Clinical trial NCT03727451: A Dose Escalation Study to Assess the Safety and Efficacy of Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis or Sarcoidosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Hypertension
Pulmonary Fibrosis
Sarcoidosis, Pulmonary
Keywords: Pulmonary Hypertension
Pulmonary Fibrosis
Sarcoidosis
Lead sponsor: Bellerophon
Sponsor class: INDUSTRY
First posted: 2018-11-01
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Eligibility 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

Primary outcomes:
measure: Measurement of mean PAP
timeFrame: During a single right heart catheterization procedure
measure: Measurement of PCWP
timeFrame: During a single right heart catheterization procedure
measure: Measurement of PVR
timeFrame: During a single right heart catheterization procedure
measure: Measurement of CO
timeFrame: During a single right heart catheterization procedure
measure: Change in 6MWD from Baseline to 16 Weeks
timeFrame: 16 weeks
Secondary outcomes:
measure: Incidence and Severity of Treatment Emergent Adverse Events
timeFrame: During a single right heart catheterization procedure
measure: Pulmonary Rebound
timeFrame: During a single right heart catheterization procedure
measure: Distance Saturation Product (DSP)
timeFrame: 16 weeks
measure: Dyspnea
timeFrame: 16 weeks
measure: Quality of Life Assessment
timeFrame: 16 weeks
measure: Incidence of Adverse Events and Serious Averse Events
timeFrame: Through study completion; an average of 1 year
measure: Integral Distance Saturation Product (IDSP)
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Falls Church
country: United States
facility: Inova Heart and Lung Vascular Institute
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Bellerophon Pulse Technologies
name: Edward Parsley, DO
role: STUDY_DIRECTOR
References: