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

Systemic Sclerosis Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02981082
• Other study ID #: PRO16070614
• Status: Terminated
• Phase: Phase 1
• Start date: December 2016
• Est. completion date: February 10, 2020

Study information

• Verified date: March 2022
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: February 10, 2020
• Est. primary completion date: February 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension
• Pulmonary; Hypertension
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• Dimethyl Fumarate (DMF)
Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.
• Placebo Oral Tablet
Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)

Locations

Country	Name	City	State
United States	John Hopkins	Baltimore	Maryland
United States	Boston University	Boston	Massachusetts
United States	National Jewish	Denver	Colorado
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Robert Lafyatis	Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical Worsening	The change in time to clinical worsening in DMF compared to placebo treated patients.	Baseline to Week 24
Secondary	Borg Dyspnea Index (BDI)	The change in Borg Dyspnea Index (BDI) at 24 weeks from baseline in DMF compared to placebo treated patients	Baseline to Week 24
Secondary	Serum Markers of Oxidative Stress	The change from baseline of serum markers of oxidative stress at 24 weeks, comparing DMF to placebo treated patients.	Baseline to Week 24
Secondary	Proteomic Biomarkers	The change from baseline in proteomic biomarkers, including BNP, at 24 weeks, comparing DMF to placebo treated patients.	Baseline to Week 24