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

Sponsor

Kevin Winthrop (Other)

Overall Status

Completed

CT.gov ID

NCT03038178

Collaborator

Insmed Incorporated (Industry), The University of Texas Health Science Center at Tyler (Other)

Enrollment

Locations

Arm

Actual Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The proposed study will assess the efficacy, safety and tolerability of once daily dosing of Liposomal-Amikacin for Inhalation (LAI) 590 mg for 12 months plus standard of care (SOC) mycobacterial multi-drug regimen in accordance with the 2007 ATS/ IDSA guidelines, for treatment of mycobacterium abscessus lung disease.

Condition or Disease	Intervention/Treatment	Phase
Mycobacterium Infections, Nontuberculous Mycobacteria, Atypical	Drug: LAI plus multi-drug regimen	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label Study of Efficacy, Safety and Tolerability of Liposomal Amikacin for Inhalation (LAI) Once Daily in Addition to Standard Multi-antibiotic Therapy in the Treatment of Mycobacterium Abscessus Lung Disease

Actual Study Start Date :

Oct 1, 2016

Actual Primary Completion Date :

Oct 31, 2019

Actual Study Completion Date :

Dec 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LAI plus multi-drug regimen once daily dosing of Liposomal-Amikacin for Inhalation (LAI) 590 mg for 12 months plus standard of care (SOC) mycobacterial multi-drug regimen in accordance with the 2007 ATS/ IDSA guidelines	Drug: LAI plus multi-drug regimen Liposomal Amikacin for Inhalation (LAI) is the experimental treatment which, in this single arm will be taken in conjunction with standard of care multi-drug treatment regimen Other Names: ARIKAYCE™

Arm

Intervention/Treatment

Experimental: LAI plus multi-drug regimen

once daily dosing of Liposomal-Amikacin for Inhalation (LAI) 590 mg for 12 months plus standard of care (SOC) mycobacterial multi-drug regimen in accordance with the 2007 ATS/ IDSA guidelines

Drug: LAI plus multi-drug regimen

Liposomal Amikacin for Inhalation (LAI) is the experimental treatment which, in this single arm will be taken in conjunction with standard of care multi-drug treatment regimen

Other Names:

ARIKAYCE™

Outcome Measures

Primary Outcome Measures

Change from Baseline sputum culture at 12 months [Sputum examined for culture change from Baseline at 12 months]

Secondary Outcome Measures

Change from Baseline 6-minute Walk Test at 6 months [6-minute Walk Test results examined for change from Baseline at 6 months]
Change from Baseline 6-minute Walk Test at 12 months [6-minute Walk Test results examined for change from Baseline at 12 months]
Change from End of Treatment (EOT) sputum culture at 3 months post EOT [Sputum examined for culture change from EOT at 3 months post EOT]
Number of Hospitalizations for pulmonary exacerbations [Number of Hospitalizations for pulmonary exacerbations that occur between Baseline and 12 months]
Number of Adverse Events [Number of Patient-reported and Investigator-reported Adverse Events at 12 months]
Number of subjects discontinuing study drug due to Adverse Event [Number of subjects who discontinue study drug before 12 months due to Adverse Event will be examined at 12 months]

Other Outcome Measures

Change from Baseline reported nontuberculous mycobacterium (NTM) symptoms at End of Treatment (EOT) [Patient-reported NTM symptoms examined for change from Baseline at EOT (12 months)]
Change from Baseline Chest CT at End of Treatment (EOT) [CT scan examined for change from Baseline at EOT (12 months)]
Change from Baseline body weight at End of Treatment (EOT) [body weight of patient examined for change from Baseline at EOT (12 months)]
Change from Baseline Body Mass Index (BMI) at End of Treatment (EOT) [BMI of patient examined for change from Baseline at EOT (12 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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