A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis

Sponsor

Bellerophon (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT05747508

Collaborator

(none)

Enrollment

Locations

Arms

71.1

Anticipated Duration (Months)

3.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A randomized, double-blind, placebo-controlled dose escalation study to assess the safety and efficacy of pulsed, inhaled nitric oxide (iNO) in subjects with pulmonary fibrosis on long term oxygen therapy.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Fibrosis Pulmonary Hypertension	Combination Product: INOpulse® Combination Product: Placebo Combination Product: Long Term Follow Up	Phase 2

Detailed Description

A Phase 2b, randomized, double-blind, placebo-controlled dose escalation clinical study to assess the safety and efficacy of pulsed, inhaled nitric oxide in subjects with and without pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy (Part 1 and Part 2)

Study Design

Study Type:

Interventional

Actual Enrollment :

85 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 Clinical Study to Assess the Safety and Efficacy of Pulsed Inhaled Nitric Oxide (iNO) in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis on Long Term Oxygen Therapy (Part 1 and Part 2)

Actual Study Start Date :

Dec 29, 2017

Actual Primary Completion Date :

Nov 22, 2019

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Inhaled Nitric Oxide (iNO) Pulsed inhaled iNO30, 45 and 75 mcg/kg Ideal Body Weight (IBW)/hour (hr)	Combination Product: INOpulse® Patients 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 Patients will be treated by means of an INOpulse® device using an INOpulse® nasal cannula
Active Comparator: Long Term Follow Up Pulsed inhaled iNO30, 45 or 75 mcg/kg IBW/hr	Combination Product: Long Term Follow Up Patients will be treated by means of an INOpulse® device using an INOpulse® nasal cannula

Arm

Intervention/Treatment

Active Comparator: Inhaled Nitric Oxide (iNO)

Pulsed inhaled iNO30, 45 and 75 mcg/kg Ideal Body Weight (IBW)/hour (hr)

Combination Product: INOpulse®

Patients 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

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

Active Comparator: Long Term Follow Up

Pulsed inhaled iNO30, 45 or 75 mcg/kg IBW/hr

Combination Product: Long Term Follow Up

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

Outcome Measures

Primary Outcome Measures

Efficacy of escalating doses of iNO in patient's life participation as assessed in minutes per day of moderate to vigorous activity. [Change from baseline to week 8 or 16]
Part 1 - Blinded Treatment Period

Other Outcome Measures

Change in 6-minute walking test (6MWT) from baseline [Change from baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Difference in activity as measured using ActiGraph devices [Change from baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Percentage of patients with ≥15% decrease in activity [Change from baseline to to week 8 or 16]
Part 1 - Blinded Treatment Period
Difference in dyspnea as measured by University of California San Diego Shortness of Breath Questionnaire [Change from baseline to to week 8 or 16]
The University of California San Diego Shortness of Breath Questionnaire 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).
Difference in St. George Respiratory Questionnaire and sub-groups [Change from baseline to to week 8 or 16]
St. George Respiratory Questionnaire and sub-groups 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)
Percentage of patients with a clinically meaningful difference (reduction of at least 4 points) in the disease-specific quality of life measured using the disease specific St. George Respiratory Questionnaire (SGRQ) [Change from baseline to to week 8 or 16]
Part 1 - Blinded Treatment Period
Change in N-terminal (NT)-ProBNP (absolute and percentage) [Change from baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Time to clinical improvement [Baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Time to clinical worsening [Baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Incidence and severity of treatment emergent adverse events, including those related to INOpulse® device deficiency [Baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Adverse events that may be due to rebound associated with a temporal acute withdrawal of investigational study drug [Baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Change in diffusing capacity of the lungs for carbon monoxide (DLCO) [Baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Mortality [Baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Hospitalization (all cause and for cardiopulmonary or other cause) [Baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Change in Forced Expiratory Volume at 1 minute (FEV1) [Baseline to week 8 or 16]
Part 1 - Blinded Treatment Period
Change in Forced Vital Capacity (FVC) [Baseline to week 8 or 16]
Part 1 - Blinded Treatment Period

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosed with pulmonary fibrosis by high resolution CT scan performed in the 6 months prior to screening associated with one of the following conditions and confirmed using one of the following guidelines, as per American Thoracic Society (AGS) / European Respiratory Society (ERS) / Japanese Respiratory Society (JRS) / Latin American

Thoracic Association (ALAT):

Major idiopathic interstitial pneumonias (IIPs) 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
Have been using oxygen therapy by nasal cannula for at least 4 weeks
6-Minute Walk Distance (6MWD) ≥ 100 meters and ≤ 450 meters at screening and Baseline/Randomization visits
World Health Organization (WHO) Functional Class II-IV
Forced Vital Capacity ≥ 40% predicated within the last 6 months prior to the screening run-in period
Age between 18 and 85 years (inclusive)

Exclusion Criteria:

Pregnant or breastfeeding females at Screening
In the last 6 months prior to screening, evidence of any connective tissue disease with FVC > 60% unless there is evidence of moderate to severe fibrosis on CT scan in the opinion of the local radiologist/Investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Pulmonary Specialists	Phoenix	Arizona	United States	85012
2	University of California	Los Angeles	California	United States	90024
3	University of California Davis Health	Sacramento	California	United States	95817
4	University of Colorado Hospital	Aurora	Colorado	United States	80045
5	University of Miami	Miami	Florida	United States	33125
6	Avanza Medical Research Center	Pensacola	Florida	United States	32503
7	Emory University	Atlanta	Georgia	United States	30322
8	Piedmont Healthcare Pulmonary & Critical Care Research	Austell	Georgia	United States	30106
9	Loyola University	Chicago	Illinois	United States	60153
10	Norton Pulmonary Specialists	Louisville	Kentucky	United States	40202-1332
11	University of Michigan	Ann Arbor	Michigan	United States	48109
12	The Lung Research Center (St. Luke's)	Chesterfield	Missouri	United States	63017
13	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27517
14	University of Cincinnati College of Medicine	Cincinnati	Ohio	United States	45267
15	Thomas Jefferson University Korman Respiratory Institute	Philadelphia	Pennsylvania	United States	19017
16	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
17	Medical University of South Carolina	Charleston	South Carolina	United States	29425
18	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
19	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
20	University of Utah Health Sciences	Salt Lake City	Utah	United States	84108
21	Inova Heart and Vascular Institute Advanced Lung Disease Clinic	Falls Church	Virginia	United States	22042
22	Pulmonary Associates of Richmond	Richmond	Virginia	United States	23229
23	University of Washington Medical Center	Seattle	Washington	United States	98195