Study to Evaluate Efficacy of LAI When Added to Multi-drug Regimen Compared to Multi-drug Regimen Alone

NCT02344004 | Completed Phase 3 Results DMC

• 2 other identifiers: INS-2122014-005010-31
• Study Type: interventional
• Target: 336
• Locations: 0 countries
• Sites: N/A

Brief Summary

A study to evaluate the effectiveness of Liposomal Amikacin for Inhalation (LAI) 590 mg administered once daily (QD) when added to multi-drug regimen (MDR) in participants with Nontuberculous Mycobacterial (NTM) lung infection caused by Mycobacterium Avium Complex (MAC) that were refractory to treatment. Participants were randomized 2:1 to LAI 590 mg administered QD + MDR or MDR alone.

Conditions

Mycobacterium Infections, Nontuberculous

Keywords

ALIS; ARIKAYCE

Outcome Measures

Primary Outcomes (2)

• Number of Participants Achieving Culture Conversion by Month 6 in the Liposomal Amikacin for Inhalation (LAI) + Multi-drug Regimen (MDR) Arm Compared to the MDR Alone Arm

  Sputum specimens were collected at Screening (Visit 1), Baseline (Visit 2), and at Visits 3 (Month 1) through 8 (Month 6). A negative culture result reflected a negative culture result for all sputum samples collected at each visit. Participants met the primary endpoint of culture conversion by Month 6 if they had 3 consecutive monthly MAC-negative sputum cultures during the first 6 months of the study. A participant needed to achieve the first of 3 consecutive negative sputum cultures (that defined culture conversion) by Month 4 in order to meet the primary endpoint by Month 6. Each participant in the intent to treat (ITT) population (ie, all randomized participants) was classified as either a converter or non-converter by Month 6.

  by Month 6

• Number of Participants Achieving Durable Culture Conversion Through 3 Months Off Treatment in the LAI + MDR Arm Compared to the MDR Arm Alone

  Sputum specimens were collected at screening, baseline (Day 1), during treatment, and at Months 1, 3, 6, and 12 months off treatment. Culture conversion with durability was defined as achieving culture conversion by Month 6 and then having no more than 2 consecutive broth positive cultures and no Agar positive culture up to 3 months off treatment. Converters with missing broth or Agar sputum culture result after Month 6 up to 3 months off treatment were considered as not achieving culture conversion with durability except those participants who are unable to produce sputum despite reasonable efforts, as reported by source documentation. Participants who had relapse/recurrence, had "rescue" medication and/or died before reaching 3 months off treatment were considered as not achieving culture conversion with durability.

  up to Month 19

Secondary Outcomes (5)

• Change From Baseline (Day 1) to Month 6 in the Six-Minute Walk Test (6MWT) Distance in the LAI + MDR Arm Compared to the MDR Alone Arm

  at Month 6

• Time to Culture Conversion by Month 6 in the LAI + MDR Arm Compared to the MDR Alone Arm

  by Month 6

• Number of Participants Achieving Sustained Culture Conversion at the End of Treatment (EOT) in the LAI + MDR Arm Compared to the MDR Arm Alone

  up to Month 16

• Change in 6-Minute Walk Test (6MWT) Distance at EOT in the LAI Arm Compared to a Multi-drug Regimen Alone

  up to Month 16

• Change From Baseline (Day 1) at Month 6 in the St. George's Respiratory Questionnaire (SGRQ) Total Score

  at Month 6

Study Arms (2)

Multi-drug Regimen

NO INTERVENTION

Participants received their already prescribed anti-mycobacterial regimen (based on the 2007 American Thoracic Society/Infectious Diseases Society of America \[ATS/IDSA\] Guidelines)

LAI + Multi-drug Regimen

EXPERIMENTAL

Participants received LAI 590 mg QD in addition to their already prescribed anti-mycobacterial regimen (based on the 2007 ATS/IDSA Guidelines) LAI 590 mg QD, administered by inhaling drug product that had been aerosolized in an eFlow nebulizer over approximately 14 minutes

Drug: LAI (Liposomal Amikacin for Inhalation) 590 mg

Interventions

LAI (Liposomal Amikacin for Inhalation) 590 mg DRUG

LAI 590 mg QD, administered by inhaling drug product that had been aerosolized in an eFlow nebulizer over approximately 14 minutes.

