Prolonged-Use of Inhaled Gaseous Nitric Oxide (gNO) for Adult With Non-Tuberculous Mycobacteria Infection

An open labeled Study (NCT03331445) is demonstrating encouraging safety and efficacy results for most subjects receiving 160ppm nitric oxide gas (gNO) for treatment of non-tuberculous mycobacteria (NTM) over a 15 day treatment regimen. In one subject, who had a reduction in sputum culture concentration of Bacterium bolletii from plus 3 to plus 1 corresponding to a 2-3 log10 cfu/gm reduction during the treatment, the one-week post treatment follow-up sputum culture had increased to plus 2. It is hypothesized that a longer treatment period may be necessary to fully eradicate NTM from the sputum culture in chronic lung disease. This study will extend the period of gNO exposure for a prolonged period of time (3 months) to attempt to fully eradicate the NTM in this single subject. This study will transition from the medical clinic to supervised delivery in the patient's home environment.

Primary Objective: Determine the efficacy of prolonged delivery of inhaled nitric oxide to treat an adult patient with pulmonary NTM Primary Endpoint: Eradication of NTM growth in sputum cultures. Efficacy will be assessed by the antimicrobial effect of inhaled NO on the density of NTM species and other microorganisms in the sputum.

• as confirmed by measurement of semi-quantitative culture sputum growth which has been verified with serial dilution technique on Day 7, 14, 21 and every 21 days thereafter for 90 days as compared to pre-treatment baseline sputum culture.

Secondary Objective(s): Determine the safety \& efficacy of inhaled nitric oxide

Secondary Endpoint(s):

1. Safety

   • as evaluated by the number of unanticipated adverse events during home delivery in clinical labs (hematology, coagulation, and serum chemistries); in vitals; in inspired concentration of NO, O2 and NO2 delivered to subject and; in methemoglobin and oxygen saturation levels.
2. Efficacy

   * as determined by improvement in lung function as measured by spirometry, endurance as measured by six minute walk-test and quality of life as determined by self-reporting quality of life questionnaire (CFQ-R) on Day 7, 14, 21 and every 21 days thereafter for 90 days as compared to pre-treatment baseline data.
   * as assessed by recurrence of NTM in sputum as confirmed by measurement of semi-quantitative culture sputum growth on Day 30 and 60 post treatment.

Eligibility Criteria:
Inclusion Criteria:

* Written informed consent.
* Has been previously diagnosed with NTM. \[NTM defined as positive culture(s) of at least one species of Mycobacterium avium Complex (MAC) or Mycobacterium abscessus Complex (MABSC)\]
* Has been previously treated with gNO for 15 days without complete eradication of NTM but with a decrease of at least 1-2 points on cultures.
* Male or female ≥19 years of age.
* Female not pregnant at time of study.
* Oxygen saturation on room air ≥92% at screening. (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.

Exclusion Criteria:

* History of frequent epistaxis (\>1 episode/month)
* History of reactive pulmonary vascular hypertension
* Methemoglobin \>3% at screening
* Liver function insufficiency aspartate aminotransferase/alanine aminotransferase (AST/ALT) \>3 of normal values)
* Hemoglobin \<10 g/dl
* Thrombocytopenia (platelet count \<100,000/mm3) at screening
* Prothrombin time international ratio (INR) \> 1.3 at screening
* 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.