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

NCT04371666 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: FGCL-3019-0932020-000698-26
• Study Type: interventional
• Target: 98
• Locations: 13 countries
• Sites: 52

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).

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne Muscular Dystrophy, DMD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Total Score of Performance of Upper Limb (PUL) 2.0 Version at Week 52

  The PUL module is an observer-administered performance battery of upper extremity mobility tasks for the shoulder (upper, 6 items, 12 points), elbow (middle, 9 items, 17 points) and wrist/hand (distal, 7 items, 13 points). Higher scores indicate higher level of function. Total score ranges from 0-42 points and is the sum of the scores for the 3 subscales. Analysis was done using a random coefficient model (RCM), which included fixed effects of time (as a continuous variable), treatment, and treatment-by-time interaction, with baseline ordinal PUL entry score as covariate.

  Baseline, Week 52

Secondary Outcomes (4)

• Change From Baseline in Percent Predicted Forced Vital Capacity (ppFVC) at Week 52, Assessed by Spirometry

  Baseline, Week 52

• Change From Baseline in the Grip Strength of the Hands at Week 52, Assessed by Hand Held Myometry (HHM)

  Baseline, Week 52

• Change From Baseline in Left Ventricular Ejection Fraction Percentage (LVEF %) at Week 52, Assessed by Magnetic Resonance Imaging (MRI)

  Baseline, Week 52

• Change From Baseline in Percent Predicted Peak Expiratory Flow (ppPEF) at Week 52, Assessed by Spirometry

  Baseline, Week 52

Study Arms (2)

Pamrevlumab

EXPERIMENTAL

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

Drug: Pamrevlumab; Drug: Corticosteroids

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Corticosteroids

Interventions

Pamrevlumab DRUG

Pamrevlumab per dose and schedule specified in the arm description

Also known as: FG-3019

Pamrevlumab

Placebo DRUG

Matching placebo per schedule specified in the arm description

Placebo

Corticosteroids DRUG

Systemic deflazacort or equivalent potency of corticosteroids administered orally

Pamrevlumab; Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males at least 12 years of age, non-ambulatory at screening initiation
• Written consent by participant and/or legal guardian as per regional/ country and/or Institutional Review Board (IRB)/Independent Ethics Committee (IEC) requirements
• 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.
• Medical history includes diagnosis of DMD and confirmed Duchenne mutation using a validated genetic test
• Brooke Score for Arms and Shoulders ≤5
• Able to undergo MRI test for the upper arm extremities (Biceps Brachii muscle) and cardiac muscle
• Able to perform spirometry
• Average (of Screening and Day 0) percent predicted forced vital capacity (FVC) between 45 and 85, inclusive
• Left ventricular ejection fraction ≥50% as determined by local cardiac MRI read at screening or within 3 months prior to randomization (Day 0)
• 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.
• 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.
• Agreement to receive annual influenza vaccinations during the course of the study.
• Adequate renal function: cystatin C ≤1.4 mg/liter (L)
• Adequate hematology and electrolytes parameters:
• Platelets \>100,000/microliter (μL)

You may not qualify if:

• Previous exposure to pamrevlumab
• BMI ≥40 kg/square meter (m\^2) or weight \>117 kg
• History of:
• allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies
• hypersensitivity to study drug or any component of study drug
• hypersensitivity reaction to Gadolinium-based Contrast Agents (GBCA) required for MRI acquisition
• 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
• Severe uncontrolled heart failure (NYHA Classes III-IV), or renal dysfunction, including any of the following:
• Need for intravenous diuretics or inotropic support within 8 weeks prior to screening
• Hospitalization for a heart failure exacerbation or arrhythmia within 8 weeks prior to screening
• 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
• Arrhythmia requiring anti-arrhythmic therapy
• Requires ≥16 hours continuous ventilation
• Hospitalization due to respiratory failure within the 8 weeks prior to screening
• 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

Sponsors & Collaborators

• Kyntra Bio: lead

Study Sites (53)

Arkansas Children's

Little Rock, Arkansas, 72202, United States

Location

University of California Los Angeles Medical Center

Los Angeles, California, 90045, United States

Location

UC Davis Health

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30318, United States

Location

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

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Fairway, Kansas, 66205, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

UMASS Med School

Worcester, Massachusetts, 01655, United States

Location

C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109-4234, United States

Location

Spectrum Health Hospitals Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Washington University School of Medicine in Saint Louis

St Louis, Missouri, 63110, United States

Location

Carolinas HealthCare System Neurosciences Institute-Neurology - Charlotte

Charlotte, North Carolina, 28207, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2664, United States

Location

Shriners Hospital for Children

Portland, Oregon, 97239, United States

Location

Penn State Health Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Children's Health Dallas/UTSW

Dallas, Texas, 75207, United States

Location

University of Utah Health

Salt Lake City, Utah, 84108, United States

Location

Children's Specialty Group - Medical Center Office

Norfolk, Virginia, 23507, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

Klinik Favoriten

Vienna, 1100, Austria

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Centre Hospitalier Régional de la Citadelle

Liège, 4000, Belgium

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400015, China

Location

West China Second University Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, 100730, China

Location

Fakultní Nemocnice Brno - Dětská Nemocnice

Brno, 613 00, Czechia

Location

Klinika dÄ>tské neurologie, Neuromuskulární centrum

Prague, 150 06, Czechia

Location

CHU de Nantes - Hotel Dieu

Nantes, 44093, France

Location

Association Institut de Myologie

Paris, 75012, France

Location

Hopital Hautepierre

Strasbourg, 67098, France

Location

The Chaim Sheba Medical Center

Tel Aviv, 5265601, Israel

Location

The Edith Wolfson Medical Center

Tel Aviv, 5822012, Israel

Location

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

Lecco, 23842, Italy

Location

IRRCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Rome, 00168, Italy

Location

Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo

Rome, 165, Italy

Location

Radboud Universitair Medisch Centrum

Nijmegen, Gelderland, 6525, Netherlands

Location

Leiden Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Hospital General Universitario de Alicante

Alicante, 3010, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Inselspital Universitätsspital Bern

Bern, 3010, Switzerland

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS1 3EX, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, WC1N 3BG, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

pamrevlumab; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: FibroGen, Inc.

FG3019-093DMDStudy@fibrogen.com

415-978-1441

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2020
• First Posted: May 1, 2020
• Study Start: August 10, 2020
• Primary Completion: February 13, 2023
• Study Completion: August 17, 2023
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2024-02

Locations

CH (1); BE (3); US (24); ES (3); GB (3); CA (1); IL (2); IT (4); CZ (2); FR (3); AU (1); NL (2); CN (3)