Clinical trial NCT02283762: Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Scleroderma, Systemic
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-11-05
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline in Modified Rodnan Skin Score (mRSS) to Week 52
timeFrame: Baseline to week 52
Secondary outcomes:
measure: CRISS (American College of Rheumatology Composite Response Index for Clinical Trials) at Week 52 Reported as Number of Participants With a CRISS Probability >=0.60 or <0.60 From Baseline to Week 52
timeFrame: Week 52
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score to Week 52
timeFrame: Baseline to week 52
measure: Change From Baseline in Patient's Global Assessment Score to Week 52
timeFrame: Baseline to week 52
measure: Change From Baseline in Physician's Global Assessment Score to Week 52
timeFrame: Baseline to week 52
measure: Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted to Week 52
timeFrame: Baseline to week 52
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - Scottsdale
state: Arizona
city: Los Angeles
country: United States
facility: UCLA David Geffen School of Medicine
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson Medical School
state: New Jersey
city: Charleston
country: United States
facility: Medical University of South Carolina Medical Center
state: South Carolina
city: Houston
country: United States
facility: Memorial Hermann-Texas Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Care
state: Utah
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Bruxelles - Brussel
country: Belgium
facility: CU Saint-Luc/UZ St-Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare - Hamilton
state: Ontario
city: Newmarket
country: Canada
facility: Arthritis Program Research Group, Inc.
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Hospital
state: Quebec
city: Praha 2
country: Czechia
facility: Revmatologicky ustav
city: Bordeaux
country: France
facility: Hôpital Pellegrin - Bordeaux
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire - Grenoble
city: Lille
country: France
facility: Hopital Claude-Huriez CHRU
city: Paris
country: France
facility: Cochin - Paris
city: Strasbourg
country: France
facility: CHU STRASBOURG - Hôpital de Hautepierre
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik GmbH
state: Hessen
city: Köln
country: Germany
facility: Universitätsklinikum Köln
state: Nordrhein-Westfalen
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Roma
country: Italy
facility: A.O.U. Policlinico Umberto I
state: Lazio
city: Cagliari
country: Italy
facility: A.O.U. di Cagliari
state: Sardegna
city: Firenze
country: Italy
facility: A.O.U. Careggi
state: Toscana
city: Pisa
country: Italy
facility: A.O.U. Pisana
state: Toscana
city: Padova
country: Italy
facility: A.O. di Padova
state: Veneto
city: Maebashi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Institute of Rheumatology Tokyo Women's Medical University
state: Tokyo
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Sankt Gallen
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
city: Adana
country: Turkey
facility: Cukurova Univ. Tip. Fak. Balcali Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi Tip Fakultesi
city: Salford
country: United Kingdom
facility: Hope Hospital
state: Manchester
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: Tyne And Wear
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Distler O, Pope J, Denton C, Allanore Y, Matucci-Cerinic M, de Oliveira Pena J, Khanna D. RISE-SSc: Riociguat in diffuse cutaneous systemic sclerosis. Respir Med. 2017 Jan;122 Suppl 1:S14-S17. doi: 10.1016/j.rmed.2016.09.011. Epub 2016 Sep 28.