An Open-Label Safety Extension Study to a Multicenter Study of Liposomal Amikacin for Inhalation (LAI) in Adult Patients With Nontuberculous Mycobacterial (NTM) Lung Infections Caused by Mycobacterium Avium Complex (MAC) That Are Refractory to Treatment
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Insmed Incorporated
- Enrollment
- 163
- Primary Endpoint
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •had successfully completed the Month 6 and End of Treatment visits in Study INS-212
- •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-
Exclusion Criteria
- •achieved culture conversion without relapse or recurrence in the Study INS-212 study by Month 6
Arms & Interventions
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.
Intervention: LAI 590 mg (Drug)
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.
Intervention: Multi-drug regimen (Drug)
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.
Intervention: LAI 590 mg (Drug)
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.
Intervention: Multi-drug regimen (Drug)
Outcomes
Primary Outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From baseline to 28 days after end of treatment, up to 13 months
TEAEs are defined as those AEs that occurred on or after the date of first dose of study medication in INS-312 and within 28 days after the last dose. If it couldn't be determined whether the AE is treatment emergent due to a partial onset date, then it was classified as treatment emergent.
Secondary Outcomes
- Change From Baseline (Day 1) to Month 6 and Month 12 in the 6MWT Distance(From baseline to Month 12 or end of treatment)
- Number of Participants Achieving Culture Conversion by Month 6 and Month 12(by Month 6 and Month 12)
- Time to Culture Conversion(by Month 12)