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

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ClinicalTrials.gov Identifier: NCT03267108
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : July 12, 2018
Sponsor:
Collaborator:
Bellerophon
Information provided by (Responsible Party):
Bellerophon ( Bellerophon Pulse Technologies )

Brief Summary:
A phase 2b, randomized, double-blind, placebo-controlled clinical study to assess the safety and efficacy of pulsed, inhaled nitric oxide (iNO) versus placebo in subjects with pulmonary fibrosis on long term oxygen therapy (Part 1 and Part 2).

Condition or disease Intervention/treatment Phase
Pulmonary Fibrosis Pulmonary Hypertension Drug: Inhaled Nitric Oxide Drug: Placebo Phase 2

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 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 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 : December 29, 2017
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo

Part 1: Placebo at a dose setting of 30 mcg/kg IBW/hr for up to 24 hours per day for 1 week run-in period and 8 week treatment period.

Part 2: iNO at a dose setting of 30 mcg/kg IBW/hr for up to 24 hours per day for open label treatment period.

Drug: Placebo
Placebo

Experimental: Inhaled Nitric Oxide 30 mcg/kg IBW/hr

Part 1: Placebo at a dose setting of 30 mcg/kg IBW/hr for up to 24 hours per day for 1 week run-in period followed by iNO at a dose setting of 30 mcg/kg IBW/hr for up to 24 hours per day for the 8 week treatment period.

Part 2: iNO at a dose setting of 30 mcg/kg IBW/hr for up to 24 hours per day for open label treatment period.

Drug: Inhaled Nitric Oxide
Inhaled Nitric Oxide 30 mcg/kg IBW/hr for treatment randomization period (Day 0 to Week 8). Continued open label treatment is available following completion of randomized treatment period.
Other Name: iNO




Primary Outcome Measures :
  1. 6 Minute Walk Distance (6MWD) [ Time Frame: 8 weeks ]
    Change in 6MWD from baseline to Week 8


Secondary Outcome Measures :
  1. Right Ventricular Function (RVF) [ Time Frame: 8 weeks ]
    Change in RVF as measured by RV Tei index and RV free wall longitudinal strain from baseline to Week 8


Other Outcome Measures:
  1. Nadir SpO2 [ Time Frame: 8 weeks ]
    Difference in Nadir SpO2 during 6MWT from baseline to Week 8

  2. Oxygen desaturation [ Time Frame: 8 weeks ]
    Difference in oxygen desaturation during 6MWT from baseline to Week 8

  3. Distance Saturation Product (DSP) [ Time Frame: 8 weeks ]
    Difference in DSP from baseline to Week 8

  4. Integral Distance Saturation Product (IDSP) [ Time Frame: 8 weeks ]
    Difference in IDSP from baseline to Week 8

  5. Activity [ Time Frame: 8 weeks ]
    Difference in Activity as measured by activity monitoring from baseline to Week 8

  6. Dyspnea [ Time Frame: 8 weeks ]
    Difference in Dyspnea as measured by UCSD Shortness of Breath (SOB) questionnaire from baseline to Week 8

  7. Quality of Life [ Time Frame: 8 weeks ]
    Difference in disease-specific Quality of Life as measured by St. George Respiratory questionnaire (SGRQ) from baseline to Week 8



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed Informed Consent Form (and assent as appropriate) prior to the initiation of any study mandated procedures or assessments.
  2. 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 guidelines, as per American Thoracic Society (ATS) / European Respiratory Society (ERS) / Japanese Respiratory Society (JRS) / Latin American Thoracic Association (ALAT):

    2.1 Major IIPs (idiopathic interstitial pneumonias) 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

    2.2 Chronic hypersensitivity pneumonitis

    2.3 Occupational lung disease

  3. At least 50% of the subjects will have confirmed intermediate or high probability of pulmonary hypertension as determined by echocardiography according to the 2015 ESC/ERS Guidelines for Diagnosis and Treatment of Pulmonary Hypertension.
  4. Have been using oxygen therapy by nasal cannula for at least 4 weeks prior to the screening run-in period.
  5. 6MWD ≥ 100 meters and ≤ 450 meters prior to randomization.
  6. WHO Functional Class II-IV
  7. Forced Vital Capacity ≥ 40% predicted within last 6 months prior to screening the screening run-in period.
  8. For at least 1 week prior to Baseline/Randomization, subjects must demonstrate the ability to consistently use the device greater than 12 hrs/day in the opinion of the Investigator.
  9. Female subjects of childbearing potential must have a negative pre-treatment pregnancy test (serum or urine). All female subjects should take adequate precaution to avoid pregnancy.
  10. Subjects must have completed at least 1 week of activity monitoring prior to the Baseline/Randomization visit.
  11. Age between 18 and 80 years (inclusive)
  12. Subject should be clinically stable for at least 4 weeks prior to Baseline/Randomization in the opinion of the Principal Investigator.

