Dimethyl Fumarate (DMF) in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

NCT02981082 | Terminated Phase 1 Results DMC

• 1 other identifier: PRO16070614
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

A double-blinded, placebo-controlled study of Dimethyl fumarate (DMF) in 34 Systemic Sclerosis-Pulmonary Hypertension (SSc-PAH) patients. The study will determine safety and the primary outcome variability for DMF in treating SSc-PAH; the primary outcome of clinical efficacy in this pilot trial will be improvement in 6-minute walk distance (6MWD).

Conditions

Systemic Sclerosis; Pulmonary; Hypertension

Keywords

Systemic Sclerosis, Scleroderma, PAH, Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• 6 Minute Walk Distance (6MWD)

  The primary outcome of clinical efficacy in this study is improvement in 6-minute walk distance (6MWD). Data depict the mean change (%) at end-of-study-treatment (Week 24) from baseline in both treatment groups, utilizing the Last Observation Carried Forward of withdrawn subjects.

  Baseline to Week 24

Secondary Outcomes (4)

• Clinical Worsening

  Baseline to Week 24

• Borg Dyspnea Index (BDI)

  Baseline to Week 24

• Serum Markers of Oxidative Stress

  Baseline to Week 24

• Proteomic Biomarkers

  Baseline to Week 24

Study Arms (2)

Dimethyl Fumarate (DMF)

ACTIVE COMPARATOR

Twice daily oral doses of Dimethyl Fumarate (DMF) 120mg for the first 7 days followed by the maintenance dose of Dimethyl Fumarate (DMF) 240mg twice a day. Subjects will be dosed for 24 weeks

Drug: Dimethyl Fumarate (DMF)

Placebo

PLACEBO COMPARATOR

Twice daily oral doses of placebo for 12 weeks

Drug: Placebo Oral Tablet

Interventions

Dimethyl Fumarate (DMF) DRUG

Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.

Also known as: Tecfidera

Dimethyl Fumarate (DMF)

Placebo Oral Tablet DRUG

Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed inform consent prior to any study-mandated procedures
• Adult patients 18-80 years of age
• World Health Organization Group 1 PAH associated with scleroderma (SSc-PAH)
• WHO functional Class II-III
• MWD 150 to 450 meters
• Right heart catheterization demonstrating mPAP≥ 25 mmHg and PCWP or left ventricular end diastolic pressure ≤15mm Hg and pulmonary vascular resistance ≥240 dynes/cm-5 (3 Wood units) within 12 weeks prior to study entry.
• ACR defined systemic sclerosis

You may not qualify if:

• Pulmonary hypertension associated with
• PAH of any etiology other than scleroderma
• PH of any etiology other than WHO Group I PAH
• Pulmonary venous hypertension defined as PCWP or LVEDP \>15 mHg
• Untreated sleep apnea with AHI \>20 or SaO2 Nadir \<87%
• Chronic thromboembolic disease
• Sarcoidosis
• Participation in a clinical investigational study within the previous 30 days
• Moderate to severe hepatic impairment (e.g., Child-Pugh Class B or C)
• Renal failure defined as:
• estimated creatinine clearance \<30 m/min
• serum creatinine\>2.5 mg/dl
• Serum aspartate aminotransferase (AST) and or alanine aminotransferase (ALT) \> 1.5 times the upper limit of normal
• Systolic blood pressure \< 90mmHg
• Recently started (\< 8 weeks prior to randomization) or planned cardiopulmonary rehabilitation program based on exercise

Sponsors & Collaborators

• Robert Lafyatis: lead
• Biogen: collaborator

Study Sites (4)

National Jewish

Denver, Colorado, 80206, United States

Location

John Hopkins

Baltimore, Maryland, 21205, United States

Location

Boston University

Boston, Massachusetts, 02118, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Scleroderma, Systemic; Hypertension, Pulmonary; Scleroderma, Diffuse

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Limitations and Caveats

Early study termination due to low recruitment; not enough participants for statistically reliable analyses.

Results Point of Contact

• Title: Dr. Robert Lafyatis
• Organization: University of Pittsburgh

lafyatis@pitt.edu

412-648-7040

Study Officials

• Robert A Lafyatis, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine and the Thomas Medsger Professor in Arthritis Research

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 2, 2016
• Study Start: December 1, 2016
• Primary Completion: February 10, 2020
• Study Completion: February 10, 2020
• Last Updated: March 17, 2022
• Results First Posted: March 17, 2022

Record last verified: 2022-03

Locations

US (4)