Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids in Participants With Ambulatory DMD

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of pamrevlumab versus placebo in combination with systemic corticosteroids administered every 2 weeks in ambulatory participants with Duchenne muscular dystrophy (DMD) (age 6 to <12 years).

Detailed Description
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This is a global, randomized, double-blind, trial of pamrevlumab or placebo in combination with systemic corticosteroids in participants with DMD, aged 6 to <12 years (ambulatory participants only). Approximately 70 participants will be randomized at a 1:1 ratio to Arm A (pamrevlumab + systemic deflazacort or equivalent potency of corticosteroids administered orally) or Arm B (placebo+ systemic deflazacort or equivalent potency of corticosteroids administered orally), respectively. Randomization will be stratified by exon 44 deletion for analysis. Stratification has no impact upon treatment assignment nor dosage. Participants must be fully informed of the potential benefits of approved products and make an informed decision when participating in a clinical trial in which they could be randomized to placebo. The main study has 3 study periods: Screening period: Up to 4 weeks Treatment period: 52 weeks Safety Follow-up period/final assessment: A visit 28 days (+/- 3 Days) and a final safety follow-up phone call 60 days (+ 3 Days) after the last dose Each participant will receive pamrevlumab or placebo at 35 mg/kg every 2 weeks for up to 52 weeks. Participants who complete 52 weeks of treatment may be eligible for an open-label extension (OLE), offering extended treatment with pamrevlumab. Participants who discontinue study treatment for any reason should be encouraged to return to the investigative site to complete final safety and efficacy assessments.

Official Title
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A Phase 3, Randomized, Double-Blind, Trial of Pamrevlumab (FG-3019) or Placebo in Combination With Systemic Corticosteroids in Ambulatory Subjects With Duchenne Muscular Dystrophy (DMD)

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: Pamrevlumab
* Drug: Placebo
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age, and consent: Males at least 6 to <12 years of age at screening initiation Written consent by participant and/or legal guardian as per regional/ country and/or Institutional Review Board (IRB)/Independent Ethics Committee (IEC) requirements DMD diagnosis: Medical history includes diagnosis of DMD and confirmed Duchenne mutation, including status of exon 44 using a validated genetic test. Pulmonary criteria: Average (of screening and Day 0) percent predicted forced vital capacity (FVC) above 45% On a stable dose of systemic corticosteroids for a minimum of 6 months, with no substantial change in dosage for a minimum of 3 months (except for adjustments for changes in body weight) prior to screening. Corticosteroid dosage should be in compliance with the DMD Care Considerations Working Group recommendations (for example, prednisone or prednisolone 0.75 mg/kg per day or deflazacort 0.9 mg/kg per day) or stable dose. A reasonable expectation is that dosage and dosing regimen would not change significantly for the duration of the study. Performance criteria: Able to complete 6-minute walking distance (6MWD) test with a distance of at least 270 meters but no more than 450 meters on two occasions within 3 months prior to randomization with ≤10% variation between these two tests. Able to rise (TTSTAND) from floor in <10 seconds (without aids/orthoses) at screening visit. Able to undergo magnetic resonance imaging (MRI) test for the lower extremities vastus lateralis muscle. Vaccination: Agreement to receive annual influenza vaccinations during the conduct of the study. Laboratory criteria: Adequate renal function: cystatin C ≤1.4 mg/liter (L) Adequate hematology and electrolytes parameters: Platelets >100,000/microliter (μL) Hemoglobin >12 grams (g)/deciliter (dL) Absolute neutrophil count >1500/μL Serum calcium (Ca), potassium (K), sodium (Na), magnesium (Mg) and phosphorus (P) levels are within a clinically accepted range for DMD participants Adequate hepatic function: No history or evidence of liver disease Gamma glutamyl transferase (GGT) ≤3x upper limit of normal (ULN) Total bilirubin ≤1.5xULN Exclusion Criteria: General Criteria: Concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function Severe intellectual impairment (for example, severe autism, severe cognitive impairment, severe behavioral disturbances) preventing the ability to perform study assessments in the Investigator's judgment Previous exposure to pamrevlumab Body mass index (BMI) ≥40 kg/square meter (m^2) or weight >117 kg History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies hypersensitivity to study drug or any component of study drug Exposure to any investigational drug (for DMD or not), in the 30 days prior to screening initiation or use of approved DMD therapies (for example, eteplirsen, ataluren, golodirsen, casimersen) within 5 half-lives of screening, whichever is longer with the exception of the systemic corticosteroids, including deflazacort Pulmonary and Cardiac criteria: Requires ≥16 hours continuous ventilation Poorly controlled asthma or underlying lung disease such as bronchitis, bronchiectasis, emphysema, recurrent pneumonia that in the opinion of the investigator might impact respiratory function Hospitalization due to respiratory failure within the 8 weeks prior to screening Severe uncontrolled heart failure (New York Heart Association [NYHA] Classes III-IV) or renal dysfunction, including any of the following: Need for intravenous diuretics or inotropic support within 8 weeks prior to screening Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to screening Participants with glomerular filtration rate (GFR) of less than 30 mL/minute (min)/1.73 m^2 or with other evidence of acute kidney injury as determined by investigator Arrhythmia requiring anti-arrhythmic therapy Any other evidence of clinically significant structural or functional heart abnormality Clinical judgment: The Investigator judges that the participant will be unable to fully participate in the study and complete it for any reason, including inability to comply with study procedures and treatment, or any other relevant medical, surgical or psychiatric conditions

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pamrevlumab<br>Pamrevlumab 35 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks | Drug: Pamrevlumab<br>* Pamrevlumab will be administered per dose and schedule specified in the arm description.<br>* Other names: FG-3019;Drug: Corticosteroids<br>* Systemic deflazacort or equivalent potency of corticosteroids administered orally<br>|
| Placebo Comparator: Placebo<br>Matching placebo IV every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks | Drug: Placebo<br>* Placebo will be administered per schedule specified in the arm description.<br>Drug: Corticosteroids<br>* Systemic deflazacort or equivalent potency of corticosteroids administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52 |  | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 4-Stair Climb Velocity (4SCV) Assessment at Week 52 |  | Baseline, Week 52 | 
| Change From Baseline in the 10-Meter Walk/Run Test at Week 52 |  | Baseline, Week 52 | 
| Change From Baseline in Time to Stand (TTSTAND) at Week 52 |  | Baseline, Week 52 | 
| Time to Loss of Ambulation (LoA) From Baseline to Week 52 |  | Baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duchenne Muscular Dystrophy, DMD, Muscular Dystrophies, Muscular Dystrophy, Duchenne, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases, Genetic Diseases, Inborn, Genetic Diseases, X-Linked