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

Pulmonary Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03727451
• Other study ID #: PULSE-PHPF-002
• Status: Completed
• Phase: Phase 2
• Start date: January 30, 2019
• Est. completion date: June 15, 2022

Study information

• Verified date: February 2022
• Source: Bellerophon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: June 15, 2022
• Est. primary completion date: September 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Fibrosis
• Pulmonary Hypertension
• Sarcoidosis
• Sarcoidosis, Pulmonary

Intervention

Combination Product:
• iNO
inhaled nitric oxide

Locations

Country	Name	City	State
United States	University of Cincinnati	Cincinnati	Ohio
United States	Inova Heart and Lung Vascular Institute	Falls Church	Virginia
United States	University of Miami	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Temple University	Philadelphia	Pennsylvania
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Bellerophon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Change in 6MWD from Baseline to 16 Weeks	Change in 6 minute walk distance	16 weeks
Secondary	Incidence and Severity of Treatment Emergent Adverse Events	Including adverse events related to device deficiency	During a single right heart catheterization procedure
Secondary	Pulmonary Rebound	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
Secondary	Distance Saturation Product (DSP)	Difference in DSP from baseline to Week 16; Difference in DSP from baseline to 16 weeks	16 weeks
Secondary	Dyspnea	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
Secondary	Quality of Life Assessment	Difference in disease specific Quality of Life as measured by St. George's Respiratory Questionnaire	16 weeks
Secondary	Incidence of Adverse Events and Serious Averse Events	Evaluation of adverse events and serious adverse events	Through study completion; an average of 1 year
Secondary	Integral Distance Saturation Product (IDSP)	Difference in IDSP from baseline to Week 16	16 weeks