Evaluation of Pamrevlumab for the Treatment of Male Patients Affected by Non-ambulatory Duchenne Muscular Dystrophy and just Treated with Corticosteroids

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]; MedDRA version: 20.0Level: PTClassification code 10013801Term: Duchenne muscular dystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; on-ambulatory Duchenne Muscular Dystrophy

• Registration Number: EUCTR2020-000698-26-AT
• Lead Sponsor: FibroGen, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-08-17
• Last Update Posted: 13 November 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 92

Inclusion Criteria

Double-blind phase:
Age, Consent, and Contraception
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 12 weeks after the last dose of study drug.

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

Performance criteria:
5. Brooke Score for Arms and Shoulders =5:
6. Able to undergo MRI test for the upper arm extremities (Biceps Brachii muscle) andcardiac muscle;
7. Able to perform spirometry.

Pulmonary and Cardiac criteria:
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. If subjects have a history of cardiomyopathy, then subject must be on a stable dose for cardiomyopathy/ heart failure medications (e.g., angiotensin converting enzyme inhibitors, aldosterone receptors blockers, angiotensin-receptor blockers, and beta-blockers) for at least 1 month prior to screening. If subjects have no diagnosis of cardiomyopathy, then no dose of cardiomyopathy/heart failure medication is required for eligibility.
11. On a stable dose of systemic corticosteroids for a minimum of 6 months, with nos ubstantial 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) orstable dose. A reasonable expectation is that dosage and dosing regimen would not change significantly for the duration of the study.

Vaccination:
12. Agreement to receive annual influenza vaccinations during the course of the study.

Laboratory criteria:
13. Adequate renal function: cystatin C =1.4 mg/L;
14. Adequate hematology and electrolytes parameters:
a. Platelets >100,000/mcL
b. Hemoglobin >12 g/dL
c. Absolute neutrophil count >1500 /µL
d. Serum calcium (Ca), potassium (K), sodium (Na), magnesium (Mg) and phosphorus(P) levels are within a clinically accepted range for DMD patients.
15. Adequate hepatic function:
a. No history or evidence of liver disease
b. Gamma glutamyl transferase (GGT) =3x upper limit of normal (ULN)
c. Total bilirubin =1.5xULN.

Open-label extension phase:
All patients must have completed treatment through the primary endpoint and completed the Week 52 visit on the double-blind phase. The study investigator must consider the subject medically stable for continued treatment. Written consent/assent by the patients and/or their legal guardian must be obtained prior to the patient’s participation in the open-label extension phase.
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Both phases:
General criteria:
1. Previous exposure to pamrevlumab;
2. BMI =40 kg/m2 or weight >117 kg;
3. History of:
a. allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies,
b. hypersensitivity to study drug or any component of study drug,
c. hypersensitivity reaction to Gadolinium-based Contrast Agents (GBCA) required for MRI acquisition;
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 (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.

Cardiac, Renal and Pulmonary assessment:
5.Severe uncontrolled heart failure (NYHA Classes III-IV), or renal dysfunction, including any of the following:
a. Need for intravenous diuretics or inotropic support within 8 weeks prior to screening,
b. Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to screening,
c. Patients with glomerular filtration rate (GFR) of less than 30 mL/min/1.73m2 or with other evidence of acute kidney injury as determined by investigator
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.

Clinical judgments:
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 which could confound efficacy assessment and/or safety assessment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified