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

NCT ID: NCT04632940

Last Updated: 2024-08-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-03
• Study Completion Date: 2023-12-14

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.

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 will be administered 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

Placebo will be administered per schedule specified in the arm description.

Corticosteroids

Intervention Type: DRUG

Systemic deflazacort or equivalent potency of corticosteroids administered orally

Interventions

Pamrevlumab

Pamrevlumab will be administered per dose and schedule specified in the arm description.

Intervention Type: DRUG

Placebo

Placebo will be administered 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

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

FibroGen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

University of California Davis Children's Hospital

Sacramento, California, United States

University of California San Diego Health

San Diego, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

University of Florida Health Shands Hospital

Gainesville, Florida, United States

Rare Disease Research - Tampa

Tampa, Florida, United States

Rare Disease Research Center

Atlanta, Georgia, United States

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

Chicago, Illinois, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center Research Institute

Fairway, Kansas, United States

Kennedy Krieger Institute

Baltimore, Maryland, United States

University of Massachusetts Memorial Center

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 St. Louis

St Louis, Missouri, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Shriners Hospital for Children

Portland, Oregon, United States

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Texas Children's Hospital

Houston, Texas, United States

University of Utah Health

Salt Lake City, Utah, United States

University of Virginia Children's Hospital

Charlottesville, Virginia, United States

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Children's Wisconsin Corporate Center

Milwaukee, Wisconsin, United States

Murdoch Children's Research Institute

Parkville, Victoria, Australia

Klinik Favoriten

Vienna, Vienna, Austria

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, Flemish Brabant, Belgium

Centre Hospitalier Régional de la Citadelle

Liège, Liege, Belgium

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, Belgium

London Health Sciences Centre

London, Ontario, Canada

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

The 1st Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Xiangya Hospital Central South University

Changsha, Hunan, China

West China Second University Hospital, Sichuan University

Chengdu, Sichuan, China

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, , China

Hôpital Hautepierre

Strasbourg, Bas-Rhin, France

Centre Hospitalier Universitaire Nantes - Hôtel Dieu

Nantes, , France

Association Institut de Myologie

Paris, , France

IRRCS Ospedale San Raffaele

Milan, Milan, Italy

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

Bosisio Parini, , Italy

Centro Clinico NeMO

Milan, , Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, , Italy

Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo

Roma, , Italy

Leiden Universitair Medisch Centrum

Leiden, , Netherlands

Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

Hospital Universitari Vall d'Hebrón

Barcelona, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Leeds Teaching Hospitals NHS Trust

Leeds, England, United Kingdom

Oxford University Hospitals NHS Foundation Trust

Oxford, England, United Kingdom

Countries

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-000699-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FGCL-3019-094

Identifier Type: -

Identifier Source: org_study_id