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

Study Overview
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Brief Summary
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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

Detailed Description
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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

Official Title
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A 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 of Pulmonary Hypertension Associated With Pulmonary Fibrosis on Long Term Oxygen Therapy (Part 1 and Part 2) - REBUILD

Conditions
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Pulmonary Fibrosis, Pulmonary Hypertension

Intervention / Treatment
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* Combination Product: INOpulse®
* Combination Product: Placebo
* Combination Product: Open Label Extension


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Inhaled Nitric Oxide (iNO)<br>Pulsed inhaled iNO 45 mcg/kg Ideal Body Weight (IBW)/hour (hr) | Combination Product: INOpulse®<br>* Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.<br>|
| Placebo Comparator: Placebo<br>Pulsed inhaled N2, 99.999% gas | Combination Product: Placebo<br>* Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.<br>|
| Other: Open Label Extension<br>Pulsed inhaled iNO 45 mcg/kg IBW/hr | Combination Product: Open Label Extension<br>* Subjects will be treated by means of an INOpulse® device using an INOpulse® nasal cannula.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Moderate to Vigorous Physical Activity (MVPA) as Measured by Actigraphy | Part 1 - Blinded Treatment Period | Baseline to Month 4 | 
| Adverse Events and Serious Adverse Events with Long Term INOpulse Therapy | Part 2 - Open Label Extension (OLE) | Baseline to Month 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Overall Activity as Measured by Actigraphy | Part 1 - Blinded Treatment Period | Baseline to M4 | 
| Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ) | Part 1 Blinded Treatment Period: The UCSD SOBQ is a 24-item questionnaire developed to measure breathlessness associated with activities of daily living, on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The responses to all items are summed up to provide the overall score that can range from 0 (best outcome) to 120 (worst outcome). | Baseline to Month 4 | 
| Change in St. George Respiratory Questionnaire (SGRQ) - Activity, Impacts & Total | Part 1 Blinded Treatment Period: SGRQ is a tool for assessing quality of life that has previously been validated for the use with patients with interstitial lung disease. It is a responsive tool that has three domains: symptoms, activity and impact (on daily life) | Baseline to Month 4 | 
| Time to Clinical Worsening | Part 1 - Blinded Treatment Period | Baseline to Month 4 | 
| Time to Clinical Deterioration | Part 1 Blinded Treatment Period | Baseline to Month 4 | 
| Time to Clinical Improvement | Part 1 Blinded Treatment Period | Baseline to Month 4 | 
| Change in 6 Minute Walk Distance | Part 1 Blinded Treatment Period | Baseline to Month 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Fibrosis, PF, Pulmonary Hypertension, Inhaled Nitric Oxide, iNO, Long Term Oxygen Therapy, Oxygen, REBUILD, INOpulse, pulsed inhaled nitric oxide, fILD, fibrotic interstitial lung disease, portable pulsed inhaled nitric oxide