<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03038178</url>
  </required_header>
  <id_info>
    <org_study_id>LAI/INS-IIR-01</org_study_id>
    <nct_id>NCT03038178</nct_id>
  </id_info>
  <brief_title>Liposomal Amikacin for Inhalation (LAI) in the Treatment of Mycobacterium Abscessus Lung Disease</brief_title>
  <official_title>An Open-label Study of Efficacy, Safety and Tolerability of Liposomal Amikacin for Inhalation (LAI) Once Daily in Addition to Standard Multi-antibiotic Therapy in the Treatment of Mycobacterium Abscessus Lung Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kevin Winthrop</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Insmed Incorporated</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>The University of Texas Health Science Center at Tyler</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Oregon Health and Science University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The proposed study will assess the efficacy, safety and tolerability of once daily dosing of&#xD;
      Liposomal-Amikacin for Inhalation (LAI) 590 mg for 12 months plus standard of care (SOC)&#xD;
      mycobacterial multi-drug regimen in accordance with the 2007 ATS/ IDSA guidelines, for&#xD;
      treatment of mycobacterium abscessus lung disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label study of efficacy, safety and tolerability of once daily dosing of&#xD;
      Liposomal-Amikacin for Inhalation (LAI), in addition to a standard multi-drug antibiotic&#xD;
      therapy in accordance with the 2007 ATS/ IDSA guidelines, in patients with Mycobacterium&#xD;
      abscessus lung disease. The multi-drug therapy is determined at the discretion of the&#xD;
      Investigator. After screening, all eligible patients will enter the trial and will receive&#xD;
      LAI 590 mg once daily for 12 months. If deemed necessary by the investigator, dose may be&#xD;
      adjusted from a minimum of three times per week up to daily, in cases of adverse events&#xD;
      relating to tolerability.&#xD;
&#xD;
      All patients who enter the study will have subsequent study visits at Months 1,2,4,6,9, at&#xD;
      End-of-Study or Month 12, and at 1 and 3 months post study drug discontinuation. At each&#xD;
      visit (including screening), review of concomitant medications, review of adverse events, and&#xD;
      physical exam, will be performed. Chest CT scan will be performed at baseline, 6 months, and&#xD;
      12 months, unless a chest CT scan has already been performed within 6 months on this time&#xD;
      point. The 6 minute walk test and QOL-B-NTM will be performed at baseline, 6 months, 12&#xD;
      months, and 3 months post study drug discontinuation. All patients will have inducted sputum&#xD;
      collected at each study visit, and patients will self-collect expectorated sputum during&#xD;
      intervening monthly time-points until study completion to determine changes in mycobacterial&#xD;
      smear and culture status.&#xD;
&#xD;
      Unscheduled visits will occur as needed should subjects' symptoms worsen between visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Actual">December 31, 2019</completion_date>
  <primary_completion_date type="Actual">October 31, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline sputum culture at 12 months</measure>
    <time_frame>Sputum examined for culture change from Baseline at 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline 6-minute Walk Test at 6 months</measure>
    <time_frame>6-minute Walk Test results examined for change from Baseline at 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline 6-minute Walk Test at 12 months</measure>
    <time_frame>6-minute Walk Test results examined for change from Baseline at 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from End of Treatment (EOT) sputum culture at 3 months post EOT</measure>
    <time_frame>Sputum examined for culture change from EOT at 3 months post EOT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Hospitalizations for pulmonary exacerbations</measure>
    <time_frame>Number of Hospitalizations for pulmonary exacerbations that occur between Baseline and 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Adverse Events</measure>
    <time_frame>Number of Patient-reported and Investigator-reported Adverse Events at 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects discontinuing study drug due to Adverse Event</measure>
    <time_frame>Number of subjects who discontinue study drug before 12 months due to Adverse Event will be examined at 12 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change from Baseline reported nontuberculous mycobacterium (NTM) symptoms at End of Treatment (EOT)</measure>
    <time_frame>Patient-reported NTM symptoms examined for change from Baseline at EOT (12 months)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline Chest CT at End of Treatment (EOT)</measure>
    <time_frame>CT scan examined for change from Baseline at EOT (12 months)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline body weight at End of Treatment (EOT)</measure>
    <time_frame>body weight of patient examined for change from Baseline at EOT (12 months)</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change from Baseline Body Mass Index (BMI) at End of Treatment (EOT)</measure>
