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)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- FibroGen
- 入组人数
- 98
- 试验地点
- 53
- 主要终点
- Change From Baseline in the Total Score of Performance of Upper Limb (PUL) 2.0 Version at Week 52
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Pamrevlumab
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
干预措施: Pamrevlumab (Drug)
Pamrevlumab
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
干预措施: Corticosteroids (Drug)
Placebo
Matching placebo IV every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks
干预措施: Placebo (Drug)
Placebo
Matching placebo IV every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Change From Baseline in the Total Score of Performance of Upper Limb (PUL) 2.0 Version at Week 52
时间窗: Baseline, Week 52
The PUL module is an observer-administered performance battery of upper extremity mobility tasks for the shoulder (upper, 6 items, 12 points), elbow (middle, 9 items, 17 points) and wrist/hand (distal, 7 items, 13 points). Higher scores indicate higher level of function. Total score ranges from 0-42 points and is the sum of the scores for the 3 subscales. Analysis was done using a random coefficient model (RCM), which included fixed effects of time (as a continuous variable), treatment, and treatment-by-time interaction, with baseline ordinal PUL entry score as covariate.
次要结局
- Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF %) at Week 52, Assessed by Magnetic Resonance Imaging (MRI)(Baseline, Week 52)
- Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 52, Assessed by Spirometry(Baseline, Week 52)
- Change From Baseline in Percent Predicted Peak Expiratory Flow (ppPEF) at Week 52, Assessed by Spirometry(Baseline, Week 52)
- Change From Baseline in the Grip Strength of the Hands at Week 52, Assessed by Hand Held Myometry (HHM)(Baseline, Week 52)