Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Patients With Ischemic Digital Ulcers Associated With Systemic Sclerosis

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.