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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Fibrosis; Pulmonary Hypertension
• Intervention / Treatment: Combination product: INOpulse®; Combination product: Placebo; Combination product: Long Term Follow Up

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 Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Pulmonary Specialists
  • California
    • Los Angeles, California, United States, 90024
      • University of California
    • Sacramento, California, United States, 95817
      • University of California Davis Health
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Florida
    • Miami, Florida, United States, 33125
      • University of Miami
    • Pensacola, Florida, United States, 32503
      • Avanza Medical Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Austell, Georgia, United States, 30106
      • Piedmont Healthcare Pulmonary & Critical Care Research
  • Illinois
    • Chicago, Illinois, United States, 60153
      • Loyola University
  • Kentucky
    • Louisville, Kentucky, United States, 40202-1332
      • Norton Pulmonary Specialists
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • The Lung Research Center (St. Luke's)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • The University of North Carolina at Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati College of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19017
      • Thomas Jefferson University Korman Respiratory Institute
  • South Carolina
    • 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
      • University of Texas Southwestern Medical Center
  • 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

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: 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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6-minute walking test (6MWT) from baseline	Part 1 - Blinded Treatment Period	Change from baseline to week 8 or 16
Difference in activity as measured using ActiGraph devices	Part 1 - Blinded Treatment Period	Change from baseline to week 8 or 16
Percentage of patients with ≥15% decrease in activity	Part 1 - Blinded Treatment Period	Change from baseline to to week 8 or 16
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
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
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
Change in N-terminal (NT)-ProBNP (absolute and percentage)	Part 1 - Blinded Treatment Period	Change from baseline to week 8 or 16
Time to clinical improvement	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Time to clinical worsening	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
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
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
Change in diffusing capacity of the lungs for carbon monoxide (DLCO)	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Mortality	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Hospitalization (all cause and for cardiopulmonary or other cause)	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Change in Forced Expiratory Volume at 1 minute (FEV1)	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16
Change in Forced Vital Capacity (FVC)	Part 1 - Blinded Treatment Period	Baseline to week 8 or 16

Collaborators and Investigators

• Sponsor: Bellerophon
• Investigators: Study Director: Ashika Ahmed, MD, Bellerophon Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2017
• Primary Completion (Actual): November 22, 2019
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: July 27, 2021
• First Submitted That Met QC Criteria: February 17, 2023
• First Posted (Estimate): February 28, 2023

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 17, 2023
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Oxygen; Inhaled Nitric Oxide; iNO; Long Term Oxygen Therapy; Pulmonary Fibrosis (PF)
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Hypertension; Pulmonary Fibrosis; Hypertension, Pulmonary
• Other Study ID Numbers: PULSE-PHPF-001 Phase 2

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