Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis

Inclusion Criteria:

- Men or women aged 18 years and older

- Systemic sclerosis, as defined by ACR/EULAR (American College of Rheumatology/European
League Against Rheumatism) 2013 criteria

- dcSSc (diffuse cutaneous systemic sclerosis) according to the LeRoy criteria, ie, skin
fibrosis proximal to the elbows and knees in addition to acral fibrosis

- Disease duration of ≤ 18 months (defined as time from the first non−Raynaud's
phenomenon manifestation)

- ≥ 10 and ≤ 22 mRSS (modified Rodnan skin score) units at the screening visit

- FVC (forced vital capacity) ≥ 45% of predicted at screening

- DLCO (diffusion capacity of the lung for carbon monoxide) ≥ 40% of predicted
(hemoglobin-corrected) at screening

- Negative serum pregnancy test in a woman of childbearing potential at the screening
visit

- Women of childbearing potential must agree to use adequate contraception when sexually
active. "Adequate contraception" is defined as any combination of at least 2 effective
methods of birth control, of which at least 1 is a physical barrier (e.g. condom with
hormonal contraception like implants or combined oral contraceptives, condom with
intrauterine devices). This applies since signing of the informed consent form until
30 (+5) days after the last study drug administration.

Exclusion Criteria:

- Limited cutaneous SSc (systemic sclerosis) at screening

- Major surgery (including joint surgery) within 8 weeks prior to screening

- Hepatic insufficiency classified as Child-Pugh C

- Patients with isolated AST or ALT >3xULN or bilirubin >2xULN can be included in the
trial under the condition of additional monitoring during the trial

- Estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m^2 (Modification of Diet
in Renal Disease formula) or on dialysis at the screening visit. Patients entering the
trial with eGFR 15-29 mL/min/1.73 m^2 will be undergo additional monitoring of renal
function

- Any prior history of renal crisis

- Sitting SBP (systolic blood pressure) < 95 mmHg at the screening visit

- Sitting heart rate < 50 beats per minute (BPM) at the screening visit

- Left ventricular ejection fraction < 40% prior to screening

- Any form of pulmonary hypertension as determined by right heart catheterization

- Pulmonary disease with FVC < 45% of predicted or DLCO (hemoglobin-corrected) < 40% of
predicted at screening

- Active state of hemoptysis or pulmonary hemorrhage, including those events managed by
bronchial artery embolization

- Not permitted prior and concomitant medication

- Pregnant or breast feeding women

- Women of childbearing potential not willing to use adequate contraception and not
willing to agree to 4-weekly pregnancy testing from Visit 1 (first administration of
study drug) onwards until 30 (+5) days after last study drug intake.