A Randomized, Open-label, Multicenter Study of Liposomal Amikacin for Inhalation (LAI) in Adult Patients With Nontuberculous Mycobacterial (NTM) Lung Infection Caused by Mycobacterium Avium Complex (MAC) That Are Refractory to Treatment

clinicaltrials.gov

Overall, there remains a lack of sufficiently powered, prospective clinical trials aimed at the treatment of pulmonary MAC infection. Many of the drugs used in the prolonged, multi-drug recommended regimens are expensive and poorly tolerated. It is clear from these single-site studies that there is an unmet need for more effective, less-toxic therapeutic options.

INS- 212 is a randomized, open-label study of efficacy, safety and tolerability of once daily dosing of 590 mg LAI plus a multi-drug regimen compared to a multi-drug regimen alone in subjects with NTM lung infections that are refractory to therapy. Eligible subjects are those diagnosed with MAC and with persistently positive cultures while adhering to a multi-drug treatment regimen for a minimum duration of 6 months with treatment either ongoing or completed no more than 12 months prior to Screening.

One to three sputum samples collected at Screening will be used to determine eligibility of the subject. Subjects will start or continue on a multi-drug anti-mycobacterial regimen and will be randomized to LAI (590 mg) QD plus a multi-drug regimen or to a multi-drug regimen alone for a minimum of 8 months. Subjects who demonstrate culture conversion at Month 6 will complete a total treatment course of 12 months from the first negative culture that defines culture conversion. Randomization will be stratified according to subject smoking status (current smoker or not) and current multi-drug regimen status (on treatment or off treatment for at least 3 months), at Screening.

Inclusion Criteria

  • Be continually positive for MAC on sputum culture while adhering to a multi-drug treatment regimen for a minimum duration of 6 months which is either ongoing or was completed no more than 12 months before screening
  • Be diagnosed with MAC NTM lung infection with evidence of nodular bronchiectasis and/or fibrocavitary disease by chest CT
  • Be willing to adhere to multi-drug treatment regimen during the course of the study

Exclusion Criteria

  • Patients with cystic fibrosis
  • Positive pregnancy test or lactation at screening. All women of child bearing potential will be tested. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrheic for at least 1 year), or surgically or naturally sterile
  • Active pulmonary tuberculosis requiring treatment at screening
  • History of lung transplantation
  • Prior exposure to LAI (including clinical study)

Primary Outcome Measures
Proportion of patients achieving culture conversion in the LAI plus a multi-drug regimen arm compared to a multi-drug regimen alone with no relapse or recurrence [ Time Frame: by 6 months ]

Secondary Outcome Measures
Change from baseline in 6 Minute Walk Test (MWT) distance in the LAI plus a multi-drug regimen compared to a multi-drug regimen alone [ Time Frame: 6 months and up to 16 months ]

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