Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients
Condition: Systemic Sclerosis; Ulcers
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis; Ulcer
Intervention: macitentan 3mg; macitentan 10mg; placebo
Intervention description: macitentan 3mg tablet once daily; macitentan 10mg tablet once daily; matching placebo 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: 289.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: systemic sclerosis; digital ulcers

Summary:

      The DUAL-1 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 will continue on their original randomized treatment into Period 2, until the last
      randomized patient has completed Period 1.

      Patients will be 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.

      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 digital ulcers (DU) at baseline

          -  History of at least one additional recent active ischemic DU

        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 the normal range (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 type-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 ERAs within 3 months.

          -  Systemic antibiotics to treat infected DU(s) within 4 weeks.