Amikacin Liposome Inhalation Suspension for Mycobacterium avium Complex Lung Disease: A 12-Month Open-Label Extension Clinical Trial.

Abstract

Rationale: Patients with refractory Mycobacterium avium complex (MAC) lung disease have limited treatment options. In the CONVERT study, amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) increased culture conversion rates versus GBT alone by Month 6. Limited data are available regarding >6-month treatment in a refractory population.Objectives: Evaluate 12-month safety, tolerability, and efficacy of ALIS+GBT.Methods: Adults with refractory MAC lung disease not achieving culture conversion by CONVERT Month 6 could enroll in this open-label extension (INS-312) to receive 590 mg once-daily ALIS+GBT for 12 months. Two cohorts enrolled: the "ALIS-naive" cohort included patients randomized to GBT alone in CONVERT, and the "prior-ALIS" cohort included those randomized to ALIS+GBT in CONVERT. Safety and tolerability of ALIS over 12 months (primary endpoint) and culture conversion by Months 6 and 12 were assessed.Results: In the ALIS-naive cohort, 83.3% of patients (n = 75/90) experienced respiratory treatment-emergent adverse events (TEAEs), and 35.6% (n = 32) had serious TEAEs; 26.7% (n = 24) achieved culture conversion by Month 6 and 33.3% (n = 30) by Month 12. In the prior-ALIS cohort, 46.6% of patients (n = 34/73) experienced respiratory TEAEs, and 27.4% (n = 20) had serious TEAEs; 9.6% (n = 7) achieved culture conversion by Month 6 (≤14 mo ALIS exposure) and 13.7% (n = 10) by Month 12 (≤20 mo ALIS exposure). Nephrotoxicity-related TEAEs and measured hearing decline were infrequent in both cohorts.Conclusions: In up to 20 months of ALIS use, respiratory TEAEs were common, nephrotoxicity and hearing decline were infrequent, and culture conversion continued beyond 6 months of therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02628600).

• Authors: Kevin L Winthrop, Patrick A Flume, Rachel Thomson, Kevin C Mange, Dayton W Yuen, Monika Ciesielska, Kozo Morimoto, Stephen J Ruoss, Luigi R Codecasa, Jae-Joon Yim, Theodore K Marras, Jakko van Ingen, Richard J Wallace Jr, Barbara A Brown-Elliott, Chris Coulter, David E Griffith
• Journal: Annals of the American Thoracic Society (Ann Am Thorac Soc) Vol. 18 Issue 7 Pg. 1147-1157 (07 2021) ISSN: 2325-6621 [Electronic] United States
• PMID: 33326356 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Liposomes
• Amikacin

Topics

• Administration, Inhalation
• Adult
• Amikacin (adverse effects)
• Anti-Bacterial Agents (adverse effects)
• Humans
• Liposomes (therapeutic use)
• Lung Diseases (drug therapy)
• Mycobacterium avium Complex
• Mycobacterium avium-intracellulare Infection (drug therapy)
• Treatment Outcome