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

October 30, 2017 updated by: Bayer

A Randomized, Double-blind, Placebo-controlled Phase II Study to Investigate the Efficacy and Safety of Riociguat (0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID) in Patients With Symptomatic Pulmonary Hypertension Associated With Idiopathic Interstitial Pneumonias (IIP).

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
147

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
    • Buenos Aires
      • Mar del Plata, Buenos Aires, Argentina
    • Ciudad Auton. de Buenos Aires
      • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1280AEB
      • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, 1426
    • Mendoza
      • Godoy Cruz, Mendoza, Argentina, 5501
    • Tucuman
      • San Miguel de Tucumán, Tucuman, Argentina, 4000
  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
      • Darlinghurst, New South Wales, Australia, 2010
      • Sydney, New South Wales, Australia, 2751
    • Queensland
      • Chermside, Queensland, Australia, 4032
    • South Australia
      • Adelaide, South Australia, Australia, 5000
    • Victoria
      • Prahran, Victoria, Australia, 3181
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
  • Belgium
      • Leuven, Belgium, 3000
  • Canada
      • Quebec, Canada, G1V 4G5
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
    • Ontario
      • Ottawa, Ontario, Canada, K1Y 4W7
      • Toronto, Ontario, Canada, M5G 2N2
  • Colombia
      • Bogotá, Colombia
      • Santafe de Bogotá, Colombia
    • Distrito Capital de Bogotá
      • Bogotá, Distrito Capital de Bogotá, Colombia
    • Santander
      • Floridablanca-Bucaramanga, Santander, Colombia
    • Valle del Cauca
      • Cali, Valle del Cauca, Colombia
  • Denmark
      • Aarhus N, Denmark, 8200
  • France
      • Bron, France, 69500
      • Lille Cedex, France, 59037
      • Marseille, France, 13915
      • Paris Cedex 15, France, 75908
  • Germany
      • Grosshansdorf, Germany, 22927
    • Bayern
      • München, Bayern, Germany, 81377
      • München, Bayern, Germany, 80539
      • Würzburg, Bayern, Germany, 97074
    • Hessen
      • Gießen, Hessen, Germany, 35392
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30625
    • Nordrhein-Westfalen
      • Essen, Nordrhein-Westfalen, Germany, 45239
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
  • Greece
      • Athens, Greece, 11527
      • Haidari, Greece, 12462
      • Ioannina, Greece, 45500
      • Thessaloniki, Greece, 570 10
  • Israel
      • Haifa, Israel, 3436212
      • Jerusalem, Israel, 91120
      • Petah Tikva, Israel, 4941492
      • Ramat Gan, Israel, 5262000
  • Italy
    • Emilia-Romagna
      • Forlì-Cesena, Emilia-Romagna, Italy, 47121
    • Lazio
      • Roma, Lazio, Italy, 00133
    • Lombardia
      • Monza-Brianza, Lombardia, Italy, 20900
    • Sicilia
      • Palermo, Sicilia, Italy, 90127
    • Toscana
      • Siena, Toscana, Italy, 53100
  • Japan
      • Chiba, Japan, 260-8677
    • Aichi
      • Seto, Aichi, Japan, 489-8642
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 236-0051
    • Osaka
      • Sakai, Osaka, Japan, 591-8555
    • Tokyo
      • Shibuya-ku, Tokyo, Japan, 151-8528
  • New Zealand
      • Auckland, New Zealand, 1051
      • Christchurch, New Zealand, 8011
  • Portugal
      • Coimbra, Portugal, 3000-075
      • Porto, Portugal, 4200
      • Vila Nova de Gaia, Portugal, 4434-502
  • Russian Federation
      • Moscow, Russian Federation, 105077
      • Moscow, Russian Federation, 107564
      • St. Petersburg, Russian Federation, 197022
      • Vladimir, Russian Federation, 600023
  • Saudi Arabia
      • Riyadh, Saudi Arabia, 11211
      • Riyadh, Saudi Arabia, 11461
      • Riyadh, Saudi Arabia, 11525
  • Spain
      • Barcelona, Spain, 08036
      • Barcelona, Spain, 08003
      • Valencia, Spain, 46014
  • Switzerland
      • Bern, Switzerland, 3010
      • Genève, Switzerland, 1205
      • Zürich, Switzerland, 8091
  • Turkey
      • Denizli, Turkey, 20070
      • Izmir, Turkey, 35100
  • United Kingdom
      • London, United Kingdom, SW3 6NP
      • Newcastle, United Kingdom, NE7 7DN
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
    • West Dunbartonshire
      • Clydebank, West Dunbartonshire, United Kingdom, G81 4DY
  • United States
    • California
      • Los Angeles, California, United States, 90024
        • University of California, Los Angeles
      • San Francisco, California, United States, 94143
    • Colorado
      • Aurora, Colorado, United States, 80045
    • Florida
      • Miami, Florida, United States, 33136
      • Orlando, Florida, United States, 32803
    • Kansas
      • Wichita, Kansas, United States, 67208
        • Via Christi Clinic
    • Kentucky
      • Louisville, Kentucky, United States, 40202
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
    • Ohio
      • Cincinnati, Ohio, United States, 45219
      • Cleveland, Ohio, United States, 44195
      • Columbus, Ohio, United States, 43221
    • Oregon
      • Portland, Oregon, United States, 97213
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
    • Tennessee
      • Nashville, Tennessee, United States, 37232-5735
    • Texas
      • Dallas, Texas, United States, 75235-3858
    • Virginia
      • Falls Church, Virginia, United States, 22042

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: 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.
Placebo Comparator: 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.
Drug: 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.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Change in 6 Minute Walking Distance (6MWD) From Baseline to Week 26
Time Frame: Baseline to 26 weeks
The 6MWD test is designed to evaluate a patient's exercise capacity while performing an everyday activity.
Baseline to 26 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Clinical Worsening
Time Frame: From baseline to week 26
The combined endpoint "time to clinical worsening", made up of the following components, defined by the first occurrence: all-cause mortality; need for hospitalization due to worsening cardiopulmonary (CP) status, attributable to progression of disease (including but not limited to increased shortness of breath or increased leg swelling); >15% decrease in the 6MWD test; worsening of WHO functional class.
From baseline to week 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 4, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 5, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 14, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 15, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 15, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 4, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 13605
  • 2010-024332-42 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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