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

NCT04632940 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: FGCL-3019-0942020-000699-39
• Study Type: interventional
• Target: 73
• Locations: 10 countries
• Sites: 51

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).

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 52

  The NSAA consisted of 17 activities, each scored as 0 (activity could not be performed), 1 (modified method but achieved goal without physical assistance from another), or 2 (normal, achieved goal without assistance). The sum of these 17 scores was used to form a total score ranging from 0 (worst) to 34 (fully independent function). If fewer than 15 of the 17 activities were performed, the total score was considered missing. If 15 to 16 activities were performed, the total score was calculated by multiplying the sum of the scores in the x activities that were performed by 17/x. If an activity could not be performed due to disease progression/loss of ambulation, a score of 0 was assigned. Higher scores indicated better functioning. Least square (LS) mean and standard error (SE) were analyzed using a mixed model for repeated measure (MMRM).

  Baseline, Week 52

Secondary Outcomes (4)

• Change From Baseline in 4-Stair Climb Velocity (4SCV) Assessment at Week 52

  Baseline, Week 52

• Change From Baseline in the 10-Meter Walk/Run Test at Week 52

  Baseline, Week 52

• Change From Baseline in Time to Stand (TTSTAND) at Week 52

  Baseline, Week 52

• Time to Loss of Ambulation (LoA) From Baseline to Week 52

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

Also known as: FG-3019

Pamrevlumab

Placebo DRUG

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

Placebo

Corticosteroids DRUG

Systemic deflazacort or equivalent potency of corticosteroids administered orally

Pamrevlumab; Placebo

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age, and consent:
• Males at least 6 to \<12 years of age 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
• DMD diagnosis:
• Medical history includes diagnosis of DMD and confirmed Duchenne mutation, including status of exon 44 using a validated genetic test.
• Pulmonary criteria:
• Average (of screening and Day 0) percent predicted forced vital capacity (FVC) above 45%
• 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:
• 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.
• Able to rise (TTSTAND) from floor in \<10 seconds (without aids/orthoses) at screening visit.
• Able to undergo magnetic resonance imaging (MRI) test for the lower extremities vastus lateralis muscle.
• Vaccination:
• Agreement to receive annual influenza vaccinations during the conduct of the study.
• Laboratory criteria:

You may not qualify if:

• General Criteria:
• Concurrent illness other than DMD that can cause muscle weakness and/or impairment of motor function
• 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
• Previous exposure to pamrevlumab
• Body mass index (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
• 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:
• Requires ≥16 hours continuous ventilation
• 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
• Hospitalization due to respiratory failure within the 8 weeks prior to screening
• Severe uncontrolled heart failure (New York Heart Association \[NYHA\] Classes III-IV) or renal dysfunction, including any of the following:
• Need for intravenous diuretics or inotropic support within 8 weeks prior to screening

Sponsors & Collaborators

• Kyntra Bio: lead

Study Sites (52)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California Davis Children's Hospital

Sacramento, California, 95817, United States

Location

University of California San Diego Health

San Diego, California, 92161, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Florida Health Shands Hospital

Gainesville, Florida, 32610, United States

Location

Rare Disease Research - Tampa

Tampa, Florida, 33614, United States

Location

Rare Disease Research Center

Atlanta, Georgia, 30329, United States

Location

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

Chicago, Illinois, 60611, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center Research Institute

Fairway, Kansas, 66205, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

University of Massachusetts Memorial Center

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 St. Louis

St Louis, Missouri, 63110, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3026, United States

Location

Shriners Hospital for Children

Portland, Oregon, 97239, United States

Location

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Utah Health

Salt Lake City, Utah, 84108, United States

Location

University of Virginia Children's Hospital

Charlottesville, Virginia, 22903, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children's Wisconsin Corporate Center

Milwaukee, Wisconsin, 53226, United States

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

Klinik Favoriten

Vienna, Vienna, 1100, Austria

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, Flemish Brabant, 3000, Belgium

Location

Centre Hospitalier Régional de la Citadelle

Liège, Liege, 4000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 401122, China

Location

The 1st Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, 410008, 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

Hôpital Hautepierre

Strasbourg, Bas-Rhin, 67200, France

Location

Centre Hospitalier Universitaire Nantes - Hôtel Dieu

Nantes, 44093, France

Location

Association Institut de Myologie

Paris, 75012, France

Location

IRRCS Ospedale San Raffaele

Milan, Milan, 20132, Italy

Location

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

Bosisio Parini, 23842, Italy

Location

Centro Clinico NeMO

Milan, 20162, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 168, Italy

Location

Ospedale Pediatrico Bambino Gesù - Roma - Gianicolo

Roma, Italy

Location

Leiden Universitair Medisch Centrum

Leiden, Netherlands

Location

Radboud Universitair Medisch Centrum

Nijmegen, Netherlands

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Leeds Teaching Hospitals NHS Trust

Leeds, England, LS1 3EX, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, England, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked

Interventions

pamrevlumab; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

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.

FG3019-094DMDStudy@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: November 12, 2020
• First Posted: November 17, 2020
• Study Start: March 3, 2021
• Primary Completion: June 12, 2023
• Study Completion: December 14, 2023
• Last Updated: August 26, 2024
• Results First Posted: August 26, 2024

Record last verified: 2024-07

Locations

AU (1); NL (2); GB (2); FR (3); BE (3); ES (2); US (27); CA (1); CN (5); IT (5)