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Trial record 2 of 2 for:    riociguat scleroderma

Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis

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ClinicalTrials.gov Identifier: NCT02283762
Recruitment Status : Completed
First Posted : November 5, 2014
Results First Posted : January 25, 2019
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

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

Condition or disease Intervention/treatment Phase
Scleroderma, Systemic Drug: Riociguat (Adempas, BAY63-2521) Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 121 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : January 15, 2015
Actual Primary Completion Date : December 15, 2017
Actual Study Completion Date : March 28, 2019


Arm Intervention/treatment
Experimental: Riociguat
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.
Drug: Riociguat (Adempas, BAY63-2521)
Starting dose 0.5 mg TID, increase by 0.5 mg very 2 weeks until highest possible dose of 2.5 mg TID

Placebo Comparator: Placebo
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.
Drug: Placebo
Sham-titration




Primary Outcome Measures :
  1. Change From Baseline in Modified Rodnan Skin Score (mRSS) to Week 52 [ Time Frame: Baseline 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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: 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.

  2. Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score to Week 52 [ Time Frame: Baseline 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).

  3. Change From Baseline in Patient's Global Assessment Score to Week 52 [ Time Frame: Baseline 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.

  4. Change From Baseline in Physician's Global Assessment Score to Week 52 [ Time Frame: Baseline 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.

  5. Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted to Week 52 [ Time Frame: Baseline to week 52 ]
    Negative change in FVC percent predicted indicates worsening.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02283762


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Locations
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United States, Arizona
Mayo Clinic - Scottsdale
Scottsdale, Arizona, United States, 85259-5404
United States, California
UCLA David Geffen School of Medicine
Los Angeles, California, United States, 90095-1670
Stanford University School of Medicine
Palo Alto, California, United States, 94304
United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
United States, New Jersey
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08901
United States, South Carolina
Medical University of South Carolina Medical Center
Charleston, South Carolina, United States, 29425
United States, Texas
Memorial Hermann-Texas Medical Center
Houston, Texas, United States, 77030
United States, Utah
University of Utah Health Care
Salt Lake City, Utah, United States, 84132
Australia, New South Wales
Liverpool Hospital
Liverpool, New South Wales, Australia, 2170
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Monash Medical Centre
Clayton, Victoria, Australia, 3168
St Vincent's Hospital
Fitzroy, Victoria, Australia, 3065
Australia, Western Australia
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Belgium
CU Saint-Luc/UZ St-Luc
Bruxelles - Brussel, Belgium, 1200
UZ Gent
Gent, Belgium, 9000
UZ Leuven Gasthuisberg
Leuven, Belgium, 3000
Canada, Ontario
St. Joseph's Healthcare - Hamilton
Hamilton, Ontario, Canada, L8N 1Y2
Arthritis Program Research Group, Inc.
Newmarket, Ontario, Canada, L3Y 3R7
Mount Sinai Hospital
Toronto, Ontario, Canada, M5T 3L9
Canada, Quebec
Sir Mortimer B. Davis Jewish General Hospital
Montreal, Quebec, Canada, H3T1E2
Czechia
Revmatologicky ustav
Praha 2, Czechia, 128 50
France
Hôpital Pellegrin - Bordeaux
Bordeaux, France, 33000
Centre Hospitalier Universitaire - Grenoble
Grenoble, France, 38043
Hopital Claude-Huriez CHRU
Lille, France, 59037
Cochin - Paris
Paris, France, 75674
CHU STRASBOURG - Hôpital de Hautepierre
Strasbourg, France, 67098
Germany
Universitätsklinikum Ulm
Ulm, Baden-Württemberg, Germany, 89081
Universitätsklinikum Erlangen
Erlangen, Bayern, Germany, 91054
Kerckhoff-Klinik GmbH
Bad Nauheim, Hessen, Germany, 61231
Universitätsklinikum Köln
Köln, Nordrhein-Westfalen, Germany, 50937
Hungary
Debreceni Egyetem Klinikai Kozpont
Debrecen, Hungary, 4032
Pecsi Tudomanyegyetem Klinikai Kozpont
Pecs, Hungary, 7632
Italy
A.O.U. Policlinico Umberto I
Roma, Lazio, Italy, 00161
A.O.U. di Cagliari
Cagliari, Sardegna, Italy, 09042
A.O.U. Careggi
Firenze, Toscana, Italy, 50139
A.O.U. Pisana
Pisa, Toscana, Italy, 56126
A.O. di Padova
Padova, Veneto, Italy, 35128
Japan
Gunma University Hospital
Maebashi, Gunma, Japan, 371-8511
Hokkaido University Hospital
Sapporo, Hokkaido, Japan, 060-8648
Tohoku University Hospital
Sendai, Miyagi, Japan, 980-8574
Nippon Medical School Hospital
Bunkyo-ku, Tokyo, Japan, 113-8603
Institute of Rheumatology Tokyo Women's Medical University
Shinjuku-ku, Tokyo, Japan, 162-0054
Netherlands
Universitair Medisch Centrum St. Radboud
Nijmegen, Netherlands, 6525 GA
University Medical Center Utrecht
Utrecht, Netherlands, 3584 CX
New Zealand
Wellington Hospital
Wellington, New Zealand, 6021
Switzerland
Kantonsspital St. Gallen
St. Gallen, Sankt Gallen, Switzerland, 9007
Universitätsspital Basel
Basel, Switzerland
UniversitätsSpital Zürich
Zürich, Switzerland, 8091
Turkey
Cukurova Univ. Tip. Fak. Balcali Hastanesi
Adana, Turkey, 01330
Hacettepe Universitesi Tip Fakultesi
Ankara, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi
Istanbul, Turkey, 34093
Dokuz Eylul Universitesi Tip Fakultesi
Izmir, Turkey, 35340
United Kingdom
Hope Hospital
Salford, Manchester, United Kingdom, M6 8HD
Freeman Hospital
Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN
Ninewells Hospital
Dundee, United Kingdom, DD1 9SY
Aintree University Hospital
Liverpool, United Kingdom, L9 7AL
Royal Free Hospital
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Bayer
Investigators
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Study Director: Bayer Study Director Bayer
  Study Documents (Full-Text)

Documents provided by Bayer:
Study Protocol  [PDF] April 17, 2018
Statistical Analysis Plan  [PDF] December 22, 2017


Publications:
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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02283762     History of Changes
Other Study ID Numbers: 16277
2014-001353-16 ( EudraCT Number )
First Posted: November 5, 2014    Key Record Dates
Results First Posted: January 25, 2019
Last Update Posted: April 17, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Connective Tissue Diseases
Skin Diseases
Riociguat
Enzyme Activators
Molecular Mechanisms of Pharmacological Action