Phase 3 Trial of Pamrevlumab or Placebo With Systemic Corticosteroids in Participants With Non-ambulatory Duchenne Muscular Dystrophy (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 in participants with non-ambulatory Duchenne muscular dystrophy (age 12 years and older).

Detailed Description
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This is a global, Phase 3, randomized, double-blind trial of pamrevlumab or placebo in combination with systemic corticosteroids in participants with non-ambulatory Duchenne muscular dystrophy, aged 12 years and older. Approximately 90 male participants will be randomized at a 1:1 ratio to Arm A (pamrevlumab + systemic corticosteroid) or Arm B (placebo+ systemic corticosteroid), respectively. Participants must be fully informed of the potential benefits of approved products and make an informed decision that they prefer to participate in a clinical trial in which they could be randomized to placebo. This trial has 3 study periods: Screening period: Up to 4 weeks Treatment period: 52 weeks Safety Follow-up period/End of Study (EOS): A visit 28 days (+/- 3 Days) and a final safety follow-up phone call 60 days (+ 3 Days) after the last dose In the screening period, participants will be evaluated per the protocol inclusion/exclusion criteria to determine eligibility for participation in this trial. During the treatment period, each participant will receive pamrevlumab or placebo at 35 mg/kg every 2 weeks for up to 52 weeks. Participants who complete the 52-week study (either arm) may be eligible for rollover into an open-label extension treatment (OLE) with pamrevlumab + systemic corticosteroids. 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 Subjects With Non-ambulatory 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: Males at least 12 years of age, non-ambulatory 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 Male participants with partners of childbearing potential must use contraception during the conduct of the study, and for 12 weeks after the last dose of study drug. Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a validated genetic test Brooke Score for Arms and Shoulders ≤5 Able to undergo MRI test for the upper arm extremities (Biceps Brachii muscle) and cardiac muscle Able to perform spirometry Average (of Screening and Day 0) percent predicted forced vital capacity (FVC) between 45 and 85, inclusive Left ventricular ejection fraction ≥50% as determined by local cardiac MRI read at screening or within 3 months prior to randomization (Day 0) If participants have a history of cardiomyopathy, then participant must be on a stable dose of cardiomyopathy/ heart failure medications (for example, angiotensin converting enzyme inhibitors, aldosterone receptors blockers, angiotensin-receptor blockers, and betablockers) for at least 1 month prior to screening. If participants have no diagnosis of cardiomyopathy, then no dose of cardiomyopathy/heart failure medication is required for eligibility. 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. Agreement to receive annual influenza vaccinations during the course of the study. 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: Previous exposure to pamrevlumab 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 hypersensitivity reaction to Gadolinium-based Contrast Agents (GBCA) required for MRI acquisition 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 [exondys 51], ataluren, golodirsen [vyondys 53], casimersen [amondys 45]) within 5 half-lives of screening, whichever is longer, with the exception of the systemic corticosteroids, including deflazacort Severe uncontrolled heart failure (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 Requires ≥16 hours continuous ventilation Hospitalization due to respiratory failure within the 8 weeks prior to screening 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 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 or psychiatric conditions

Ages Eligible for Study
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Minimum Age: 12 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 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>* Matching placebo 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 |
| --- | --- | --- |
| Functional Assessment: Change From Baseline in the Total Score of Performance of Upper Limb (PUL) 2.0 Version at Week 52 |  | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Assessment: Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 52, Assessed by Spirometry |  | Baseline, Week 52 | 
| Performance Assessment: Change From Baseline in the Grip Strength of the Hands at Week 52, Assessed by Hand Held Myometry (HHM) |  | Baseline, Week 52 | 
| Cardiac Assessment: Change From Baseline in Left Ventricular Ejection Fraction percentage (LVEF %) at Week 52, Assessed by Magnetic Resonance Imaging (MRI) |  | Baseline, Week 52 | 
| Pulmonary Assessment: Change From Baseline in Percent Predicted Peak Expiratory Flow (ppPEF) at Week 52, Assessed by Spirometry |  | Baseline, 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