Trial of Pamrevlumab (FG-3019), in Non-Ambulatory Participants With Duchenne Muscular Dystrophy (DMD)

NCT ID: NCT02606136

Last Updated: 2024-08-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-04
• Study Completion Date: 2023-08-09

Brief Summary

This is a Phase 2, open-label, single arm trial of pamrevlumab (FG-3019) to estimate pamrevlumab's safety and efficacy in non-ambulatory participants with DMD.

Detailed Description

The study will include a screening period, main study period, open-label extension (OLE) period, and follow-up period 4 weeks after the last dose. All participants who complete the main portion of the study for a minimum of 104 weeks (2 years) will be rolled over to an OLE for up to an additional 208 weeks (4 years).

Conditions

Duchenne Muscular Dystrophy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pamrevlumab

Participants will receive pamrevlumab 35 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 2 weeks for a minimum of 104 weeks. Participants who complete the main study, will continue to receive pamrevlumab 35 mg/kg by IV infusion every 2 weeks for a minimum of up to 208 weeks in the OLE.

Group Type: EXPERIMENTAL

Pamrevlumab

Intervention Type: DRUG

Pamrevlumab, 10 milligrams (mg)/milliliter (mL), single dose vials

Interventions

Pamrevlumab

Pamrevlumab, 10 milligrams (mg)/milliliter (mL), single dose vials

Intervention Type: DRUG

Other Intervention Names

Monoclonal Antibody to Connective tissue growth factor (CTGF), FG-3019

Eligibility Criteria

Inclusion Criteria

• Written consent/assent by participant and/or legal guardian as per regional and/or institutional review board (IRB) requirements
• Non-ambulatory
• Brooke Score for Arms and Shoulders ≤5
• Diagnosis of DMD by medical history and confirmed Duchenne mutation in available genetic testing using a validated genetic test
• Able to perform spirometry
• Able to undergo cardiac and extremity (upper arm) MRI
• Percent predicted FVC between 40 and 90, inclusive
• At least one historical ppFVC predicted value within 18 months of baseline
• Left ventricular ejection fraction ≥ 45% as determined by cardiac MRI at screening or within 3 months prior to Day 0
• Participants currently receiving heart failure cardiac medications (for example, angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, and beta-blockers) must achieve a stable regimen for at least 3 months prior to screening
• On a stable dose of corticosteroids for a minimum of 6 months prior to screening with no substantial change in dosage for a minimum of 3 months (except for adjustments for changes in body weight) prior to screening and no foreseen change in corticosteroid use during the course of study participation
• Received pneumococcal vaccine and is receiving annual influenza vaccinations
• Adequate renal function: cystatin C ≤1.4 mg/liter (L)
• Adequate hematological function

1. Platelets >100,000/microliter (μL)

2. Hemoglobin >12 grams (g)/deciliter (dL)

3. Absolute neutrophil count >1500/μL

• Adequate hepatic function

1. No history or evidence of liver disease

2. Gamma glutamyl transferase (GGT) ≤3 x upper limit of normal (ULN)

3. Total bilirubin ≤1.5 x ULN

• If sexually active, will use medically accepted contraceptives during participation in the study and for 3 months after the last dose of study drug

Exclusion Criteria

• Requires ≥16 hours continuous ventilation
• Prior or ongoing medical condition that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of 156 weeks of treatment and follow-up would be completed, or could impair the assessment of study results
• Anticipated spine surgery within 156 weeks
• Severe uncontrolled heart disease, including any of the following:

1. Need for intravenous diuretics or inotropic support within 3 months prior to screening

2. Hospitalization for a heart failure exacerbation or arrhythmia in last 3 months

• Arrhythmia requiring anti-arrhythmic therapy
• Hospitalization due to respiratory failure in the last 6 weeks
• Poorly controlled asthma or underlying lung disease such as bronchopulmonary dysplasia
• Known or suspected active hepatitis B or C or history of human immunodeficiency virus (HIV)
• Body mass index (BMI) ≥40 kilograms (kg)/square meter (m^2) or weight >117 kg
• Exposure to another investigational drug or another approved product for DMD (for example, eteplirsen or golodirsen) within 28 days prior to start of study treatment
• Exposure to another investigational drug or another approved product for DMD (e.g. eteplirsen) within 28 days prior to start of study treatment (or 5 half-lives of the product whichever is longer) prior to first screening visit with the exception of deflazacort. Use of deflazacort, if regarded by the principal investigator as standard of care, is allowed.

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

Sponsors

FibroGen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

University of California San Francisco - Benioff Children's Hospital

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Rare Disease Research

Atlanta, Georgia, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Washington University in St. Louis School of Medicine

St Louis, Missouri, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Shriner's Hospital for Children - Portland

Portland, Oregon, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Medical Center Ambulatory Care Pavilion

Dallas, Texas, United States

Countries

United States

References

Rayego-Mateos S, Morgado-Pascual JL, Lavoz C, Rodrigues-Diez RR, Marquez-Exposito L, Tejera-Munoz A, Tejedor-Santamaria L, Rubio-Soto I, Marchant V, Ruiz-Ortega M. CCN2 Binds to Tubular Epithelial Cells in the Kidney. Biomolecules. 2022 Feb 3;12(2):252. doi: 10.3390/biom12020252.

Reference Type: DERIVED

PMID: 35204752 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2023-000321-80

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FGCL-3019-079

Identifier Type: -

Identifier Source: org_study_id