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An Open Label Safety Study of Inhaled Gaseous Nitric Oxide (gNO) for Adults & Adolescents With Non-Tuberculous Mycobacteria, Burkholderia Spp, Aspergillus Spp and Corona-like Viral (Sub-Study) Infections

Trial Profile

An Open Label Safety Study of Inhaled Gaseous Nitric Oxide (gNO) for Adults & Adolescents With Non-Tuberculous Mycobacteria, Burkholderia Spp, Aspergillus Spp and Corona-like Viral (Sub-Study) Infections

Status: Active, no longer recruiting
Phase of Trial: Phase I/II

Latest Information Update: 02 Apr 2020

At a glance

  • Drugs Nitric oxide (Primary)
  • Indications Aspergillosis; Burkholderia infections; COVID 2019 infections; Mycobacterium avium complex infections; Nontuberculous mycobacterium infections
  • Focus Adverse reactions
  • Acronyms NONTM
  • Most Recent Events

    • 24 Mar 2020 Planned End Date changed from 31 Dec 2020 to 31 Mar 2021.
    • 06 Dec 2019 Planned End Date changed from 31 Dec 2018 to 31 Dec 2020.
    • 06 Dec 2019 Planned primary completion date changed from 31 Dec 2018 to 31 Dec 2020.

Trial Overview

Purpose

Non tuberculous mycobacteria (NTM) infections in the lung are almost impossible to eradicate with conventional antibiotics. These patients have few options to treat their lung infection. It has been shown that nitric oxide was safe to be inhaled for similar cystic fibrosis patients and reduced drug resistant bacteria in the lungs. Further, research indicates that clinical isolates of NTM can be eradicated by 160ppm NO exposure in the laboratory petri dish. This is not the first time inhaled NO treatment has been used in patients with NTM (case studies). This study will provide more data to see if NO therapy can reduce the NTM bacterial load in the lungs and help the patients breath better.

Primary Endpoints

Measure the safety of 160ppm inhaled nitric oxide delivery in NTM subjects

description: Measure the number of unanticipated adverse events over the duration of the study protocol
time_frame: 26 Days

Other Endpoints

Measure the effect of 160ppm inhaled nitric oxide delivery on lung spirometry in NTM subjects

description: Measure the change in absolute FEV1.0 change from baseline during 160 ppm inhalation therapy
time_frame: Day 5,12,19 and 26

Measure the antimicrobial effect of 160ppm inhaled nitric oxide on lung NTM bacterial load in the sputum

description: Measure the difference from baseline NTM species bacterial load (0 to +4) in sputum during 160ppm nitric oxide inhalation therapy
time_frame: Day 19 and 26

Measure the effect of 160ppm inhaled nitric oxide on Quality of Life (CRISS) Score

description: Measure the difference from baseline CRISS (0-100) during 160ppm nitric oxide inhalation therapy (lower score represents higher quality of life)
time_frame: Day 19 and 26

Sub-Study Primary Endpoint(s): Efficacy to reduce respiratory interventions

description: Measuring reduction in the incidence of mechanical assistance including oxygen therapy, BIPAP, CPAP, intubation and mechanical ventilation during the study period.
time_frame: Day 26

Efficacy in reduction of mortality

description: Measured by death from all causes
time_frame: Day 26

Antiviral effect

description: Assessed by time to negative conversion of COVID-19 RT-PCR from upper respiratory tract
time_frame: Day 26

Efficacy on clinical improvement

description: Time to clinical recovery as measured by resolution of clinical signs
time_frame: Day 26

Efficacy on the respiratory symptoms

description: Measured by change in the Modified Jackson Cold Score
time_frame: Day 26 [1]

Diseases Treated

Indication Qualifiers Patient Segments
Aspergillosis treatment -
Burkholderia infections treatment -
COVID 2019 infections treatment -
Mycobacterium avium complex infections treatment -
Nontuberculous mycobacterium infections treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 10

