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

Study Description

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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 subjects with DMD.

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy	Drug: pamrevlumab (FG-3019)	Phase 2

Detailed Description:

Each subject will receive pamrevlumab (35 mg/kg) every two weeks by intravenous infusion for up to 156 weeks. After at least 10 to 12 subjects complete one year of treatment interim analysis may increase total subjects enrolled to approximately 32. All subjects will be closely monitored for safety. Efficacy assessments will be performed routinely over the course of the study.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	22 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Trial of Pamrevlumab (FG-3019), a Monoclonal Antibody to Connective Tissue Growth Factor, in Non-Ambulatory Subjects With Duchenne Muscular Dystrophy
Actual Study Start Date :	November 2015
Estimated Primary Completion Date :	April 2020
Estimated Study Completion Date :	April 2021

Arms and Interventions

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Arm	Intervention/treatment
Experimental: pamrevlumab (FG-3019); Each subject will receive pamrevlumab (FG-3019) (35 mg/kg, every 2 weeks) for up to 156 weeks.	Drug: pamrevlumab (FG-3019); pamrevlumab (FG-3019), 10 mg/mL, single dose vials; Other Name: Monoclonal Antibody to CTGF

Outcome Measures

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Primary Outcome Measures :

1. Annual change in percent predicted annual forced vital capacity (FVC) during treatment with pamrevlumab. [ Time Frame: From baseline to 104 weeks ]

Secondary Outcome Measures :

1. Change in forced expiratory volume (FEV1) [ Time Frame: From baseline to 104 weeks ]
2. Change in maximum inspiratory pressure (MIP) [ Time Frame: From baseline to 104 weeks ]
3. Change in maximum expiratory pressure (MEP) [ Time Frame: From baseline to 104 weeks ]
4. Change in peak expiratory flow (PEF) [ Time Frame: From baseline to 104 weeks ]
5. Change in peak cough flow [ Time Frame: From baseline to 104 weeks ]
6. Change in left ventricular ejection fraction (LVEF) [ Time Frame: From baseline to 104 weeks ]
7. Change in Performance of Upper Limb (PUL) Score [ Time Frame: From baseline to 104 weeks ]
8. Change in grip strength [ Time Frame: From baseline to 104 weeks ]
9. Change in pinch strength [ Time Frame: From baseline to 104 weeks ]
10. Change in Brooke scale for upper extremity [ Time Frame: From baseline to 104 weeks ]
11. Change in cardiac fibrosis score assessed by MRI [ Time Frame: From baseline to 104 weeks ]
12. Change in upper arm (bicep) muscle fat and fibrosis assessed by MRI [ Time Frame: From baseline to 104 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	12 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• At least 12 years of age
• Written consent/assent by patient and/or legal guardian as per regional and/or 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 FVC% 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
• Subjects currently receiving heart failure cardiac medications (e.g. 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/L

• Adequate hematological function

  1. Platelets >100,000/mcL
  2. Hemoglobin >12 g/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 ≤1.5xULN
• 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 subject, 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

  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 HIV
• BMI ≥40 kg/m^2 or weight >117 kg
• Exposure to another investigational drug 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.

Contacts and Locations

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Locations

United States, California
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
University of California San Francisco - Benioff Children's Hospital
San Francisco, California, United States, 94143
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Rare Disease Research
Atlanta, Georgia, United States, 30318
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University in St. Louis School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Oregon
Shriner's Hospital for Children - Portland
Portland, Oregon, United States, 97239
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Children's Medical Center Ambulatory Care Pavilion
Dallas, Texas, United States, 75207

Sponsors and Collaborators

FibroGen

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	FibroGen
ClinicalTrials.gov Identifier:	NCT02606136 History of Changes
Other Study ID Numbers:	FGCL-3019-079
First Posted:	November 17, 2015
Last Update Posted:	April 18, 2018
Last Verified:	April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Studies a U.S. FDA-regulated Drug Product:		Yes

Keywords provided by FibroGen:

Duchenne; muscular; dystrophy; DMD; non-ambulatory

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases	Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Antibodies; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs