3 months with androgens or human growth
hormone.
12. Current treatment with immunosuppressant therapies (other than glucocorticoid
steroids), aminoglycosides (eg, gentamicin), multi vitamins with iron and iron
supplements and other investigational therapies (including idebenone).
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Terminated
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
24/11/2014
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
23/11/2018
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
121
Query!
Recruitment in Australia
Recruitment state(s)
QLD
Query!
Recruitment hospital [1]
0
0
Lady Cilento Children's Hospital - South Brisbane
Query!
Recruitment postcode(s) [1]
0
0
4101 - South Brisbane
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
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Funding & Sponsors
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Pfizer
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Summary
Brief summary
This is a Phase 2 randomized, 2-period, double-blind, placebo-controlled, multiple ascending
dose study to evaluate the safety, efficacy, PK and PD of PF-06252616 administered to
ambulatory boys diagnosed with Duchenne Muscular Dystrophy. Three intravenous (IV) dose
levels will be investigated in a within subject dose escalating fashion. Subjects will be
randomly assigned to 1 of 3 sequence groups for approximately 96 weeks (2 periods of 48 weeks
each). In period 1, two of the sequence groups will receive PF-06252616 and one sequence
group will receive placebo. In period 2, the placebo group will switch to PF-06252616 and the
two remaining sequence groups will either receive placebo or PF-06252616. Efficacy will be
based on an observed mean change from baseline on function (4 stair climb) of PF-06252616 as
compared to the placebo at the end of period 1. Period 2 provides an opportunity to evaluate
PK. Subjects will receive monthly IV infused doses of either PF-06252616 or placebo and will
undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI),
functional evaluations (pulmonary function testing, 4 stair climb, range of motion, strength
testing, Northstar Ambulatory Assessment, upper limb functional testing and the six minute
walk test), pharmacokinetic testing and pharmacodynamic testing to evaluate changes in muscle
volume (MRI).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02310763
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Pfizer CT.gov Call Center
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Pfizer
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Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02310763
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