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

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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:
Information provided by (Responsible Party):
Insmed Incorporated

Tracking Information
First Submitted Date  ICMJE December 8, 2015
First Posted Date  ICMJE December 11, 2015
Results First Submitted Date  ICMJE October 15, 2019
Results First Posted Date  ICMJE November 19, 2019
Last Update Posted Date February 10, 2020
Actual Study Start Date  ICMJE February 5, 2016
Actual Primary Completion Date October 17, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 10, 2015)
Frequency of treatment-emergent adverse events (TEAEs) [ Time Frame: 13 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2019)
  • 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).
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2015)
Proportion of subjects achieving culture conversion at Month 6 [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open-label Safety Extension Study Assessing Safety and Tolerability of LAI in Patients Who Participated in Study INS-212
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE NTM Lung Infection Due to MAC
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: LAI 590 mg
    • Drug: Multi-drug regimen
  • 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.
    Interventions:
    • Drug: LAI 590 mg
    • Drug: Multi-drug regimen
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 15, 2019)
163
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2015)
200
Actual Study Completion Date  ICMJE October 17, 2018
Actual Primary Completion Date October 17, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Canada,   Germany,   Japan,   Netherlands,   New Zealand,   Spain,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02628600
Other Study ID Numbers  ICMJE INS-312
2015-003170-33 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Insmed Incorporated
Study Sponsor  ICMJE Insmed Incorporated
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kevin Mange, MD Insmed Incorporated
PRS Account Insmed Incorporated
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP