Principal Investigator: Mary  Scholand
Keywords: Pulmonary , Pulmonary Hypertension , Nitric Oxide , IPF , Idiopathic Pulmonary Fibrosis , UIP , Usual Interstitial Pneumonia , ILD , Interstitial Lung Disease Department: Pulmonary
IRB Number: 00138396
Specialty: Pulmonary
Sub Specialties: Pulmonary Fibrosis
Recruitment Status: Active, not recruiting

Contact Information

Cassie Larsen
cassie.larsen@hsc.utah.edu
8015815811

Brief Summary

Part 1:

Primary Objective: The primary objective of this study is to verify the efficacy of INOpulse in study participants with fibrotic interstitial lung disease (fILD) currently receiving treatment with oxygen therapy.


Safety Objectives: The safety objective of this study is to evaluate the safety and tolerability of INOpulse in study participants with fILD currently receiving treatment with oxygen therapy.

Part 2: Open Label Extension (OLE)
Objective: To evaluate the long term safety and tolerability of INOpulse in study participants with fILD currently receiving treatment with oxygen therapy.

Inclusion Criteria

Part 1:

1. Signed Informed Consent Form prior to the initiation of any study mandated procedures or

assessments.

2. Diagnosed with pulmonary fibrosis by high resolution CT scan performed in the 6 months

prior to screening associated with one of the following conditions and confirmed using

guidelines, as per American Thoracic Society (ATS) / European Respiratory Society (ERS) /

Japanese Respiratory Society (JRS) / Latin American Thoracic Association (ALAT):

  • Major IIPs (idiopathic interstitial pneumonias) diagnosis 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
  • Chronic hypersensitivity pneumonitis
  • Occupational lung disease

3. Historical right heart catheterization (within 3 years) or current Echocardiogram (within 3

months) as assessed by the Investigator/Radiologist confirming low, intermediate / high

probability of pulmonary hypertension

4. Have been using oxygen therapy (at rest or only with exertion and ≤ 10 L/min of oxygen

supplementation) by nasal cannula for at least 4 weeks prior to the screening run-in period

5. 6MWD ≥ 100 meters and ≤ 400 meters at screening and Baseline/Randomization visits.

6. WHO Functional Class II-IV

7. Forced Vital Capacity ≥ 40% predicted within last 6 months prior to the screening run-in period

8. Willingness to use INOpulse delivery device for as long as possible every day but no less than

12 hours per day and willingness to wear the activity monitor for as long as possible every day

but no less than at least 10 hours per day while awake

9. Female study participants of childbearing potential must have a negative pre-treatment

pregnancy test (serum or urine). All female study participants must take adequate precaution

to avoid pregnancy.

10. Have completed at least 3 weeks (+/- 3 days) of activity monitoring at time of

Baseline/Randomization

11. During the Screening Run-In period prior to Baseline/Randomization, study participants must demonstrate the ability to consistently use the INOpulse device greater than 12 hrs/day in the opinion of the Investigator.

12. Age between 18 and 80 years (inclusive)

13. The study participant must be clinically stable for at least 4 weeks in the opinion of the Principal Investigator.

14. Demonstrate ability to wear the activity monitor consistently. Wear compliance will be

assessed during the 14 days prior to Baseline/Randomization visit and is defined as at least 8

compliant days, that includes 2 weekend days, with at least 10 hours of wear time while awake

per day.

Part 2:

1. All study participants must have completed Part 1 – Blinded Treatment Period study
assessments. For Cohort 3 only, study participants must have been compliant with the
INOpulse device use.
2. In the opinion of the investigator, the study participant would benefit from continued therapy with INOpulse.

Exclusion Criteria

Part 1:

1. Demonstrate symptomatic rebound defined as significant cardiopulmonary instability, such as

hypoxemia, bradycardia, tachycardia, systemic hypotension, shortness of breath, nearsyncope,

and syncope, occurring within 1 hour of acute iNO dosing

2. Episodes of disease worsening within 1 month (4 weeks) prior to Baseline/Randomization in

the opinion of the investigator

3. Use of a prostacyclin analogue, guanylate cyclase stimulator, or endothelin-receptor antagonist

(ERA) PAH-specific medications regardless of reason for use, except for phospho-diesterase

type -5 (PDE5) inhibitors. (The use of PDE5 inhibitors regardless of reason for use is allowed

as long as the dose has been stable for at least 3 months prior to screening and there are no

plans to adjust the dose during the study.)

4. Acute or chronic physical impairment (other than dyspnea due to ILD +/- pulmonary

hypertension) that would limit the ability to comply with study procedures (i.e., 6MWT) or

adherence to therapy, including carrying and wearing the INOpulse delivery device per study

protocol, or medical problem(s) likely to preclude completion of the study

5. For women of child-bearing potential: Pregnant or breastfeeding females at Screening, or

planning to get pregnant, or unwilling to use appropriate contraception if sexually active to

avoid pregnancy during the study and for at least 30 days after discontinuation of the study

drug.

6. Administered L-arginine within 1 week prior to Screening

7. The concurrent use of the INOpulse device with a continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or any other positive airway pressure device

8. Use of investigational drugs or devices (including COVID-19 vaccination) within 1 month

prior to Screening

9. Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes

the study participant an unsuitable candidate for the study including the inablity to complete

6MWT

10. Any study participant who has been enrolled in any previous clinical study with inhaled NO

11. A definitive diagnosis of a connective tissue disease (eg, systemic scerlosis, Lupus, Sjögren’s, mixed CTD or other CTD’s via ACR/EULAR classification criteria)

12. The presence of emphysema unless the extent of fibrotic changes is greater than the extent of

emphysema on the most recent HRCT scan in the opinion of the local radiologist/Investigator.

13. A study participant must not start a rehabilitation program during the study, not have started

within 3 months of screening or change the nature of their rehabilitation program at any time

during the blinded portion of the study

14. Chronic use of a nitric oxide donor agent such as nitroglycerin or drugs known to increase

methemoglobin such as lidocaine, prilocaine, benzocaine, nitroprusside, isosorbide, or dapsone

at Screening

15. Heart failure with reduced ejection fraction (HFrEF; systolic heart failure) with an ejection

fraction of < 40%; or severe HF with preserved EF (HFpEF; diastolic HF) as assessed by the

Principal Investigator

16. History of sarcoidosis

17. History of chronic thrombo-embolic pulmonary hypertension (CTEPH; WHO group 4 PH)

18. Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the study

19. Body mass index (BMI) >40 kg/m2 at screening

20. Known permanent atrial fibrillation, in the opinion of the Principal Investigator

21. Documented pulmonary veno-occlusive disease (PVOD)

22. Known severe hepatic impairment, in the opinion of the Principal Investigator

23. Known severe renal impairment (Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) 2009 equation [Levy 2009] calculated creatinine clearance <30 ml/min) at screening

24. Life expectancy < 6 months, in the opinion of the Principal Investigator

25. Positive COVID-19 infection (positive test or high clinical suspicion) in the 2 months prior to

screening unless the potential study participant has had a negative COVID-19 test at least 6

weeks prior to screening and, they are free of COVID-19 related symptoms (in which case,

they are eligible for study participation).

Part 2:

1. Use of a prostacyclin analogue, guanylate cyclase stimulator or and ERA PAH-specific
medication regardless of reason for use (use of PDE5 inhibitors regardless of reason for use is
allowed)
2. The concurrent use of the INOpulse device with a continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or any other positive airway pressure device