Digital Ulcera in Systemic Sclerodermia patients MedDRA version: 14.1 Level: PT Classification code 10053400 Term: Endothelin increased System Organ Class: 10022891 - Investigations
Conditions
Sponsors
Actelion Pharmaceuticals Nederland bv
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects willing and able to sign informed consent; 2. Male and female subjects > 18 years diagnosed with SSc; 3. Early or active SSc pattern, measured with nailfold capillar Microscopy (NFM); 4. Women of childbearing potential must have a negative pregnancy test and use a reliable form of contraception; 5. Ongoing digital ulcer disease; 6. A history of 1 or more DUs within 2 years prior to inclusion; 7. No use of bosentan in the past. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 56 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Parenteral Prostanoid treatment for DU < 3 months ago; 2. Chronic treatment with PDE-5 inhibitor or ERA; 3. History of bosentan use; 4. Other types of systemic or connective tissue diseases; 5. Significant peripheral (macro-) vascular disease due to e.g. diabetes, hyperlipidemia, uncontrolled systemic hypertension, coagulopathy; 6. Any serious medical co morbidity (eg, active malignancy) such that the subjects life expectancy is < 12 months; 7. Known AST and/or ALT elevations higher than 3 times Upper Limit Normal (ULN); 8. Moderate to severe liver function disorder; 9. Pregnancy or breastfeeding; 10. Treatment with Glibenclamide, Fluconazole, Cyclosporin A, Tacrolimus or other calcineurin inhibitors; 11. Hypersensitivity for bosentan or one of its components; 12. Subjects not able to follow the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the effect of bosentan on the blood flow in the hands from baseline to 12 weeks, measured by laser Doppler imaging, in SSc subjects with an early or active SSc pattern, measured with nailfold capillaroscopy (NFM), with ongoing digital ulcer disease and a history of DU disease in the past 2 years. ;Secondary Objective: - Evaluate the effect of bosentan on the blood flow of different regions (ROI 1, ROI 2 and ROI 3, see 7.6.2) in the hands from baseline to 12 weeks, 26 weeks and 52 weeks; - Evaluate the effect of bosentan on the hand function, pain perception and quality of life from baseline to 12 weeks, 26 weeks and 52 weeks; - Evaluate the effect of bosentan on the skin involvement measured with the modified Rodnan skin score from baseline to 12 weeks, 26 weeks and 52 weeks; - Evaluate the effect of bosentan on the development of new digital ulcers and pitting scars from baseline to 12 weeks, 26 weeks and 52 weeks; ;Primary end point(s): Change in blood flow in the hands after 12 weeks of bosentan treatment compared to the blood flow at 0 weeks, as measured by laser Doppler imaging.;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in blood flow in different regions of the hands after 12 weeks of treatment with bosentan, and after 26 and 52 weeks, compared to the baseline, measured by Laser Doppler imaging; - Change in the modified Rodnan Skin Score after 12 weeks of treatment with bosentan, and after 26 and 52 weeks, compared to the baseline; - Change in the selected components of the Scleroderma Health Assessment Questionnaire after 12 weeks of bosentan treatment, and after 26 and 52 weeks, compared to the baseline; - Change in the EQ 5D after 12 weeks of treatment with bosentan, and after 26 and 52 weeks, compared to the baseline; - The total number of new digital ulcers and pitting scars developed after 12 weeks of treatment with bosentan, and after 26 and 52 weeks, compared to the baseline. - Change in the DU risk score after 12 weeks of treatment with bosentan, and after 26 and 52 weeks, compared with the baseline; - Change in blood flow in different regions of the hands in SSc-DU patients with no history of iloprost use, after 12 weeks of treatment with bosentan, and after 26 and 52 weeks compared to the baseline, measured by Laser Doppler imaging; - Change on nailfold capillaries, after 12 weeks of treatment with bosentan, and after 26 and 52 weeks compared to the baseline, measured by NFM;Timepoint(s) of evaluation of this end point: Each secundary end point will be evaluated after 12, 26 and 52 weeks. | — |
Countries
Netherlands
Contacts
Public ContactAffiliate Medical Director
Actelion Pharmaceuticals Nederland bv
Outcome results
None listed