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

July 25, 2023 updated by: Bellerophon Pulse Technologies

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

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

Study Overview

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

Study Type

Interventional

Enrollment (Actual)

145

Phase

  • Phase 3

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • University of British Columbia
    • Ontario
      • Kingston, Ontario, Canada, K7L 5G2
        • Queen's University/Hotel Dieu Hospital
      • London, Ontario, Canada, K7L 2V6
        • London Health Sciences Centre
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama
    • Arizona
      • Phoenix, Arizona, United States, 85012
        • Arizona Pulmonary Specialists, Ltd.
      • Phoenix, Arizona, United States, 85006
        • Banner - University Medical Center Arizona
    • California
      • Fresno, California, United States, 93701
        • University of California San Francisco
      • Los Angeles, California, United States, 90024
        • University of California
      • Northridge, California, United States, 91324
        • Amicis Research
      • Paloma, California, United States, 92675
        • Paloma Medical Group
      • Sacramento, California, United States, 95817
        • University of California Davis Health
      • Stanford, California, United States, 94305
        • Stanford University Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80046
        • UC Denver Anschutz Medical Center
      • Denver, Colorado, United States, 80206
        • National Jewish
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University
    • Florida
      • Clearwater, Florida, United States, 33765
        • St. Francis Sleep Allergy and Lung Institute
      • Loxahatchee Groves, Florida, United States, 33470
        • Advanced Pulmonary Research Institute
      • Miami, Florida, United States, 33125
        • University of Miami
      • Pensacola, Florida, United States, 32503
        • Avanza Medical Research Center
      • Tampa, Florida, United States, 33612
        • University of South Florida
      • Weston, Florida, United States, 33331
        • Cleveland Clinic
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
      • Austell, Georgia, United States, 30106
        • Piedmont Healthcare
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern
      • Evanston, Illinois, United States, 60201
        • North Shore University Hospital
      • Maywood, Illinois, United States, 60153
        • Loyola University
      • Springfield, Illinois, United States, 62702 / 62794
        • Southern Illinois University
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Ascension St. Vincent Hospital
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville
      • Louisville, Kentucky, United States, 40202
        • Norton Pulmonary Specialists
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • The Lung Research Center, LLC
    • Nebraska
      • Omaha, Nebraska, United States, 68124
        • Creighton University
    • New Jersey
      • Summit, New Jersey, United States, 07901
        • Atlantic Health Respiratory Institute
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10065
        • Weill Cornell Medical Center
      • New York, New York, United States, 10016
        • NYU Langone
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Hospital
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27517
        • The University of North Carolina at Chapel Hill Marsico Clinical Research Center
      • Greensboro, North Carolina, United States, 27403
        • Pulmonix, LLC/LeBauer Cone Health
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati
      • Cleveland, Ohio, United States, 44106
        • University Hospitals
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Oregon
      • Portland, Oregon, United States, 97220
        • The Oregon Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University
      • Philadelphia, Pennsylvania, United States, 19017
        • Thomas Jefferson University Korman Respiratory Institute
      • Pittsburgh, Pennsylvania, United States, 15123
        • University of Pittsburgh
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • AnMed Health
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center
      • Houston, Texas, United States, 77030
        • University of Texas Health Science Center at Houston
      • McKinney, Texas, United States, 75069
        • Metroplex Pulmonary and Sleep
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • University of Utah Health Sciences
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Heart and Vascular Institute Advanced Lung Disease Clinic
      • Richmond, Virginia, United States, 23229
        • Pulmonary Associates of Richmond
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center

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

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

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
Intervention / Treatment
Active Comparator: Inhaled Nitric Oxide (iNO)
Pulsed inhaled iNO 45 mcg/kg Ideal Body Weight (IBW)/hour (hr)
Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.
Placebo Comparator: Placebo
Pulsed inhaled N2, 99.999% gas
Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.
Other: Open Label Extension
Pulsed inhaled iNO 45 mcg/kg IBW/hr
Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Moderate to Vigorous Physical Activity (MVPA) as Measured by Actigraphy
Time Frame: Baseline to Month 4
Part 1 - Blinded Treatment Period
Baseline to Month 4
Adverse Events and Serious Adverse Events with Long Term INOpulse Therapy
Time Frame: Baseline to Month 4
Part 2 - Open Label Extension (OLE)
Baseline to Month 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Overall Activity as Measured by Actigraphy
Time Frame: Baseline to M4
Part 1 - Blinded Treatment Period
Baseline to M4
Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ)
Time Frame: Baseline to Month 4
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
Change in St. George Respiratory Questionnaire (SGRQ) - Activity, Impacts & Total
Time Frame: Baseline to Month 4
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
Time to Clinical Worsening
Time Frame: Baseline to Month 4
Part 1 - Blinded Treatment Period
Baseline to Month 4
Time to Clinical Deterioration
Time Frame: Baseline to Month 4
Part 1 Blinded Treatment Period
Baseline to Month 4
Time to Clinical Improvement
Time Frame: Baseline to Month 4
Part 1 Blinded Treatment Period
Baseline to Month 4
Change in 6 Minute Walk Distance
Time Frame: Baseline to Month 4
Part 1 Blinded Treatment Period
Baseline to Month 4

Collaborators and Investigators

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

Investigators

  • Study Director: Ashika Ahmed, Bellerophon Therapeutics

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.

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)

December 14, 2020

Primary Completion (Actual)

June 9, 2023

Study Completion (Actual)

June 30, 2023

Study Registration Dates

First Submitted

August 27, 2017

First Submitted That Met QC Criteria

August 27, 2017

First Posted (Actual)

August 30, 2017

Study Record Updates

Last Update Posted (Actual)

July 27, 2023

Last Update Submitted That Met QC Criteria

July 25, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

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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