Clinical trial NCT02138825: Efficacy and Safety of Riociguat in Patients With Symptomatic Pulmonary Hypertension (PH) Associated With Idiopathic Interstitial Pneumonias (IIP)
Official title: 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).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Idiopathic Interstitial Pneumonias / Hypertension,Pulmonary
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-05-15
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean Change in 6 Minute Walking Distance (6MWD) From Baseline to Week 26
timeFrame: Baseline to 26 weeks
Secondary outcomes:
measure: Number of Participants With Clinical Worsening
timeFrame: From baseline to week 26
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Wichita
country: United States
facility: Via Christi Clinic
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Pittsburgh
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Falls Church
country: United States
state: Virginia
city: Mar del Plata
country: Argentina
state: Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Godoy Cruz
country: Argentina
state: Mendoza
city: San Miguel de Tucumán
country: Argentina
state: Tucuman
city: Camperdown
country: Australia
state: New South Wales
city: Darlinghurst
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Chermside
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Prahran
country: Australia
state: Victoria
city: Murdoch
country: Australia
state: Western Australia
city: Leuven
country: Belgium
city: Vancouver
country: Canada
state: British Columbia
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Quebec
country: Canada
city: Bogotá
country: Colombia
state: Distrito Capital de Bogotá
city: Floridablanca-Bucaramanga
country: Colombia
state: Santander
city: Cali
country: Colombia
state: Valle del Cauca
city: Bogotá
country: Colombia
city: Santafe de Bogotá
country: Colombia
city: Aarhus N
country: Denmark
city: Bron
country: France
city: Lille Cedex
country: France
city: Marseille
country: France
city: Paris Cedex 15
country: France
city: München
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: Würzburg
country: Germany
state: Bayern
city: Gießen
country: Germany
state: Hessen
city: Hannover
country: Germany
state: Niedersachsen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Dresden
country: Germany
state: Sachsen
city: Grosshansdorf
country: Germany
city: Athens
country: Greece
city: Haidari
country: Greece
city: Ioannina
country: Greece
city: Thessaloniki
country: Greece
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petah Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Forlì-Cesena
country: Italy
state: Emilia-Romagna
city: Roma
country: Italy
state: Lazio
city: Monza-Brianza
country: Italy
state: Lombardia
city: Palermo
country: Italy
state: Sicilia
city: Siena
country: Italy
state: Toscana
city: Seto
country: Japan
state: Aichi
city: Yokohama
country: Japan
state: Kanagawa
city: Sakai
country: Japan
state: Osaka
city: Shibuya-ku
country: Japan
state: Tokyo
city: Chiba
country: Japan
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Coimbra
country: Portugal
city: Porto
country: Portugal
city: Vila Nova de Gaia
country: Portugal
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Vladimir
country: Russian Federation
city: Riyadh
country: Saudi Arabia
city: Riyadh
country: Saudi Arabia
city: Riyadh
country: Saudi Arabia
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Valencia
country: Spain
city: Bern
country: Switzerland
city: Genève
country: Switzerland
city: Zürich
country: Switzerland
city: Denizli
country: Turkey
city: Izmir
country: Turkey
city: Cambridge
country: United Kingdom
state: Cambridgeshire
city: Clydebank
country: United Kingdom
state: West Dunbartonshire
city: London
country: United Kingdom
city: Newcastle
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.