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

Pulmonary Hypertension Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05747508
• Other study ID #: PULSE-PHPF-001 Phase 2
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 29, 2017
• Est. completion date: December 2023

Study information

• Verified date: March 2022
• Source: Bellerophon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 85
• Est. completion date: December 2023
• Est. primary completion date: November 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Combination Product:
• INOpulse®
Patients will be treated by means of an INOpulse® device using an INOpulse® nasal cannula
• Placebo
Patients will be treated by means of an INOpulse® device using an INOpulse® nasal cannula
• Long Term Follow Up
Patients will be treated by means of an INOpulse® device using an INOpulse® nasal cannula

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Piedmont Healthcare Pulmonary & Critical Care Research	Austell	Georgia
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	The Lung Research Center (St. Luke's)	Chesterfield	Missouri
United States	Loyola University	Chicago	Illinois
United States	University of Cincinnati College of Medicine	Cincinnati	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Inova Heart and Vascular Institute Advanced Lung Disease Clinic	Falls Church	Virginia
United States	University of California	Los Angeles	California
United States	Norton Pulmonary Specialists	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Avanza Medical Research Center	Pensacola	Florida
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Korman Respiratory Institute	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists	Phoenix	Arizona
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

Sponsors (1)

Lead Sponsor	Collaborator
Bellerophon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in 6-minute walking test (6MWT) from baseline	Part 1 - Blinded Treatment Period	Change from baseline to week 8 or 16
Other	Difference in activity as measured using ActiGraph devices	Part 1 - Blinded Treatment Period	Change from baseline to week 8 or 16
Other	Percentage of patients with =15% decrease in activity	Part 1 - Blinded Treatment Period	Change from baseline to to week 8 or 16
Other	Difference in dyspnea as measured by University of California San Diego Shortness of Breath Questionnaire	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).	Change from baseline to to week 8 or 16
Other	Difference in St. George Respiratory Questionnaire and sub-groups	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)	Change from baseline to to week 8 or 16
Other	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)	Part 1 - Blinded Treatment Period	Change from baseline to to week 8 or 16
Other	Change in N-terminal (NT)-ProBNP (absolute and percentage)	Part 1 - Blinded Treatment Period	Change from baseline to week 8 or 16
Other	Time to clinical improvement	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Other	Time to clinical worsening	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Other	Incidence and severity of treatment emergent adverse events, including those related to INOpulse® device deficiency	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Other	Adverse events that may be due to rebound associated with a temporal acute withdrawal of investigational study drug	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Other	Change in diffusing capacity of the lungs for carbon monoxide (DLCO)	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Other	Mortality	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Other	Hospitalization (all cause and for cardiopulmonary or other cause)	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Other	Change in Forced Expiratory Volume at 1 minute (FEV1)	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Other	Change in Forced Vital Capacity (FVC)	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Primary	Efficacy of escalating doses of iNO in patient's life participation as assessed in minutes per day of moderate to vigorous activity.	Part 1 - Blinded Treatment Period	Change from baseline to week 8 or 16