Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis

Bayer

Status and phase: Completed; Phase 2

Conditions: Scleroderma, Systemic

Treatments: Drug: Riociguat (Adempas, BAY63-2521); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02283762

2014-001353-16 (EudraCT Number)

16277

Details and patient eligibility

About

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

Enrollment: 121 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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121 participants in 2 patient groups, including a placebo group

Riociguat

Experimental group

Description:

Main treatment phase of 52 weeks: participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a-titration period of up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received sham-titration in a dose-titration period of up to 10 weeks followed by a maintenance period.

Treatment:

Drug: Riociguat (Adempas, BAY63-2521)

Placebo

Placebo Comparator group

Description:

Main treatment phase of 52 weeks: participants received matching placebo tablets to riociguat as sham titration in a dose-titration period up to 10 weeks and a maintenance period of up to 42 weeks. Long-term extension phase: starting after the completion of the Main Treatment Phase in Week 52, participants received increasing doses of riociguat by 0.5 mg every 2 weeks up to 2.5 mg 3 times a day (TID) in a dose-titration period of up to 10 weeks followed by a maintenance period.

Treatment:

Drug: Placebo