<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/NCT02212886</url>
  </required_header>
  <id_info>
    <org_study_id>MI GA Depot - 001</org_study_id>
    <nct_id>NCT02212886</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and Efficacy of Monthly Long-acting IM Injection of 80 or 40 mg GA Depot in Subjects With RRMS</brief_title>
  <official_title>A Prospective 1-year, Open-label, Two Arms, Multicenter, Phase IIa Study to Assess Safety, Tolerability and Efficacy of Once a Month Long-acting Intramuscular Injection of 80 or 40 mg Glatiramer Acetate (GA Depot) in Subjects With Relapsing Remitting Multiple Sclerosis (RRMS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mapi Pharma Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mapi Pharma Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      -  This is a phase IIa study in which GA Depot 80 or 40mg is administered as an IM&#xD;
           injection to subjects with RRMS at 4 week intervals for 52 weeks of treatment.&#xD;
&#xD;
        -  The purpose of the study is to assess safety, tolerability, and efficacy of a monthly&#xD;
           long-acting IM injection of 80 or 40mg GA Depot in subjects with RRMS. The study will&#xD;
           include subjects switching from daily or thrice weekly administration of 20 mg or 40mg&#xD;
           respectively of glatiramer acetate (GA, i.e., Copaxone®) injection&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  25 Subjects with a diagnosis of relapsing remitting multiple sclerosis (RRMS) who are&#xD;
           treated with daily or thrice weekly subcutaneous injections of 20 mg or 40 mg&#xD;
           respectively of GA (Copaxone®) during the previous 12 months&#xD;
&#xD;
        -  Study product is GA long-acting injection (GA Depot) which is a combination of&#xD;
           extended-release microspheres for injection and diluent (water for injection) for&#xD;
           parenteral use. GA Depot will be administered intramuscularly (IM).&#xD;
&#xD;
        -  The study duration for an individual subject in the core study will be 60 weeks,&#xD;
           consisting of 4 weeks of screening evaluation (weeks -4 to 0), followed by a 52-week&#xD;
           open-label treatment period, and a 4 weeks follow up period: through a total of 17&#xD;
           visits.&#xD;
&#xD;
        -  For both arms, subjects who completed 13 injections and who consented (by signing an&#xD;
           informed consent) are able to enter the optional 8 years extension period. During the&#xD;
           extension period subjects will receive 40 mg of GA Depot IM once every 4 weeks.&#xD;
&#xD;
        -  Physical, vital signs and safety assessment - will be performed at each visit during the&#xD;
           whole study. Physical examination will be performed quarterly during the extension&#xD;
           period.&#xD;
&#xD;
        -  MRI at visit 1 (screenings), at week 24, week 52 (end of core study) and every 6 months&#xD;
           during the extension period.&#xD;
&#xD;
        -  Neurological and safety laboratory tests at screening visit, on visits in weeks 4, 12,&#xD;
           24, 36, 52 (end of core study) and every 6 months during the extension period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Anticipated">November 2024</completion_date>
  <primary_completion_date type="Actual">May 2017</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety / Adverse events</measure>
    <time_frame>During the study (1 year treatment)</time_frame>
    <description>Number of patients experiencing adverse events and assessments of localized skin reactions at injection sites.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy/Change in Relapse Rate</measure>
    <time_frame>During the study (1 year treatment)</time_frame>
    <description>Relapse rate detected during the study compared to relapse rate observed in the 12 months prior to study start.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy/Changes in brain MRI</measure>
    <time_frame>During the study (1 year treatment)</time_frame>
    <description>Changes from baseline to end of treatment visit in the number of enhancing lesions and new lesions images of brain MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy/Changes in EDSS</measure>
    <time_frame>1 year</time_frame>
    <description>Change from baseline to end of treatment visit of Expanded Disability Status Scale (EDSS) score.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>GA Depot 80mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Monthly IM injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GA Depot 40mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Monthly IM injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GA Depot 80 mg</intervention_name>
    <description>Recruitment completed</description>
    <arm_group_label>GA Depot 80mg</arm_group_label>
    <other_name>Microspheres containing GA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GA Depot 40 mg</intervention_name>
    <description>Recruitment completed</description>
    <arm_group_label>GA Depot 40mg</arm_group_label>
    <other_name>Microspheres containing GA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects with a diagnosis of RRMS.&#xD;
&#xD;
          -  Diagnosis of multiple sclerosis (MS) consistent with the McDonald Criteria (revisions&#xD;
             of 2010).&#xD;
&#xD;
          -  Treatment with 20 mg or 40 mg of GA (Copaxone®) during the previous 12 months with&#xD;
             ongoing treatment at the Screening Visit.&#xD;
&#xD;
          -  Normal renal function.&#xD;
&#xD;
          -  Normal liver function.&#xD;
&#xD;
          -  Normal hemoglobin concentration.&#xD;
&#xD;
          -  Absence of any clinically significant medical, psychiatric or laboratory&#xD;
             abnormalities.&#xD;
&#xD;
          -  Ability to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any relevant medical, surgical, or psychiatric condition, laboratory value, or&#xD;
             concomitant medication which, in the opinion of the investigator, makes the subject&#xD;
             unsuitable for study entry or potentially unable to complete all aspects of the study.&#xD;
&#xD;
          -  Concomitant Autoimmune disease.&#xD;
&#xD;
          -  Severe anemia (hemoglobin &lt; 10 g/dL).&#xD;
&#xD;
          -  Abnormal renal function (serum creatinine &gt; 1.5xULN).&#xD;
&#xD;
          -  Abnormal liver function (transaminases &gt;2xULN).&#xD;
&#xD;
          -  Pregnant or breast-feeding women.&#xD;
&#xD;
          -  Women capable of child bearing must have a negative urine pregnancy test at screening&#xD;
             visit and use an adequate contraceptive method throughout the study. Women who are&#xD;
             surgically sterile (hysterectomy or tubal ligation) or whose last menstruation was 12&#xD;
             months or more prior to the Screening Visit are considered to be of non-child-bearing&#xD;
             potential. Acceptable forms of contraception include oral, implanted, or injected&#xD;
             contraceptives; intrauterine devices in place for at least 3 months; estrogen patch;&#xD;
             and adequate barrier methods in conjunction with spermicide. Abstinence is considered&#xD;
             an acceptable contraceptive regimen.&#xD;
&#xD;
          -  History of any anaphylactic reaction and/or serious allergic reaction following a&#xD;
             vaccination, a proven hypersensitivity to any component of the study drug, e.g. GA,&#xD;
             polylactic-co-glycolic acid (PLGA), polyvinyl alcohol (PVA).&#xD;
&#xD;
          -  Known or suspected history of drug or alcohol abuse.&#xD;
&#xD;
          -  Positive test for HIV, hepatitis, venereal disease research laboratory test (VDRL), or&#xD;
             tuberculosis.&#xD;
&#xD;
          -  Participation in an investigational drug study within 30 days prior to start of this&#xD;
             study.&#xD;
&#xD;
          -  Active malignant disease of any kind. However, a patient, who has had a malignant&#xD;
             disease in the past, was treated and is currently disease - free for at least 5 years,&#xD;
             may be considered to be enrolled in the study. In this case the sponsor medical expert&#xD;
             approval is required.&#xD;
&#xD;
          -  Treatment with any kind of steroids during the last 30 days.&#xD;
&#xD;
          -  Confirmed relapse during the last 30 days.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shlomo Flechter, M.D</last_name>
    <role>Principal Investigator</role>
  </overall_official>
  <location>
    <facility>
      <name>Barzilai Medical Center</name>
      <address>
        <city>Ashkelon</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Medical Center</name>
      <address>
        <city>Haifa</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TASMC</name>
      <address>
        <city>Tel Aviv</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 5, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>October 30, 2022</last_update_submitted>
  <last_update_submitted_qc>October 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Glatiramer acetate</keyword>
  <keyword>Copaxone®</keyword>
  <keyword>Multiple sclerosis</keyword>
  <keyword>Relapsing remitting multiple sclerosis</keyword>
  <keyword>RRMS</keyword>
  <keyword>GA Depot</keyword>
  <keyword>Monthly injection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Relapsing-Remitting</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <!-- 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/NCT02212886
org study id: MI GA Depot - 001
nct id: NCT02212886
lead sponsor: 
has dmc: No
-  This is a phase IIa study in which GA Depot 80 or 40mg is administered as an IM
           injection to subjects with RRMS at 4 week intervals for 52 weeks of treatment.

