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

NCT ID: NCT02981082

Last Updated: 2022-03-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2020-02-10

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).

Detailed Description

A double-blinded, placebo-controlled study of Dimethyl fumarate (DMF) in 34 Systemic Sclerosis-Pulmonary Hypertension (SSc-PAH) patients. The study medication will be added to stable background PAH medication(s). Subjects will be dosed for 24 weeks, will undergo examination every 8 weeks, and will be finally evaluated 12 weeks after completion of treatment. Dosage will begin at once daily oral doses of 120mg for the first 7 days and follow the up-titration schedule to a maintenance dose of 240mg twice a day (or highest tolerated dose of a minimum of 120mg twice a day by the start of Week 8) for the remainder of the study. Participation will be for a total of 40 weeks, including a 4-week screening period, 24 weeks of drug, and a safety follow-up 12 weeks after the last dose. The study will determine the 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dimethyl Fumarate (DMF)

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

Group Type: ACTIVE_COMPARATOR

Dimethyl Fumarate (DMF)

Intervention Type: DRUG

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

Placebo

Twice daily oral doses of placebo for 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)

Interventions

Dimethyl Fumarate (DMF)

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

Intervention Type: DRUG

Placebo Oral Tablet

Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)

Intervention Type: DRUG

Other Intervention Names

Tecfidera

Eligibility Criteria

Inclusion Criteria

1. Signed inform consent prior to any study-mandated procedures

2. Adult patients 18-80 years of age

3. World Health Organization Group 1 PAH associated with scleroderma (SSc-PAH)

4. WHO functional Class II-III

5. 6MWD 150 to 450 meters

6. 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.

7. ACR defined systemic sclerosis

Exclusion Criteria

1. 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

2. Participation in a clinical investigational study within the previous 30 days

3. Moderate to severe hepatic impairment (e.g., Child-Pugh Class B or C)

4. Renal failure defined as:

• estimated creatinine clearance <30 m/min
• serum creatinine>2.5 mg/dl

5. Serum aspartate aminotransferase (AST) and or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal

6. Systolic blood pressure < 90mmHg

7. Recently started (< 8 weeks prior to randomization) or planned cardiopulmonary rehabilitation program based on exercise

8. Pregnant or lactating women

9. Need for HAART therapy

10. Planned treatment or treatment with another investigational drug within 1 month prior to start

11. Moderate to severe interstitial lung disease, defined by FVC < 80% or evidence on HRCT of fibrosis or ground glass changes involving more than 30% of lung parenchyma

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: collaborator

Robert Lafyatis

OTHER

Sponsor Role: lead

Responsible Party

Robert Lafyatis

Professor of Medicine and the Thomas Medsger Professor in Arthritis Research

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Robert A Lafyatis, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

National Jewish

Denver, Colorado, United States

John Hopkins

Baltimore, Maryland, United States

Boston University

Boston, Massachusetts, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

PRO16070614

Identifier Type: -

Identifier Source: org_study_id