Duchenne disease Duchenne Muscular Dystrophy
Conditions
Interventions
The duration of total involvement in the study will be approximately 64 weeks
(4 weeks in screening, 52 weeks of treatment and a safety follow-up visit 28
days (+/- 3 days) and a final safety follow
Sponsors
FibroGen, Inc.
Eligibility
Age
16 Years to 64 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria in order to be eligible for the study: 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 =50% as determined by local cardiac MRI read 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 of 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 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. Vaccination: 12. Agreement to receive annual influenza vaccinations during the course of the study. Laboratory criteria: 13. Adequate renal function: cystatin C 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)
Exclusion criteria
Exclusion criteria: Subjects must not meet any of the following criteria in order to be eligible: 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 Constrast Agens (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 assessments: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Function assessment: • Change in the total score of Performance of Upper Limb (PUL) 2.0 version, from baseline to Week 52. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: • Change in percent predicted forced vital capacity (ppFVC) from baseline to Week 52, assessed by spirometry. • Change in the Grip strength of the hands from baseline to Week 52, assessed by Hand Held Myometry (HHM). • Change in Left Ventricular Ejection Fraction percentage (LVEF %) from baseline to Week 52, assessed by MRI. • Change in percent predicted peak expiratory flow (ppPEF) from baseline to Week 52, assessed by spirometry. Safety assessments • Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), clinically significant laboratory test abnormalities, discontinuation of treatment due to TEAEs. • Number and percentage of subjects with hospitalizations due to any serious adverse events with pulmonary and/or cardiac cause(s), after the first dose of investigational product (IP). • Number and percentage of subjects with bone fractures • Ulna length measurements for indirect measure of growth velocity (cm/year) for subjects under the age of 18 Exploratory Endpoints • Change in the subscores of three regional dimensions (High-level (shoulder), Mid-level (elbow), Distallevel (wrist and hand)) of PUL, from baseline to Week 52 • Change in Duchenne Video Assessment severity percentage from baseline to Week 52. • Change in percent predicted forced expiratory volume at 1 second (FEV1) from baseline to Week 52. • Analysis of progression of dilated cardiomyopathy (DCM) by genetic analysis. Fibrosis/MRI assessments: • Changes in fibrosis score of the biceps brachii, from baseline to Week 52, assessed by MRI. • Changes in Cardiac fibrosis score from baseline to Week 52, assessed by Late Gadolinium Enhancement (LGE). • Change in Myocardial Circumferential Strain [Global Circumferential Strain (GCS)] percentage from baseline to Week 52, assessed by cardiac MRI. Pharmacokinetics/pharmacodynamics (PK/PD) assessment • Population PK/PD analysis. | — |
Countries
Netherlands
Outcome results
None listed