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

Sponsor
Bellerophon Pulse Technologies (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03267108
Collaborator
(none)
300
58
3
35.5
5.2
0.1

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
  • Combination Product: INOpulse®
  • Combination Product: Placebo
  • Combination Product: Open Label Extension
Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
300 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 14, 2020
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Inhaled Nitric Oxide (iNO)

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

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

Placebo Comparator: Placebo

Pulsed inhaled N2, 99.999% gas

Combination Product: Placebo
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

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

Outcome Measures

Primary Outcome Measures

  1. Change in Moderate to Vigorous Physical Activity (MVPA) as Measured by Actigraphy [Baseline to Month 4]

    Part 1 - Blinded Treatment Period

  2. Adverse Events and Serious Adverse Events with Long Term INOpulse Therapy [Baseline to Month 4]

    Part 2 - Open Label Extension (OLE)

Secondary Outcome Measures

  1. Change in Overall Activity as Measured by Actigraphy [Baseline to M4]

    Part 1 - Blinded Treatment Period

  2. Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ) [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).

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

  4. Time to Clinical Worsening [Baseline to Month 4]

    Part 1 - Blinded Treatment Period

  5. Time to Clinical Deterioration [Baseline to Month 4]

    Part 1 Blinded Treatment Period

  6. Time to Clinical Improvement [Baseline to Month 4]

    Part 1 Blinded Treatment Period

  7. Change in 6 Minute Walk Distance [Baseline to Month 4]

    Part 1 Blinded Treatment Period

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Alabama Birmingham Alabama United States 35294
2 Banner - University Medical Center Arizona Phoenix Arizona United States 85006
3 Arizona Pulmonary Specialists, Ltd. Phoenix Arizona United States 85012
4 Amicis Research Northridge California United States 91324
5 Paloma Medical Group Paloma California United States 92675
6 University of California Davis Health Sacramento California United States 95817
7 Stanford University Medical Center Stanford California United States 94305
8 UC Denver Anschutz Medical Center Aurora Colorado United States 80046
9 National Jewish Denver Colorado United States 80206
10 Georgetown University Washington District of Columbia United States 20007
11 St. Francis Sleep Allergy and Lung Institute Clearwater Florida United States 33765
12 Advanced Pulmonary Research Institute Loxahatchee Groves Florida United States 33470
13 University of Miami Miami Florida United States 33125
14 Avanza Medical Research Center Pensacola Florida United States 32503
15 University of South Florida Tampa Florida United States 33612
16 Emory University Atlanta Georgia United States 30322
17 Northside Hospital Atlanta Georgia United States 30342
18 Piedmont Healthcare Austell Georgia United States 30106
19 Loyola University Chicago Illinois United States 60153
20 Northwestern Chicago Illinois United States 60611
21 North Shore University Hospital Evanston Illinois United States 60201
22 Southern Illinois University Springfield Illinois United States 62702 / 62794
23 Ascension St. Vincent Hospital Indianapolis Indiana United States 46260
24 Norton Pulmonary Specialists Louisville Kentucky United States 40202
25 University of Louisville Louisville Kentucky United States 40202
26 Johns Hopkins Hospital Baltimore Maryland United States 21205
27 Brigham and Women's Hospital Boston Massachusetts United States 02115
28 University of Michigan Ann Arbor Michigan United States 48109
29 Henry Ford Hospital Detroit Michigan United States 48202
30 The Lung Research Center, LLC Chesterfield Missouri United States 63017
31 Creighton University Omaha Nebraska United States 68124
32 Atlantic Health Respiratory Institute Summit New Jersey United States 07901
33 NYU Langone New York New York United States 10016
34 Mt Sinai Hospital New York New York United States 10029
35 Weill Cornell Medical Center New York New York United States 10065
36 Stony Brook University Hospital Stony Brook New York United States 11794
37 The University of North Carolina at Chapel Hill Marsico Clinical Research Center Chapel Hill North Carolina United States 27517
38 Pulmonix Greensboro North Carolina United States 27403
39 University of Cincinnati Cincinnati Ohio United States 45267
40 University Hospitals Cleveland Ohio United States 44106
41 The Ohio State University Columbus Ohio United States 43210
42 The Oregon Clinic Portland Oregon United States 97220
43 Thomas Jefferson University Korman Respiratory Institute Philadelphia Pennsylvania United States 19017
44 University of Pennsylvania Philadelphia Pennsylvania United States 19104
45 Temple University Philadelphia Pennsylvania United States 19140
46 AnMed Health Anderson South Carolina United States 29621
47 Medical University of South Carolina Charleston South Carolina United States 29425
48 Vanderbilt University Medical Center Nashville Tennessee United States 37232
49 Baylor University Medical Center Dallas Texas United States 75246
50 UT Southwestern Medical Center Dallas Texas United States 75390
51 University of Texas Health Science Center at Houston Houston Texas United States 77030
52 Metroplex Pulmonary and Sleep McKinney Texas United States 75069
53 University of Utah Health Sciences Salt Lake City Utah United States 84108
54 Inova Heart and Vascular Institute Advanced Lung Disease Clinic Falls Church Virginia United States 22042
55 Pulmonary Associates of Richmond Richmond Virginia United States 23229
56 University of Washington Medical Center Seattle Washington United States 981195
57 University of British Columbia Vancouver British Columbia Canada V5Z 1M9
58 London Health Sciences Centre London Ontario Canada K7L 2V6

Sponsors and Collaborators

  • Bellerophon Pulse Technologies

Investigators

  • Study Director: Edward Parsley, DO, Bellerophon Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Bellerophon Pulse Technologies
ClinicalTrials.gov Identifier:
NCT03267108
Other Study ID Numbers:
  • PULSE-PHPF-001
First Posted:
Aug 30, 2017
Last Update Posted:
Aug 10, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
Yes
Keywords provided by Bellerophon Pulse Technologies
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 10, 2022