A Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids, in Subjects With Non-ambulatory Duchenne Muscular Dystrophy (DMD)

• Status: Recruiting
• Trial end date: 2022-09-30
• Target enrollment: 0
• Participant gender: Male

Summary

To evaluate the efficacy and safety of pamrevlumab versus placebo in combination with systemic corticosteroids in subjects with non-ambulatory Duchenne muscular dystrophy (age 12 years and older).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: FibroGen

Criteria

Inclusion Criteria:

1. Males at least 12 years of age, non-ambulatory at screening initiation

2. Written consent by patient and/or legal guardian as per regional/ country and/or IRB/IEC requirements

3. Male subjects with partners of childbearing potential must use contraception during the conduct of the study, and for 3 months after the last dose of study drug.

4. Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a validated genetic test

5. Brooke Score for Arms and Shoulders ≤5

6. Able to undergo MRI test for the upper arm extremities (Biceps Brachii muscle) and cardiac muscle

7. Able to perform spirometry

8. Average (of Screening and Day 0) percent predicted FVC between 45 and 85, inclusive

9. Left ventricular ejection fraction ≥50% as determined by cardiac MRI at screening or within 3 months prior to randomization (Day 0)

10. Prior diagnosis of cardiomyopathy, subjects must be on a stable regimen dose for cardiomyopathy/ heart failure medications (e.g., angiotensin converting enzyme inhibitors, aldosterone receptors blockers, angiotensin-receptor blockers, and betablockers) for at least 1 month prior to screening

11. 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 (e.g.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.

12. Received pneumococcal vaccine (PPSV23) (or any other pneumococcal polysaccharide vaccine as per national recommendations) and is receiving annual influenza vaccinations

13. Adequate renal function: cystatin C ≤1.4 mg/L

14. Adequate hematology and electrolytes parameters:

1. Platelets >100,000/mcL

2. Hemoglobin >12 g/dL

3. Absolute neutrophil count >1500 /μL

4. Serum calcium (Ca), potassium (K), sodium (Na), magnesium (Mg) and phosphorus (P) levels are within a clinically accepted range

15. Adequate hepatic function:

1. No history or evidence of liver disease

2. Gamma glutamyl transferase (GGT) ≤3x upper limit of normal (ULN)

3. Total bilirubin ≤1.5xULN

Exclusion Criteria:

1. Previous exposure to pamrevlumab

2. BMI ≥40 kg/m2 or weight >117 kg

3. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies

4. Exposure to any investigational drug (for DMD or not), in the 30 days prior to screening initiation or use of approved DMD therapies (e.g., eteplirsen, ataluren, golodirsen) within 5 half-lives of screening, whichever is longer, with the exception of the systemic corticosteroids, including deflazacort

5. Severe uncontrolled heart failure (NYHA Classes III-IV), including any of the following:

1. Need for intravenous diuretics or inotropic support within 8 weeks prior to screening

2. Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to screening

6. Arrhythmia requiring anti-arrhythmic therapy

7. Requires ≥16 hours continuous ventilation

8. Hospitalization due to respiratory failure within the 8 weeks prior to screening

9. 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

10. The Investigator judges that the subject 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