Efficacy and Safety of Riociguat in Patients With Symptomatic Pulmonary Hypertension (PH) Associated With Idiopathic Interstitial Pneumonias (IIP)

NCT ID: NCT02138825

Last Updated: 2017-12-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 147 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-04
• Study Completion Date: 2016-09-14

Brief Summary

To evaluate the efficacy and safety of 26-weeks of treatment with riociguat vs. placebo in patients with symptomatic PH (pulmonary hypertension) associated with IIP (idiopathic interstitial pneumonias).

Detailed Description

Number of participants with Adverse Events (AEs) will be reported in Adverse Events section.

Conditions

Idiopathic Interstitial Pneumonias / Hypertension,Pulmonary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Riociguat (Adempas, BAY63-2521)

In the main study treatment phase participants received Riociguat titrated to optimal dose within range of 0.5 mg TID (3 times a day) to 2.5 mg TID for 10 weeks followed by maintenance period of 16 weeks. This phase was followed by a long-term extension phase, which included a blinded sham titration phase of 10 weeks followed by an open-label extension phase. During the open-label extension phase participants were to be treated with Riociguat until commercial access in the indication of pulmonary hypertension (PH) associated with idiopathic interstitial pneumonias (IIP) or until an agreed time point is defined with the individual country, local regulatory authority and the Sponsor's global team.

Group Type: EXPERIMENTAL

Riociguat (Adempas, BAY63-2521)

Intervention Type: DRUG

Active drug 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID/day as per individual dose titration. The starting dose will be 0.5 mg TID, and the dose will be adjusted every two weeks for ten weeks in 0.5 mg increments up to a maximum dose of 2.5 mg TID based on patient's systolic blood pressure and well-being.

Placebo

In the main study treatment phase participants received sham titration within range of 0.5 mg TID to 2.5 mg TID for 10 weeks followed by maintenance period of 16 weeks. This phase was followed by a long-term extension phase, which included a blinded titration phase to optimal dose of Riociguat of 10 weeks followed by an open-label extension phase. During the open-label extension phase participants were to be treated with Riociguat until commercial access in the indication of PH associated with IIP or until an agreed time point is defined with the individual country, local regulatory authority and the Sponsor's global team.

Group Type: PLACEBO_COMPARATOR

Riociguat (Adempas, BAY63-2521)

Intervention Type: DRUG

Active drug 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID/day as per individual dose titration. The starting dose will be 0.5 mg TID, and the dose will be adjusted every two weeks for ten weeks in 0.5 mg increments up to a maximum dose of 2.5 mg TID based on patient's systolic blood pressure and well-being.

Placebo

Intervention Type: DRUG

Inactive dosed at 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID/day as per individual dose titration for 26 weeks

Interventions

Riociguat (Adempas, BAY63-2521)

Active drug 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID/day as per individual dose titration. The starting dose will be 0.5 mg TID, and the dose will be adjusted every two weeks for ten weeks in 0.5 mg increments up to a maximum dose of 2.5 mg TID based on patient's systolic blood pressure and well-being.

Intervention Type: DRUG

Placebo

Inactive dosed at 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID/day as per individual dose titration for 26 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Men or women aged from ≥18 to ≤80 years
• Diagnosed with one of the following (confirmed using a multidisciplinary approach, as per ATS(American Thoracic Society) / ERS(European Respiratory Society) / JRS (Japanese Respiratory Society) / ALAT(Latin American Thoracic Association) guidelines:

• Major IIPs (idiopathic interstitial pneumonias) diagnosis or suspected as one of the following:
• Idiopathic pulmonary fibrosis
• Idiopathic nonspecific interstitial pneumonia
• Respiratory bronchiolitis-interstitial lung disease
• Desquamative interstitial pneumonia
• Cryptogenic organizing pneumonia
• Acute interstitial pneumonia
• Rare IIPs diagnosis by one of the following:
• Idiopathic lymphoid interstitial pneumonia
• Idiopathic pleuroparenchymal fibroelastosis
• Unclassifiable idiopathic interstitial pneumonias
• Forced Vital Capacity (FVC) ≥ 45 %
• 6MWD (6 minutes walking distance) ≥ 150 m to ≤ 450 m {under stable O2(oxygen) supplementation via nasal cannula}
• Diagnosis of PH (pulmonary hypertension) confirmed by right heart catheter (RHC) with (mean artery pulmonary artery pressure )mPAP ≥ 25 mmHg and (pulmonary artery wedge pressure)PAWP ≤15 mmHg at rest
• Systolic blood pressure (SBP) ≥ 95 mmHg and no signs or symptoms of hypotension
• WHO functional class II-IV
• Women of childbearing potential can only be included in the study if a pregnancy test is negative. 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 one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Adequate contraception is required from the signing of the informed consent form up until 4 weeks after the last study drug administration

Exclusion Criteria

• Known significant left heart disease:

• Pulmonary venous hypertension indicated by baseline pulmonary capillary wedge pressure > 15 mmHg
• Symptomatic coronary artery disease
• Systolic left-ventricular dysfunction with an left ventricular ejection fraction (LVEF) <45%
• Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization
• Any history of bronchial artery embolization or massive hemoptysis within 3 months prior to screening. Massive hemoptysis being defined as acute bleeding >240 mL in a 24-hour period or recurrent bleeding >100 mL/d over several days
• Difference > 15% between the eligibility and the baseline 6MWD test
• Forced expiratory volume in one second (FEV1) / Forced Vital Capacity (FVC) <0.65 after bronchodilator administration
• Initiation in cytotoxic, immunosuppressive, cytokine modulating therapy initiated within 3 months prior to screening. Such agents might include. azathioprine, cyclophosphamide, corticosteroids, etanercept, tumor necrosis factor alpha (TNFα) inhibitors and others
• Any specific treatment for (pulmonary arterial hypertension) PAH/PH (pulmonary hypertension )within 3 months prior to screening
• Concomitant use of the following medication: nitrates or (nitric oxide) NO donors (such as amyl nitrite) in any form, phosphodiesterase 5 inhibitors (such as sildenafil, tadalafil, vardenafil) and non-specific phosphodiesterase (PDE) inhibitors (theophylline, dipyridamole),
• Pregnant women (i.e. positive pregnancy test or other signs of pregnancy), or breast feeding women, or women of childbearing potential not using adequate contraception (as defined in the aforementioned inclusion criterion) and not willing to agree to 4 weekly pregnancy testing from Visit 1(first administration of study drug) onwards until 4 weeks after last study drug intake

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

University of California, Los Angeles

Los Angeles, California, United States

San Francisco, California, United States

Aurora, Colorado, United States

Miami, Florida, United States

Orlando, Florida, United States

Via Christi Clinic

Wichita, Kansas, United States

Louisville, Kentucky, United States

Columbia University Medical Center

New York, New York, United States

Durham, North Carolina, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States

Portland, Oregon, United States

Pittsburgh, Pennsylvania, United States

Nashville, Tennessee, United States

Dallas, Texas, United States

Falls Church, Virginia, United States

Mar del Plata, Buenos Aires, Argentina

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina

Godoy Cruz, Mendoza Province, Argentina

San Miguel de Tucumán, Tucumán Province, Argentina

Camperdown, New South Wales, Australia

Darlinghurst, New South Wales, Australia

Sydney, New South Wales, Australia

Chermside, Queensland, Australia

Adelaide, South Australia, Australia

Prahran, Victoria, Australia

Murdoch, Western Australia, Australia

Leuven, , Belgium

Vancouver, British Columbia, Canada

Ottawa, Ontario, Canada

Toronto, Ontario, Canada

Québec, , Canada

Bogotá, Bogota D.C., Colombia

Floridablanca-Bucaramanga, Santander Department, Colombia

Cali, Valle del Cauca Department, Colombia

Bogotá, , Colombia

Aarhus N, , Denmark

Bron, , France

Lille, , France

Marseille, , France

Paris, , France

München, Bavaria, Germany

München, Bavaria, Germany

Würzburg, Bavaria, Germany

Giessen, Hesse, Germany

Hanover, Lower Saxony, Germany

Essen, North Rhine-Westphalia, Germany

Dresden, Saxony, Germany

Großhansdorf, , Germany

Athens, , Greece

Haidari, , Greece

Ioannina, , Greece

Thessaloniki, , Greece

Haifa, , Israel

Jerusalem, , Israel

Petah Tikva, , Israel

Ramat Gan, , Israel

Forlì-Cesena, Emilia-Romagna, Italy

Rome, Lazio, Italy

Monza-Brianza, Lombardy, Italy

Palermo, Sicily, Italy

Siena, Tuscany, Italy

Seto, Aichi-ken, Japan

Yokohama, Kanagawa, Japan

Sakai, Osaka, Japan

Shibuya-ku, Tokyo, Japan

Chiba, , Japan

Auckland, , New Zealand

Christchurch, , New Zealand

Coimbra, , Portugal

Porto, , Portugal

Vila Nova de Gaia, , Portugal

Moscow, , Russia

Moscow, , Russia

Saint Petersburg, , Russia

Vladimir, , Russia

Riyadh, , Saudi Arabia

Riyadh, , Saudi Arabia

Riyadh, , Saudi Arabia

Barcelona, , Spain

Barcelona, , Spain

Valencia, , Spain

Bern, , Switzerland

Geneva, , Switzerland

Zurich, , Switzerland

Denizli, , Turkey (Türkiye)

Izmir, , Turkey (Türkiye)

Cambridge, Cambridgeshire, United Kingdom

Clydebank, West Dunbartonshire, United Kingdom

London, , United Kingdom

Newcastle, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Canada; Colombia; Denmark; France; Germany; Greece; Israel; Italy; Japan; New Zealand; Portugal; Russia; Saudi Arabia; Spain; Switzerland; Turkey (Türkiye); United Kingdom

References

Nathan SD, Behr J, Collard HR, Cottin V, Hoeper MM, Martinez FJ, Corte TJ, Keogh AM, Leuchte H, Mogulkoc N, Ulrich S, Wuyts WA, Yao Z, Boateng F, Wells AU. Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study. Lancet Respir Med. 2019 Sep;7(9):780-790. doi: 10.1016/S2213-2600(19)30250-4. Epub 2019 Aug 12.

Reference Type: DERIVED

PMID: 31416769 (View on PubMed)

Related Links

http://www.clinicaltrialsregister.eu/

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

Other Identifiers

2010-024332-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

13605

Identifier Type: -

Identifier Source: org_study_id