NCT03267108

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

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
145

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Dec 2020

Typical duration for phase_3

Geographic Reach
2 countries

64 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 27, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 30, 2017

Completed
3.3 years until next milestone

Study Start

First participant enrolled

December 14, 2020

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 9, 2023

Completed
21 days until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2023

Completed
Last Updated

July 27, 2023

Status Verified

July 1, 2023

Enrollment Period

2.5 years

First QC Date

August 27, 2017

Last Update Submit

July 25, 2023

Conditions

Keywords

Pulmonary FibrosisPFPulmonary HypertensionInhaled Nitric OxideiNOLong Term Oxygen TherapyOxygenREBUILDINOpulsepulsed inhaled nitric oxidefILDfibrotic interstitial lung diseaseportable pulsed inhaled nitric oxide

Outcome Measures

Primary Outcomes (2)

  • Change in Moderate to Vigorous Physical Activity (MVPA) as Measured by Actigraphy

    Part 1 - Blinded Treatment Period

    Baseline to Month 4

  • Adverse Events and Serious Adverse Events with Long Term INOpulse Therapy

    Part 2 - Open Label Extension (OLE)

    Baseline to Month 4

Secondary Outcomes (7)

  • Change in Overall Activity as Measured by Actigraphy

    Baseline to M4

  • Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ)

    Baseline to Month 4

  • Change in St. George Respiratory Questionnaire (SGRQ) - Activity, Impacts & Total

    Baseline to Month 4

  • Time to Clinical Worsening

    Baseline to Month 4

  • Time to Clinical Deterioration

    Baseline to Month 4

  • +2 more secondary outcomes

Study Arms (3)

Inhaled Nitric Oxide (iNO)

ACTIVE COMPARATOR

Pulsed inhaled iNO 45 mcg/kg Ideal Body Weight (IBW)/hour (hr)

Combination Product: INOpulse®

Placebo

PLACEBO COMPARATOR

Pulsed inhaled N2, 99.999% gas

Combination Product: Placebo

Open Label Extension

OTHER

Pulsed inhaled iNO 45 mcg/kg IBW/hr

Combination Product: Open Label Extension

Interventions

INOpulse®COMBINATION_PRODUCT

Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.

Inhaled Nitric Oxide (iNO)
PlaceboCOMBINATION_PRODUCT

Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.

Placebo
Open Label ExtensionCOMBINATION_PRODUCT

Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.

Open Label Extension

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • +6 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (64)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Banner - University Medical Center Arizona

Phoenix, Arizona, 85006, United States

Location

Arizona Pulmonary Specialists, Ltd.

Phoenix, Arizona, 85012, United States

Location

University of California San Francisco

Fresno, California, 93701, United States

Location

University of California

Los Angeles, California, 90024, United States

Location

Amicis Research

Northridge, California, 91324, United States

Location

Paloma Medical Group

Paloma, California, 92675, United States

Location

University of California Davis Health

Sacramento, California, 95817, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

UC Denver Anschutz Medical Center

Aurora, Colorado, 80046, United States

Location

National Jewish

Denver, Colorado, 80206, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

St. Francis Sleep Allergy and Lung Institute

Clearwater, Florida, 33765, United States

Location

Advanced Pulmonary Research Institute

Loxahatchee Groves, Florida, 33470, United States

Location

University of Miami

Miami, Florida, 33125, United States

Location

Avanza Medical Research Center

Pensacola, Florida, 32503, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Cleveland Clinic

Weston, Florida, 33331, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Piedmont Healthcare

Austell, Georgia, 30106, United States

Location

Northwestern

Chicago, Illinois, 60611, United States

Location

North Shore University Hospital

Evanston, Illinois, 60201, United States

Location

Loyola University

Maywood, Illinois, 60153, United States

Location

Southern Illinois University

Springfield, Illinois, 62702 / 62794, United States

Location

Ascension St. Vincent Hospital

Indianapolis, Indiana, 46260, United States

Location

Norton Pulmonary Specialists

Louisville, Kentucky, 40202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

The Lung Research Center, LLC

Chesterfield, Missouri, 63017, United States

Location

Creighton University

Omaha, Nebraska, 68124, United States

Location

Atlantic Health Respiratory Institute

Summit, New Jersey, 07901, United States

Location

NYU Langone

New York, New York, 10016, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

The University of North Carolina at Chapel Hill Marsico Clinical Research Center

Chapel Hill, North Carolina, 27517, United States

Location

Pulmonix, LLC/LeBauer Cone Health

Greensboro, North Carolina, 27403, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

University Hospitals

Cleveland, Ohio, 44106, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

The Oregon Clinic

Portland, Oregon, 97220, United States

Location

Thomas Jefferson University Korman Respiratory Institute

Philadelphia, Pennsylvania, 19017, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15123, United States

Location

AnMed Health

Anderson, South Carolina, 29621, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Metroplex Pulmonary and Sleep

McKinney, Texas, 75069, United States

Location

University of Utah Health Sciences

Salt Lake City, Utah, 84108, United States

Location

Inova Heart and Vascular Institute Advanced Lung Disease Clinic

Falls Church, Virginia, 22042, United States

Location

Pulmonary Associates of Richmond

Richmond, Virginia, 23229, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Queen's University/Hotel Dieu Hospital

Kingston, Ontario, K7L 5G2, Canada

Location

London Health Sciences Centre

London, Ontario, K7L 2V6, Canada

Location

Related Publications (1)

  • Nathan SD, Rajicic N, Dudenhofer R, Hussain R, Argula R, Bandyopadhyay D, Luckhardt T, Muehlemann N, Flaherty KR, Glassberg MK, Lancaster L, Raghu G, Fernandes P. Inhaled Nitric Oxide in Fibrotic Lung Disease: A Randomized, Double-Blind, Placebo-controlled Trial. Ann Am Thorac Soc. 2024 Dec;21(12):1661-1669. doi: 10.1513/AnnalsATS.202406-662OC.

MeSH Terms

Conditions

Pulmonary FibrosisHypertension, Pulmonary

Condition Hierarchy (Ancestors)

Lung Diseases, InterstitialLung DiseasesRespiratory Tract DiseasesFibrosisPathologic ProcessesPathological Conditions, Signs and SymptomsHypertensionVascular DiseasesCardiovascular Diseases

Study Officials

  • Ashika Ahmed

    Bellerophon Therapeutics

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 27, 2017

First Posted

August 30, 2017

Study Start

December 14, 2020

Primary Completion

June 9, 2023

Study Completion

June 30, 2023

Last Updated

July 27, 2023

Record last verified: 2023-07

Data Sharing

IPD Sharing
Will not share

Locations