Phase 3 Trial of Pamrevlumab or Placebo With Systemic Corticosteroids in Participants With Non-ambulatory Duchenne Muscular Dystrophy (DMD)

NCT ID: NCT04371666

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-10
• Study Completion Date: 2023-08-17

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.

Conditions

Duchenne Muscular Dystrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pamrevlumab

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

Group Type: EXPERIMENTAL

Pamrevlumab

Intervention Type: DRUG

Pamrevlumab per dose and schedule specified in the arm description

Corticosteroids

Intervention Type: DRUG

Systemic deflazacort or equivalent potency of corticosteroids administered orally

Placebo

Matching placebo IV every 2 weeks + systemic deflazacort or equivalent potency of corticosteroids administered orally for up to 52 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo per schedule specified in the arm description

Corticosteroids

Intervention Type: DRUG

Systemic deflazacort or equivalent potency of corticosteroids administered orally

Interventions

Pamrevlumab

Pamrevlumab per dose and schedule specified in the arm description

Intervention Type: DRUG

Placebo

Matching placebo per schedule specified in the arm description

Intervention Type: DRUG

Corticosteroids

Systemic deflazacort or equivalent potency of corticosteroids administered orally

Intervention Type: DRUG

Other Intervention Names

FG-3019

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

FibroGen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arkansas Children's

Little Rock, Arkansas, United States

University of California Los Angeles Medical Center

Los Angeles, California, United States

UC Davis Health

Sacramento, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Rare Disease Research, LLC

Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

University of Iowa

Iowa City, Iowa, United States

University of Kansas Medical Center

Fairway, Kansas, United States

Kennedy Krieger Institute

Baltimore, Maryland, United States

UMASS Med School

Worcester, Massachusetts, United States

C.S. Mott Children's Hospital

Ann Arbor, Michigan, United States

Spectrum Health Hospitals Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Washington University School of Medicine in Saint Louis

St Louis, Missouri, United States

Carolinas HealthCare System Neurosciences Institute-Neurology - Charlotte

Charlotte, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Shriners Hospital for Children

Portland, Oregon, United States

Penn State Health Children's Hospital

Hershey, Pennsylvania, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Children's Health Dallas/UTSW

Dallas, Texas, United States

University of Utah Health

Salt Lake City, Utah, United States

Children's Specialty Group - Medical Center Office

Norfolk, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Murdoch Children's Research Institute

Parkville, Victoria, Australia

Klinik Favoriten

Vienna, , Austria

Universitair Ziekenhuis Gent

Ghent, , Belgium

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, , Belgium

Centre Hospitalier Régional de la Citadelle

Liège, , Belgium

London Health Sciences Centre

London, Ontario, Canada

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

West China Second University Hospital, Sichuan University

Chengdu, Sichuan, China

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, , China

Fakultní Nemocnice Brno - Dětská Nemocnice

Brno, , Czechia

Klinika dÄ>tské neurologie, Neuromuskulární centrum

Prague, , Czechia

CHU de Nantes - Hotel Dieu

Nantes, , France

Association Institut de Myologie

Paris, , France

Hopital Hautepierre

Strasbourg, , France

The Chaim Sheba Medical Center

Tel Aviv, , Israel

The Edith Wolfson Medical Center

Tel Aviv, , Israel

Istituto di Ricovero e Cura a Carattere Scientifico Eugenio Medea - Lombardia

Lecco, , Italy

IRRCS Ospedale San Raffaele

Milan, , Italy

Fondazione Policlinico Universitario Agostino Gemelli

Rome, , Italy

Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo

Rome, , Italy

Radboud Universitair Medisch Centrum

Nijmegen, Gelderland, Netherlands

Leiden Universitair Medisch Centrum

Leiden, , Netherlands

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital Universitari Vall d'Hebrón

Barcelona, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Inselspital Universitätsspital Bern

Bern, , Switzerland

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; China; Czechia; France; Israel; Italy; Netherlands; Spain; Switzerland; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-000698-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FGCL-3019-093

Identifier Type: -

Identifier Source: org_study_id