Liposomal Amikacin for Inhalation (LAI) for Nontuberculous Mycobacteria

NCT01315236 | Completed Phase 2 Results DMC

• 1 other identifier: TR02-112
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 19

Brief 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.

Conditions

Mycobacterium Infections, Nontuberculous

Keywords

Amikacin Liposome Inhalation Suspension (ALIS); Arikayce

Outcome Measures

Primary Outcomes (1)

• Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84.

  The endpoint used the 7-step semi-quantitative scale (SQS) for mycobacterial culture reporting in both solid and liquid growth media, with step 1 = culture negative in both solid and liquid media, step 2 = growth in liquid medium only, 3 = solid medium positive, 4 = 50 to 100 colonies in solid medium \& growth in liquid, 5 = \>100 to 200 colonies in solid medium \& growth in liquid, 6 = \>200 to 500 colonies in solid medium \& growth in liquid, 7 = \>500 colonies in solid medium \& growth in liquid. Full scale range is 1 (best score) to 7 (worst score). The change in step measures the growth at Day 84 compared to the growth at Baseline. The negative values represent reduction in colony growth.

  Baseline and end of double-blind phase of 84 days

Secondary Outcomes (7)

• Number of Subjects With Negative NTM Culture for the LAI Arm at Day 84 Compared to the Placebo Arm at Day 84

  84 days double-blind phase

• Time to Negative NTM Culture….During the 84-day Double-blind Treatment Phase

  84 days double-blind phase

• Ordinal, 3-level Response From Baseline on the SQS for Mycobacterial Culture for the LAI Arm at Day 84 Compared to the Placebo Arm at Day 84

  Baseline and end of double-blind phase of 84 days

• Change From Baseline in Respiratory and Systemic Symptoms Questionnaire (RSSQ) Score at Day 84 for the LAI Arm Compared to the Placebo Arm

  Baseline to day 84.

• Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm

  Baseline and end of double-blind phase of 84 days

Study Arms (2)

LAI 590 mg QD

EXPERIMENTAL

LAI 590 mg QD

Drug: Liposomal amikacin for inhalation (LAI)

Placebo

PLACEBO COMPARATOR

placebo QD

Drug: placebo

Interventions

Liposomal amikacin for inhalation (LAI) DRUG

* 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.

Also known as: Amikacin Liposome Inhalation Suspension (ALIS), Arikayce

LAI 590 mg QD

placebo DRUG

* 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.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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).
• Positive sputum culture obtained at screening visit with either Mycobacterium avium complex or Mycobacterium abscessus or mixed infection with one dominant species.
• 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.
• 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.
• Female of childbearing potential agrees to practice an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD).

You may not qualify if:

• Forced Expiratory Volume in 1 second (FEV1) \<30% of predicted at Screening.
• Subjects with hemoptysis of ≥60 mL in a 24 hour period within 4 weeks prior to screening.
• 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.
• 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.
• Pulmonary tuberculosis requiring treatment or treated within 2 years prior to screening.
• History of lung transplantation.
• Hypersensitivity to aminoglycosides.
• Any change in chronic NTM multi-drug regimen within 28 days prior to Study Day 1.
• Evidence of biliary cirrhosis with portal hypertension.
• History of daily, continuous oxygen supplementation.
• 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.

Sponsors & Collaborators

• Insmed Incorporated: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (19)

Unknown Facility

Birmingham, Alabama, United States

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Stanford, California, United States

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Denver, Colorado, United States

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Washington D.C., District of Columbia, United States

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Gainesville, Florida, United States

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Miami, Florida, United States

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Tampa, Florida, United States

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Kansas City, Kansas, United States

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Bethesda, Maryland, United States

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Rochester, Minnesota, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Cleveland, Ohio, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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Tyler, Texas, United States

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Milwaukee, Wisconsin, United States

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Hamilton, Ontario, Canada

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Related Publications (2)

• Rubino CM, Onufrak NJ, van Ingen J, Griffith DE, Bhavnani SM, Yuen DW, Mange KC, Winthrop KL. Population Pharmacokinetic Evaluation of Amikacin Liposome Inhalation Suspension in Patients with Treatment-Refractory Nontuberculous Mycobacterial Lung Disease. Eur J Drug Metab Pharmacokinet. 2021 Mar;46(2):277-287. doi: 10.1007/s13318-020-00669-7. Epub 2021 Feb 17.

  PMID: 33595792 DERIVED

• Olivier KN, Griffith DE, Eagle G, McGinnis JP 2nd, Micioni L, Liu K, Daley CL, Winthrop KL, Ruoss S, Addrizzo-Harris DJ, Flume PA, Dorgan D, Salathe M, Brown-Elliott BA, Gupta R, Wallace RJ Jr. Randomized Trial of Liposomal Amikacin for Inhalation in Nontuberculous Mycobacterial Lung Disease. Am J Respir Crit Care Med. 2017 Mar 15;195(6):814-823. doi: 10.1164/rccm.201604-0700OC.

  PMID: 27748623 DERIVED

MeSH Terms

Conditions

Mycobacterium Infections, Nontuberculous

Interventions

Inhalation

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Results Point of Contact

• Title: Kevin Mange (Senior VP, Clinical Development)
• Organization: Insmed Incorporated

kevin.mange@insmed.com

908-947-2651

Study Officials

• Gina Eagle

  Insmed Incorporated

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2011
• First Posted: March 15, 2011
• Study Start: April 19, 2012
• Primary Completion: August 18, 2014
• Study Completion: June 18, 2015
• Last Updated: August 21, 2019
• Results First Posted: August 21, 2019

Record last verified: 2019-08

Locations

CA (1); US (18)