Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients

Inclusion Criteria :

• Patients ≥ 18 years of age

• Women of childbearing potential must use two reliable methods of contraception

• Diagnosis of SSc according to the classification criteria of the American College of Rheumatology (ACR)

• At least one visible, active ischemic DU at baseline

• History of at least one additional recent active ischemic digital ulcer

Exclusion Criteria :

• DUs due to condition other than SSc

• Symptomatic pulmonary arterial hypertension (PAH)

• Body mass index (BMI) < 18 kg/m^2

• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN)

• Hemoglobin < 75% of the lower limit of the normal range

• Systolic blood pressure < 95 mmHg or diastolic blood pressure < 50 mmHg

• Severe malabsorption; any severe organ failure (e.g., lung, kidney), or any life-threatening condition

• Females who are pregnant or breastfeeding or plan to do so during the course of this study

• Substance or alcohol abuse or dependence, or tobacco use at any level

• Treatment with phosphodiesterase-5 (PDE5) inhibitors

• Patients on statins, who have received treatment for less than 3 months prior to Screening or whose treatment has not been stable during this period

• Patients on vasodilators, who have received treatment for less than 2 weeks prior to Screening or whose treatment has not been stable during this period

• Treatment with prostanoids within 3 months

• Treatment with disease modifying agents if present for less than 3 months prior to Screening or whose treatment has not been stable for at least 1 month prior to Screening

• Treatment with oral corticosteroids (> 10 mg/day of prednisone or equivalent).

• Treatment with endothelin receptor antagonists (ERAs) within 3 months

• Systemic antibiotics to treat infected DU(s) within 4 weeks