n Ulcer, Scleroderma, Systemic
Conditions
Brief summary
This is a research study of an investigational drug called ambrisentan (Letairis) in the treatment and prevention of digital ulcers in patients with systemic sclerosis.
Detailed description
Ambrisentan is an endothelin blocker approved for the treatment of pulmonary arterial hypertension. Patients with systemic sclerosis can have damage to their blood vessels, resulting in increased levels of endothelin in their bloodstream that then causes decreased blood flow to the digits. This can result in very painful digital ulcers. We hope to learn whether blocking the action of endothelin with ambrisentan will be helpful in the treatment and prevention of digital ulcers in patients with systemic sclerosis. This therapy is not approved for the treatment of systemic sclerosis, but this study will help us learn whether ambrisentan is safe and effective in the treatment and prevention of digital ulcers in patients with systemic sclerosis.
Interventions
DRUGAmbrisentan
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of limited or diffuse systemic sclerosis (SSc) according to American College of Rheumatology or LeRoy criteria * Age greater than 18 years of age * At least one digital ulcer located on the volar or lateral surface at or distal to the proximal interphalangeal joints * At least one new DU that developed within 12 weeks prior to screening * Vasodilator therapies, including calcium channel blockers, alpha-1-antagonists, ACE-inhibitors, nitroglycerin, and angiotensin receptor blockers, are permitted as long as the doses are stable for 2 weeks prior to screening and throughout the study * Treatment with omeprazole or other proton pump inhibitors must be stable for 2 weeks prior to screening and throughout the study
Exclusion criteria
* Patients with pulmonary arterial hypertension, NYHA Class III or IV * Patients who are hemodynamically unstable, or have acute renal, cardiac or pulmonary failure * Concurrent malignancy except non-melanoma skin cancers * Patients who have required systemic antibiotics for infected digital ulcers within 2 weeks of screening * Patients receiving phosphodiesterase-5 inhibitors, endothelin receptor antagonists, or prostanoids within 4 weeks of screening * Patients receiving cyclosporine within 6 weeks of screening * Patients who have participated in any investigational study within 30 days of screening * Pregnant or nursing women * Patients with a history of drug or alcohol abuse within 6 months of screening * History of hepatitis B, hepatitis C, or HIV infection * Any medical condition that, in the opinion of the investigator, might interfere with the subject's participation in the study or poses an added risk for the subject * Inability to comply with study and follow-up procedures * Transaminase elevation \> 3X the upper limit of normal at screening * Hemoglobin less than 8.5 g/dL * Platelet count less than 100 X 109/L * White blood cell count less than 3.0 X 109/L * Serum creatinine less than 2.0 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| New Digital Ulcers (DU) 4 Weeks Prior to Week 24 | 4 weeks prior to week 24 | The number of new digital ulcers (DU) that have developed in the preceding 4 weeks assessed at week 24 from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| New DU 4 Weeks Prior to Week 12 | 4 weeks prior to week 12 | The number of new DU that have developed in the preceding 4 weeks assessed at week 12 from baseline. |
| Subjects Experiencing Complete (Total Reepithelialization) Healing of All Baseline DU at Week 12. | 12 weeks | — |
| Subjects Experiencing Complete Healing of > 50% of the Number of Baseline DU at Week 12. | 12 weeks | — |
| Change in the Scleroderma Health Assessment Questionnaire (SHAQ) at Week 24 Compared With Baseline. | 24 weeks | Range is 0-3 with 0 meaning the least amount of disability and 3 the greatest of disability. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Ambrisentan
Ambrisentan | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Active |
|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 13.8 |
| Mean diameter of baseline digital ulcers | 3.3 mm STANDARD_DEVIATION 1.6 |
| Mean number of total baseline digital ulcers | 3.1 digital ulcers STANDARD_DEVIATION 2.1 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 20 |
| serious Total, serious adverse events | 3 / 20 |
Outcome results
Primary
New Digital Ulcers (DU) 4 Weeks Prior to Week 24
The number of new digital ulcers (DU) that have developed in the preceding 4 weeks assessed at week 24 from baseline.
Time frame: 4 weeks prior to week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | New Digital Ulcers (DU) 4 Weeks Prior to Week 24 | 0.06 new digital ulcers | Standard Deviation 0.68 |
Secondary
Change in the Scleroderma Health Assessment Questionnaire (SHAQ) at Week 24 Compared With Baseline.
Range is 0-3 with 0 meaning the least amount of disability and 3 the greatest of disability.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in the Scleroderma Health Assessment Questionnaire (SHAQ) at Week 24 Compared With Baseline. | -0.06 units on a scale | Standard Deviation 0.62 |
Secondary
New DU 4 Weeks Prior to Week 12
The number of new DU that have developed in the preceding 4 weeks assessed at week 12 from baseline.
Time frame: 4 weeks prior to week 12
Population: At 12 weeks only 1 patient had withdrawn from the study and 19 remained in the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | New DU 4 Weeks Prior to Week 12 | -0.26 new digital ulcers | Standard Deviation 1.1 |
Secondary
Subjects Experiencing Complete Healing of > 50% of the Number of Baseline DU at Week 12.
Time frame: 12 weeks
Population: At 12 weeks only 1 patient had withdrawn from the study and 19 remained in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Subjects Experiencing Complete Healing of > 50% of the Number of Baseline DU at Week 12. | 12 Participants |
Secondary
Subjects Experiencing Complete (Total Reepithelialization) Healing of All Baseline DU at Week 12.
Time frame: 12 weeks
Population: At 12 weeks only 1 patient had withdrawn from the study and 19 remained in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active | Subjects Experiencing Complete (Total Reepithelialization) Healing of All Baseline DU at Week 12. | 7 Participants |