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

LAI + Multi-drug Regimen

Eligibility Criteria

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

You may qualify if:

• Be continually positive for MAC on sputum culture while adhering to a multi-drug treatment regimen for a minimum duration of 6 months which is either ongoing or was completed no more than 12 months before screening
• Be diagnosed with MAC NTM lung infection with evidence of nodular bronchiectasis and/or fibrocavitary disease by chest CT
• Be willing to adhere to multi-drug treatment regimen during the course of the study

You may not qualify if:

• Patients with cystic fibrosis
• Positive pregnancy test or lactation at screening. All women of child bearing potential will be tested. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrheic for at least 1 year), or surgically or naturally sterile.
• Active pulmonary tuberculosis requiring treatment at screening
• History of lung transplantation
• Prior exposure to LAI (including clinical study).

Sponsors & Collaborators

• Insmed Incorporated: lead

Related Publications (5)

• Yamazaki Y, Nakagawa T, Jumadilova Z, Yuen D, Villa R, Hasegawa N. Management and Resolution of Hypersensitivity Pneumonitis-Related Events in Japanese Patients Treated with Amikacin Liposome Inhalation Suspension in the CONVERT and INS-312 Clinical Trials. Infect Dis Ther. 2025 Nov 4. doi: 10.1007/s40121-025-01247-7. Online ahead of print.

  PMID: 41186908 DERIVED

• Morimoto K, Nonaka M, Yamazaki Y, Nakagawa T, Takasaki J, Tsuyuguchi K, Kitada S, Jumadilova Z, Yuen DW, Ciesielska M, Hasegawa N. Amikacin liposome inhalation suspension for Mycobacterium avium complex pulmonary disease: A subgroup analysis of Japanese patients in the randomized, phase 3, CONVERT study. Respir Investig. 2024 Mar;62(2):284-290. doi: 10.1016/j.resinv.2023.12.012. Epub 2024 Jan 25.

  PMID: 38277865 DERIVED

• Griffith DE, Thomson R, Flume PA, Aksamit TR, Field SK, Addrizzo-Harris DJ, Morimoto K, Hoefsloot W, Mange KC, Yuen DW, Ciesielska M, Wallace RJ Jr, van Ingen J, Brown-Elliott BA, Coulter C, Winthrop KL; CONVERT Study Group. Amikacin Liposome Inhalation Suspension for Refractory Mycobacterium avium Complex Lung Disease: Sustainability and Durability of Culture Conversion and Safety of Long-term Exposure. Chest. 2021 Sep;160(3):831-842. doi: 10.1016/j.chest.2021.03.070. Epub 2021 Apr 19.

  PMID: 33887244 DERIVED

• 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

• Griffith DE, Eagle G, Thomson R, Aksamit TR, Hasegawa N, Morimoto K, Addrizzo-Harris DJ, O'Donnell AE, Marras TK, Flume PA, Loebinger MR, Morgan L, Codecasa LR, Hill AT, Ruoss SJ, Yim JJ, Ringshausen FC, Field SK, Philley JV, Wallace RJ Jr, van Ingen J, Coulter C, Nezamis J, Winthrop KL; CONVERT Study Group. Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study. Am J Respir Crit Care Med. 2018 Dec 15;198(12):1559-1569. doi: 10.1164/rccm.201807-1318OC.

  PMID: 30216086 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 Vice President, Clinical Development & Medical Affairs, ALIS)
• Organization: Insmed Inc

kevin.mange@insmed.com

908-947-2651

Study Officials

• Gina Eagle, MD

  Insmed Incorporated

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2015
• First Posted: January 22, 2015
• Study Start: May 27, 2015
• Primary Completion: July 3, 2018
• Study Completion: April 3, 2019
• Last Updated: May 7, 2020
• Results First Posted: November 20, 2018

Record last verified: 2020-02