    <time_frame>BMI of patient examined for change from Baseline at EOT (12 months)</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Mycobacterium Infections, Nontuberculous</condition>
  <condition>Mycobacteria, Atypical</condition>
  <arm_group>
    <arm_group_label>LAI plus multi-drug regimen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>once daily dosing of Liposomal-Amikacin for Inhalation (LAI) 590 mg for 12 months plus standard of care (SOC) mycobacterial multi-drug regimen in accordance with the 2007 ATS/ IDSA guidelines</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LAI plus multi-drug regimen</intervention_name>
    <description>Liposomal Amikacin for Inhalation (LAI) is the experimental treatment which, in this single arm will be taken in conjunction with standard of care multi-drug treatment regimen</description>
    <arm_group_label>LAI plus multi-drug regimen</arm_group_label>
    <other_name>ARIKAYCE™</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients 12 years and older&#xD;
&#xD;
          -  Diagnosis of M. abscessus, including all subspecies, abscessus, bolleti, and&#xD;
             massiliense lung disease according to the 2007 ATS/IDSA criteria&#xD;
&#xD;
          -  Both newly diagnosed and currently on treatment or previously treated patients will be&#xD;
             included&#xD;
&#xD;
          -  Culture positive (either sputum or bronchoscopy) for M. abscessus at time of screening&#xD;
&#xD;
          -  Willingness to adhere to a treatment regimen, study visits, and study procedures&#xD;
             during the course of the study.&#xD;
&#xD;
          -  Ability to produce at approximately 3.0 mL of sputum or be willing to undergo an&#xD;
             induction that produces approximately 3.0 mL of sputum for culture collection&#xD;
&#xD;
          -  Female of childbearing potential agrees to practice an acceptable method of birth&#xD;
             control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD)&#xD;
&#xD;
          -  Written informed consent or assent obtained from the patient, parent or legal guardian&#xD;
             prior to the performance of any study related procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active pulmonary tuberculosis requiring treatment at screening&#xD;
&#xD;
          -  Treatment with inhaled or intravenous Amikacin within 14 days prior to baseline&#xD;
&#xD;
          -  Known hypersensitivity to aminoglycosides&#xD;
&#xD;
          -  Aspartate aminotransferase or alanine aminotransferase ≥ 3 times the upper limit of&#xD;
             normal or total bilirubin ≥ 2 times the upper limit of normal (ULN) at screening&#xD;
&#xD;
          -  Current addiction to alcohol or illicit drug abuse&#xD;
&#xD;
          -  Any condition which in the opinion of the Investigator interferes with ability to&#xD;
             adhere to study requirements&#xD;
&#xD;
          -  Primary immunodeficiency syndromes and acquired immunodeficiency syndromes (e.g.,&#xD;
             HIV-positive patients regardless of CD4 counts)&#xD;
&#xD;
          -  Absolute neutrophil count ≤500/μL at Screening&#xD;
&#xD;
          -  Significant (as determined by the investigator) hearing loss, vestibular dysfunction,&#xD;
             neuromuscular weakness or a diagnosis of myasthenia gravis, where the potential risk&#xD;
             of aminoglycoside toxicity outweighs the potential benefit&#xD;
&#xD;
          -  Serum creatinine &gt;2 times ULN at Screening&#xD;
&#xD;
          -  History of lung transplantation&#xD;
&#xD;
          -  Any condition that, in the judgment of the Investigator, would compromise the ability&#xD;
             of the subject to complete the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kevin L Winthrop, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oregon Health and Science University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Health Science Center</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>March 2, 2020</last_update_submitted>
  <last_update_submitted_qc>March 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Oregon Health and Science University</investigator_affiliation>
    <investigator_full_name>Kevin Winthrop</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Mycobacterium Infections, Nontuberculous</keyword>
  <keyword>Mycobacteria, Atypical</keyword>
  <keyword>Amikacin</keyword>
  <keyword>Inhalation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycobacterium Infections</mesh_term>
    <mesh_term>Mycobacterium Infections, Nontuberculous</mesh_term>
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Respiratory Aspiration</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>April 18, 2022</submitted>
    <returned>May 10, 2022</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03038178
org study id: LAI/INS-IIR-01
nct id: NCT03038178
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The proposed study will assess the efficacy, safety and tolerability of once daily dosing of
      Liposomal-Amikacin for Inhalation (LAI) 590 mg for 12 months plus standard of care (SOC)
      mycobacterial multi-drug regimen in accordance with the 2007 ATS/ IDSA guidelines, for
      treatment of mycobacterium abscessus lung disease.
