check_circleStudy Completed

Scleroderma, Systemic

Bayer Identifier:

16277

ClinicalTrials.gov Identifier:

NCT02283762

EudraCT Number:

2014-001353-16

EU CT Number:

Not Available
Efficacy and safety of Riociguat in patients with systemic sclerosis

Trial purpose

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

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - 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.
  • - 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 summary

Enrollment Goal
121
Trial Dates
January 2015 - March 2019
Phase
Phase 2
Could I Receive a placebo
Yes
Products
Adempas (Riociguat, BAY63-2521)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Revmatologicky ustavPraha 2, 128 50, Czechia
Withdrawn
Hospital Universitario 12 de OctubreMadrid, 28041, Spain
Completed
UZ Leuven GasthuisbergLEUVEN, 3000, Belgium
Completed
UZ GentGENT, 9000, Belgium
Completed
CU Saint-Luc/UZ St-LucBRUXELLES - BRUSSEL, 1200, Belgium
Completed
A.O.U. CareggiFirenze, 50139, Italy
Completed
A.O.U. Policlinico Umberto IRoma, 00161, Italy
Withdrawn
ASST Spedali Civili di BresciaBrescia, 25123, Italy
Completed
A.O.U. di CagliariCagliari, 09042, Italy
Completed
A.O.U. di PadovaPadova, 35128, Italy
Completed
A.O.U. PisanaPisa, 56126, Italy
Completed
St Vincent's HospitalFitzroy, 3065, Australia
Completed
Monash Medical CentreClayton, 3168, Australia
Completed
Royal Adelaide HospitalAdelaide, 5000, Australia
Completed
Istanbul Universitesi Istanbul Tip FakultesiIstanbul, 34093, Turkey
Completed
Hacettepe Universitesi Tip FakultesiAnkara, Turkey
Completed
Universitätsklinikum KölnKöln, 50937, Germany
Completed
Universitätsklinikum ErlangenErlangen, 91054, Germany
Completed
Kerckhoff-Klinik GmbHBad Nauheim, 61231, Germany
Completed
Royal Perth Hospital6000, PERTH, Australia
Completed
Universitair Medisch Centrum St. RadboudNijmegen, 6525 GA, Netherlands
Completed
University Medical Center UtrechtUtrecht, 3584 CX, Netherlands
Completed
UniversitätsSpital ZürichZürich, 8091, Switzerland
Completed
Royal Free HospitalLondon, NW3 2QG, United Kingdom
Completed
Freeman HospitalNewcastle Upon Tyne, NE7 7DN, United Kingdom
Completed
Hope HospitalSalford, M6 8HD, United Kingdom
Withdrawn
Chapel Allerton HospitalLeeds, LS7 4SA, United Kingdom
Completed
Aintree University HospitalLiverpool, L9 7AL, United Kingdom
Withdrawn
Royal National Hospital for Rheumatic DiseasesBath, BA1 1RL, United Kingdom
Withdrawn
Hospital for Special SurgeryNew York, 10021, United States
Completed
Hopital Claude-Huriez CHRULILLE, 59037, France
Completed
Centre Hospitalier Universitaire - GrenobleGRENOBLE, 38043, France
Completed
Stanford HospitalPalo Alto, 94304, United States
Completed
University of Utah Health CareSalt Lake City, 84132, United States
Completed
UCLA David Geffen School of MedicineLos Angeles, 90095-1670, United States
Completed
Mayo Clinic - ScottsdaleScottsdale, 85259-5404, United States
Completed
Rutgers Robert Wood Johnson Medical SchoolNew Brunswick, 08901, United States
Completed
University of Michigan Health SystemAnn Arbor, 48109, United States
Completed
MedStar Georgetown University HospitalWashington, 20007, United States
Completed
Memorial Hermann-Texas Medical CenterHouston, 77030, United States
Completed
Arthritis Program Research Group, Inc.Newmarket, L3Y 3R7, Canada
Completed
Universitätsspital BaselBasel, Switzerland
Completed
Hokkaido University HospitalSapporo, 060-8648, Japan
Completed
Tohoku University HospitalSendai, 980-8574, Japan
Completed
Institute of Rheumatology Tokyo Women's Medical UniversityShinjuku-ku, 162-0054, Japan
Completed
Nippon Medical School HospitalBunkyo-ku, 113-8603, Japan
Completed
University of Connecticut Health CenterFarmington, 06030, United States
Completed
Medical University of South Carolina Medical CenterCharleston, 29425, United States
Completed
Sir Mortimer B. Davis Jewish General HospitalMontreal, H3T1E2, Canada
Completed
Mount Sinai HospitalToronto, M5T 3L9, Canada
Completed
Debreceni Egyetem Klinikai KozpontDebrecen, 4032, Hungary
Completed
Pecsi Tudomanyegyetem Klinikai KozpontPecs, 7632, Hungary
Completed
Cochin - ParisPARIS, 75674, France
Completed
CHU STRASBOURG - Hôpital de HautepierreSTRASBOURG, 67098, France
Withdrawn
Hopital Saint Antoine - ParisClamart, 92141, France
Completed
Hôpital Pellegrin - BordeauxBORDEAUX, 33000, France
Completed
St. Joseph's Healthcare - HamiltonHamilton, L8N 1Y2, Canada
Completed
Gunma University HospitalMaebashi, 371-8511, Japan
Withdrawn
Tokyo Women's Medical University HospitalShinjuku-ku, 162-8666, Japan
Withdrawn
University of Pittsburgh Medical Center Health SystemPittsburgh, 15213, United States
Withdrawn
New Queen Elizabeth Hospital BirminghamBirmingham, B15 2GW, United Kingdom
Completed
Ninewells HospitalDundee, DD1 9SY, United Kingdom
Completed
Liverpool HospitalLiverpool, 2170, Australia
Completed
Wellington HospitalWellington, 6021, New Zealand
Withdrawn
Waikato HospitalHamilton, 3204, New Zealand
Completed
Universitätsklinikum UlmUlm, 89081, Germany
Withdrawn
John Hunter HospitalNew Lambton, 2305, Australia
Withdrawn
Gaziantep Universitesi Tip FakultesiGaziantep, 27070, Turkey
Withdrawn
Trakya Univ. Tip Fak.Edirne, 22030, Turkey
Completed
Cukurova Univ. Tip. Fak. Balcali HastanesiAdana, 01330, Turkey
Completed
Dokuz Eylul Universitesi Tip FakultesiIzmir, 35340, Turkey
Completed
Kantonsspital St. GallenSt. Gallen, 1009, Switzerland

