A Pilot Study to Assess the Effect of Intermittent iNO on the Treatment of NTM Lung Infection in CF and Non-CF Patients

Study Overview
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Brief Summary
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The purpose of this open-label, multicenter, non-randomized, pilot study is to assess the safety of high dose intermittent iNO for treatment of NTM infection in CF and non-CF patients.

Detailed Description
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The study will include 20 patients from up to four clinical sites in Australia. The overall treatment plan includes 2 weeks of inhalation treatments (intensive phase) of iNO four times per day at 4.5-hour intervals followed by 10 weeks of inhalation treatments (maintenance phase) at the maximum tolerated dose (a maximum of 250 ppm NO) inhaled twice daily.

Official Title
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A Pilot Study to Assess the Effect of Intermittent Inhaled Nitric Oxide on the Treatment of Nontuberculous Mycobacteria (NTM) Lung Infection in Cystic Fibrosis and Non-Cystic Fibrosis Patients

Conditions
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Non-Tuberculous Mycobacterial Pneumonia, Cystic Fibrosis, Mycobacterial Pneumonia, Mycobacterium Abscessus Infection, Mycobacterium Avium Complex

Intervention / Treatment
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* Device: LungFit


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed with refractory NTM (MAC or MAbs) pulmonary infection CF and Non-CF patients Exclusion Criteria: Diagnosis of methemoglobinemia or MetHb ≥2% at screening; treatment with any drug known to increase MetHb; known or suspected hemoglobinopathy. History of or current myeloproliferative disease, leukemia or other hematological malignancy; known or suspected immunodeficiency disease. Subjects with advanced cardiovascular disease or CHF Use of an investigational drug during the 30 days prior to enrollment. History of frequent epistaxis (>1 episode/month); significant hemoptysis (during the 30 days prior to enrollment. Subject on non-constant dose of systemic steroids within 30 days prior to enrollment; subjects on constant systemic steroids if the daily dose is higher than 10 mg/d prednisolone or equivalent. Active pulmonary malignancy (primary or metastatic) or any malignancy; history of lung transplantation. Pulmonary tuberculosis requiring treatment or treated within 2 years prior to screening. Uncontrolled hypertension within 3 months prior to or at screening Diagnosis of significant pulmonary hypertension indicated on echocardiogram at screening Clinically significant renal or liver laboratory abnormalities History of daily, continuous oxygen supplementation. Women of childbearing potential - pregnant or breastfeeding, or not on medically acceptable double methods of contraception from enrollment until Day 84. Smoking tobacco or any substance within 6 months prior to screening or anticipated inability to refrain from smoking throughout the study. Patient receiving drugs that have a contraindication with NO

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inhaled NO delivered using LungFit<br>Inhaled Nitric Oxide in doses up to 250 ppm | Device: LungFit<br>* LungFit for NTM is an experimental device that produces Nitric Oxide from the ambient air.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-Emergent SAEs | The primary endpoint of the study is the number of patients with treatment-emergent SAEs | Day 1 to Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in NTM bacterial load from baseline to Day 174 | Changes in NTM bacterial load will be assessed by sputum culture in liquid and solid media. | Day 1 to Day 174 | 
| Number of patients with culture conversion at Day 174 | NTM culture conversion will be defined as having at least three consecutive negative NTM cultures | Day 1 to Day 174 | 
| Changes in quality of life assessed by CFQ-R for or QOL-B with NTM module | Changes in quality of life assessed by Cystic Fibrosis Questionnaire Revised [CFQ R] for CF patients or Quality of Life Questionnaire-Bronchiectasis [QOL-B] with NTM module for non-CF patients. | Day 1 to Day 174 | 
| Changes in FEV1 from baseline to Day 174 | Respiratory function will be assessed by spirometry including FEV1. | Day 1 to Day 174 | 
| Changes in activity tracker data as assessed by changes in distance from baseline to Day 174. | Patients will collect activity tracker data from 2 weeks before treatment and from Day 1 to Day 174. | Day 1 to Day 174 | 
| Change in 6 Minute Walking Test | Change in 6 Minute Walking Test will be assessed by changes in distance between baseline and Day 84 | Day 1 to Day 84 |