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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/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
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
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
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
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
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
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
Sex
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
15/01/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/03/2019
Sample size
Target
Accrual to date
Final
121
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
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Italy
State/province [29] 0 0
Toscana
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Italy
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Veneto
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Japan
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Gunma
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Japan
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Hokkaido
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Japan
State/province [33] 0 0
Miyagi
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Japan
State/province [34] 0 0
Tokyo
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Netherlands
State/province [35] 0 0
Nijmegen
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Netherlands
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Utrecht
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New Zealand
State/province [37] 0 0
Wellington
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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
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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/ct2/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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02283762