Clinical trial NCT04632940: Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids in Participants With Ambulatory DMD
Official title: A Phase 3, Randomized, Double-Blind, Trial of Pamrevlumab (FG-3019) or Placebo in Combination With Systemic Corticosteroids in Ambulatory Subjects With Duchenne Muscular Dystrophy (DMD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Duchenne Muscular Dystrophy
Keywords: 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
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
First posted: 2020-11-17
Enrollment: 73
Sex: MALE
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: This is a global, randomized, double-blind, trial of pamrevlumab or placebo in combination with systemic corticosteroids in participants with DMD, aged 6 to \<12 years (ambulatory participants only). Approximately 70 participants will be randomized at a 1:1 ratio to Arm A (pamrevlumab + systemic deflazacort or equivalent potency of corticosteroids administered orally) or Arm B (placebo+ systemic deflazacort or equivalent potency of corticosteroids administered orally), respectively. Randomization will be stratified by exon 44 deletion for analysis. Stratification has no impact upon treatment assignment nor dosage.

Participants must be fully informed of the potential benefits of approved products and make an informed decision when participating in a clinical trial in which they could be randomized to placebo.

The main study has 3 study periods:

* Screening period: Up to 4 weeks
* Treatment period: 52 weeks
* Safety Follow-up period/final assessment: A visit 28 days (+/- 3 Days) and a final safety follow-up phone call 60 days (+ 3 Days) after the last dose

Each participant will receive pamrevlumab or placebo at 35 mg/kg every 2 weeks for up to 52 weeks. Participants who complete 52 weeks of treatment may be eligible for an open-label extension (OLE), offering extended treatment with pamrevlumab.

Participants who discontinue study treatment for any reason should be encouraged to return to the investigative site to complete final safety and efficacy assessments.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Change From Baseline in 4-Stair Climb Velocity (4SCV) Assessment at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in the 10-Meter Walk/Run Test at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Time to Stand (TTSTAND) at Week 52
timeFrame: Baseline, Week 52
measure: Time to Loss of Ambulation (LoA) From Baseline to Week 52
timeFrame: Baseline to Week 52
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California Davis Children's Hospital
state: California
city: San Diego
country: United States
facility: University of California San Diego Health
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Health Shands Hospital
state: Florida
city: Tampa
country: United States
facility: Rare Disease Research - Tampa
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research Center
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Fairway
country: United States
facility: University of Kansas Medical Center Research Institute
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Memorial Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals Helen DeVos Children's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Shriners Hospital for Children
state: Oregon
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Children's Hospital
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Children's Wisconsin Corporate Center
state: Wisconsin
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: Wien
country: Austria
facility: Klinik Favoriten
state: Vienna
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
state: Flemish Brabant
city: Liège
country: Belgium
facility: Centre Hospitalier Régional de la Citadelle
state: Liege
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
city: Guangzhou
country: China
facility: The 1st Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Chengdu
country: China
facility: West China Second University Hospital, Sichuan University
state: Sichuan
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
city: Strasbourg
country: France
facility: Hôpital Hautepierre
state: Bas-Rhin
city: Nantes
country: France
facility: Centre Hospitalier Universitaire Nantes - Hôtel Dieu
city: Paris
country: France
facility: Association Institut de Myologie
city: Milano
country: Italy
facility: IRRCS Ospedale San Raffaele
state: Milan
city: Bosisio ParIni
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea - Lombardia
city: Milano
country: Italy
facility: Centro Clinico NeMO
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo
city: Leiden
country: Netherlands
facility: Leiden Universitair Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
state: England
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
state: England
Study officials:
References: