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

August 9, 2022 updated by: Bellerophon

A Dose Escalation Study to Assess the Safety and Efficacy of Pulsed, Inhaled Nitric Oxide in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis or Sarcoidosis on Long Term Oxygen Therapy Followed by an Optional Open-Label Long Term Extension Safety Study

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

Study Overview

Detailed Description

A phase 2b, open label study to assess the hemodynamic effects of increasing doses of pulsed, inhaled nitric oxide (iNO) in subjects with pulmonary hypertension associated with pulmonary fibrosis or sarcoidosis on long term oxygen therapy followed by an open label extension study

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Florida
      • Miami, Florida, United States, 33125
        • University of Miami
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Heart and Lung Vascular Institute
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Signed informed consent
  2. A primary diagnosis of sarcoidosis as defined by the ATS/ERS/WASOG statement or pulmonary fibrosis associated with one of the following conditions:

    2.1 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

    2.2 Chronic hypersensitivity pneumonitis

    2.3 Occupational lung disease

    2.4 Connective tissue disease with evidence of significant pulmonary fibrosis

  3. Intermediate or high probability of PH by echocardiogram as assessed by local Radiologist/Investigator, or PH as determined by a right heart catheterization (RHC) within 5 years prior to Baseline with the following parameters:

    1. Pulmonary vascular resistance (PVR) ˃3 Wood Units (WU) (320 dynes.sec.cm-5)
    2. A left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg
    3. A mean pulmonary arterial pressure (mPAP) of ≥ 25 mmHg
  4. 6MWD ≥ 100 meters and ≤ 450 meters
  5. WHO Functional Class II-IV
  6. Forced Vital Capacity ≥ 40% predicted within last 6 weeks prior to screening
  7. Females of childbearing potential must have a negative pre-treatment pregnancy test (urine).
  8. Age between 18 and 85 years (inclusive)
  9. Clinically stable for at least 4 weeks prior to Baseline in the opinion of the Investigator
  10. If on therapy for their parenchymal lung disease and/or sarcoidosis, then the subject should be on a stable well-tolerated dose of the medication(s) for at least 4 weeks prior to enrollment.

Exclusion Criteria:

  1. Use of any type of PAH specific therapies
  2. Episodes of disease worsening within 3 months prior to Baseline
  3. Pregnant or breastfeeding females at Screening
  4. Administered L-arginine within 1 month prior to Screening
  5. Any subject who has been enrolled in any previous clinical study with inhaled NO administered through pulsed delivery
  6. On more than 6 L/min of oxygen at rest by nasal cannula for less than 4 weeks
  7. 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
  8. 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
  9. 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
  10. For subjects continuing on open label therapy, the concurrent use of the INOpulse device with a CPAP/BiPAP, or any other positive pressure device
  11. Significant heart failure in the opinion of the Investigator

    1. LVEF<40% or
    2. PCWP on last RHC>15 mmHg (unless concurrent LVEDP <15 mmHg) or
    3. Significant diastolic dysfunction on echocardiogram

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: PH-Pulmonary Fibrosis

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

inhaled nitric oxide
Other Names:
  • iNOPulse
EXPERIMENTAL: PH-Sarcoidosis

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

inhaled nitric oxide
Other Names:
  • iNOPulse

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of mean PAP
Time Frame: During a single right heart catheterization procedure
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
Time Frame: During a single right heart catheterization procedure
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
Time Frame: During a single right heart catheterization procedure
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
Time Frame: During a single right heart catheterization procedure
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
Time Frame: 16 weeks
Change in 6 minute walk distance
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and Severity of Treatment Emergent Adverse Events
Time Frame: During a single right heart catheterization procedure
Including adverse events related to device deficiency
During a single right heart catheterization procedure
Pulmonary Rebound
Time Frame: During a single right heart catheterization procedure
Symptoms associated with acute withdrawal of iNO: systemic arterial oxygen desaturation, hypoxemia, bradycardia, tachycardia, systemic hypotension, shortness of breath, near-syncope and syncope
During a single right heart catheterization procedure
Distance Saturation Product (DSP)
Time Frame: 16 weeks

Difference in DSP from baseline to Week 16

Difference in DSP from baseline to 16 weeks

16 weeks
Dyspnea
Time Frame: 16 weeks
Difference in dyspnea as measured by UCSD Medical Center Pulmonary Rehabilitation Program Shortness of Breath Questionnaire on a scale from 0 (none at all) to 5 (maximal or unable to do because of breathlessness) from baseline to Week 16
16 weeks
Quality of Life Assessment
Time Frame: 16 weeks
Difference in disease specific Quality of Life as measured by St. George's Respiratory Questionnaire
16 weeks
Incidence of Adverse Events and Serious Averse Events
Time Frame: Through study completion; an average of 1 year
Evaluation of adverse events and serious adverse events
Through study completion; an average of 1 year
Integral Distance Saturation Product (IDSP)
Time Frame: 16 weeks
Difference in IDSP from baseline to Week 16
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 30, 2019

Primary Completion (ACTUAL)

September 7, 2021

Study Completion (ACTUAL)

June 15, 2022

Study Registration Dates

First Submitted

October 30, 2018

First Submitted That Met QC Criteria

October 30, 2018

First Posted (ACTUAL)

November 1, 2018

Study Record Updates

Last Update Posted (ACTUAL)

August 10, 2022

Last Update Submitted That Met QC Criteria

August 9, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

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

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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