A Phase 3 Trial of Pamrevlumab (FG-3019) or Placebo in Combination With Systemic Corticosteroids, in Ambulatory Subjects With Duchenne Muscular Dystrophy (DMD)

Sponsor: FibroGen

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


TIPOLOGIA STUDIO

Interventistico

FASE

Fase 3


TRATTAMENTO

  • Pamrevlumab
  • Placebo

OBIETTIVO PRIMARIO

  • Misura: Ambulatory function assessment:
  • Tempo: baseline to Week 52
  • Descrizione: Change in NorthStar Ambulatory Assessment (NSAA) Linearized total score

OBIETTIVO SECONDARIO

  • Misura: Other Muscle function assessments:
  • Tempo: baseline to Week 52
  • Descrizione: Change in 4-stair climb Velocity (4SCV) assessment
  • Misura: Other Muscle function assessments:
  • Tempo: baseline to Week 52
  • Descrizione: Change in the 10-meter walk/run test
  • Misura: Other Muscle function assessments:
  • Tempo: baseline to Week 52
  • Descrizione: Changes in Time to Stand (TTSTAND)
  • Misura: Other Muscle function assessments:
  • Tempo: baseline to Week 52
  • Descrizione: Time to Loss of Ambulation (LoA)

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 legal guardian as per regional/ country and/or IRB/IEC requirements DMD diagnosis: 3. Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a validated genetic test. Pulmonary criteria: 4. Average (of screening and day 0) percent predicted 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 (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: 6. 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. 7. Able to rise (TTSTAND) from floor in <10 seconds (without aids/orthoses) at screening visit. 8. Able to undergo MRI test for the lower extremities vastus lateralis muscle. Vaccination: 9. Received pneumococcal vaccine (PPSV23) (or any other pneumococcal polysaccharide vaccine as per national recommendations) and is receiving annual influenza vaccinations. Laboratory criteria: 10. Adequate renal function: cystatin C ≤1.4 mg/L 11. 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 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 (eg, 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. BMI ≥40 kg/m2 or weight >117 kg 5. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies 6. 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: 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 (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 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 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


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,

REFERENTE PER INFORMAZIONI

Jessica Charpentier
415.978.1346
LELANTOS@fibrogen.com