This is an open-label study of efficacy, safety and tolerability of once daily dosing of
      Liposomal-Amikacin for Inhalation (LAI), in addition to a standard multi-drug antibiotic
      therapy in accordance with the 2007 ATS/ IDSA guidelines, in patients with Mycobacterium
      abscessus lung disease. The multi-drug therapy is determined at the discretion of the
      Investigator. After screening, all eligible patients will enter the trial and will receive
      LAI 590 mg once daily for 12 months. If deemed necessary by the investigator, dose may be
      adjusted from a minimum of three times per week up to daily, in cases of adverse events
      relating to tolerability.

      All patients who enter the study will have subsequent study visits at Months 1,2,4,6,9, at
      End-of-Study or Month 12, and at 1 and 3 months post study drug discontinuation. At each
      visit (including screening), review of concomitant medications, review of adverse events, and
      physical exam, will be performed. Chest CT scan will be performed at baseline, 6 months, and
      12 months, unless a chest CT scan has already been performed within 6 months on this time
      point. The 6 minute walk test and QOL-B-NTM will be performed at baseline, 6 months, 12
      months, and 3 months post study drug discontinuation. All patients will have inducted sputum
      collected at each study visit, and patients will self-collect expectorated sputum during
      intervening monthly time-points until study completion to determine changes in mycobacterial
      smear and culture status.

      Unscheduled visits will occur as needed should subjects' symptoms worsen between visits.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from Baseline sputum culture at 12 months
time frame: Sputum examined for culture change from Baseline at 12 months
measure: Change from Baseline 6-minute Walk Test at 6 months
time frame: 6-minute Walk Test results examined for change from Baseline at 6 months
measure: Change from Baseline 6-minute Walk Test at 12 months
time frame: 6-minute Walk Test results examined for change from Baseline at 12 months
measure: Change from End of Treatment (EOT) sputum culture at 3 months post EOT
time frame: Sputum examined for culture change from EOT at 3 months post EOT
measure: Number of Hospitalizations for pulmonary exacerbations
time frame: Number of Hospitalizations for pulmonary exacerbations that occur between Baseline and 12 months
measure: Number of Adverse Events
time frame: Number of Patient-reported and Investigator-reported Adverse Events at 12 months
measure: Number of subjects discontinuing study drug due to Adverse Event
time frame: Number of subjects who discontinue study drug before 12 months due to Adverse Event will be examined at 12 months
measure: Change from Baseline reported nontuberculous mycobacterium (NTM) symptoms at End of Treatment (EOT)
time frame: Patient-reported NTM symptoms examined for change from Baseline at EOT (12 months)
measure: Change from Baseline Chest CT at End of Treatment (EOT)
time frame: CT scan examined for change from Baseline at EOT (12 months)
measure: Change from Baseline body weight at End of Treatment (EOT)
time frame: body weight of patient examined for change from Baseline at EOT (12 months)
measure: Change from Baseline Body Mass Index (BMI) at End of Treatment (EOT)
time frame: BMI of patient examined for change from Baseline at EOT (12 months)
arm group label: LAI plus multi-drug regimen
arm group type: Experimental
description: once daily dosing of Liposomal-Amikacin for Inhalation (LAI) 590 mg for 12 months plus standard of care (SOC) mycobacterial multi-drug regimen in accordance with the 2007 ATS/ IDSA guidelines
intervention type: Drug
intervention name: LAI plus multi-drug regimen
description: Liposomal Amikacin for Inhalation (LAI) is the experimental treatment which, in this single arm will be taken in conjunction with standard of care multi-drug treatment regimen
arm group label: LAI plus multi-drug regimen
other name: ARIKAYCE™
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Kevin L Winthrop, MD, MPH
role: Principal Investigator
affiliation: Oregon Health and Science University
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Oregon Health and Science University
investigator full name: Kevin Winthrop
investigator title: Associate Professor
mesh term: Mycobacterium Infections
mesh term: Mycobacterium Infections, Nontuberculous
mesh term: Lung Diseases
mesh term: Respiratory Aspiration
sharing ipd: No
submitted: April 18, 2022
returned: May 10, 2022