Amikacin Liposome Inhalation Suspension in Newly Diagnosed Mycobacterium avium Complex Lung Disease: A Phase 3b, Double-blind, Randomized Clinical Trial (ENCORE)

Abstract Rationale Current recommended front-line multidrug therapy (MDT) for Mycobacterium avium complex lung disease (MACLD) produces suboptimal outcomes. Amikacin liposome inhalation suspension (ALIS) with MDT is approved for refractory MACLD; however, clinical trial evidence in newly diagnosed MACLD is lacking. Objectives To evaluate efficacy and safety of ALIS with MDT in the phase 3b, randomized, double-blind, placebo-controlled superiority trial in adults newly diagnosed with MACLD who have not initiated antibiotics (ENCORE NCT04677569). Methods Patients (N = 425) were randomized 1:1 to receive ALIS 590 mg (n = 213) or placebo (n = 212) plus azithromycin 250 mg and ethambutol 15 mg/kg once daily for 12 months. Primary endpoint was change from baseline to month 13 in Respiratory Symptom Score (RSS). Pre-specified secondary endpoints included culture conversion (CC) at clinically important timepoints, durable culture conversion (DCC), and safety. Results Median age was 68.0 years, 62.8% were White, and 79.3% were female. Significantly greater improvements in RSS were observed in the ALIS versus comparator arm at 1 month post-treatment (month 13; LS mean change: 17.77 vs 14.66 points; treatment difference 3.11 points; P=0.0299), with improvements sustained at 3 months post-treatment (month 15; treatment arm difference 4.80 points; nominal P=0.0015). Significantly greater proportions of patients achieved CC by month 13 and DCC at month 15 in the ALIS arm versus comparator arm (82.4% vs 55.6% and 76.2% vs 47.6%, respectively; both P<0.0001). No new safety signals were observed. Conclusions ALIS with MDT was superior to the comparator arm for improving respiratory symptoms and CC in patients newly diagnosed with MACLD.