Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids in Participants With Ambulatory DMD (LELANTOS-2)
Duchenne Muscular Dystrophy
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring Duchenne Muscular Dystrophy, DMD, Muscular Dystrophies, Muscular Dystrophy, Duchenne, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases, Genetic Diseases, Inborn, Genetic Diseases, X-Linked
Eligibility Criteria
Inclusion Criteria:
Age, and consent:
- Males at least 6 to <12 years of age at screening initiation
Written consent by legal guardian as per regional/ country and/or IRB/IEC requirements
DMD diagnosis:
Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a validated genetic test.
Pulmonary criteria:
- Average (of screening and day 0) percent predicted FVC above 45%
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.
Performance criteria:
- Able to complete 6MWD test with a distance of at least 270M but no more than 450M on two occasions within 3 months prior to Randomization with ≤10% variation between these two tests.
- Able to rise (TTSTAND) from floor in <10 seconds (without aids/orthoses) at screening visit.
Able to undergo MRI test for the lower extremities vastus lateralis muscle.
Vaccination:
Received pneumococcal vaccine (PPSV23) (or any other pneumococcal polysaccharide vaccine as per national recommendations) and is receiving annual influenza vaccinations.
Laboratory criteria:
- Adequate renal function: cystatin C ≤1.4 mg/L
Adequate hematology and electrolytes parameters:
- Platelets >100,000/mcL
- Hemoglobin >12 g/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
Adequate hepatic function:
- No history or evidence of liver disease
- Gamma glutamyl transferase (GGT) ≤3x upper limit of normal (ULN)
- Total bilirubin ≤1.5xULN
Exclusion Criteria:
General Criteria:
- Concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function
- Severe intellectual impairment (eg, severe autism, severe cognitive impairment, severe behavioral disturbances) preventing the ability to perform study assessments in the Investigator's judgment
- Previous exposure to pamrevlumab
- BMI ≥40 kg/m2 or weight >117 kg
- History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies
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
Pulmonary and Cardiac criteria:
- Requires ≥16 hours continuous ventilation
- 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
- Hospitalization due to respiratory failure within the 8 weeks prior to screening
Severe uncontrolled heart failure (NYHA Classes III-IV), 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
- Arrhythmia requiring anti-arrhythmic therapy
Any other evidence of clinically significant structural or functional heart abnormality
Clinical judgment:
- 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, surgical or psychiatric conditions
Sites / Locations
- Arkansas Children's Hospital
- Children's Hospital Los Angeles
- University of California Davis Children's Hospital
- University of California San Diego Health
- Children's Hospital Colorado
- University of Florida Health Shands Hospital
- Rare Disease Research - Tampa
- Rare Disease Research Center
- Ann & Robert H. Lurie Children's Hospital of Chicago
- University of Iowa Hospitals and Clinics
- University of Kansas Medical Center Research Institute
- Kennedy Krieger Institute
- University of Massachusetts Memorial Center
- C.S. Mott Children's Hospital
- Spectrum Health Hospitals Helen DeVos Children's Hospital
- Washington University School of Medicine in St. Louis
- Cincinnati Children's Hospital Medical Center
- Shriners Hospital for Children
- Penn State Health Milton S. Hershey Medical Center
- Children's Hospital of Philadelphia
- Vanderbilt University Medical Center
- Texas Children's Hospital
- University of Utah Health
- University of Virginia Children's Hospital
- Children's Hospital of The King's Daughters
- Seattle Children's Hospital
- Children's Wisconsin Corporate Center
- Murdoch Children's Research Institute
- Klinik Favoriten
- Universitair Ziekenhuis Leuven - Campus Gasthuisberg
- Centre Hospitalier Régional de la Citadelle
- Universitair Ziekenhuis Gent
- London Health Sciences Centre
- Children's Hospital of Chongqing Medical University
- The 1st Affiliated Hospital, Sun Yat-sen University
- Xiangya Hospital Central South University
- West China Second University Hospital, Sichuan University
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
- Hôpital Hautepierre
- Centre Hospitalier Universitaire Nantes - Hôtel Dieu
- Association Institut de Myologie
- IRRCS Ospedale San Raffaele
- Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea - Lombardia
- Centro Clinico NeMO
- Fondazione Policlinico Universitario Agostino Gemelli
- Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo
- Leiden Universitair Medisch Centrum
- Radboud Universitair Medisch Centrum
- Hospital Universitari Vall d'Hebrón
- Hospital Universitari i Politecnic La Fe de Valencia
- Leeds Teaching Hospitals NHS Trust
- Oxford University Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Pamrevlumab
Placebo
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
Matching placebo IV every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks