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

NCT02138825 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 136052010-024332-42
• Study Type: interventional
• Target: 147
• Locations: 21 countries
• Sites: 93

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).

Conditions

Idiopathic Interstitial Pneumonias / Hypertension,Pulmonary

Outcome Measures

Primary Outcomes (1)

• Mean Change in 6 Minute Walking Distance (6MWD) From Baseline to Week 26

  The 6MWD test is designed to evaluate a patient's exercise capacity while performing an everyday activity.

  Baseline to 26 weeks

Secondary Outcomes (1)

• Number of Participants With Clinical Worsening

  From baseline to week 26

Study Arms (2)

Riociguat (Adempas, BAY63-2521)

EXPERIMENTAL

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.

Drug: Riociguat (Adempas, BAY63-2521)

Placebo

PLACEBO COMPARATOR

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.

Drug: Riociguat (Adempas, BAY63-2521); Drug: Placebo

Interventions

Riociguat (Adempas, BAY63-2521) 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; Riociguat (Adempas, BAY63-2521)

Placebo 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

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 %
• MWD (6 minutes walking distance) ≥ 150 m to ≤ 450 m {under stable O2(oxygen) supplementation via nasal cannula}

You may not qualify if:

• 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),

Sponsors & Collaborators

• Bayer: lead

Study Sites (93)

University of California, Los Angeles

Los Angeles, California, 90024, United States

Location

Unknown Facility

San Francisco, California, 94143, United States

Location

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

Miami, Florida, 33136, United States

Location

Unknown Facility

Orlando, Florida, 32803, United States

Location

Via Christi Clinic

Wichita, Kansas, 67208, United States

Location

Unknown Facility

Louisville, Kentucky, 40202, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Cincinnati, Ohio, 45219, United States

