Clinical trial NCT03267108: A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension
Official title: A Randomized, Double-Blind, Placebo-Controlled Dose Escalation and Verification Clinical Study to Assess the Safety and Efficacy of Pulsed Inhaled Nitric Oxide (iNO) in Subjects at Risk of Pulmonary Hypertension Associated With Pulmonary Fibrosis on Long Term Oxygen Therapy (Part 1 and Part 2) - REBUILD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pulmonary Fibrosis
Pulmonary Hypertension
Keywords: Pulmonary Fibrosis
PF
Pulmonary Hypertension
Inhaled Nitric Oxide
iNO
Long Term Oxygen Therapy
Oxygen
REBUILD
INOpulse
pulsed inhaled nitric oxide
fILD
fibrotic interstitial lung disease
portable pulsed inhaled nitric oxide
Lead sponsor: Bellerophon
Sponsor class: INDUSTRY
First posted: 2017-08-30
Enrollment: 145
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: A randomized, double-blind, placebo-controlled dose escalation and verification study to assess the safety and efficacy of pulsed inhaled nitric oxide (iNO) in subjects at risk for pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy (Part 1 and Part 2) - REBUILD

Detailed description: This is a Phase 3, randomized, double-blind, placebo-controlled dose escalation and verification clinical study to assess the safety and efficacy of pulsed inhaled nitric oxide (iNO) in subjects at risk for pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy (Part 1 and Part 2) - REBUILD

Eligibility criteria: Inclusion criteria:

* A high resolution CT scan performed in the 6 months prior to screening associated with one of the following conditions and confirmed using guidelines, as per American Thoracic Society (ATS) / European Respiratory Society (ERS) / Japanese Respiratory Society (JRS) / Latin American Thoracic Association (ALAT):

  * 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

    * Chronic hypersensitivity pneumonitis
    * Occupational lung disease
  * Connective Tissue Disease associated with IPF (CTD-ILD)
  * Interstitial Pneumonia with Autoimmune Features (IPAF)
* Have been using oxygen therapy by nasal cannula for at least 4 weeks (including use limited to exertion)
* 6MWD ≥ 100 meters and ≤ 400 meters at screening and Baseline/Randomization visits.
* World Health Organization (WHO) Functional Class II-IV
* Forced Vital Capacity ≥ 40% predicted within the 60 day Screening period
* Age between 18 and 80 years (inclusive) at screening

Exclusion criteria:

* For women of child-bearing potential: Pregnant or breastfeeding females at Screening, or planning to get pregnant, or unwilling to use appropriate contraception if sexually active to avoid pregnancy during the study and for at least 30 days after discontinuation of the study drug.
* Heart failure with reduced ejection fraction (HFrEF; systolic heart failure) with an ejection fraction of \< 40%; or severe HF with preserved EF (HFpEF; diastolic HF)
* History of sarcoidosis
* History of chronic thrombo-embolic pulmonary hypertension (CTEPH; WHO group 4 PH)
* Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the study
* Body mass index (BMI) \>40 kg/m2 at screening
* Intermittent uncontrolled atrial fibrillation, in the opinion of the Principal Investigator
* Known severe hepatic impairment, in the opinion of the Principal Investigator
* Known severe renal impairment (Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) 2009 equation \[Levy 2009\] calculated creatinine clearance \<30 ml/min) at screening

Primary outcomes:
measure: Change in Moderate to Vigorous Physical Activity (MVPA) as Measured by Actigraphy
timeFrame: Baseline to Month 4
measure: Adverse Events and Serious Adverse Events with Long Term INOpulse Therapy
timeFrame: Baseline to Month 4
Secondary outcomes:
measure: Change in Overall Activity as Measured by Actigraphy
timeFrame: Baseline to M4
measure: Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ)
timeFrame: Baseline to Month 4
measure: Change in St. George Respiratory Questionnaire (SGRQ) - Activity, Impacts & Total
timeFrame: Baseline to Month 4
measure: Time to Clinical Worsening
timeFrame: Baseline to Month 4
measure: Time to Clinical Deterioration
timeFrame: Baseline to Month 4
measure: Time to Clinical Improvement
timeFrame: Baseline to Month 4
measure: Change in 6 Minute Walk Distance
timeFrame: Baseline to Month 4
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Banner - University Medical Center Arizona
state: Arizona
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists, Ltd.
state: Arizona
city: Fresno
country: United States
facility: University of California San Francisco
state: California
city: Los Angeles
country: United States
facility: University of California
state: California
city: Northridge
country: United States
facility: Amicis Research
state: California
city: Paloma
country: United States
facility: Paloma Medical Group
state: California
city: Sacramento
country: United States
facility: University of California Davis Health
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: UC Denver Anschutz Medical Center
state: Colorado
city: Denver
country: United States
facility: National Jewish
state: Colorado
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Clearwater
country: United States
facility: St. Francis Sleep Allergy and Lung Institute
state: Florida
city: Loxahatchee Groves
country: United States
facility: Advanced Pulmonary Research Institute
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Pensacola
country: United States
facility: Avanza Medical Research Center
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Austell
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Chicago
country: United States
facility: Northwestern
state: Illinois
city: Evanston
country: United States
facility: North Shore University Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent Hospital
state: Indiana
city: Louisville
country: United States
facility: Norton Pulmonary Specialists
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Chesterfield
country: United States
facility: The Lung Research Center, LLC
state: Missouri
city: Omaha
country: United States
facility: Creighton University
state: Nebraska
city: Summit
country: United States
facility: Atlantic Health Respiratory Institute
state: New Jersey
city: New York
country: United States
facility: NYU Langone
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill Marsico Clinical Research Center
state: North Carolina
city: Greensboro
country: United States
facility: Pulmonix, LLC/LeBauer Cone Health
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: The Oregon Clinic
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Korman Respiratory Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: McKinney
country: United States
facility: Metroplex Pulmonary and Sleep
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences
state: Utah
city: Falls Church
country: United States
facility: Inova Heart and Vascular Institute Advanced Lung Disease Clinic
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Kingston
country: Canada
facility: Queen's University/Hotel Dieu Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: Bellerophon Therapeutics
name: Ashika Ahmed
role: STUDY_DIRECTOR
References: