E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this trial is to estimate pamrevlumab’s efficacy in non-ambulatory participants with DMD. |
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E.2.2 | Secondary objectives of the trial |
The Secondary objectives of the trial are: - To evaluate safety and tolerability of pamrevlumab administered intravenously (IV) every 2 weeks - To assess pharmacokinetics (PK) of pamrevlumab in the targeted pediatric population - To evaluate pharmacodynamic (PD) markers of pamrevlumab’s effects in DMD |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written consent/assent by participant and/or legal guardian as per regional and/or institutional review board (IRB) requirements • Non-ambulatory • Brooke Score for Arms and Shoulders ≤5 • Diagnosis of DMD by medical history and confirmed Duchenne mutation in available genetic testing using a validated genetic test • Able to perform spirometry • Able to undergo cardiac and extremity (upper arm) magnetic resonance imaging (MRI) • Percent predicted forced vital capacity (FVC) between 40 and 90, inclusive • At least one historical percent predicted forced vital capacity (ppFVC) predicted value within 18 months of baseline • Left ventricular ejection fraction ≥ 45% as determined by cardiac MRI at screening or within 3 months prior to Day 0 • Participants currently receiving heart failure cardiac medications (for example, angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, and beta-blockers) must achieve a stable regimen for at least 3 months prior to screening • On a stable dose of corticosteroids for a minimum of 6 months prior to screening with no substantial change in dosage for a minimum of 3 months (except for adjustments for changes in body weight) prior to screening and no foreseen change in corticosteroid use during the course of study participation • Received pneumococcal vaccine and is receiving annual influenza vaccinations • Adequate renal function: cystatin C ≤1.4 mg/liter (L) • Adequate hematological function 1. Platelets >100,000/microliter (μL) 2. Hemoglobin >12 grams (g)/deciliter (dL) 3. Absolute neutrophil count >1500/μL • Adequate hepatic function 1. No history or evidence of liver disease 2. Gamma glutamyl transferase (GGT) ≤3 x upper limit of normal (ULN) 3. Total bilirubin ≤1.5 x ULN • If sexually active, will use medically accepted contraceptives during participation in the study and for 3 months after the last dose of study drug
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E.4 | Principal exclusion criteria |
• Requires ≥16 hours continuous ventilation • Prior or ongoing medical condition that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of 156 weeks of treatment and follow-up would be completed, or could impair the assessment of study results • Anticipated spine surgery within 156 weeks • Severe uncontrolled heart disease, including any of the following: 1. Need for intravenous diuretics or inotropic support within 3 months prior to screening 2. Hospitalization for a heart failure exacerbation or arrhythmia in last 3 months • Arrhythmia requiring anti-arrhythmic therapy • Hospitalization due to respiratory failure in the last 6 weeks • Poorly controlled asthma or underlying lung disease such as bronchopulmonary dysplasia • Known or suspected active hepatitis B or C or history of human immunodeficiency virus (HIV) • Body mass index (BMI) ≥40 kilograms (kg)/square meter (m^2) or weight >117 kg • Exposure to another investigational drug or another approved product for DMD (for example, eteplirsen or golodirsen) within 28 days prior to start of study treatment • Exposure to another investigational drug or another approved product for DMD (e.g. eteplirsen) within 28 days prior to start of study treatment (or 5 half-lives of the product whichever is longer) prior to first screening visit with the exception of deflazacort. Use of deflazacort, if regarded by the principal investigator as standard of care, is allowed.
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E.5 End points |
E.5.1 | Primary end point(s) |
Annual Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 104 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Change From Baseline in Percent Predicted Forced Expiratory Volume at 1 Second (ppFEV1) at Week 104 2. Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 104 3. Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF%) at Week 104 4. Change From Baseline in Performance of Upper Limb (PUL) Total Score at Week 104 5. Change From Baseline in Grip Strength by Hand, as Measured by Hand Held Myometry (HHM) at Week 104 6. Change From Baseline in Pinch Strength, as Measured by HHM at Week 104 7. Change From Baseline in Cardiac Fibrosis (Scar Mass), as Measured by Magnetic Resonance Imaging (MRI) at Week 104 8. Change From Baseline in Upper Arm (Biceps Brachii MRI) Muscle Fat and Fibrosis Score, as Measured by MRI at Week 104 9. Change From Baseline in Fat Fraction Percentage (%F), as Measured by MRI at Week 104
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |