A Study to Assess Pulsed Inhaled Nitric Oxide in Subjects With Pulmonary Fibrosis at Risk for Pulmonary Hypertension

A randomized, double-blind, placebo-controlled dose escalation and verification study to assess the safety and efficacy of pulsed inhaled nitric oxide (iNO) in subjects at risk for pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy (Part 1 and Part 2) - REBUILD

This is a Phase 3, randomized, double-blind, placebo-controlled dose escalation and verification clinical study to assess the safety and efficacy of pulsed inhaled nitric oxide (iNO) in subjects at risk for pulmonary hypertension associated with pulmonary fibrosis on long term oxygen therapy (Part 1 and Part 2) - REBUILD

Eligibility Criteria:
Inclusion criteria:

* A 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
  * Connective Tissue Disease associated with IPF (CTD-ILD)
  * Interstitial Pneumonia with Autoimmune Features (IPAF)
* Have been using oxygen therapy by nasal cannula for at least 4 weeks (including use limited to exertion)
* 6MWD ≥ 100 meters and ≤ 400 meters at screening and Baseline/Randomization visits.
* World Health Organization (WHO) Functional Class II-IV
* Forced Vital Capacity ≥ 40% predicted within the 60 day Screening period
* Age between 18 and 80 years (inclusive) at screening

Exclusion criteria:

* 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.
* 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)
* History of sarcoidosis
* History of chronic thrombo-embolic pulmonary hypertension (CTEPH; WHO group 4 PH)
* Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the study
* Body mass index (BMI) \>40 kg/m2 at screening
* Intermittent uncontrolled atrial fibrillation, in the opinion of the Principal Investigator
* Known severe hepatic impairment, in the opinion of the Principal Investigator
* Known severe renal impairment (Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) 2009 equation \[Levy 2009\] calculated creatinine clearance \<30 ml/min) at screening