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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

Tracking Information
First Submitted Date  ICMJE November 3, 2014
First Posted Date  ICMJE November 5, 2014
Results First Submitted Date  ICMJE December 13, 2018
Results First Posted Date  ICMJE January 25, 2019
Last Update Posted Date April 17, 2019
Actual Study Start Date  ICMJE January 15, 2015
Actual Primary Completion Date December 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 3, 2014)
Change in mRSS (modified Rodnan skin score) [ Time Frame: Baseline to week 52 ]
Change History Complete list of historical versions of study NCT02283762 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2019)
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2014)
  • mRSS progression rate [ Time Frame: 52 weeks ]
  • mRSS regression rate [ Time Frame: 52 weeks ]
  • Patient's global health assessment on a scaled rating [ Time Frame: Baseline to 52 weeks ]
  • Physician's global health assessment on a scaled rating [ Time Frame: Baseline to 52 weeks ]
  • HRQoL (health related quality of life) assessment via patient questionnaires [ Time Frame: Baseline to 52 weeks ]
  • Digital ulcer net burden (defined as total number of ulcers at time point minus number of ulcers at baseline) [ Time Frame: Baseline to 52 weeks ]
  • Proportion of patients who do not develop new ulcers [ Time Frame: 52 weeks ]
  • Change in FVC (forced vital capacity) [ Time Frame: Baseline to 52 weeks ]
  • Change in DLCO (diffusion capacity of the lung for carbon monoxide) [ Time Frame: Baseline to 52 weeks ]
  • Combined Response Index for Systemic Sclerosis (CRISS) [ Time Frame: 52 weeks ]
  • Number of participants with need for escape therapy [ Time Frame: 52 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis
Official Title  ICMJE 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)
Brief Summary To investigate if Riociguat is effective in the treatment of systemic sclerosis
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Scleroderma, Systemic
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Sham-titration
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Riociguat (Adempas, BAY63-2521)
  • 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.
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 13, 2017)
121
Original Estimated Enrollment  ICMJE
 (submitted: November 3, 2014)
130
Actual Study Completion Date  ICMJE March 28, 2019
Actual Primary Completion Date December 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Czechia,   France,   Germany,   Hungary,   Italy,   Japan,   Netherlands,   New Zealand,   Switzerland,   Turkey,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Spain
 
Administrative Information
NCT Number  ICMJE NCT02283762
Other Study ID Numbers  ICMJE 16277
2014-001353-16 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP