Clinical trial NCT03748992: A Proof of Concept Study of Inhaled Nitric Oxide for Adults With Pulmonary Non-Tuberculous Mycobacterial Infection
Official title: A Proof of Concept Study of Inhaled Nitric Oxide for Adults With Pulmonary Non-Tuberculous Mycobacterial Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nontuberculous Mycobacterium Infection
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
name: Oregon Health and Science University
First posted: 2018-11-21
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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.

Exclusion Criteria:

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:

6-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.

Primary outcomes:
measure: Percent Patients With Negative Sputum Culture
timeFrame: End of Treatment (Day 15)
Secondary outcomes:
measure: Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE (Common Terminology Criteria for Adverse Events)
timeFrame: Treatment Day 1 through End of Treatment (3 Months)
measure: Number of Participants With a Reduction in Semiquantitative Cultures
timeFrame: At day 15 from baseline
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Patrick Flume
role: PRINCIPAL_INVESTIGATOR
References: