A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension

Pulmonary Hypertension Clinical Trial

— REBUILD  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03267108
• Other study ID #: PULSE-PHPF-001
• Status: Terminated
• Phase: Phase 3
• Start date: December 14, 2020
• Est. completion date: June 30, 2023

Study information

• Verified date: July 2023
• Source: Bellerophon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 145
• Est. completion date: June 30, 2023
• Est. primary completion date: June 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Fibrosis
• Pulmonary Hypertension

Intervention

Combination Product:
• INOpulse®
Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.
• Placebo
Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.
• Open Label Extension
Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.

Locations

Country	Name	City	State
Canada	Queen's University/Hotel Dieu Hospital	Kingston	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
United States	AnMed Health	Anderson	South Carolina
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	UC Denver Anschutz Medical Center	Aurora	Colorado
United States	Piedmont Healthcare	Austell	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	The University of North Carolina at Chapel Hill Marsico Clinical Research Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	The Lung Research Center, LLC	Chesterfield	Missouri
United States	Northwestern	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	St. Francis Sleep Allergy and Lung Institute	Clearwater	Florida
United States	University Hospitals	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	National Jewish	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	North Shore University Hospital	Evanston	Illinois
United States	Inova Heart and Vascular Institute Advanced Lung Disease Clinic	Falls Church	Virginia
United States	University of California San Francisco	Fresno	California
United States	Pulmonix, LLC/LeBauer Cone Health	Greensboro	North Carolina
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Ascension St. Vincent Hospital	Indianapolis	Indiana
United States	University of California	Los Angeles	California
United States	Norton Pulmonary Specialists	Louisville	Kentucky
United States	University of Louisville	Louisville	Kentucky
United States	Advanced Pulmonary Research Institute	Loxahatchee Groves	Florida
United States	Loyola University	Maywood	Illinois
United States	Metroplex Pulmonary and Sleep	McKinney	Texas
United States	University of Miami	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Mount Sinai Hospital	New York	New York
United States	NYU Langone	New York	New York
United States	Weill Cornell Medical Center	New York	New York
United States	Amicis Research	Northridge	California
United States	Creighton University	Omaha	Nebraska
United States	Paloma Medical Group	Paloma	California
United States	Avanza Medical Research Center	Pensacola	Florida
United States	Temple University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Korman Respiratory Institute	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists, Ltd.	Phoenix	Arizona
United States	Banner - University Medical Center Arizona	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	The Oregon Clinic	Portland	Oregon
United States	Pulmonary Associates of Richmond	Richmond	Virginia
United States	University of California Davis Health	Sacramento	California
United States	University of Utah Health Sciences	Salt Lake City	Utah
United States	University of Washington Medical Center	Seattle	Washington
United States	Southern Illinois University	Springfield	Illinois
United States	Stanford University Medical Center	Stanford	California
United States	Stony Brook University Hospital	Stony Brook	New York
United States	Atlantic Health Respiratory Institute	Summit	New Jersey
United States	University of South Florida	Tampa	Florida
United States	Georgetown University	Washington	District of Columbia
United States	Cleveland Clinic	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bellerophon Pulse Technologies

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Moderate to Vigorous Physical Activity (MVPA) as Measured by Actigraphy	Part 1 - Blinded Treatment Period	Baseline to Month 4
Primary	Adverse Events and Serious Adverse Events with Long Term INOpulse Therapy	Part 2 - Open Label Extension (OLE)	Baseline to Month 4
Secondary	Change in Overall Activity as Measured by Actigraphy	Part 1 - Blinded Treatment Period	Baseline to M4
Secondary	Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ)	Part 1 Blinded Treatment Period: The UCSD SOBQ is a 24-item questionnaire developed to measure breathlessness associated with activities of daily living, on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The responses to all items are summed up to provide the overall score that can range from 0 (best outcome) to 120 (worst outcome).	Baseline to Month 4
Secondary	Change in St. George Respiratory Questionnaire (SGRQ) - Activity, Impacts & Total	Part 1 Blinded Treatment Period: SGRQ is a tool for assessing quality of life that has previously been validated for the use with patients with interstitial lung disease. It is a responsive tool that has three domains: symptoms, activity and impact (on daily life)	Baseline to Month 4
Secondary	Time to Clinical Worsening	Part 1 - Blinded Treatment Period	Baseline to Month 4
Secondary	Time to Clinical Deterioration	Part 1 Blinded Treatment Period	Baseline to Month 4
Secondary	Time to Clinical Improvement	Part 1 Blinded Treatment Period	Baseline to Month 4
Secondary	Change in 6 Minute Walk Distance	Part 1 Blinded Treatment Period	Baseline to Month 4

External Links

•   Study website link