Efficacy and Safety of Riociguat in Patients With Systemic Sclerosis

NCT02283762 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 162772014-001353-16
• Study Type: interventional
• Target: 121
• Locations: 15 countries
• Sites: 59

Brief Summary

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

Conditions

Scleroderma, Systemic

Outcome Measures

Primary Outcomes (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.

  Baseline to week 52

Secondary Outcomes (5)

• 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

  Week 52

• Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score to Week 52

  Baseline to week 52

• Change From Baseline in Patient's Global Assessment Score to Week 52

  Baseline to week 52

• Change From Baseline in Physician's Global Assessment Score to Week 52

  Baseline to week 52

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

  Baseline to week 52

Study Arms (2)

Riociguat

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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

Interventions

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

Riociguat

Placebo DRUG

Sham-titration

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (59)

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85259-5404, United States

Location

UCLA David Geffen School of Medicine

Los Angeles, California, 90095-1670, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Rutgers Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

Medical University of South Carolina Medical Center

Charleston, South Carolina, 29425, United States

Location

Memorial Hermann-Texas Medical Center

Houston, Texas, 77030, United States

Location

University of Utah Health Care

Salt Lake City, Utah, 84132, United States

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

CU Saint-Luc/UZ St-Luc

Bruxelles - Brussel, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

St. Joseph's Healthcare - Hamilton

Hamilton, Ontario, L8N 1Y2, Canada

Location

Arthritis Program Research Group, Inc.

Newmarket, Ontario, L3Y 3R7, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5T 3L9, Canada

Location

Sir Mortimer B. Davis Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Revmatologicky ustav

Prague, 128 50, Czechia

Location

Hôpital Pellegrin - Bordeaux

Bordeaux, 33000, France

Location

Centre Hospitalier Universitaire - Grenoble

Grenoble, 38043, France

Location

Hopital Claude-Huriez CHRU

Lille, 59037, France

Location

Cochin - Paris

Paris, 75674, France

Location

CHU STRASBOURG - Hôpital de Hautepierre

Strasbourg, 67098, France

Location

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Kerckhoff-Klinik GmbH

Bad Nauheim, Hesse, 61231, Germany

Location

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Pecsi Tudomanyegyetem Klinikai Kozpont

Pécs, 7632, Hungary

Location

A.O.U. Policlinico Umberto I

Rome, Lazio, 00161, Italy

Location

A.O.U. di Cagliari

Cagliari, Sardinia, 09042, Italy

Location

A.O.U. Careggi

Florence, Tuscany, 50139, Italy

Location

A.O.U. Pisana

Pisa, Tuscany, 56126, Italy

Location

A.O. di Padova

Padua, Veneto, 35128, Italy

Location

Gunma University Hospital

Maebashi, Gunma, 371-8511, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Nippon Medical School Hospital

Bunkyo-ku, Tokyo, 113-8603, Japan

Location

Institute of Rheumatology Tokyo Women's Medical University

Shinjuku-ku, Tokyo, 162-0054, Japan

Location

Universitair Medisch Centrum St. Radboud

Nijmegen, 6525 GA, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Wellington Hospital

Wellington, 6021, New Zealand

Location

Kantonsspital St. Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

Universitätsspital Basel

Basel, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Cukurova Univ. Tip. Fak. Balcali Hastanesi

Adana, 01330, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi

Ankara, Turkey (Türkiye)

Location

Istanbul Universitesi Istanbul Tip Fakultesi

Istanbul, 34093, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Tip Fakultesi

Izmir, 35340, Turkey (Türkiye)

Location

Hope Hospital

Salford, Manchester, M6 8HD, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom

Location

Ninewells Hospital

Dundee, DD1 9SY, United Kingdom

Location

Aintree University Hospital

Liverpool, L9 7AL, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 27746061 BACKGROUND

• 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.

  PMID: 38460548 DERIVED

• 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.

  PMID: 38251533 DERIVED

Related Links

• Click here to find results for studies related to Bayer products
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

riociguat

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

+1 888-8422937

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2014
• First Posted: November 5, 2014
• Study Start: January 15, 2015
• Primary Completion: December 15, 2017
• Study Completion: March 28, 2019
• Last Updated: February 5, 2020
• Results First Posted: January 25, 2019

Record last verified: 2020-01

Locations

CZ (1); HU (2); FR (5); BE (3); IT (5); GB (5); AU (5); TU (4); NL (2); NZ (1); US (10); DE (4); CH (3); JP (5); CA (4)