Liposomal Amikacin for Inhalation (LAI) for Nontuberculous Mycobacteria
Condition: Mycobacterium Infections, Nontuberculous
MeSH terms: Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Respiratory Aspiration
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to evaluate the efficacy, safety and tolerability of 84 days of
      daily dosing of 590 mg of LAI versus placebo in patients with treatment refractory NTM lung
      disease.

      The first part of the study is the 84-day double-blind phase to evaluate the primary and
      secondary endpoints.
    

Detailed description: 
      This was a Phase 2, randomized, double-blind study of efficacy, safety, and tolerability of
      once daily (QD) dosing of LAI 590 mg versus placebo for 84 days in subjects with treatment
      refractory NTM lung infection on a stable multidrug regimen. At the conclusion of the
      randomized double-blind phase of the study, subjects who consented to continue in the
      open-label phase of the study received LAI 590 mg QD for 84 additional days. All subjects
      were required to complete a 28-day safety follow-up after their end of treatment study visit
      (Day 168). Subjects completing this study were consented for enrollment in a long-term
      follow-up phase and were asked to return to the study site at 12 months and 24 months (per
      protocol Amendment #3, the 24-month follow-up visit was no longer required) (visit window ± 2
      months) after the last dose of study drug (either after completing the randomized
      double-blind phase or the open-label phase). Subjects were stratified upon entering the study
      based on the presence or absence of cystic fibrosis (CF) and Mycobacterium avium complex
      versus M abscessus as the predominate NTM organism at baseline and were block randomized to
      receive either LAI or placebo in a 1:1 ratio in the double-blind phase.

      Subjects completing the main study, and subjects who completed the 84-day open-label phase,
      were consented for enrollment in a post-LAI safety follow-up assessment and were asked to
      return to the study site 12 months (visit window ± 2 months) after the last dose of study
      drug (either after completing the randomized double-blind phase or the open-label phase). The
      screening period required obtaining 3 morning sputum specimens (spontaneous or induced) for
      mycobacteriology. At each post-screening sputum timepoint, at least 2 and preferably 3 sputum
      specimens were obtained. At Day 1 (baseline), subjects were evaluated pre-dose and post-dose
      at the study site. Subjects returned to the study site briefly on Day 2 for collection of
      serum samples to determine creatinine clearance. On Days 28, 56, and 84, study drug was
      administered at the site and the efficacy, safety, and tolerability of study drug were
      evaluated. At Day 85, those subjects continuing in the open-label phase of the study received
      LAI 590 mg at the study site with pre-dose and post-dose assessments for safety and efficacy.
      Subjects returned every 28 days (Days 112, 140, and 168) in the open-label phase. A 28-day,
      post-dose follow-up visit occurred at either Day 112 for those subjects who did not continue
      in the open-label phase or at Day 196 for those subjects who continued in the open-label
      phase.

      Subjects completing the main study, and subjects who completed the 84-day open-label phase,
      were consented for enrollment in a post-LAI safety follow-up assessment and were asked to
      return to the study site 12 months (visit window ± 2 months) after the last dose of study
      drug (either after completing the randomized double-blind phase or the open-label phase).
      Arikace™, Arikayce™, Liposomal Amikacin for Inhalation (LAI), and Amikacin Liposome
      Inhalation Suspension (ALIS) may be used interchangeably throughout this study and other
      studies evaluating amikacin liposome inhalation suspension.
    

Intervention name(s): Liposomal amikacin for inhalation (LAI); placebo
Intervention type(s): Drug; Drug
Intervention description(s): Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.
590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
Administration time is approximately 13 minutes.
Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
Subjects can continue with 84 additional days of dosing in the open label extension.; Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.
Administration procedures, volume and administration time are similar to LAI.
Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Other intervention name(s): Amikacin Liposome Inhalation Suspension (ALIS); Arikayce
Intervention MeSH terms: Amikacin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Amikacin Liposome Inhalation Suspension (ALIS); Arikayce