Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids in Participants With Ambulatory DMD

Sponsor: FibroGen

Sommario: To evaluate the efficacy and safety of pamrevlumab versus placebo in combination with systemic corticosteroids administered every 2 weeks in ambulatory participants with Duchenne muscular dystrophy (DMD) (age 6 to <12 years).


TIPOLOGIA STUDIO

Interventistico

FASE

Fase 3


TRATTAMENTO

  • Pamrevlumab
  • Placebo
  • Corticosteroids

OBIETTIVO PRIMARIO

  • Misura: Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52
  • Tempo: Baseline, Week 52
  • Descrizione:

OBIETTIVO SECONDARIO

  • Misura: Change From Baseline in 4-Stair Climb Velocity (4SCV) Assessment at Week 52
  • Tempo: Baseline, Week 52
  • Descrizione:
  • Misura: Change From Baseline in the 10-Meter Walk/Run Test at Week 52
  • Tempo: Baseline, Week 52
  • Descrizione:
  • Misura: Change From Baseline in Time to Stand (TTSTAND) at Week 52
  • Tempo: Baseline, Week 52
  • Descrizione:
  • Misura: Change From Baseline in Time to Loss of Ambulation (LoA) at Week 52
  • Tempo: Baseline, Week 52
  • Descrizione:

CRITERI DI ELIGIBILITA'

  • Criteri di inclusione e esclusione

    Inclusion Criteria: Age, and consent: 1. Males at least 6 to <12 years of age at screening initiation 2. Written consent by participant and/or legal guardian as per regional/ country and/or Institutional Review Board (IRB)/Independent Ethics Committee (IEC) requirements DMD diagnosis: 3. Medical history includes diagnosis of DMD and confirmed Duchenne mutation, including status of exon 44 using a validated genetic test. Pulmonary criteria: 4. Average (of screening and Day 0) percent predicted forced vital capacity (FVC) above 45% 5. 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 (for example, 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: 6. Able to complete 6-minute walking distance (6MWD) test with a distance of at least 270 meters but no more than 450 meters on two occasions within 3 months prior to randomization with ≤10% variation between these two tests. 7. Able to rise (TTSTAND) from floor in <10 seconds (without aids/orthoses) at screening visit. 8. Able to undergo magnetic resonance imaging (MRI) test for the lower extremities vastus lateralis muscle. Vaccination: 9. Agreement to receive annual influenza vaccinations during the conduct of the study. Laboratory criteria: 10. Adequate renal function: cystatin C ≤1.4 mg/liter (L) 11. Adequate hematology and electrolytes parameters: 1. Platelets >100,000/microliter (μL) 2. Hemoglobin >12 grams (g)/deciliter (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 for DMD participants 12. 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: General Criteria: 1. Concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function 2. Severe intellectual impairment (for example, severe autism, severe cognitive impairment, severe behavioral disturbances) preventing the ability to perform study assessments in the Investigator's judgment 3. Previous exposure to pamrevlumab 4. Body mass index (BMI) ≥40 kg/square meter (m^2) or weight >117 kg 5. History of 1. allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies 2. hypersensitivity to study drug or any component of study drug 6. Exposure to any investigational drug (for DMD or not), in the 30 days prior to screening initiation or use of approved DMD therapies (for example, eteplirsen, ataluren, golodirsen, casimersen) within 5 half-lives of screening, whichever is longer with the exception of the systemic corticosteroids, including deflazacort Pulmonary and Cardiac criteria: 7. Requires ≥16 hours continuous ventilation 8. 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 9. Hospitalization due to respiratory failure within the 8 weeks prior to screening 10. Severe uncontrolled heart failure (New York Heart Association [NYHA] Classes III-IV) or renal dysfunction, 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 3. Participants with glomerular filtration rate (GFR) of less than 30 mL/minute (min)/1.73 m^2 or with other evidence of acute kidney injury as determined by investigator 11. Arrhythmia requiring anti-arrhythmic therapy 12. Any other evidence of clinically significant structural or functional heart abnormality Clinical judgment: 13. The Investigator judges that the participant 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


SESSO

Maschi


ETA' MINIMA

Età Minima: 6 Years
Età Massima: 11 Years


LUOGO

IRRCS Ospedale San Raffaele
Milano, 20132

Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea - Lombardia
Bosisio ParIni, 23842

Centro Clinico NeMO
Milano, 20162

Fondazione Policlinico Universitario Agostino Gemelli
Roma, 168

Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo
Roma,