Primary Outcome

  • Change from baseline in modified Rodnan skin score (mRSS) to Week 52
    The mRSS is a validated physical examination method for estimating skin thickness. It correlates with biopsy measures of collagen in the dermis and reflects prognosis and visceral involvement, especially in early disease. It is scored on 0 (normal) to 3+ (severe induration) ordinal scales over 17 body areas, with a maximum score of 51 (higher score means worse situation) and is used to categorize severity of SSc. A decrease in the mean change of mRSS shows mRSS improved.
    date_rangeTime Frame:
    Baseline to week 52
    enhanced_encryption
    Safety Issue:
    No

Secondary Outcome

  • 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
    CRISS forms a composite response index consisting of SSc-related organ involvement and the following five variables: mRSS, FVC percent predicted, physician’s and patient’s global assessments, and HAQ-DI score (from SHAQ patient-reported outcome). The resulting index is a 2-step process that captures clinically meaningful worsening of internal organ involvement and the core variables that show change. Patients for whom the predicted CRISS probability was ≥ 0.60 were considered improved, while patients for whom the predicted probability was < 0.60 were considered not improved.
    date_rangeTime Frame:
    Week 52
    enhanced_encryption
    Safety Issue:
    No
  • Change from baseline in Health Assessment Questionnaire disability index (HAQ-DI) score to Week 52
    The HAQ-DI is a composite measure from which a ‘Standard Disability Index’ score can be computed to assess a patient’s disability level. Generally, a score of 0–1 represents mild to moderate difficulty, 1–2 moderate to severe disability and 2–3 severe to very severe disability. The HAQ-DI comprises 20 items that assess patient abilities across 8 functional activities: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item is rated on a 4-point scale: 0=Without ANY difficulty, 1=With SOME difficulty, 2=With MUCH difficulty, 3=UNABLE to do. The 8 scores of the 8 sections are summed and divided by 8. In the event that one section is not completed by a subject then the summed score would be divided by 7. The final overall HAQ-DI score ranges from 0 to 3 and positive change indicates worse health-related quality of life (HRQoL).
    date_rangeTime Frame:
    Baseline to week 52
    enhanced_encryption
    Safety Issue:
    No
  • Change from baseline in patient’s global assessment score to Week 52
    The patient’s global assessments (a self-report) quantified the overall disease activity or severity of SSc, with scores ranging from 0 (good) to 10 (worse). Positive change in the patient’s global assessments score indicates worsening.
    date_rangeTime Frame:
    Baseline to week 52
    enhanced_encryption
    Safety Issue:
    No
  • Change from baseline in physician’s global assessment score to Week 52
    The physician’s global assessments (reported by the physician) quantified the overall disease activity or severity of SSc, with scores ranging from 0 (good) to 10 (worse). Positive change in the physician’s global assessments score indicates worsening.
    date_rangeTime Frame:
    Baseline to week 52
    enhanced_encryption
    Safety Issue:
    No
  • Change from baseline in forced vital capacity (FVC) percent predicted to Week 52
    Negative change in FVC percent predicted indicates worsening.
    date_rangeTime Frame:
    Baseline to week 52
    enhanced_encryption
    Safety Issue:
    No

Trial design

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)
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Double Blind
Assignment
Parallel Assignment
Trial Arms
2

Additional Information

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