Liposomal Amikacin for Inhalation (LAI) for Nontuberculous Mycobacteria
Condition: Mycobacterium Infections, Nontuberculous
MeSH terms: Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Respiratory Aspiration
Intervention: Liposomal amikacin for inhalation (LAI); placebo
Intervention description: 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.
Intervention MeSH terms: Amikacin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Amikacin Liposome Inhalation Suspension (ALIS); Arikayce

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.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Diagnosis of pulmonary nontuberculous mycobacterial lung disease in accordance with
             the 2007 ATS/IDSA criteria with evidence of nodular bronchiectasis and/or cavitary
             disease by chest computed tomography (CT).

          2. History of chronic infection with either Mycobacterium avium complex or Mycobacterium
             abscessus or mixed infection with both species (defined as at least 2 documented
             positive cultures in the prior 2 years, of which at least one was obtained in the 6
             months prior to screening).

          3. Positive sputum culture obtained at screening visit with either Mycobacterium avium
             complex or Mycobacterium abscessus or mixed infection with one dominant species.

          4. Receiving ATS/IDSA guidelines-based treatment regimen defined as: adherent to a
             multi-drug regimen for at least 6 months prior to screening with persistently positive
             mycobacterial cultures.

          5. Ability to produce at least 3 mL of sputum or be willing to undergo an induction that
             produces at least 3 mL of sputum for clinical evaluation.

          6. Female of childbearing potential agrees to practice an acceptable method of birth
             control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or
             IUD).

        Key Exclusion Criteria:

          1. Forced Expiratory Volume in 1 second (FEV1) <30% of predicted at Screening.

          2. Presence of any clinically significant cardiac disease as determined by Investigator.
             The QTc criteria for Exclusion is QTc> 450 msec for males or QTc> 470 msec for
             females.

          3. Subjects with hemoptysis of ≥60 mL in a 24 hour period within 4 weeks prior to
             screening.

          4. Active pulmonary malignancy (primary or metastatic) or any malignancy requiring
             chemotherapy or radiation therapy within one year prior to screening or anticipated
             during the study period.

          5. Active allergic bronchopulmonary mycosis or any other condition requiring systemic
             steroids at a dose > equivalent of 10 mg/day of prednisone within 3 months prior to
             screening or anticipated during the study period.

          6. Pulmonary tuberculosis requiring treatment or treated within 2 years prior to
             screening.

          7. History of lung transplantation.

          8. Hypersensitivity to aminoglycosides.

          9. Any change in chronic NTM multi-drug regimen within 28 days prior to Study Day 1.

         10. Evidence of biliary cirrhosis with portal hypertension.

         11. History of daily, continuous oxygen supplementation.

         12. Smoking tobacco or any substance within 6 months prior to screening or anticipated
             inability to refrain from smoking throughout the study.

        Subjects with CF or primary ciliary dyskinesia were eligible to participate in the study if
        all eligibility criteria defined above were met. Subjects with CF were required to have
        documented confirmation of CF to be eligible for the study. The CF diagnosis had to be
        documented by a positive sweat test ≥ 60 mmol/L or by DNA analysis revealing both mutated
        alleles consistent with CF disease.