Liposomal Amikacin for Inhalation (LAI) in the Treatment of Mycobacterium Abscessus Lung Disease

This is an open-label study of efficacy, safety and tolerability of once daily dosing of
Liposomal-Amikacin for Inhalation (LAI), in addition to a standard multi-drug antibiotic
therapy in accordance with the 2007 ATS/ IDSA guidelines, in patients with Mycobacterium
abscessus lung disease. The multi-drug therapy is determined at the discretion of the
Investigator. After screening, all eligible patients will enter the trial and will receive
LAI 590 mg once daily for 12 months. If deemed necessary by the investigator, dose may be
adjusted from a minimum of three times per week up to daily, in cases of adverse events
relating to tolerability.

All patients who enter the study will have subsequent study visits at Months 1,2,4,6,9, at
End-of-Study or Month 12, and at 1 and 3 months post study drug discontinuation. At each
visit (including screening), review of concomitant medications, review of adverse events, and
physical exam, will be performed. Chest CT scan will be performed at baseline, 6 months, and
12 months, unless a chest CT scan has already been performed within 6 months on this time
point. The 6 minute walk test and QOL-B-NTM will be performed at baseline, 6 months, 12
months, and 3 months post study drug discontinuation. All patients will have inducted sputum
collected at each study visit, and patients will self-collect expectorated sputum during
intervening monthly time-points until study completion to determine changes in mycobacterial
smear and culture status.

Unscheduled visits will occur as needed should subjects' symptoms worsen between visits.

Inclusion Criteria:

- Male or female patients 12 years and older

- Diagnosis of M. abscessus, including all subspecies, abscessus, bolleti, and
massiliense lung disease according to the 2007 ATS/IDSA criteria

- Both newly diagnosed and currently on treatment or previously treated patients will be
included

- Culture positive (either sputum or bronchoscopy) for M. abscessus at time of screening

- Willingness to adhere to a treatment regimen, study visits, and study procedures
during the course of the study.

- Ability to produce at approximately 3.0 mL of sputum or be willing to undergo an
induction that produces approximately 3.0 mL of sputum for culture collection

- Female of childbearing potential agrees to practice an acceptable method of birth
control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD)

- Written informed consent or assent obtained from the patient, parent or legal guardian
prior to the performance of any study related procedures

Exclusion Criteria:

- Active pulmonary tuberculosis requiring treatment at screening

- Treatment with inhaled or intravenous Amikacin within 14 days prior to baseline

- Known hypersensitivity to aminoglycosides

- Aspartate aminotransferase or alanine aminotransferase ≥ 3 times the upper limit of
normal or total bilirubin ≥ 2 times the upper limit of normal (ULN) at screening

- Current addiction to alcohol or illicit drug abuse

- Any condition which in the opinion of the Investigator interferes with ability to
adhere to study requirements

- Primary immunodeficiency syndromes and acquired immunodeficiency syndromes (e.g.,
HIV-positive patients regardless of CD4 counts)

- Absolute neutrophil count ≤500/μL at Screening

- Significant (as determined by the investigator) hearing loss, vestibular dysfunction,
neuromuscular weakness or a diagnosis of myasthenia gravis, where the potential risk
of aminoglycoside toxicity outweighs the potential benefit

- Serum creatinine >2 times ULN at Screening

- History of lung transplantation

- Any condition that, in the judgment of the Investigator, would compromise the ability
of the subject to complete the study