Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients
Condition: Digital Ulcers
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Skin Ulcer; Sclerosis; Ulcer
Intervention: Macitentan 3 mg; Macitentan 10 mg; Placebo
Intervention description: Macitentan 3-mg tablet once daily; Macitentan 10-mg tablet once daily; Placebo tablet matching macitentan tablet, once daily
Intervention MeSH terms: Macitentan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 265.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: digital ulcers; systemic sclerosis

Summary:

      The DUAL-2 study is designed as a multicenter, double-blind two-period study with an initial
      fixed 16-week Period 1, followed by a Period 2 of variable duration. All patients completing
      Period 1 continue on their original randomized treatment into Period 2, until the last
      randomized patient has completed Period 1.

      Patients are randomized in a 1:1:1 ratio (macitentan 3mg: macitentan 10mg: placebo).

      The primary objective is to demonstrate the effect of macitentan on the reduction of the
      number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcers
      (DU).

      Other objectives include:

        -  the evaluation of the efficacy of macitentan on hand functionality and DU burden at Week
           16 in SSc patients with ongoing DU disease.

        -  the evaluation of the safety and tolerability of macitentan in these patients.

        -  the evaluation of the efficacy of macitentan on time to first DU complication during the
           entire treatment period.
    

Eligibility criteria:

        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