        -  The purpose of the study is to assess safety, tolerability, and efficacy of a monthly
           long-acting IM injection of 80 or 40mg GA Depot in subjects with RRMS. The study will
           include subjects switching from daily or thrice weekly administration of 20 mg or 40mg
           respectively of glatiramer acetate (GA, i.e., Copaxone®) injection
-  25 Subjects with a diagnosis of relapsing remitting multiple sclerosis (RRMS) who are
           treated with daily or thrice weekly subcutaneous injections of 20 mg or 40 mg
           respectively of GA (Copaxone®) during the previous 12 months

        -  Study product is GA long-acting injection (GA Depot) which is a combination of
           extended-release microspheres for injection and diluent (water for injection) for
           parenteral use. GA Depot will be administered intramuscularly (IM).

        -  The study duration for an individual subject in the core study will be 60 weeks,
           consisting of 4 weeks of screening evaluation (weeks -4 to 0), followed by a 52-week
           open-label treatment period, and a 4 weeks follow up period: through a total of 17
           visits.

        -  For both arms, subjects who completed 13 injections and who consented (by signing an
           informed consent) are able to enter the optional 8 years extension period. During the
           extension period subjects will receive 40 mg of GA Depot IM once every 4 weeks.

        -  Physical, vital signs and safety assessment - will be performed at each visit during the
           whole study. Physical examination will be performed quarterly during the extension
           period.

        -  MRI at visit 1 (screenings), at week 24, week 52 (end of core study) and every 6 months
           during the extension period.

        -  Neurological and safety laboratory tests at screening visit, on visits in weeks 4, 12,
           24, 36, 52 (end of core study) and every 6 months during the extension period.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety / Adverse events
time frame: During the study (1 year treatment)
description: Number of patients experiencing adverse events and assessments of localized skin reactions at injection sites.
measure: Efficacy/Change in Relapse Rate
time frame: During the study (1 year treatment)
description: Relapse rate detected during the study compared to relapse rate observed in the 12 months prior to study start.
measure: Efficacy/Changes in brain MRI
time frame: During the study (1 year treatment)
description: Changes from baseline to end of treatment visit in the number of enhancing lesions and new lesions images of brain MRI
measure: Efficacy/Changes in EDSS
time frame: 1 year
description: Change from baseline to end of treatment visit of Expanded Disability Status Scale (EDSS) score.
arm group label: GA Depot 80mg
arm group type: Experimental
description: Monthly IM injection
arm group label: GA Depot 40mg
arm group type: Experimental
description: Monthly IM injection
intervention type: Drug
intervention name: GA Depot 80 mg
description: Recruitment completed
arm group label: GA Depot 80mg
other name: Microspheres containing GA
intervention type: Drug
intervention name: GA Depot 40 mg
description: Recruitment completed
arm group label: GA Depot 40mg
other name: Microspheres containing GA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Shlomo Flechter, M.D
role: Principal Investigator
facility: 
facility: 
facility: 
country: Israel
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Relapsing-Remitting
mesh term: Sclerosis