A Proof of Concept Study of Inhaled Nitric Oxide for Adults With Pulmonary Non-Tuberculous Mycobacterial Infection

NCT03748992 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro 00081838
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of open-label exposure of gNO in patients with NTM lung disease. Subjects will receive the study drug by inhaling through a nasal mask. Subjects will be treated for 3 weeks (5 days per week) and followed monthly for 3 months.

Conditions

Nontuberculous Mycobacterium Infection

Outcome Measures

Primary Outcomes (1)

• Percent Patients With Negative Sputum Culture

  Sputum culture will be assessed for any sputum growth. A negative culture represents no mycobacterial growth.

  End of Treatment (Day 15)

Secondary Outcomes (2)

• Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE (Common Terminology Criteria for Adverse Events)

  Treatment Day 1 through End of Treatment (3 Months)

• Number of Participants With a Reduction in Semiquantitative Cultures

  At day 15 from baseline

Study Arms (1)

gNO

EXPERIMENTAL

Subjects will be receiving nitric oxide every week day for 3 weeks.

Drug: gNO

Interventions

gNO DRUG

This is a proof-of-concept study in which all subjects will be treated with gNO (i.e. no control) to see if there can be a microbiological effect by conversion to negative sputum cultures and how long that effect can be sustained following treatment. Participants will be treated for 3 weeks (5 days per week), Monday through Friday, and followed monthly for 3 months. The treatment period includes a physical exam, vital signs, blood tests, echocardiogram, spirometry test, sputum sample, questionnaires, and the inhalation gas treatment. During the inhalation gas treatment, participants will wear a face mask (similar to an oxygen mask) and will be given nitric oxide gas through the participants nose for three treatments with fifty minutes each time. They will then be followed up monthly during the Follow-up period with tests that include a physical exam and questionnaires.

gNO

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects are \>18 years of age and able to provide informed consent.
• Subjects have NTM lung disease as defined by each of the following:
• Sputum cultures positive for NTM (MAC or M abscessus) Radiologic studies that demonstrate features consistent with disease such as nodular bronchiectasis and/or cavities Symptoms consistent with disease including respiratory (e.g. cough, sputum production, hemoptysis, chest pain) and constitutional (e.g. fevers, night sweats, fatigue, myalgias, arthralgias, weight loss) Subjects are able to produce sputum for culture (either spontaneous or induced).
• Subjects have a history of persistently positive sputum cultures for NTM defined as \>4 number of cultures over 24 months with \>75% positive AND a positive culture in the last 3 months.
• Clinically stable with no significant changes in health status within 14 days prior to Screening or Day 1 Subjects are willing and able to perform requirements of the study.

You may not qualify if:

• Smoking history in the prior 6 months Significant hemoptysis within 30 days prior to screening (\>5 ml of blood in one coughing episode or \>30 ml of blood in a 24 hour period) Forced expiratory volume at one second (FEV1) \<40% of predicted On supplemental oxygen or SaO2 \<90% at screening or Day 1, or within 30 days prior to enrollment.
• Known cardiac (left heart) insufficiency (defined as LVEF \<35%) prior to screening Known pulmonary hypertension Known or suspected hemoglobinopathy Initiation of NTM treatment regimen or a change in the regimen was made in the prior 6 months. Subjects on active treatment can be enrolled if they have been on a stable anti-NTM regimen for at least 6 months.
• Initiation of new chronic therapy within 4 weeks prior to screening Use of drugs known to increase methemoglobin (see 12.2.7) at screening
• Any of the following abnormal lab values at screening:
• GPD deficiency Hemoglobin \<10g/dl Platelet count \<100,000/mm3 Prothrombin time international ratio (INR) \>1.5 Abnormal liver function defined as any two of the following ALT \>3x ULN AST \>3x ULN ALP \>3x ULN GGT \>3x ULN
• Abnormal renal function defined as:
• Calculated Creatinine Clearance \<50 ml (as calculated by Cockcroft/Gault)
• 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 15 (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent) Use of an investigational drug within 30 days prior to screening Intravenous or oral steroids (\>10 mg/d prednisone equivalent) in the 14 days prior to screening Any condition that the Investigator believes would interfere with the intent of this study or would make participation not in the best interest of the subject.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• Cystic Fibrosis Foundation: collaborator
• Oregon Health and Science University: collaborator

Study Sites (2)

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Mycobacterium Infections, Nontuberculous

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Patrick Flume, MD
• Organization: Medical University of South Carolina

flumepa@musc.edu

843-792-3167

Study Officials

• Patrick Flume

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: November 21, 2018
• Study Start: January 28, 2019
• Primary Completion: March 26, 2020
• Study Completion: March 26, 2020
• Last Updated: May 18, 2021
• Results First Posted: May 18, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)