WS02.3 Randomized, double-blind (DB), placebo-controlled study and open-label (OL) extension of liposomal amikacin for inhalation (LAI) in patients with refractory nontuberculous mycobacterial (NTM) lung disease (LD)

Abstract

Objective NTM-LD management often requires lengthy multidrug antibiotic regimens (MDARs) and can be complicated by drug toxicity and poor prognosis. Efficacy, safety, and tolerability of LAI, a novel amikacin formulation, were evaluated in refractory NTM-LD. Methods In the 84-day DB phase, eligible patients whose NTM infection was refractory to guideline-based MDARs for ≥6 mo were stratified by presence/absence of CF and Mycobacterium avium complex (MAC) vs M. abscessus infection. Patients were randomized 1:1 to LAI 590 mg QD or placebo via nebulizer added to their ongoing stable MDARs. In the OL phase, eligible patients received LAI 590 mg QD for another 84 days. Efficacy endpoints included change from baseline on the full semi-quantitative scale for mycobacterial culture, NTM culture negativity, and distance walked on the 6-minute walk test (6MWT) up to Day 168. Adverse events were monitored up to Day 196. Results Of 136 screened patients, 90 were randomized (CF 19%, non-CF 81%; MAC 64%, M. abscessus 36%). 54% were aged >60 y; 31%, >40–60 y; 14%, 18–40 y. At end of study, 80 and 59 patients had completed the DB and OL phases, respectively. LAI achieved statistical significance in the clinically important endpoint of culture negativity at Day 84 (LAI vs placebo, mITT population: 11/44 vs 3/45 patients; P = 0.01) and in the 6MWT (LAI vs placebo: 23.90 vs −25.03 m; P = 0.009). Complete study results showing continuation of these trends will be presented. Conclusions Full study results will provide efficacy and safety profiles of LAI QD added to a MDAR. These data will increase understanding of NTM-LD, including shifting NTM-LD management paradigms.