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

Primary Purpose

Systemic Sclerosis, Pulmonary; Hypertension

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Dimethyl Fumarate (DMF)

Placebo Oral Tablet

About this trial

This is an interventional treatment trial for Systemic Sclerosis focused on measuring Systemic Sclerosis, Scleroderma, PAH, Pulmonary Hypertension

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
6MWD 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

Exclusion Criteria:

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
Pregnant or lactating women
Need for HAART therapy
Planned treatment or treatment with another investigational drug within 1 month prior to start
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

Sites / Locations

National Jewish
John Hopkins
Boston University
University of Pittsburgh

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Dimethyl Fumarate (DMF)

Placebo

Arm Description

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

Twice daily oral doses of placebo for 12 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Clinical Worsening

The change in time to clinical worsening in DMF compared to placebo treated patients.

Borg Dyspnea Index (BDI)

The change in Borg Dyspnea Index (BDI) at 24 weeks from baseline in DMF compared to placebo treated patients

Serum Markers of Oxidative Stress

The change from baseline of serum markers of oxidative stress at 24 weeks, comparing DMF to placebo treated patients.

Proteomic Biomarkers

The change from baseline in proteomic biomarkers, including BNP, at 24 weeks, comparing DMF to placebo treated patients.

Full Information

NCT ID

NCT02981082

First Posted

November 30, 2016

Last Updated

March 15, 2022

Sponsor

Robert Lafyatis

Collaborators

Biogen

1. Study Identification

Unique Protocol Identification Number

NCT02981082

Brief Title

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

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Terminated

Why Stopped

Low recruitment

Study Start Date

December 2016 (undefined)

Primary Completion Date

February 10, 2020 (Actual)

Study Completion Date

February 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Robert Lafyatis

Collaborators

Biogen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Systemic Sclerosis, Pulmonary; Hypertension

Keywords

Systemic Sclerosis, Scleroderma, PAH, Pulmonary Hypertension

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dimethyl Fumarate (DMF)

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Twice daily oral doses of placebo for 12 weeks

Intervention Type

Drug

Intervention Name(s)

Dimethyl Fumarate (DMF)

Other Intervention Name(s)

Tecfidera

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Tablet

Intervention Description

Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)

Primary Outcome Measure Information:

Title

6 Minute Walk Distance (6MWD)

Description

Time Frame

Baseline to Week 24

Secondary Outcome Measure Information:

Title

Clinical Worsening

Description

The change in time to clinical worsening in DMF compared to placebo treated patients.

Time Frame

Baseline to Week 24

Title

Borg Dyspnea Index (BDI)

Description

The change in Borg Dyspnea Index (BDI) at 24 weeks from baseline in DMF compared to placebo treated patients

Time Frame

Baseline to Week 24

Title

Serum Markers of Oxidative Stress

Description

The change from baseline of serum markers of oxidative stress at 24 weeks, comparing DMF to placebo treated patients.

Time Frame

Baseline to Week 24

Title

Proteomic Biomarkers

Description

The change from baseline in proteomic biomarkers, including BNP, at 24 weeks, comparing DMF to placebo treated patients.

Time Frame

Baseline to Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 6MWD 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 Exclusion Criteria: 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 Pregnant or lactating women Need for HAART therapy Planned treatment or treatment with another investigational drug within 1 month prior to start 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert A Lafyatis, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Jewish

City

Denver

State/Province

Colorado

ZIP/Postal Code

80206

Country

United States

Facility Name

John Hopkins

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21205

Country

United States

Facility Name

Boston University

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02118

Country

United States

Facility Name

University of Pittsburgh

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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