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

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ClinicalTrials.gov Identifier: NCT03727451
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
Bellerophon

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

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Pulmonary Fibrosis Sarcoidosis, Pulmonary Combination Product: iNO Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 30, 2019
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


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

Combination Product: iNO
inhaled nitric oxide
Other Name: 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

Combination Product: iNO
inhaled nitric oxide
Other Name: iNOPulse




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. Change in 6MWD from Baseline to 16 Weeks [ Time Frame: 16 weeks ]
    Change in 6 minute walk distance


Secondary Outcome Measures :
  1. Incidence and Severity of Treatment Emergent Adverse Events [ Time Frame: During a single right heart catheterization procedure ]
    Including adverse events related to device deficiency

  2. 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

  3. Distance Saturation Product (DSP) [ Time Frame: 16 weeks ]

    Difference in DSP from baseline to Week 16

    Difference in DSP from baseline to 16 weeks


  4. 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

  5. Quality of Life Assessment [ Time Frame: 16 weeks ]
    Difference in disease specific Quality of Life as measured by St. George's Respiratory Questionnaire

  6. 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

  7. Integral Distance Saturation Product (IDSP) [ Time Frame: 16 weeks ]
    Difference in IDSP from baseline to Week 16



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT03727451


Contacts
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Contact: Valerie Parker 908.574.2661 valerie.parker@bellerophon.com
Contact: Amy Edmonds 908.574.4765 amy.edmonds@bellerophon.com

Locations
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United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33125
Contact: Emmanuelle Simonet    305-243-3728      
Principal Investigator: Roger Alvarez         
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Joyce Zigler    513-584-6252      
Principal Investigator: Robert Baughman         
United States, Pennsylvania
Temple University Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Dee Fehrlee    215-707-8043      
Principal Investigator: Jeffrey Stewart         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Jim DelGreco    615-936-2298      
Principal Investigator: Jim Loyd, MD         
United States, Virginia
Inova Heart and Lung Vascular Institute Recruiting
Falls Church, Virginia, United States, 22042
Contact: Serina Zorrilla    703-776-6147      
Principal Investigator: Kareem Ahmad         
United States, Washington
University of Washington Medical Center Not yet recruiting
Seattle, Washington, United States, 98195
Contact: Chessa Goss    206-616-5459      
Principal Investigator: Bridget Collins         
Sponsors and Collaborators
Bellerophon
Investigators
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Study Director: Hunter Gillies, MD Bellerophon Pulse Technologies

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Responsible Party: Bellerophon
ClinicalTrials.gov Identifier: NCT03727451     History of Changes
Other Study ID Numbers: PULSE-PHPF-002
First Posted: November 1, 2018    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bellerophon:
Pulmonary Hypertension
Pulmonary Fibrosis
Sarcoidosis
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Pulmonary Fibrosis
Sarcoidosis, Pulmonary
Hypertension
Sarcoidosis
Fibrosis
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Lung Diseases, Interstitial
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