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

• ClinicalTrials.gov Identifier: NCT02628600
• Recruitment Status: Completed
• First Posted: December 11, 2015
• Results First Posted: November 19, 2019
• Last Update Posted: February 10, 2020
• Sponsor: Insmed Incorporated
• Information provided by (Responsible Party): Insmed Incorporated

Study Description

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).

Condition or disease	Intervention/treatment	Phase
NTM Lung Infection Due to MAC	Drug: LAI 590 mg; Drug: Multi-drug regimen	Phase 3

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 (Clinical Trial)
• Actual Enrollment: 163 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 5, 2016
• Actual Primary Completion Date: October 17, 2018
• Actual Study Completion Date: October 17, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: 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; Other Names: Amikacin Liposome Inhalation Suspension (ALIS); ARIKAYCE®; Drug: Multi-drug regimen; Multidrug antimycobacterial regimen from study INS-212
Experimental: 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.	Drug: 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; Other Names: Amikacin Liposome Inhalation Suspension (ALIS); ARIKAYCE®; Drug: Multi-drug regimen; Multidrug antimycobacterial regimen from study INS-212

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. Number of Participants Achieving Culture Conversion by Month 6 and Month 12 [ Time Frame: 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).

2. Time to Culture Conversion [ Time Frame: by Month 12 ]
   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.
3. 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 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key 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.

Key Exclusion Criteria:

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

Contacts and Locations

Sponsors and Collaborators

Insmed Incorporated

Investigators

• Study Director: Kevin Mange, MD; Insmed Incorporated

  Study Documents (Full-Text)

Documents provided by Insmed Incorporated:

Statistical Analysis Plan  [PDF] November 13, 2018

Study Protocol  [PDF] May 25, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Insmed Incorporated
• ClinicalTrials.gov Identifier: NCT02628600
• Other Study ID Numbers: INS-312; 2015-003170-33 ( EudraCT Number )
• First Posted: December 11, 2015
• Results First Posted: November 19, 2019
• Last Update Posted: February 10, 2020
• Last Verified: January 2020

Keywords provided by Insmed Incorporated:

ALIS; ARIKAYCE

Additional relevant MeSH terms:

Infections; Amikacin; Anti-Bacterial Agents; Anti-Infective Agents