Location

Unknown Facility

Cleveland, Ohio, 44195, United States

Location

Unknown Facility

Columbus, Ohio, 43221, United States

Location

Unknown Facility

Portland, Oregon, 97213, United States

Location

Unknown Facility

Pittsburgh, Pennsylvania, 15213, United States

Location

Unknown Facility

Nashville, Tennessee, 37232-5735, United States

Location

Unknown Facility

Dallas, Texas, 75235-3858, United States

Location

Unknown Facility

Falls Church, Virginia, 22042, United States

Location

Unknown Facility

Mar del Plata, Buenos Aires, Argentina

Location

Unknown Facility

Buenos Aires, Ciudad Auton. de Buenos Aires, 1426, Argentina

Location

Unknown Facility

Buenos Aires, Ciudad Auton. de Buenos Aires, C1280AEB, Argentina

Location

Unknown Facility

Godoy Cruz, Mendoza Province, 5501, Argentina

Location

Unknown Facility

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Unknown Facility

Camperdown, New South Wales, 2050, Australia

Location

Unknown Facility

Darlinghurst, New South Wales, 2010, Australia

Location

Unknown Facility

Sydney, New South Wales, 2751, Australia

Location

Unknown Facility

Chermside, Queensland, 4032, Australia

Location

Unknown Facility

Adelaide, South Australia, 5000, Australia

Location

Unknown Facility

Prahran, Victoria, 3181, Australia

Location

Unknown Facility

Murdoch, Western Australia, 6150, Australia

Location

Unknown Facility

Leuven, 3000, Belgium

Location

Unknown Facility

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Unknown Facility

Ottawa, Ontario, K1Y 4W7, Canada

Location

Unknown Facility

Toronto, Ontario, M5G 2N2, Canada

Location

Unknown Facility

Québec, G1V 4G5, Canada

Location

Unknown Facility

Bogotá, Bogota D.C., Colombia

Location

Unknown Facility

Floridablanca-Bucaramanga, Santander Department, Colombia

Location

Unknown Facility

Cali, Valle del Cauca Department, Colombia

Location

Unknown Facility

Bogotá, Colombia

Location

Unknown Facility

Aarhus N, 8200, Denmark

Location

Unknown Facility

Bron, 69500, France

Location

Unknown Facility

Lille, 59037, France

Location

Unknown Facility

Marseille, 13915, France

Location

Unknown Facility

Paris, 75908, France

Location

Unknown Facility

München, Bavaria, 80539, Germany

Location

Unknown Facility

München, Bavaria, 81377, Germany

Location

Unknown Facility

Würzburg, Bavaria, 97074, Germany

Location

Unknown Facility

Giessen, Hesse, 35392, Germany

Location

Unknown Facility

Hanover, Lower Saxony, 30625, Germany

Location

Unknown Facility

Essen, North Rhine-Westphalia, 45239, Germany

Location

Unknown Facility

Dresden, Saxony, 01307, Germany

Location

Unknown Facility

Großhansdorf, 22927, Germany

Location

Unknown Facility

Athens, 11527, Greece

Location

Unknown Facility

Haidari, 12462, Greece

Location

Unknown Facility

Ioannina, 45500, Greece

Location

Unknown Facility

Thessaloniki, 570 10, Greece

Location

Unknown Facility

Haifa, 3436212, Israel

Location

Unknown Facility

Jerusalem, 91120, Israel

Location

Unknown Facility

Petah Tikva, 4941492, Israel

Location

Unknown Facility

Ramat Gan, 5262000, Israel

Location

Unknown Facility

Forlì-Cesena, Emilia-Romagna, 47121, Italy

Location

Unknown Facility

Rome, Lazio, 00133, Italy

Location

Unknown Facility

Monza-Brianza, Lombardy, 20900, Italy

Location

Unknown Facility

Palermo, Sicily, 90127, Italy

Location

Unknown Facility

Siena, Tuscany, 53100, Italy

Location

Unknown Facility

Seto, Aichi-ken, 489-8642, Japan

Location

Unknown Facility

Yokohama, Kanagawa, 236-0051, Japan

Location

Unknown Facility

Sakai, Osaka, 591-8555, Japan

Location

Unknown Facility

Shibuya-ku, Tokyo, 151-8528, Japan

Location

Unknown Facility

Chiba, 260-8677, Japan

Location

Unknown Facility

Auckland, 1051, New Zealand

Location

Unknown Facility

Christchurch, 8011, New Zealand

Location

Unknown Facility

Coimbra, 3000-075, Portugal

Location

Unknown Facility

Porto, 4200, Portugal

Location

Unknown Facility

Vila Nova de Gaia, 4434-502, Portugal

Location

Unknown Facility

Moscow, 105077, Russia

Location

Unknown Facility

Moscow, 107564, Russia

Location

Unknown Facility

Saint Petersburg, 197022, Russia

Location

Unknown Facility

Vladimir, 600023, Russia

Location

Unknown Facility

Riyadh, 11211, Saudi Arabia

Location

Unknown Facility

Riyadh, 11461, Saudi Arabia

Location

Unknown Facility

Riyadh, 11525, Saudi Arabia

Location

Unknown Facility

Barcelona, 08003, Spain

Location

Unknown Facility

Barcelona, 08036, Spain

Location

Unknown Facility

Valencia, 46014, Spain

Location

Unknown Facility

Bern, 3010, Switzerland

Location

Unknown Facility

Geneva, 1205, Switzerland

Location

Unknown Facility

Zurich, 8091, Switzerland

Location

Unknown Facility

Denizli, 20070, Turkey (Türkiye)

Location

Unknown Facility

Izmir, 35100, Turkey (Türkiye)

Location

Unknown Facility

Cambridge, Cambridgeshire, CB23 3RE, United Kingdom

Location

Unknown Facility

Clydebank, West Dunbartonshire, G81 4DY, United Kingdom

Location

Unknown Facility

London, SW3 6NP, United Kingdom

Location

Unknown Facility

Newcastle, NE7 7DN, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31416769 DERIVED

Related Links

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

MeSH Terms

Conditions

Idiopathic Interstitial Pneumonias; Hypertension

Interventions

riociguat

Condition Hierarchy (Ancestors)

Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

The study was prematurely terminated following a recommendation from the independent Data Monitoring Committee, as patients receiving Riociguat showed an increased risk of mortality and serious adverse events as compared to patients receiving Placebo

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayer.com

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: May 15, 2014
• Study Start: June 4, 2014
• Primary Completion: May 5, 2016
• Study Completion: September 14, 2016
• Last Updated: December 4, 2017
• Results First Posted: June 5, 2017

Record last verified: 2017-10

Locations

PT (3); DK (1); IT (5); ES (3); AU (7); RU (4); AR (5); GR (4); US (17); BE (1); CO (4); JP (5); DE (8); CA (4); FR (4); IL (4); CH (3); GB (4); TU (2); NZ (2); SA (3)