A Dose Escalation Study to Assess the Safety and Efficacy of Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis or Sarcoidosis

NCT03727451 | Completed Phase 2 FDA Drug

• 1 other identifier: PULSE-PHPF-002
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 6

Brief Summary

A phase 2b, open label study to assess the safety and efficacy of increasing doses of pulsed, inhaled nitric oxide (iNO) in subjects with pulmonary fibrosis and sarcoidosis on long term oxygen therapy followed by a long term extension study

Conditions

Pulmonary Hypertension; Pulmonary Fibrosis; Sarcoidosis, Pulmonary

Keywords

Pulmonary Hypertension; Pulmonary Fibrosis; Sarcoidosis

Outcome Measures

Primary Outcomes (5)

• Measurement of mean PAP

  Mean pulmonary arterial pressure (mPAP) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr

  During a single right heart catheterization procedure

• Measurement of PCWP

  Pulmonary capillary wedge pressure (PCWP) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr

  During a single right heart catheterization procedure

• Measurement of PVR

  Pulmonary vascular resistance (PVR) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr

  During a single right heart catheterization procedure

• Measurement of CO

  Cardiac output (CO) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr

  During a single right heart catheterization procedure

• Change in 6MWD from Baseline to 16 Weeks

  Change in 6 minute walk distance

  16 weeks

Secondary Outcomes (7)

• Incidence and Severity of Treatment Emergent Adverse Events

  During a single right heart catheterization procedure

• Pulmonary Rebound

  During a single right heart catheterization procedure

• Distance Saturation Product (DSP)

  16 weeks

• Dyspnea

  16 weeks

• Quality of Life Assessment

  16 weeks

Study Arms (2)

PH-Pulmonary Fibrosis

EXPERIMENTAL

Part 1: 1st 4 subjects will be treated with iNO 30, 45, 75 mcg/kg IBW/hr 2nd 4 subjects will be treated with iNO 45, 75, 125 mcg/kg IBW/hr Part 2: Optional open label long term extension at the optimal dose as identified in Part 1

Combination Product: iNO

PH-Sarcoidosis

EXPERIMENTAL

Part 1: 1st 4 subjects will be treated with iNO 30, 45, 75 mcg/kg IBW/hr 2nd 4 subjects will be treated with iNO 45, 75, 125 mcg/kg IBW/hr Part 2: Optional Open label long term extension at the optimal dose as identified in Part 1

Combination Product: iNO

Interventions

iNO COMBINATION_PRODUCT

inhaled nitric oxide

Also known as: iNOPulse

PH-Pulmonary Fibrosis; PH-Sarcoidosis

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• A primary diagnosis of sarcoidosis as defined by the ATS/ERS/WASOG statement or pulmonary fibrosis associated with one of the following conditions:
• Major IIPs (idiopathic interstitial pneumonias) diagnosed 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

You may not qualify if:

• Use of any type of PAH specific therapies
• Episodes of disease worsening within 3 months prior to Baseline
• Pregnant or breastfeeding females at Screening
• Administered L-arginine within 1 month prior to Screening
• Any subject who has been enrolled in any previous clinical study with inhaled NO administered through pulsed delivery
• On more than 6 L/min of oxygen at rest by nasal cannula for less than 4 weeks
• Evidence of any connective tissue disease with FVC \> 60% in the last 6 months prior to screening unless there is evidence of moderate to severe fibrosis on CT scan in the opinion of the local radiologist/Investigator
• Evidence of clinically significant combined pulmonary fibrosis with emphysema (CPFE) if \> 15% of lung fields by CT scan show evidence of emphysema in the opinion of the local radiologist/Investigator
• For subjects with sarcoidosis, clinically significant evidence of pulmonary fibrosis on CT scan in the opinion of the local radiologist/Investigator and FVC ≥80% predicted
• For subjects continuing on open label therapy, the concurrent use of the INOpulse device with a CPAP/BiPAP, or any other positive pressure device
• Significant heart failure in the opinion of the Investigator
• LVEF\<40% or
• PCWP on last RHC\>15 mmHg (unless concurrent LVEDP \<15 mmHg) or
• Significant diastolic dysfunction on echocardiogram

Sponsors & Collaborators

• Bellerophon: lead

Study Sites (6)

University of Miami

Miami, Florida, 33125, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Inova Heart and Lung Vascular Institute

Falls Church, Virginia, 22042, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Fibrosis; Sarcoidosis, Pulmonary; Sarcoidosis

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Interstitial; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Study Officials

• Edward Parsley, DO

  Bellerophon Pulse Technologies

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: November 1, 2018
• Study Start: January 30, 2019
• Primary Completion: September 7, 2021
• Study Completion: June 15, 2022
• Last Updated: August 10, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)