Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis

A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Investigate the Efficacy and Safety of Riociguat in Patients With Diffuse Cutaneous Systemic Sclerosis (dcSSc)

To investigate if Riociguat is effective in the treatment of 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.