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

NCT03038178 | Completed Phase 2 DMC

• 1 other identifier: LAI/INS-IIR-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Mycobacterium Infections, Nontuberculous; Mycobacteria, Atypical

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change from Baseline sputum culture at 12 months

  Sputum examined for culture change from Baseline at 12 months

Secondary Outcomes (6)

• 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

Other Outcomes (4)

• 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)

Study Arms (1)

LAI plus multi-drug regimen

EXPERIMENTAL

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

Interventions

LAI plus multi-drug regimen DRUG

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

Also known as: ARIKAYCE™

LAI plus multi-drug regimen

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kevin Winthrop: lead
• Insmed Incorporated: collaborator
• The University of Texas Health Science Center at Tyler: collaborator

Study Sites (2)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Texas Health Science Center

Tyler, Texas, 75708, United States

Location

Related Publications (1)

• Siegel SAR, Griffith DE, Philley JV, Brown-Elliott BA, Brunton AE, Sullivan PE, Fuss C, Strnad L, Wallace RJ Jr, Winthrop KL. Open-Label Trial of Amikacin Liposome Inhalation Suspension in Mycobacterium abscessus Lung Disease. Chest. 2023 Oct;164(4):846-859. doi: 10.1016/j.chest.2023.05.036. Epub 2023 Jun 17.

  PMID: 37419144 DERIVED

MeSH Terms

Conditions

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kevin L Winthrop, MD, MPH

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: January 31, 2017
• Study Start: October 1, 2016
• Primary Completion: October 31, 2019
• Study Completion: December 31, 2019
• Last Updated: March 4, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)