    Actual: 20

  • Sex male & female
  • Age Group ≥ 14 years; adolescent; adult

Patient Inclusion Criteria

- Written informed consent. - Has been previously diagnosed with NTM, Burkholderia spp and Aspergillus spp. or Corona-like viral infection: 1. NTM, Burkholderia spp and Aspergillus spp defined as positive culture(s) of at least one species of Mycobacterium avium Complex (MAC) or Mycobacterium abscessus Complex (MABSCor Burkholderia spp and Aspergillus spp) or Corona-like viral infection: 2. History of repeatedly positive cultures (2 or more), irregardless of therapy - Male or female ≥14 years of age. - Female not pregnant at time of study. - Has an FEV1 ≥ 30 % of predicted. c. Suspected corona-like viral infection - Oxygen saturation on room air >92% at screening. a. Able to breathe without supplemental oxygen for 60 minutes - Non-smoker for at least 6 months prior to screening and agrees not to smoke during the study. - Willing and able to comply with the treatment schedule and procedures.

Patient Exclusion Criteria

- Use of an investigational drug within 30 days of screening - History of frequent epistaxis (>1 episode/month) - Significant hemoptysis within 30 days (≥ 5 mL of blood in one coughing episode or > 30 mL of blood in a 24 hour period) - History of reactive pulmonary vascular hypertension - Methemoglobin >3% at screening - Liver function insufficiency (ALT/ AST >3 of normal values) - Hemoglobin <11 g/dl - Thrombocytopenia (platelet count <100,000/mm3) at screening - Prothrombin time international ratio (INR) > 1.3 at screening - Changes to antibiotics (e.g. azithromycin) from 7 days prior to screening through last treatment day. (Subjects may be taking antibiotics or antivirals during this time period, but they cannot start, stop or change doses during this time period) - On supplemental oxygen during gNO treatment (SaO2 < 90% for 50 minutes while resting in a chair). - For women of child bearing potential: 1. positive pregnancy test at screening or 2. lactating or 3. unwilling to practice a medically acceptable form of contraception from screening to Day 36 (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent) - Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

Trial Details

Identifiers

Identifier Owner
NCT03331445 ClinicalTrials.gov: US National Institutes of Health
NTM-CTP01H17-02107 -

Organisations

  • Affiliations Mallinckrodt plc; Novoteris

Trial Dates

  • Initiation Dates

    Actual : 24 Oct 2017

  • Primary Completion Dates

    Planned : 31 Dec 2020

  • End Dates

    Planned : 31 Mar 2021

Substudies/Extensions

COVID-19 Sub-study

Other Details

  • Design open; prospective; sequential
  • Phase of Trial Phase I/II
  • Location Canada
  • Focus Adverse reactions

Interventions

Drugs Route Formulation
Nitric oxidePrimary Drug Inhalation
-

160 ppm Nitric Oxide

Drug: Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation (Inhaled Nitric Oxide 160ppm balance air) Other Name: Thiolanox

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Chris C Miller, Ph.D
778-899-0607
miller42@mail.ubc.ca
show details
Diamond Centre Canada
Chris C Miller, Ph.D.
778-899-0607
miller42@mail.ubc.ca
show details
-
Jeremy D Road, MD Professor
-

Centres

Centre Name Location Trial Centre Country
-
-
-
Diamond Centre Vancouver, British Columbia Canada
Novoteris, LLC
-
-
Professor
-
-
University of British Columbia
-
-

Trial History

Event Date Event Type Comment
02 Apr 2020 Other trial event Last checked against Clinicaltrials.gov record. Updated 02 Apr 2020
24 Mar 2020 Completion date Planned End Date changed from 31 Dec 2020 to 31 Mar 2021. Updated 30 Mar 2020
06 Dec 2019 Completion date Planned End Date changed from 31 Dec 2018 to 31 Dec 2020. Updated 11 Dec 2019
06 Dec 2019 Other trial event Planned primary completion date changed from 31 Dec 2018 to 31 Dec 2020. Updated 11 Dec 2019
01 Oct 2018 Status change - active, no longer recruiting Status changed from recruiting to active, no longer recruiting. Updated 10 Oct 2018
08 Nov 2017 New trial record New trial record Updated 08 Nov 2017

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
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