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

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

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.

Study Overview

• Status: Unknown
• Conditions: Cystic Fibrosis; Mycobacterium Avium Complex; Non-Tuberculous Mycobacterial Pneumonia; Mycobacterial Pneumonia; Mycobacterium Abscessus Infection
• Intervention / Treatment: Device: LungFit

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Recruiting
      • Gallipoli Medical Research Foundation
      • Contact: Rachel Thomson, MD; Email: r.thomson@uq.edu.au
      • Principal Investigator: Rachel Thomson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beyond Air Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): May 1, 2022

Study Registration Dates

• First Submitted: December 7, 2020
• First Submitted That Met QC Criteria: December 24, 2020
• First Posted (Actual): December 28, 2020

Study Record Updates

• Last Update Posted (Actual): December 28, 2020
• Last Update Submitted That Met QC Criteria: December 24, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Pancreatic Diseases; Fibrosis; Infections; Communicable Diseases; Mycobacterium Infections; Pneumonia; Cystic Fibrosis; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous
• Other Study ID Numbers: BA_NTM_AU_01.01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No