A clinical research study with macitentan evaluating its effects on digital ulcers associated with systemic sclerosis (scleroderma)

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 285

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: 0
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

1. DUs due to condition other than SSc.
2. Symptomatic pulmonary arterial hypertension (PAH).
3. Body mass index (BMI: kg/m2) <18.
4. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal (ULN).
5. Hemoglobin < 75% of the lower limit of the normal range.
6. Systolic blood pressure < 95 mmHg or diastolic blood pressure < 50
mmHg .
7. Severe malabsorption, any severe organ failure (e.g., lung, kidney), or any life-threatening condition.
8. Comorbidities, other than SSc, that could seriously affect the assessment of hand function.
9. Females who are pregnant or breastfeeding or plan to do so during the course of this study.
10. Substance or alcohol abuse or dependence, or tobacco use .
11. Treatment with PDE5 inhibitors (e.g., sildenafil, tadalafil).
12. Patients on statins (e.g., atorvastatin, simvastatin), who have received treatment for less than 3 months prior to Screening (Visit 1) or whose treatment has not been stable during this period.
13. Patients on vasodilators, N-acetylcysteine, antiplatelet aggregation therapy and low molecular weight heparin who have received treatment for less than 2 weeks prior to Screening (Visit 1) or whose treatment has not been stable during this period.
14. Treatment with prostanoids.
15. Treatment with disease modifying agents such as methotrexate and cyclophosphamide if present for less than 3 months prior to Screening (Visit 1) or whose treatment has not been stable for at least 1 month prior to Screening (Visit 1).
16. Treatment with oral corticosteroids (> 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.<br>_ To evaluate the safety and tolerability of macitentan in SSc patients with ongoing DU disease.<br>_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) :<br>Cumulative number of new DUs up to Week 16.;Timepoint(s) of evaluation of this end point: End-of-Period 1 (Week 16)

Secondary Outcome Measures

Name	Time	Method

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