Ischemic digital ulcers associated with systemic sclerosis MedDRA version: 14.1 Level: PT Classification code 10042953 Term: Systemic sclerosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Actelion Pharmaceuticals Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Diagnosis of SSc according to the classification criteria of the American College of Rheumatology (ACR), or having ever met criteria for CREST syndrome (with sclerodactyly and 2 out of the 4 remaining criteria: calcinosis, Raynaud's phenomenon, esophageal dysfunction, telangiectasia). - At least one visible, active ischemic DU at baseline, located at or distal to the proximal interphalangeal joints (PIP) or at the digital tip, and that developed or worsened within 8 weeks prior to screening. - History of at least one additional active ischemic DU within 6 months, or at least two within 12 months prior to Screening. 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 242 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 43
Exclusion criteria
Exclusion criteria: 1. DUs due to condition other than SSc. 2. Symptomatic pulmonary arterial hypertension (PAH). 3. Body mass index (BMI: kg/m2) 1.5 times the upper limit of normal (ULN). 5. Hemoglobin 10 mg/day of prednisone or equivalent). 17. Treatment with endothelin receptor antagonists (ERAs). 18. Systemic antibiotics (oral and i.v.) to treat infected DU(s) . 19. Use of topical growth factors, hyperbaric oxygen. 20. Local injection of botulinum toxin in an affected finger within 4 weeks prior to Screening. 21. Surgical sympathectomy of the upper limbs or surgical wound debridement within 1 month prior to Screening. 22. Treatment with cytochrome P450 3A (CYP3A) inducers, such as rifabutin, rifampin, rifapentin, carbamazepine, phenobarbital, phenytoin, St. John’s wort, within 4 weeks prior to Screening. 23. Known hypersensitivity to drugs of the same class as the study drug, or any of the excipients. 24. Planned treatment, or treatment with another investigational drug within 4 weeks prior to Screening. 25. Any condition that prevents compliance with the protocol or adherence to therapy, including inability to speak, read, or understand the local language well enough to complete all study assessments.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the effect of macitentan on the reduction of the cumulative number of new digital ulcers at Week 16 in patients with systemic sclerosis and ongoing digital ulcer (DU) disease.;Secondary Objective: _To evaluate the efficacy of macitentan on hand functionality and DU burden at Week 16 in systemic sclerosis (SSc) patients with ongoing DU disease. _ To evaluate the safety and tolerability of macitentan in SSc patients with ongoing DU disease. _To evaluate the efficacy of macitentan on time to first DU complication during the entire treatment period.;Primary end point(s): Primary endpoint (assessed during Period 1) : Cumulative number of new DUs up to Week 16.;Timepoint(s) of evaluation of this end point: End-of-Period 1 (Week 16) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Hand Functionality: i. HDISS-DU ii. HAQ-DI • DU Burden: i. Binary response of patients without a new DU ii. Binary response of patients with more than 1, 2, 3, etc., new DU(s) iii. Total number of DUs observed iv. Time to onset of each new DU (1st, 2nd, 3rd, 4th, etc., DU) • DU Complications: An event of DU complications is defined as the composite of the following: i. Critical ischemic crisis necessitating patient hospitalization. ii. Gangrene, (auto)amputation. iii. Failure of conservative management: Surgical and chemical sympathectomy, vascular reconstructions, or any unplanned surgery in the management of hand manifestation(s). iv. Use of parenteral prostanoids. v. Use of endothelin receptor antagonists. vi. Requiring class II, III or IV narcotics or increase in existing dose of > 50% as compared to baseline. vii. Initiation of systemic antibiotics for the treatment of infection attributed to digital ulceration.;Timepoint(s) of evaluation of this end point: - Period 1: 4 visits (week 4, 8, 12 and 16) - Period 2: variable number of visits every 3 month | — |
Countries
Argentina, Belgium, Colombia, Germany, Greece, Ireland, Mexico, Netherlands, New Zealand, Poland, Portugal, Puerto Rico, Russian Federation, South Africa, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactGlobal Medical Information
Actelion Pharmaceuticals Ltd
Outcome results
None listed