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

Primary Purpose

Mycobacterium Infections, Nontuberculous, Mycobacteria, Atypical

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

LAI plus multi-drug regimen

About this trial

This is an interventional treatment trial for Mycobacterium Infections, Nontuberculous focused on measuring Mycobacterium Infections, Nontuberculous, Mycobacteria, Atypical, Amikacin, Inhalation

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Oregon Health & Science University
University of Texas Health Science Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LAI plus multi-drug regimen

Arm Description

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

Outcomes

Primary Outcome Measures

Change from Baseline sputum culture at 12 months

Secondary Outcome Measures

Change from Baseline 6-minute Walk Test at 6 months

Change from Baseline 6-minute Walk Test at 12 months

Change from End of Treatment (EOT) sputum culture at 3 months post EOT

Number of Hospitalizations for pulmonary exacerbations

Number of Adverse Events

Number of subjects discontinuing study drug due to Adverse Event

Full Information

NCT ID

NCT03038178

First Posted

January 3, 2017

Last Updated

March 2, 2020

Sponsor

Kevin Winthrop

Collaborators

Insmed Incorporated, The University of Texas Health Science Center at Tyler

1. Study Identification

Unique Protocol Identification Number

NCT03038178

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

October 2016 (Actual)

Primary Completion Date

October 31, 2019 (Actual)

Study Completion Date

December 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Kevin Winthrop

Collaborators

Insmed Incorporated, The University of Texas Health Science Center at Tyler

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mycobacterium Infections, Nontuberculous, Mycobacteria, Atypical

Keywords

Mycobacterium Infections, Nontuberculous, Mycobacteria, Atypical, Amikacin, Inhalation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

LAI plus multi-drug regimen

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

LAI plus multi-drug regimen

Other Intervention Name(s)

ARIKAYCE™

Intervention Description

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

Primary Outcome Measure Information:

Title

Change from Baseline sputum culture at 12 months

Time Frame

Sputum examined for culture change from Baseline at 12 months

Secondary Outcome Measure Information:

Title

Change from Baseline 6-minute Walk Test at 6 months

Time Frame

6-minute Walk Test results examined for change from Baseline at 6 months

Title

Change from Baseline 6-minute Walk Test at 12 months

Time Frame

6-minute Walk Test results examined for change from Baseline at 12 months

Title

Change from End of Treatment (EOT) sputum culture at 3 months post EOT

Time Frame

Sputum examined for culture change from EOT at 3 months post EOT

Title

Number of Hospitalizations for pulmonary exacerbations

Time Frame

Number of Hospitalizations for pulmonary exacerbations that occur between Baseline and 12 months

Title

Number of Adverse Events

Time Frame

Number of Patient-reported and Investigator-reported Adverse Events at 12 months

Title

Number of subjects discontinuing study drug due to Adverse Event

Time Frame

Number of subjects who discontinue study drug before 12 months due to Adverse Event will be examined at 12 months

Other Pre-specified Outcome Measures:

Title

Change from Baseline reported nontuberculous mycobacterium (NTM) symptoms at End of Treatment (EOT)

Time Frame

Patient-reported NTM symptoms examined for change from Baseline at EOT (12 months)

Title

Change from Baseline Chest CT at End of Treatment (EOT)

Time Frame

CT scan examined for change from Baseline at EOT (12 months)

Title

Change from Baseline body weight at End of Treatment (EOT)

Time Frame

body weight of patient examined for change from Baseline at EOT (12 months)

Title

Change from Baseline Body Mass Index (BMI) at End of Treatment (EOT)

Time Frame

BMI of patient examined for change from Baseline at EOT (12 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kevin L Winthrop, MD, MPH

Organizational Affiliation

Oregon Health and Science University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Oregon Health & Science University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

University of Texas Health Science Center

City

Tyler

State/Province

Texas

ZIP/Postal Code

75708

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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