3 Part Study to Assess Inhaled Nitric Oxide on Functional Pulmonary Imaging in Subj. Pulmonary Hypertension Associated w/ COPD and IPF

NCT02267655 | Completed Phase 1

• 1 other identifier: IK-7002-COPD-006
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this exploratory study is to examine the utility of high resolution computed tomography (HRCT) to measure changes in functional pulmonary imaging parameters as a function of short term a) iNO administration and b) nitric oxide (NO) cylinder concentration using the investigational medical device INOpulse® DS-C in subjects with WHO Group 3 PH associated with COPD on LTOT (Part 1) and in Subjects with WHO Group 3 PH associated with Idiopathic Pulmonary Fibrosis (IPF) on LTOT (Part 2 and Part 3)

Conditions

Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease; Idiopathic Pulmonary Fibrosis

Keywords

Inhaled Nitric Oxide (iNO); Pulmonary Hypertension (PH); Chronic Obstructive Pulmonary Disease (COPD); Long Term Oxygen Therapy (LTOT); Idiopathic Pulmonary Fibrosis (IPF)

Outcome Measures

Primary Outcomes (1)

• Change from baseline in lobar blood volume at total lung capacity (TLC) after dosing with pulsed iNO as measured by HRCT

  Part 1: baseline to end of treatment (1 day) Part 2: baseline to end of treatment (treatment visit B will occur at least 5 days and not more than 30 days after treatment visit A)

  up to 4 weeks

Secondary Outcomes (7)

• Changes in baseline measured by HRCT after dosing with pulsed iNO in Blood vessel % and density on lobar level

  up to 4 weeks

• Changes in baseline measured by HRCT after dosing with pulsed iNO in Total lung volume at TLC

  up to 4 weeks

• Changes in baseline measured by HRCT after dosing with pulsed iNO in Lobar volumes at TLC

  up to 4 weeks

• Changes in baseline measured by HRCT after dosing with pulsed iNO in Internal airflow distribution based on lobar expansion

  up to 4 weeks

• Changes in baseline measured by HRCT after dosing with pulsed iNO in Airway volume down to generation 8-10 at TLC

  up to 4 weeks

Study Arms (4)

inhaled Nitric Oxide 30 mcg/kg IBW/hr

ACTIVE COMPARATOR

30 mcg/kg IBW/hr of inhaled Nitric Oxide Part 1

Drug: inhaled Nitric Oxide - 30 mcg/kg IBW/hr

inhaled nitric oxide 75 mcg/kg IBW/hr

ACTIVE COMPARATOR

Part 2: 75mcg/Kg IBW/hr

Drug: inhaled nitric oxide 75 mcg/kg IBW/hr

inhaled Nitric Oxide 5,10,15 mcg/Kg IBW/hr

ACTIVE COMPARATOR

Part 3a: Dose tritration 5, 10 and 15 mcg/Kg IBW/hr Part 3b: continuing on dose determined by PI in 3a for 4 weeks

Drug: inhaled Nitric Oxide 5,10,15 mcg/Kg IBW/hr

Placebo

PLACEBO COMPARATOR

Placebo for 75 mcg/kg IBW/hr

Drug: inhaled nitric oxide 75 mcg/kg IBW/hr

Interventions

inhaled Nitric Oxide - 30 mcg/kg IBW/hr DRUG

inhaled Nitric Oxide in 30 mcg/kg IBW/hr doses Part 1

Also known as: inhaled NO, inhaled Nitric Oxide, iNO

inhaled Nitric Oxide 30 mcg/kg IBW/hr

inhaled Nitric Oxide 5,10,15 mcg/Kg IBW/hr DRUG

inhaled inhaled Nitric Oxide 5,10,15 mcg/Kg IBW/hr dose titration

Also known as: inhaled NO, inhaled Nitric Oxide, iNO

inhaled Nitric Oxide 5,10,15 mcg/Kg IBW/hr

inhaled nitric oxide 75 mcg/kg IBW/hr DRUG

inhaled nitric oxide 75 mcg/kg IBW/hr -Part 2b

Also known as: iNO

Placebo; inhaled nitric oxide 75 mcg/kg IBW/hr

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A confirmed diagnosis of COPD by the Global initiative for chronic Obstructive Lung Disease (GOLD) criteria
• Pulmonary hypertension determined by one of the following within the past 12 months:
• A right heart catheterization (not obtained within ± 7 days of an exacerbation) with an mPAP ≥ 25 mmHg, or
• Current or former smokers with at least 10 pack-years of tobacco cigarette smoking before study entry
• Age ≥ 40 years, ≤ 80 years
• A post-bronchodilatory FEV1/FVC \< 0.7 and a FEV1 \< 60% predicted (values obtained within 6 months prior to screening can be used unless obtained within ± 7 days of an exacerbation; otherwise, the test must be performed during screening)
• Receiving LTOT for ≥ 3 months and ≥ 10 hours per day as determined by history
• Females of childbearing potential must have a negative pre-treatment urine pregnancy test
• Signed informed consent prior to the initiation of any study mandated procedures or assessments

You may not qualify if:

• Subjects who meet any of the following criteria are not eligible for enrollment:
• A diagnosis of asthma or other non-COPD respiratory disease, in the opinion of the Investigator
• Lack of patency of nares upon physical examination
• Experienced during the last month an exacerbation requiring:
• start of or increase in systemic oral corticosteroid therapy and/or
• hospitalization
• Left ventricular dysfunction as measured by:
• Screening echocardiographic evidence of left ventricular systolic dysfunction (left ventricular ejection fraction \[LVEF\] \< 40%), or
• Screening echocardiographic evidence of left ventricular diastolic dysfunction
• \> moderate (i.e., \> Grade 2), or
• Any history of pulmonary capillary wedge pressure (PCWP), left atrial pressure (LAP) or left ventricular end diastolic pressure (LVEDP) \> 18 mmHg as measured during cardiac catheterization within the past 6 months unless documented to have resolved by a subsequent cardiac catheterization
• Renal impairment (i.e., an estimated GFRMDRD \< 60 ml/min/1.73 m2) or history of renal failure using the equation (Levey et al., 2007):
• estimated GFRMDRD = 175×Scr -1.154×Age-0.203 ×1.212 (if black) ×0.742 (if female)
• where Scr = Standardized serum creatinine
• Known allergy to contrast media.

Sponsors & Collaborators

• Bellerophon: lead

Study Sites (1)

Antwerp University Hospital

Edegem, 2650, Belgium

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Disease, Chronic Obstructive; Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pulmonary Fibrosis; Lung Diseases, Interstitial

Study Officials

• Ashika Ahmed

  Bellerophon Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2014
• First Posted: October 17, 2014
• Study Start: May 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: June 28, 2017
• Last Updated: February 21, 2023

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)