A randomized, open-label, multicenter study of liposomal amikacin for inhalation in adult patients with nontuberculous mycobacteria (NTM) lung infections caused bymycobacterium aviumcomplex (MAC)

Mycobacterium avium: complex (MAC) lung infections are associated with significant morbidity and mortality. Treatment of NTM lung infection is complicated by lengthy multidrug regimens often associated with drug toxicity and suboptimal outcomes. Liposomal amikacin for inhalation (LAI) is a novel inhaled amikacin formulation in development for the treatment of MAC lung infections. In an initial placebo-controlled study of patients with treatment-refractory NTM lung infections, which studied both MAC and M abscessus, (TR02-112), those who had LAI added to their multidrug regimen produced more negative sputum cultures at Day 84 than those on placebo (25.0% vs 6.7%; P=.01).Study INS-212 will evaluate this further by assessing culture conversion (3 consecutive negative sputum cultures) with longer-term LAI treatment added to multidrug regimens.Up to 351 adults ≥18 years with treatment-refractory MAC lung infection (≥2 positive sputum cultures while on a multidrug regimen for ≥6 months) will be stratified by smoking status and multidrug regimen use, and randomized 2:1 to LAI 590 mg QD added to a multidrug regimen or continued on a multidrug regimen alone.The primary endpoint is the proportion of subjects achieving culture conversion by Month 6. Other endpoints include the 6-minute walk test, patient-reported outcomes, and QOL scores.Converters will continue in the study for 12 months from their first negative culture used to define culture conversion. Subjects exiting study for any reason will be contacted for safety follow-up at Month 12.