Clinical trial NCT02981082: Dimethyl Fumarate (DMF) in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension
Official title: A Double-blinded, Placebo-controlled Pilot Study of Dimethyl Fumarate (DMF) in Pulmonary Arterial Hypertension (PAH) Associated With Systemic Sclerosis (SSc-PAH): The Effect of DMF on Clinical Disease and Biomarkers of Oxidative Stress.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Systemic Sclerosis
Pulmonary; Hypertension
Keywords: Systemic Sclerosis, Scleroderma, PAH, Pulmonary Hypertension
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Biogen
First posted: 2016-12-02
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: 6 Minute Walk Distance (6MWD)
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Clinical Worsening
timeFrame: Baseline to Week 24
measure: Borg Dyspnea Index (BDI)
timeFrame: Baseline to Week 24
measure: Serum Markers of Oxidative Stress
timeFrame: Baseline to Week 24
measure: Proteomic Biomarkers
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish
state: Colorado
city: Baltimore
country: United States
facility: John Hopkins
state: Maryland
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Robert A Lafyatis, MD
role: PRINCIPAL_INVESTIGATOR
References: