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Scleroderma, SystemicPhase 2NCT02283762

Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis

A Phase 2 study testing Riociguat (Adempas, BAY63-2521) in people with Scleroderma, Systemic, run by Bayer at 59 sites in 15 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

To investigate if Riociguat is effective in the treatment of systemic sclerosis Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Scleroderma, Systemic
What is being tested?
Riociguat (Adempas, BAY63-2521)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
121 participants
Where
59 sitesin 15 countries
Study dates
15 Jan 2015to 28 Mar 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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.

Who cannot join

  • 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
Show all 15Show fewer
  • 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 locations and contacts

59 sites in 15 countries.

59 sites in 15 countries

United States10 sites
  • University of Michigan Health System

    Ann Arbor, Michigan, 48109

  • Medical University of South Carolina Medical Center

    Charleston, South Carolina, 29425

  • University of Connecticut Health Center

    Farmington, Connecticut, 06030

  • Memorial Hermann-Texas Medical Center

    Houston, Texas, 77030

  • UCLA David Geffen School of Medicine

    Los Angeles, California, 90095-1670

  • Rutgers Robert Wood Johnson Medical School

    New Brunswick, New Jersey, 08901

  • Stanford University School of Medicine

    Palo Alto, California, 94304

  • University of Utah Health Care

    Salt Lake City, Utah, 84132

  • Mayo Clinic - Scottsdale

    Scottsdale, Arizona, 85259-5404

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

Australia5 sites
  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Monash Medical Centre

    Clayton, Victoria, 3168

  • St Vincent's Hospital

    Fitzroy, Victoria, 3065

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • Royal Perth Hospital

    Perth, Western Australia, 6000

Other trials in Australia

France5 sites
  • Hôpital Pellegrin - Bordeaux

    Bordeaux, 33000

  • Centre Hospitalier Universitaire - Grenoble

    Grenoble, 38043

  • Hopital Claude-Huriez CHRU

    Lille, 59037

  • Cochin - Paris

    Paris, 75674

  • CHU STRASBOURG - Hôpital de Hautepierre

    Strasbourg, 67098

Other trials in France

Italy5 sites
  • A.O.U. di Cagliari

    Cagliari, Sardinia, 09042

  • A.O.U. Careggi

    Florence, Tuscany, 50139

  • A.O. di Padova

    Padova, Veneto, 35128

  • A.O.U. Pisana

    Pisa, Tuscany, 56126

  • A.O.U. Policlinico Umberto I

    Rome, Lazio, 00161

Other trials in Italy

Japan5 sites
  • Nippon Medical School Hospital

    Bunkyo-ku, Tokyo, 113-8603

  • Gunma University Hospital

    Maebashi, Gunma, 371-8511

  • Hokkaido University Hospital

    Sapporo, Hokkaido, 060-8648

  • Tohoku University Hospital

    Sendai, Miyagi, 980-8574

  • Institute of Rheumatology Tokyo Women's Medical University

    Shinjuku-ku, Tokyo, 162-0054

Other trials in Japan

United Kingdom5 sites
  • Ninewells Hospital

    Dundee, DD1 9SY

  • Aintree University Hospital

    Liverpool, L9 7AL

  • Royal Free Hospital

    London, NW3 2QG

  • Freeman Hospital

    Newcastle upon Tyne, Tyne and Wear, NE7 7DN

  • Hope Hospital

    Salford, Manchester, M6 8HD

Other trials in United Kingdom

Canada4 sites
  • St. Joseph's Healthcare - Hamilton

    Hamilton, Ontario, L8N 1Y2

  • Sir Mortimer B. Davis Jewish General Hospital

    Montreal, Quebec, H3T1E2

  • Arthritis Program Research Group, Inc.

    Newmarket, Ontario, L3Y 3R7

  • Mount Sinai Hospital

    Toronto, Ontario, M5T 3L9

Other trials in Canada

Germany4 sites
  • Kerckhoff-Klinik GmbH

    Bad Nauheim, Hesse, 61231

  • Universitätsklinikum Köln

    Cologne, North Rhine-Westphalia, 50937

  • Universitätsklinikum Erlangen

    Erlangen, Bavaria, 91054

  • Universitätsklinikum Ulm

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

Turkey (Türkiye)4 sites
  • Cukurova Univ. Tip. Fak. Balcali Hastanesi

    Adana, 01330

  • Hacettepe Universitesi Tip Fakultesi

    Ankara

  • Istanbul Universitesi Istanbul Tip Fakultesi

    Istanbul, 34093

  • Dokuz Eylul Universitesi Tip Fakultesi

    Izmir, 35340

Other trials in Turkey (Türkiye)

Belgium3 sites
  • CU Saint-Luc/UZ St-Luc

    Bruxelles - Brussel, 1200

  • UZ Gent

    Ghent, 9000

  • UZ Leuven Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Switzerland3 sites
  • Universitätsspital Basel

    Basel

  • Kantonsspital St. Gallen

    Sankt Gallen, Canton of St. Gallen, 9007

  • UniversitätsSpital Zürich

    Zurich, 8091

Other trials in Switzerland

Hungary2 sites
  • Debreceni Egyetem Klinikai Kozpont

    Debrecen, 4032

  • Pecsi Tudomanyegyetem Klinikai Kozpont

    Pécs, 7632

Other trials in Hungary

Netherlands2 sites
  • Universitair Medisch Centrum St. Radboud

    Nijmegen, 6525 GA

  • University Medical Center Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

Czechia1 site
  • Revmatologicky ustav

    Prague, 128 50

Other trials in Czechia

New Zealand1 site
  • Wellington Hospital

    Wellington, 6021

Other trials in New Zealand

About this study

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)

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

Being tested
Riociguat (Adempas, BAY63-2521), Placebo
Medical subject headings
Scleroderma, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Riociguat (Adempas, BAY63-2521)Drug

    Starting dose 0.5 mg TID, increase by 0.5 mg every 2 weeks until highest possible dose of 2.5 mg TID

  • PlaceboDrug

    Sham-titration

Study groups in NCT02283762
Study groupRoleWhat they receive
RiociguatExperimentalMain 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.
Receives: Drug: Riociguat (Adempas, BAY63-2521)
PlaceboPlacebo comparatorMain 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to week 52

Secondary outcomes (5)
  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

    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.

    Measured: Week 52

  2. 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).

    Measured: Baseline to week 52

  3. 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.

    Measured: Baseline to week 52

  4. 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.

    Measured: Baseline to week 52

  5. Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted to Week 52

    Negative change in FVC percent predicted indicates worsening.

    Measured: Baseline to week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2014 (estimated)
  2. Study start15 Jan 2015
  3. Primary completion15 Dec 2017
  4. Study completion28 Mar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
121 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02283762
Sponsor's protocol ID
16277
Other IDs
2014-001353-16, 2014
Status last verified
Jan 2020
First submitted
3 Nov 2014
Last updated
5 Feb 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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.

    PubMed 27746061
  • Khanna D, Kramer F, Hofler J, Ghadessi M, Sandner P, Allanore Y, Denton CP, Kuwana M, Matucci-Cerinic M, Pope JE, Atsumi T, Becvar R, Czirjak L, De Langhe E, Hachulla E, Ishii T, Ishikawa O, Johnson SR, Riccieri V, Schiopu E, Silver RM, Smith V, Stagnaro C, Steen V, Stevens W, Szucs G, Truchetet ME, Wosnitza M, Distler O. Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis. Rheumatology (Oxford). 2024 Nov 1;63(11):3124-3134. doi: 10.1093/rheumatology/keae150.

    PubMed 38460548
  • Distler O, Allanore Y, Denton CP, Kuwana M, Matucci-Cerinic M, Pope JE, Atsumi T, Becvar R, Czirjak L, Hachulla E, Ishii T, Ishikawa O, Johnson SR, De Langhe E, Stagnaro C, Riccieri V, Schiopu E, Silver RM, Smith V, Steen V, Stevens W, Szucs G, Truchetet ME, Wosnitza M, Laapas K, Kramer F, Khanna D. Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): open-label, long-term extension of a phase 2b, randomised, placebo-controlled trial. Lancet Rheumatol. 2023 Nov;5(11):e660-e669. doi: 10.1016/S2665-9913(23)00238-2.

    PubMed 38251533

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Riociguat (Adempas, BAY63-2521) in people with Scleroderma, Systemic, run by Bayer at 59 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 59 sites in United States, Australia, France, Italy, Japan and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Modified Rodnan Skin Score (mRSS) to Week 52 (time frame: Baseline to week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02283762, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.

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