Open-label Safety Extension Study Assessing Safety and Tolerability of LAI in Patients Who Participated in Study INS-212

NCT ID: NCT02628600

Last Updated: 2020-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 163 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-05
• Study Completion Date: 2018-10-17

Brief Summary

This is an open-label safety extension study to assess the safety and tolerability of once daily dosing of 590 mg Liposomal Amikacin for Inhalation (LAI) added to a multi-drug regimen in participants with nontuberculous mycobacterial (NTM) lung infections due to Mycobacterium avium complex (MAC) who were refractory to therapy and failed to convert in Study INS-212 (NCT02344004).

Detailed Description

Safety and tolerability of once daily dosing of 590 mg Liposomal Amikacin for Inhalation (LAI) added to a multi-drug regimen in participants with non-tuberculous mycobacterium (NTM) lung infections due to Mycobacterium avium complex (MAC) who are refractory to therapy and failed to convert in Study INS-212.

Participants participating in Study INS-212 who had not achieved the INS-212 protocol definition of culture conversion (3 consecutive monthly negative sputum cultures) or who had experienced a relapse or recurrence (agar positive or more than 2 consecutive broth positive results after culture conversion had occurred) by Month 6, as determined by their sputum culture results from Day 1 through Month 6 and confirmed at their scheduled Month 8 visit, were eligible to participate in Study INS-312. For participants who chose to participate in Study INS-312, the Month 8 visit of Study INS-212 became their end of treatment (EOT) visit; these participants were then asked to provide written informed consent for Study INS-312 and were enrolled directly into Study INS-312 after having met all eligibility criteria.

Participants in Study INS-212 had either received 590 mg LAI plus an MDR (LAI + MDR arm) or a multidrug regimen alone (MDR alone arm). All participants in this safety extension study were to continue the multidrug antimycobacterial regimen that they were receiving during Study INS-212 and will receive LAI 590 mg administered daily (QD) for up to 12 months. The participants will remain in the study for up to a total of 13 months (up to 12 months on-treatment plus 1 month off LAI treatment for safety follow up).

Conditions

NTM Lung Infection Due to MAC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prior LAI + Multidrug Regimen

Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR.

Group Type: EXPERIMENTAL

LAI 590 mg

Intervention Type: DRUG

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

Multi-drug regimen

Intervention Type: DRUG

Multidrug antimycobacterial regimen from study INS-212

Prior Multidrug Regimen Alone

Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR.

Group Type: EXPERIMENTAL

LAI 590 mg

Intervention Type: DRUG

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

Multi-drug regimen

Intervention Type: DRUG

Multidrug antimycobacterial regimen from study INS-212

Interventions

LAI 590 mg

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

Intervention Type: DRUG

Multi-drug regimen

Multidrug antimycobacterial regimen from study INS-212

Intervention Type: DRUG

Other Intervention Names

Amikacin Liposome Inhalation Suspension (ALIS); ARIKAYCE®

Eligibility Criteria

Inclusion Criteria

1. had successfully completed the Month 6 and End of Treatment visits in Study INS-212

2. had not achieved the INS-212 protocol definition of culture conversion by Month 6 in Study INS-212 OR had experienced a relapse or recurrence by Month 6 in Study INS-212.

Exclusion Criteria

1. achieved culture conversion without relapse or recurrence in the Study INS-212 study by Month 6

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insmed Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kevin Mange, MD

Role: STUDY_DIRECTOR

Insmed Incorporated

References

Winthrop KL, Flume PA, Thomson R, Mange KC, Yuen DW, Ciesielska M, Morimoto K, Ruoss SJ, Codecasa LR, Yim JJ, Marras TK, van Ingen J, Wallace RJ Jr, Brown-Elliott BA, Coulter C, Griffith DE. Amikacin Liposome Inhalation Suspension for Mycobacterium avium Complex Lung Disease: A 12-Month Open-Label Extension Clinical Trial. Ann Am Thorac Soc. 2021 Jul;18(7):1147-1157. doi: 10.1513/AnnalsATS.202008-925OC.

Reference Type: DERIVED

PMID: 33326356 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2015-003170-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INS-312

Identifier Type: -

Identifier Source: org_study_id