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

• Register: ClinicalTrials.gov
• Last refreshed on: 27 February 2023
• Main ID: NCT02267655
• Date of registration: 07/10/2014
• Prospective Registration: Yes
• Primary sponsor: Bellerophon
• Public title: 3 Part Study to Assess Inhaled Nitric Oxide on Functional Pulmonary Imaging in Subj. Pulmonary Hypertension Associated w/ COPD and IPF
• Scientific title: An Exploratory, 3-Part, Clinical Study to Assess the Effect of Pulsed, Inhaled Nitric Oxide (iNO) on Functional Pulmonary Imaging Parameters in Subjects With World Health Organization (WHO) Group 3 Pulmonary Hypertension (PH) Associated With Chronic Obstructive Pulmonary Disease (COPD) on Long-Term Oxygen Therapy (LTOT) (Part 1) and in Subjects With WHO Group 3 PH Associated With Idiopathic Pulmonary Fibrosis (IPF) on LTOT (Part 2 and Part 3)
• Date of first enrolment: May 2015
• Target sample size: 8
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02267655
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

Belgium

Contacts

• Name: Ashika Ahmed
• Affiliation: Bellerophon Therapeutics

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subjects must meet all of the following inclusion criteria to be enrolled and eligible
to participate in the study:

1. A confirmed diagnosis of COPD by the Global initiative for chronic Obstructive
Lung Disease (GOLD) criteria

2. Pulmonary hypertension determined by one of the following within the past 12
months:

1. A right heart catheterization (not obtained within ± 7 days of an
exacerbation) with an mPAP = 25 mmHg, or

2. An echocardiogram (not obtained within ± 7 days of an exacerbation) with a
TRV = 2.9 m/s or sPAP = 38 mmHg (Note: a subject with an acceptable mPAP =
25 mmHg determined by right heart catheterization will meet this inclusion
criteria even with a TRV < 2.9 m/s)

3. Current or former smokers with at least 10 pack-years of tobacco cigarette
smoking before study entry

4. Age = 40 years, = 80 years

5. 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)

6. Receiving LTOT for = 3 months and = 10 hours per day as determined by history

7. Females of childbearing potential must have a negative pre-treatment urine
pregnancy test

8. Signed informed consent prior to the initiation of any study mandated procedures
or assessments

Exclusion Criteria:

- Subjects who meet any of the following criteria are not eligible for enrollment:

1. A diagnosis of asthma or other non-COPD respiratory disease, in the opinion of
the Investigator

2. Lack of patency of nares upon physical examination

3. Experienced during the last month an exacerbation requiring:

1. start of or increase in systemic oral corticosteroid therapy and/or

2. hospitalization

4. Left ventricular dysfunction as measured by:

1. Screening echocardiographic evidence of left ventricular systolic
dysfunction (left ventricular ejection fraction [LVEF] < 40%), or

2. Screening echocardiographic evidence of left ventricular diastolic
dysfunction

> moderate (i.e., > Grade 2), or

3. 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

5. 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

6. Known allergy to contrast media.

7. Clinically significant valvular heart disease that may contribute to PH,
including mild or greater aortic valvular disease (aortic stenosis or
regurgitation) and/or moderate or greater mitral valve disease (mitral stenosis
or regurgitation), or status post mitral valve replacement

8. Use within 30 days of screening or current use of approved PH medications such as
sildenafil or bosentan (use of Cialis® or Viagra® for erectile dysfunction is
permitted)

9. Use of investigational drugs or devices within 30 days prior to enrollment into
the study

10. Any underlying medical or psychiatric condition that, in the opinion of the
Investigator, makes the subject an unsuitable candidate for the study



Age minimum: 40 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Hypertension

Chronic Obstructive Pulmonary Disease

Idiopathic Pulmonary Fibrosis

Intervention(s)

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

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

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

Primary Outcome(s)

Change from baseline in lobar blood volume at total lung capacity (TLC) after dosing with pulsed iNO as measured by HRCT [Time Frame: up to 4 weeks]

Secondary Outcome(s)

Changes in baseline measured by HRCT after dosing with pulsed iNO in Airway volume down to generation 8-10 at TLC [Time Frame: up to 4 weeks]

Changes in baseline measured by HRCT after dosing with pulsed iNO in Blood vessel % and density on lobar level [Time Frame: up to 4 weeks]

Changes in baseline measured by HRCT after dosing with pulsed iNO in Internal airflow distribution based on lobar expansion [Time Frame: up to 4 weeks]

Changes in baseline measured by HRCT after dosing with pulsed iNO in Lobar volumes at TLC [Time Frame: up to 4 weeks]

Changes in baseline measured by HRCT after dosing with pulsed iNO in Total lung volume at TLC [Time Frame: up to 4 weeks]

Changes in baseline measured by HRCT after dosing with pulsed iNO in Ventilation/perfusion (V/Q) matching [Time Frame: up to 4 weeks]

Changes in baseline measured by HRCT after dosing with pulsed iNO in Computational Fluid Dynamics (CFD)-based resistance on lobar level [Time Frame: up to 4 weeks]

Secondary ID(s)

IK-7002-COPD-006

Source(s) of Monetary Support

Please refer to primary and secondary sponsors