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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: Recruiting
Phase of Trial: Phase II

Latest Information Update: 10 Sep 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
  • Sponsors Nitric Solutions
  • Most Recent Events

    • 25 Aug 2020 Planned number of patients changed from 10 to 20.
    • 25 Aug 2020 Status changed from active, no longer recruiting to recruiting.
    • 24 Mar 2020 Planned End Date changed from 31 Dec 2020 to 31 Mar 2021.

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: 20

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

Patient Inclusion Criteria

COVID SubStudy Inclusion Criteria - Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol; - Men and Women ≥ 19 years of age unless local laws dictate otherwise; - English speaking; - Suspected of exposure to SARS-CoV-2 with fatigue and at least a fever (>37.90 C) or cough or sore throat or a positive swab for SAR-CoV-2 within 5 days of the of enrollment; - Must be willing to use an adequate form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP.

Patient Exclusion Criteria

Sub-Study Exclusion Criteria

Prior Tracheostomy;
Concomitant treatment involving high flow nasal cannula;
Any clinical contraindications, as judged by the attending physician;
Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
Prior COVID-19 infection or a positive swab for SARS-CoV-2 greater than 5 days from enrollment;
Family members in the same household already on the study;
Hydroxychloroquine, colchicine and other experimental antiviral medications;
unwilling to practice a medically acceptable form of contraception from screening to Day 26 (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent).

Exclusion Criteria: (Recruitment on hold for following Criteria during COVID-19 Pandemic)

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:

positive pregnancy test at screening or lactating or 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

  • Sponsors Nitric Solutions
  • Affiliations Mallinckrodt plc; Nitric Solutions; 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
Primary Endpoint:

Efficacy will be evaluated by measuring reduction in the incidence of mechanical assistance of BIPAP, CPAP, intubation and mechanical ventilation during the study period.

Secondary Endpoints:

Proportion of patients with mild COVID2019 who deteriorate to a severe form of the disease requiring mechanical intervention like BIPAP/CPAP, intubation and mechanical ventilation;
Mortality from all causes during the study period;
Negative conversion of COVID-19 RT-PCR from upper respiratory tract measured as the proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or a nasopahryngeal swab;
Time to clinical recovery defined as the time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air);
Alleviation of symptoms recorded in the Modified Jackson Cols score with particular definition of cough (defined as mild or absent in a patient reported scale of severity).

Other Details

  • Design open; prospective; sequential
  • Phase of Trial Phase 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 chris@nitricsolutions.com
show details
Diamond Centre, Nitric Solutions-Mobile Unit Canada
Chris C Miller, Ph.D.
Telephone: 778-899-0607
chris@nitricsolutions.com
show details
, Nitric Solutions Inc.
-
Jeremy D Road, MD MD
-

Centres

Centre Name Location Trial Centre Country
-
-
-
Diamond Centre Vancouver, British Columbia Canada
Mallinckrodt
-
-
MD
-
-
Nitric Solutions Inc.
-
-
Nitric Solutions-Mobile Unit Vancouver, British Columbia Canada
University of British Columbia
-
-

Trial History

Event Date Event Type Comment
10 Sep 2020 Other trial event Last checked against Clinicaltrials.gov record. Updated 10 Sep 2020
25 Aug 2020 Other trial event Planned number of patients changed from 10 to 20. Updated 04 Sep 2020
25 Aug 2020 Status change - recruiting Status changed from active, no longer recruiting to recruiting. Updated 04 Sep 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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