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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02283762




Registration number
NCT02283762
Ethics application status
Date submitted
3/11/2014
Date registered
5/11/2014
Date last updated
5/02/2020

Titles & IDs
Public title
Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis
Scientific 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)
Secondary ID [1] 0 0
2014-001353-16
Secondary ID [2] 0 0
16277
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Scleroderma, Systemic 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Riociguat (Adempas, BAY63-2521)
Treatment: Drugs - Placebo

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.

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.


Treatment: Drugs: Riociguat (Adempas, BAY63-2521)
Starting dose 0.5 mg TID, increase by 0.5 mg every 2 weeks until highest possible dose of 2.5 mg TID

Treatment: Drugs: Placebo
Sham-titration

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline to week 52
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Week 52
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
Baseline to week 52
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline to week 52
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline to week 52
Secondary outcome [5] 0 0
Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted to Week 52 - Negative change in FVC percent predicted indicates worsening.
Timepoint [5] 0 0
Baseline to week 52

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
St Vincent's Hospital - Fitzroy
Recruitment hospital [5] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
South Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
Belgium
State/province [10] 0 0
Bruxelles - Brussel
Country [11] 0 0
Belgium
State/province [11] 0 0
Gent
Country [12] 0 0
Belgium
State/province [12] 0 0
Leuven
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Czechia
State/province [15] 0 0
Praha 2
Country [16] 0 0
France
State/province [16] 0 0
Bordeaux
Country [17] 0 0
France
State/province [17] 0 0
Grenoble
Country [18] 0 0
France
State/province [18] 0 0
Lille
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
France
State/province [20] 0 0
Strasbourg
Country [21] 0 0
Germany
State/province [21] 0 0
Baden-Württemberg
Country [22] 0 0
Germany
State/province [22] 0 0
Bayern
Country [23] 0 0
Germany
State/province [23] 0 0
Hessen
Country [24] 0 0
Germany
State/province [24] 0 0
Nordrhein-Westfalen
Country [25] 0 0
Hungary
State/province [25] 0 0
Debrecen
Country [26] 0 0
Hungary
State/province [26] 0 0
Pecs
Country [27] 0 0
Italy
State/province [27] 0 0
Lazio
Country [28] 0 0
Italy
State/province [28] 0 0
Sardegna
Country [29] 0 0
Italy
State/province [29] 0 0
Toscana
Country [30] 0 0
Italy
State/province [30] 0 0
Veneto
Country [31] 0 0
Japan
State/province [31] 0 0
Gunma
Country [32] 0 0
Japan
State/province [32] 0 0
Hokkaido
Country [33] 0 0
Japan
State/province [33] 0 0
Miyagi
Country [34] 0 0
Japan
State/province [34] 0 0
Tokyo
Country [35] 0 0
Netherlands
State/province [35] 0 0
Nijmegen
Country [36] 0 0
Netherlands
State/province [36] 0 0
Utrecht
Country [37] 0 0
New Zealand
State/province [37] 0 0
Wellington
Country [38] 0 0
Switzerland
State/province [38] 0 0
Sankt Gallen
Country [39] 0 0
Switzerland
State/province [39] 0 0
Basel
Country [40] 0 0
Switzerland
State/province [40] 0 0
Zürich
Country [41] 0 0
Turkey
State/province [41] 0 0
Adana
Country [42] 0 0
Turkey
State/province [42] 0 0
Ankara
Country [43] 0 0
Turkey
State/province [43] 0 0
Istanbul
Country [44] 0 0
Turkey
State/province [44] 0 0
Izmir
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Manchester
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Tyne And Wear
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Dundee
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Liverpool
Country [49] 0 0
United Kingdom
State/province [49] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To investigate if Riociguat is effective in the treatment of systemic sclerosis
Trial website
https://clinicaltrials.gov/show/NCT02283762
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications