Clinical trial NCT04371666: Phase 3 Trial of Pamrevlumab or Placebo With Systemic Corticosteroids in Participants With Non-ambulatory Duchenne Muscular Dystrophy (DMD)
Official title: A Phase 3, Randomized, Double-Blind Trial of Pamrevlumab (FG-3019) or Placebo in Combination With Systemic Corticosteroids in Subjects With Non-ambulatory Duchenne Muscular Dystrophy (DMD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne Muscular Dystrophy, DMD
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
First posted: 2020-05-01
Enrollment: 98
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
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 in participants with non-ambulatory Duchenne muscular dystrophy (age 12 years and older).

Detailed description: This is a global, Phase 3, randomized, double-blind trial of pamrevlumab or placebo in combination with systemic corticosteroids in participants with non-ambulatory Duchenne muscular dystrophy, aged 12 years and older. Approximately 90 male participants will be randomized at a 1:1 ratio to Arm A (pamrevlumab + systemic corticosteroid) or Arm B (placebo+ systemic corticosteroid), respectively.

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

This trial has 3 study periods:

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

In the screening period, participants will be evaluated per the protocol inclusion/exclusion criteria to determine eligibility for participation in this trial.

During the treatment period, each participant will receive pamrevlumab or placebo at 35 mg/kg every 2 weeks for up to 52 weeks.

Participants who complete the 52-week study (either arm) may be eligible for rollover into an open-label extension treatment (OLE) with pamrevlumab + systemic corticosteroids.

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:

1. Males at least 12 years of age, non-ambulatory 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
3. Male participants 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.
4. Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a validated genetic test
5. Brooke Score for Arms and Shoulders ≤5
6. Able to undergo MRI test for the upper arm extremities (Biceps Brachii muscle) and cardiac muscle
7. Able to perform spirometry
8. Average (of Screening and Day 0) percent predicted forced vital capacity (FVC) between 45 and 85, inclusive
9. Left ventricular ejection fraction ≥50% as determined by local cardiac MRI read at screening or within 3 months prior to randomization (Day 0)
10. If participants have a history of cardiomyopathy, then participant must be on a stable dose of cardiomyopathy/ heart failure medications (for example, angiotensin converting enzyme inhibitors, aldosterone receptors blockers, angiotensin-receptor blockers, and betablockers) for at least 1 month prior to screening. If participants 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 (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.
12. Agreement to receive annual influenza vaccinations during the course of the study.
13. Adequate renal function: cystatin C ≤1.4 mg/liter (L)
14. 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.
15. 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:

1. Previous exposure to pamrevlumab
2. BMI ≥40 kg/square meter (m\^2) or weight \>117 kg
3. 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
   3. hypersensitivity reaction to Gadolinium-based Contrast Agents (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 (for example, 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
5. Severe uncontrolled heart failure (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
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
10. 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 or psychiatric conditions

Primary outcomes:
measure: Change From Baseline in the Total Score of Performance of Upper Limb (PUL) 2.0 Version at Week 52
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 52, Assessed by Spirometry
timeFrame: Baseline, Week 52
measure: Change From Baseline in the Grip Strength of the Hands at Week 52, Assessed by Hand Held Myometry (HHM)
timeFrame: Baseline, Week 52
measure: Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF %) at Week 52, Assessed by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Week 52
measure: Change From Baseline in Percent Predicted Peak Expiratory Flow (ppPEF) at Week 52, Assessed by Spirometry
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's
state: Arkansas
city: Los Angeles
country: United States
facility: University of California Los Angeles Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Health
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
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
state: Iowa
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Worcester
country: United States
facility: UMASS Med School
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 Saint Louis
state: Missouri
city: Charlotte
country: United States
facility: Carolinas HealthCare System Neurosciences Institute-Neurology - Charlotte
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Shriners Hospital for Children
state: Oregon
city: Hershey
country: United States
facility: Penn State Health Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Children's Health Dallas/UTSW
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Norfolk
country: United States
facility: Children's Specialty Group - Medical Center Office
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: Vienna
country: Austria
facility: Klinik Favoriten
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: Liège
country: Belgium
facility: Centre Hospitalier Régional de la Citadelle
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: 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: Brno
country: Czechia
facility: Fakultní Nemocnice Brno - Dětská Nemocnice
city: Prague
country: Czechia
facility: Klinika dÄ>tské neurologie, Neuromuskulární centrum
city: Nantes
country: France
facility: CHU de Nantes - Hotel Dieu
city: Paris
country: France
facility: Association Institut de Myologie
city: Strasbourg cedex
country: France
facility: Hopital Hautepierre
city: Tel Aviv
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: The Edith Wolfson Medical Center
city: Lecco
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea - Lombardia
city: Milan
country: Italy
facility: IRRCS Ospedale San Raffaele
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
state: Gelderland
city: Leiden
country: Netherlands
facility: Leiden Universitair Medisch Centrum
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Bern
country: Switzerland
facility: Inselspital Universitätsspital Bern
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
Study officials:
References: