Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis
Condition: Scleroderma, Systemic
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse
Intervention: Riociguat (Adempas, BAY63-2521); Placebo
Intervention description: Starting dose 0.5 mg TID, increase by 0.5 mg every 2 weeks until highest possible dose of 2.5 mg TID; Sham-titration
Intervention MeSH terms: Riociguat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 121.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      To investigate if Riociguat is effective in the treatment of systemic sclerosis
    

Eligibility criteria:

        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.