NTM Lung Infection Due to MACPhase 3NCT02628600
Open-label Safety Extension Study Assessing Safety and Tolerability of LAI in Patients Who Participated in Study INS-212
A Phase 3 study testing LAI 590 mg and Multi-drug regimen in people with NTM Lung Infection Due to MAC, run by Insmed Incorporated.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NTM Lung Infection Due to MAC
- What is being tested?
- LAI 590 mg and Multi-drug regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 163 participants
- Where
- No sites listed yet
- Study dates
- 5 Feb 2016to 17 Oct 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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-212.
Who cannot join
- 1. achieved culture conversion without relapse or recurrence in the Study INS-212 study by Month 6
About this study
Official title: 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
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).
Read the 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
- Being tested
- LAI 590 mg, Multi-drug regimen
- Keywords
- ALIS, ARIKAYCE
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAI 590 mgDrug
Also called Amikacin Liposome Inhalation Suspension (ALIS), ARIKAYCE®
LAI 590 mg QD: administered by inhaling drug product that had been aerosolized in an investigational eFlow nebulizer over approximately 14 minutes
Multi-drug regimenDrug
Multidrug antimycobacterial regimen from study INS-212
| Study group | Role | What they receive |
|---|---|---|
| Prior LAI + Multidrug Regimen | Experimental | Participants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR. Receives: Drug: LAI 590 mg; Drug: Multi-drug regimen |
| Prior Multidrug Regimen Alone | Experimental | Participants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR. Receives: Drug: LAI 590 mg; Drug: Multi-drug regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Measured: From baseline to 28 days after end of treatment, up to 13 months
Secondary outcomes (3)
Number of Participants Achieving Culture Conversion by Month 6 and Month 12
6 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 6 (last opportunity to convert was at Month 4).
12 months: Converters are defined as participants who had 3 consecutive monthly MAC-negative sputum cultures by Month 12 (last opportunity to convert was at Month 10).
Measured: by Month 6 and Month 12
Time to Culture Conversion
The time to culture conversion is defined as the date of conversion for participants achieving culture conversion is defined as the date of the first of 3-consecutive monthly negative sputum cultures. Then, the number of days to culture conversion is defined as the difference between the date of conversion and the date of first dose of LAI.
Measured: by Month 12
Change From Baseline (Day 1) to Month 6 and Month 12 in the 6MWT Distance
A 6-minute walk assessment of exertional capability was performed at Baseline (Day 1) and Month 6 and Month 12/EOT. The standardized protocol based on the American Thoracic Society (ATS) guidelines (http://doi.org/10.1164/ajrccm.166.1.at1102) was used. After assessments were performed for heart rate, blood pressure, pulse oximetry (SpO2), dyspnea, and overall fatigue using the Borg scale, participants were instructed to walk on a prescribed course as far as they could in 6 minutes. Pre-test assessment parameters were repeated after exertion. The maximum distance achieved and post exertion heart rate and SpO2 were compared to pre-test values. The maximum distance achieved was recorded in the electronic case report form.
Measured: From baseline to Month 12 or end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2015 (estimated)
- Study start5 Feb 2016
- Primary completion17 Oct 2018
- Study completion17 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for NTM Lung Infection Due to MACStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 163 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insmed Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kevin Mange, MD, Study director, Insmed Incorporated
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02628600
- Sponsor's protocol ID
- INS-312
- Other IDs
- 2015-003170-33, 2015
- Status last verified
- Jan 2020
- First submitted
- 8 Dec 2015
- Last updated
- 10 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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. 2026 Jan;15(1):365-379. doi: 10.1007/s40121-025-01247-7. Epub 2025 Nov 4.
PubMed 41186908Winthrop 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.
PubMed 33326356
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02628600
- Acronym / sponsor ID
- INS-312
- Conditions
- NTM Lung Infection Due to MAC
- Keywords
- ALIS, ARIKAYCE
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 163 participants (actual)
- Lead sponsor
- Insmed IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 5 Feb 2016 (actual)
- Primary completion
- 17 Oct 2018 (actual)
- Study completion
- 17 Oct 2018 (actual)
- First posted
- 11 Dec 2015 (estimated)
- Results
- Posted 19 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prior LAI + Multidrug Regimen | Experimental | Drug: LAI 590 mg, Drug: Multi-drug regimenParticipants in the prior Study INS-212 who received LAI+MDR. All participants in this safety extension study received LAI+MDR. |
| Prior Multidrug Regimen Alone | Experimental | Drug: LAI 590 mg, Drug: Multi-drug regimenParticipants in the prior Study INS-212 who received MDR alone. All participants in this safety extension study received LAI+MDR. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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-212.
Key exclusion criteria (1 listed)
- 1. achieved culture conversion without relapse or recurrence in the Study INS-212 study by Month 6
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LAI 590 mgAlso: Amikacin Liposome Inhalation Suspension (ALIS), ARIKAYCE®LAI 590 mg QD: administered by inhaling drug product that had been aerosolized in an investigational eFlow nebulizer over approximately 14 minutes | Drug | Prior LAI + Multidrug Regimen, Prior Multidrug Regimen Alone |
| Multi-drug regimenMultidrug antimycobacterial regimen from study INS-212 | Drug | Prior LAI + Multidrug Regimen, Prior Multidrug Regimen Alone |
Primary outcome
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.
3 secondary outcomes
Number of Participants Achieving Culture Conversion by Month 6 and Month 12
Time frame: by Month 6 and Month 12
Time to Culture Conversion
Time frame: by Month 12
Change From Baseline (Day 1) to Month 6 and Month 12 in the 6MWT Distance
Time frame: From baseline to Month 12 or end of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41186908Yamazaki 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. 2026 Jan;15(1):365-379. doi: 10.1007/s40121-025-01247-7. Epub 2025 Nov 4.
- Derived from this study: PubMed 33326356Winthrop 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.
Related trials for NTM Lung Infection Due to MAC
Enrolling by invitationObservational study
To Evaluate the Clinical Efficacy and Safety of Omadacycline in the Treatment of Mycobacterium Abscessus Infection.
Mycobacterium Abscessus Infection, NTM Lung Infection Due to MAC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Mange, MD study director
Insmed Incorporated
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LAI 590 mg and Multi-drug regimen in people with NTM Lung Infection Due to MAC, run by Insmed Incorporated.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: From baseline to 28 days after end of treatment, up to 13 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02628600, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2020.