Trial Outcomes & Findings for Dimethyl Fumarate (DMF) in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (NCT NCT02981082)
NCT ID: NCT02981082
Last Updated: 2022-03-17
Results Overview
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(Week 24) from baseline in both treatment groups, utilizing the Last Observation Carried Forward of withdrawn subjects.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
6 participants
Primary outcome timeframe
Baseline to Week 24
Results posted on
2022-03-17
Participant Flow
Participant milestones
| Measure |
Dimethyl Fumarate (DMF)
Once daily oral doses of Dimethyl Fumarate (DMF) 120mg for the first 7 days, following a titration schedule reaching a minimum of 120mg DMF twice daily, maximum 240mg twice daily, by the start of week 8. Subjects will be dosed for 24 weeks.
Dimethyl Fumarate (DMF): Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.
|
Placebo
Twice daily oral doses of placebo for 12 weeks.
Placebo Oral Tablet: Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
2
|
|
Overall Study
COMPLETED
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
3
|
1
|
Reasons for withdrawal
| Measure |
Dimethyl Fumarate (DMF)
Once daily oral doses of Dimethyl Fumarate (DMF) 120mg for the first 7 days, following a titration schedule reaching a minimum of 120mg DMF twice daily, maximum 240mg twice daily, by the start of week 8. Subjects will be dosed for 24 weeks.
Dimethyl Fumarate (DMF): Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.
|
Placebo
Twice daily oral doses of placebo for 12 weeks.
Placebo Oral Tablet: Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
|
Overall Study
Met stopping rule of low absolute lymphocyte count (<0.5L) at two visits
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
1
|
Baseline Characteristics
Dimethyl Fumarate (DMF) in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension
Baseline characteristics by cohort
| Measure |
Dimethyl Fumarate (DMF)
n=4 Participants
Once daily oral doses of Dimethyl Fumarate (DMF) 120mg for the first 7 days, following a titration schedule reaching a minimum of 120mg DMF twice daily, maximum 240mg twice daily, by the start of week 8. Subjects will be dosed for 24 weeks.
Dimethyl Fumarate (DMF): Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.
|
Placebo
n=2 Participants
Twice daily oral doses of placebo for 12 weeks.
Placebo Oral Tablet: Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)
|
Total
n=6 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66.4 years
n=99 Participants
|
72.5 years
n=107 Participants
|
69 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
6-minute walk distance (6MWD)
|
305.5 Mean 6MWD (meters)
n=99 Participants
|
243.5 Mean 6MWD (meters)
n=107 Participants
|
284.83 Mean 6MWD (meters)
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 24The 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.
Outcome measures
| Measure |
Dimethyl Fumarate (DMF)
n=4 Participants
Once daily oral doses of Dimethyl Fumarate (DMF) 120mg for the first 7 days, following a titration schedule reaching a minimum of 120mg DMF twice daily, maximum 240mg twice daily, by the start of week 8. Subjects will be dosed for 24 weeks.
Dimethyl Fumarate (DMF): Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.
|
Placebo
n=2 Participants
Twice daily oral doses of placebo for 12 weeks.
Placebo Oral Tablet: Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)
|
|---|---|---|
|
6 Minute Walk Distance (6MWD)
|
-7.07 percent change
Interval -24.69 to 8.2
|
-14.97 percent change
Interval -29.93 to 0.0
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Insufficient data collection due to low recruitment and early termination of study.
The change in time to clinical worsening in DMF compared to placebo treated patients.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Insufficient data collection due to low recruitment and early termination of study.
The change in Borg Dyspnea Index (BDI) at 24 weeks from baseline in DMF compared to placebo treated patients
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Insufficient data collection due to low recruitment and early termination of study.
The change from baseline of serum markers of oxidative stress at 24 weeks, comparing DMF to placebo treated patients.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Insufficient data collection due to low recruitment and early termination of study.
The change from baseline in proteomic biomarkers, including BNP, at 24 weeks, comparing DMF to placebo treated patients.
Outcome measures
Outcome data not reported
Adverse Events
Dimethyl Fumarate (DMF)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dimethyl Fumarate (DMF)
n=4 participants at risk
Once daily oral doses of Dimethyl Fumarate (DMF) 120mg for the first 7 days, following a titration schedule reaching a minimum of 120mg DMF twice daily, maximum 240mg twice daily, by the start of week 8. Subjects will be dosed for 24 weeks.
Dimethyl Fumarate (DMF): Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.
|
Placebo
n=2 participants at risk
Twice daily oral doses of placebo for 12 weeks.
Placebo Oral Tablet: Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)
|
|---|---|---|
|
Cardiac disorders
Worsening of heart failure and shortness of breath secondary to anemia
|
0.00%
0/4 • 36 weeks
|
50.0%
1/2 • 36 weeks
|
Other adverse events
| Measure |
Dimethyl Fumarate (DMF)
n=4 participants at risk
Once daily oral doses of Dimethyl Fumarate (DMF) 120mg for the first 7 days, following a titration schedule reaching a minimum of 120mg DMF twice daily, maximum 240mg twice daily, by the start of week 8. Subjects will be dosed for 24 weeks.
Dimethyl Fumarate (DMF): Dimethyl Fumarate (DMF) is a prescription medicine used to treat relapsing multiple sclerosis.
|
Placebo
n=2 participants at risk
Twice daily oral doses of placebo for 12 weeks.
Placebo Oral Tablet: Sugar pill manufactured to mimic Dimethyl Fumarate (DMF)
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/4 • 36 weeks
|
50.0%
1/2 • Number of events 1 • 36 weeks
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/4 • 36 weeks
|
50.0%
1/2 • Number of events 1 • 36 weeks
|
|
Eye disorders
Blurred vision
|
0.00%
0/4 • 36 weeks
|
50.0%
1/2 • Number of events 1 • 36 weeks
|
|
Investigations
Decreased CD4 lymphocytes
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Investigations
High cholesterol
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Psychiatric disorders
Depression
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
2/4 • Number of events 2 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/4 • 36 weeks
|
50.0%
1/2 • Number of events 1 • 36 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/4 • 36 weeks
|
50.0%
1/2 • Number of events 1 • 36 weeks
|
|
Gastrointestinal disorders
Small bowel bacteria overgrowth
|
0.00%
0/4 • 36 weeks
|
50.0%
1/2 • Number of events 1 • 36 weeks
|
|
Nervous system disorders
Headache
|
0.00%
0/4 • 36 weeks
|
50.0%
1/2 • Number of events 1 • 36 weeks
|
|
Infections and infestations
Shingles
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Infections and infestations
Pneumonina
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
0.00%
0/4 • 36 weeks
|
50.0%
1/2 • Number of events 1 • 36 weeks
|
|
General disorders
Localized edema
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Musculoskeletal and connective tissue disorders
Ankle swelling at night
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Musculoskeletal and connective tissue disorders
Right rotator cuff tendinopathy
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Gastrointestinal disorders
Nausea
|
75.0%
3/4 • Number of events 3 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/4 • 36 weeks
|
50.0%
1/2 • Number of events 1 • 36 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
50.0%
1/2 • Number of events 1 • 36 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Infections and infestations
Sinusitis
|
25.0%
1/4 • Number of events 1 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
2/4 • Number of events 2 • 36 weeks
|
0.00%
0/2 • 36 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place