Exclusion Criteria:

  1. Demonstrate symptomatic rebound defined as significant cardiopulmonary instability, such as systemic arterial oxygen desaturation, hypoxemia, bradycardia, tachycardia, systemic hypotension, shortness of breath, near-syncope, and syncope, occurring within 1 hour of acute iNO during rebound testing
  2. Episodes of disease worsening within 1 month prior to Baseline/Randomization
  3. Use of any type of intravenous or subcutaneous prostacyclin therapies
  4. Subjects receiving riociguat
  5. Acute or chronic physical impairment (other than dyspnea due to PF) that would limit the ability to comply with study procedures or adherence to therapy (i.e., 6MWT), including carrying and wearing the pulsed delivery device per study protocol, or medical problem(s) likely to preclude completion of the study
  6. Pregnant or breastfeeding females at Screening
  7. Administered L-arginine within 1 month prior to Screening
  8. The concurrent use of the INOpulse device with a continuous positive airway pressure (CPAP), Bilevel positive airway pressure (BPAP), or any other positive pressure device.
  9. Use of investigational drugs or devices within 1 month prior to Screening (other than acute vasodilator testing with iNO)
  10. Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study including unable to complete 6MWT.
  11. Any subject who has been enrolled in any previous clinical study with inhaled NO administered through pulse delivery
  12. Evidence of any connective tissue disease in the last 6 months prior to screening in the opinion of the Principal Investigator
  13. Evidence of clinically significant Combined Pulmonary Fibrosis and Emphysema (CPFE) in the opinion of the Investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03267108


Contacts
Contact: Sandra Hankins 908-574-4715 sandra.hankins@bellerophon.com
Contact: Amy Edmonds 908-574-4765 amy.edmonds@bellerophon.com

Locations
United States, California
University of California Davis Health Recruiting
Sacramento, California, United States, 95817
Contact: Macey Sockolov, CCRP    916-734-1554    mlsockolov@ucdavis.edu   
Principal Investigator: Roblee Allen, MD         
United States, Colorado
UC Denver Anschutz Medical Center Recruiting
Aurora, Colorado, United States, 80046
Contact: Colton Carter    303-724-7938      
Contact: Cheryl Abbott, RN, CCRP    303-724-7466      
Principal Investigator: Todd Bull, MD         
National Jewish Health Recruiting
Denver, Colorado, United States, 80206
Contact: Kris Eliopoulos    303-270-2622      
Principal Investigator: Amy Olson, MD         
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33125
Contact: Emmanuelle Simonet, MA, CCRP    305-243-3728      
Principal Investigator: Roger Alvarez, MD         
Central Florida Pulmonary Group Recruiting
Orlando, Florida, United States, 33136
Contact: Sharon Foust, CCRC    407-841-1100 ext 135    sfoust@cfpulmonary.com   
Principal Investigator: Syed Mobin, MD         
United States, Georgia
Piedmont Healthcare Recruiting
Austell, Georgia, United States, 30106
Contact: Sheila Greene, MSA    770-745-1404 ext 2    sheila.greene@piedmont.org   
Principal Investigator: Amy Case, MD         
United States, Kentucky
Kentuckiana Pulmonary Associates Recruiting
Louisville, Kentucky, United States, 40202
Contact: Kimberly Robinson    502-587-8000    krobinson@kpadocs.com   
Principal Investigator: John McConnell, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Candace Flaherty, CCRP    734-936-8301    cflah@med.umich.edu   
Contact: Christi Getty    734-232-5844    cgetty@med.umich.edu   
Principal Investigator: Elizabeth Belloli, MD         
United States, Missouri
The Lung Research Center, LLC Recruiting
Chesterfield, Missouri, United States, 63017
Contact: Anna Shipp, RRT    314-682-3653    Anna.Shipp@stlukes-stl.com   
Contact: Kathleen McNulty, MHS    314-682-3653    Kathleen.McNulty@stlukes-stl.com   
Principal Investigator: Neil A Ettinger, MD, FACCP         
United States, Pennsylvania
Temple University Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Delores Fehrle    215-707-4260    delores.fehrle@tuhs.temple.edu   
Principal Investigator: Jeffrey Stewart, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Jordyn DeMartino    843-792-8092    demartij@musc.edu   
Principal Investigator: Rahul Argula, MD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: James Del Greco, MSN, RN    615-343-7068    james.del.greco@vanderbilt.edu   
Principal Investigator: James Loyd, MD         
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Oluwatosin Igenoza    214-645-6493    oluwatosin.igenoza@utsouthwestern.edu   
Principal Investigator: Sonja Bartolome, MD         
United States, Utah
University of Utah Health Sciences Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Scott Sweeten    801-581-5811      
Principal Investigator: MaryBeth Scholand, MD         
United States, Virginia
Inova Heart and Vascular Institute Advanced Lung Disease Clinic Recruiting
Falls Church, Virginia, United States, 22042
Contact: Serina Zorrilla, RN    703-776-6147    serina.zorrilla@inova.org   
Contact: Edwinia Battle, RN    703-776-3067    edwinia.battle@inova.org   
Principal Investigator: Christopher King, MD         
Pulmonary Associates of Richmond Recruiting
Richmond, Virginia, United States, 23229
Contact: Betsy Daniel, CCRC    804-288-5945    bdaniel@paraccess.com   
Principal Investigator: Shilpa Johri, MD         
Sponsors and Collaborators
Bellerophon Pulse Technologies
Bellerophon
Investigators
Study Director: Deborah Quinn, MD Bellerophon Therapeutics

Responsible Party: Bellerophon Pulse Technologies
ClinicalTrials.gov Identifier: NCT03267108     History of Changes
Other Study ID Numbers: PULSE-PHPF-001
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: July 12, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bellerophon ( Bellerophon Pulse Technologies ):
Pulmonary Fibrosis
PF
Pulmonary Hypertension
Inhaled Nitric Oxide
iNO
Long Term Oxygen Therapy
Oxygen

Additional relevant MeSH terms:
Pulmonary Fibrosis
Hypertension
Fibrosis
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents