Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis
Scleroderma, Systemic
About this trial
This is an interventional treatment trial for Scleroderma, Systemic
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.
Sites / Locations
- Mayo Clinic - Scottsdale
- UCLA David Geffen School of Medicine
- Stanford University School of Medicine
- University of Connecticut Health Center
- Georgetown University Medical Center
- University of Michigan Health System
- Rutgers Robert Wood Johnson Medical School
- Medical University of South Carolina Medical Center
- Memorial Hermann-Texas Medical Center
- University of Utah Health Care
- Liverpool Hospital
- Royal Adelaide Hospital
- Monash Medical Centre
- St Vincent's Hospital
- Royal Perth Hospital
- CU Saint-Luc/UZ St-Luc
- UZ Gent
- UZ Leuven Gasthuisberg
- St. Joseph's Healthcare - Hamilton
- Arthritis Program Research Group, Inc.
- Mount Sinai Hospital
- Sir Mortimer B. Davis Jewish General Hospital
- Revmatologicky ustav
- Hôpital Pellegrin - Bordeaux
- Centre Hospitalier Universitaire - Grenoble
- Hopital Claude-Huriez CHRU
- Cochin - Paris
- CHU STRASBOURG - Hôpital de Hautepierre
- Universitätsklinikum Ulm
- Universitätsklinikum Erlangen
- Kerckhoff-Klinik GmbH
- Universitätsklinikum Köln
- Debreceni Egyetem Klinikai Kozpont
- Pecsi Tudomanyegyetem Klinikai Kozpont
- A.O.U. Policlinico Umberto I
- A.O.U. di Cagliari
- A.O.U. Careggi
- A.O.U. Pisana
- A.O. di Padova
- Gunma University Hospital
- Hokkaido University Hospital
- Tohoku University Hospital
- Nippon Medical School Hospital
- Institute of Rheumatology Tokyo Women's Medical University
- Universitair Medisch Centrum St. Radboud
- University Medical Center Utrecht
- Wellington Hospital
- Kantonsspital St. Gallen
- Universitätsspital Basel
- UniversitätsSpital Zürich
- Cukurova Univ. Tip. Fak. Balcali Hastanesi
- Hacettepe Universitesi Tip Fakultesi
- Istanbul Universitesi Istanbul Tip Fakultesi
- Dokuz Eylul Universitesi Tip Fakultesi
- Hope Hospital
- Freeman Hospital
- Ninewells Hospital
- Aintree University Hospital
- Royal Free Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Riociguat
Placebo
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.
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.