<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/NCT01661192</url>
  </required_header>
  <id_info>
    <org_study_id>006971ctil</org_study_id>
    <nct_id>NCT01661192</nct_id>
  </id_info>
  <brief_title>Long Term Treatment Effect of the Safety, Tolerability and Efficacy of AAT in Type 1 Diabetes</brief_title>
  <acronym>AAT Extension</acronym>
  <official_title>Open Label Study (Extension 001)to Evaluate Long Term Treatment Effect of the Safety, Tolerability and Efficacy of Intervenous ALPHA-1 ANTITRYSIN (AAT)Glasia™ in Type 1 Diabetes Mellitus (Extension to KAMADA AAt 008, PHASE I/II Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rabin Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kamada, Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Rabin Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      At a previous study the investigators have assessed the safety and efficacy of treatment with&#xD;
      AAT(Alpha 1 Antitrypsin)in newly diagnosed type 1 diabetes subjects aiming at beta cells&#xD;
      preservation .&#xD;
&#xD;
      Since treatment with AAT is expected to be a chronic treatment; stopping treatment will&#xD;
      probably result in eventual loss of the preserved beta-cell function. Indeed, other&#xD;
      investigational drugs aiming at beta cells preservation have shown that patients who were&#xD;
      initially treated and maintained their initial beta-cell function, required continuation of&#xD;
      treatment or they lost the beta-cell function.&#xD;
&#xD;
      Therefore, in this extension study, patients who were previously treated with AAT and&#xD;
      maintained clinically significant beta-cell function are offered a continuation of treatment,&#xD;
      since they are likely to benefit from use of the medication.&#xD;
&#xD;
      The proposed study is aimed to assess the long term effect of AAT in subjects with type 1&#xD;
      diabetes mellitus: safety and tolerability of treatment, and effect on beta-cell function.&#xD;
&#xD;
      Subjects who have completed all visits of the 008 study will be offered to participate in the&#xD;
      extension study.&#xD;
&#xD;
      The study will be consist off two main arms as following:&#xD;
&#xD;
      Arm 1: Subjects who maintained peak stimulated C-peptide secretion ≥ 0.2 nmol/L will continue&#xD;
      treatment with AAT for up to 18 treatments according to the dosage group they were allocated&#xD;
      to in the 008 study.&#xD;
&#xD;
      Arm 2:&#xD;
&#xD;
      Subjects who have not maintained peak stimulated C-peptide secretion ≥ 0.2nmol/L and subjects&#xD;
      with peak stimulated C -peptide secretion ≥ 0.2 nmol/L who are reluctant to receive&#xD;
      additional study drug.&#xD;
&#xD;
      Clinical follow up for all subjects in both arms will be for 3 years&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</primary_completion_date>
  <phase>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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of AAT in terms of adverse events and serious adverse events</measure>
    <time_frame>At month 36</time_frame>
    <description>We will assess at each visit until final visit (month 36)the safety and tolerability of study drug in terms of adverse events and serious adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of the AAT in terms of laboratory values</measure>
    <time_frame>At month 36</time_frame>
    <description>We will assess at each visit until final visit (month 36)the safety and tolerability of study drug in terms of laboratory values</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Beta cell function-AUC (Area Under the Curve) of stimulated C-Peptide from stimulated MMTT (mixed meal tolerance test)</measure>
    <time_frame>at month 36</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients that maintain stimulated peak C-peptide &gt;=0.2 nmol/L</measure>
    <time_frame>at month 36</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients that achieve glycemic target of HbA1c &lt;=7.5%</measure>
    <time_frame>At month 36</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily insulin dose adjusted to body weight</measure>
    <time_frame>At month 36</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Type 1 Diabetes</condition>
  <condition>Beta Cell Preservation</condition>
  <arm_group>
    <arm_group_label>AAT( Alpha 1 Antitrypsin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who maintained peak stimulated C-peptide secretion ≥ 0.2nmol/L will continue treatment with AAT according to the dosage group they were allocated to at the previous study(40mg/kg or 60mg/kg or 80mg/kg), intravenously, once a week for 6 consecutive weeks, at 24-week intervals for a duration of ~54 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Follow up group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subjects who have not maintained peak stimulated C-peptide secretion ≥ 0.2nmol/L or subjects with peak stimulated C -peptide secretion ≥ 0.2nmol/L who are reluctant to receive additional study drug, will be followed up only with no administration of investigational product</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AAT( Alpha 1 Antitrypsin)</intervention_name>
    <arm_group_label>AAT( Alpha 1 Antitrypsin)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject (or parent/guardian) willing and able to sign an informed consent&#xD;
&#xD;
          -  Ability to comply with all study requirements.&#xD;
&#xD;
          -  A patient that participated in Study 008 and received all doses of study medication,&#xD;
             per protocol.&#xD;
&#xD;
          -  Evidence of clinically significant residual beta-cell function demonstrated by MMTT&#xD;
             peak stimulated C-peptide concentrations ≥ 0.20 nmol/L (Arm 1 only).&#xD;
&#xD;
          -  Age 10-25 (inclusive) years&#xD;
&#xD;
          -  If a female is of childbearing potential, the subject is not pregnant or lactating,&#xD;
             and will use oral hormonal contraception or other equally effective contraceptive&#xD;
             methods throughout the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  IgA (immunoglobulin A ) deficient subjects.&#xD;
&#xD;
          -  Individuals with a history of severe immediate hypersensitivity reactions, including&#xD;
             anaphylaxis, to plasma products.&#xD;
&#xD;
          -  History of life threatening allergy, anaphylactic reaction, or systemic response to&#xD;
             human plasma derived products.&#xD;
&#xD;
          -  The subject is receiving immunosuppressive or immunomodulating agents or cytotoxic&#xD;
             therapy or any medication that in the opinion of the Investigator might interfere with&#xD;
             the study.&#xD;
&#xD;
          -  Clinically significant intercurrent illnesses, including (but not limited to):&#xD;
             cardiac, hepatic, renal, neurological, hematological, neoplastic, immunological,&#xD;
             skeletal or other) that in the opinion of the investigator, could interfere with the&#xD;
             safety, compliance or other aspects of this study. Patients with well-controlled,&#xD;
             chronic diseases could be possibly included after consultation with the treating&#xD;
             physician.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yael Lebenthal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rabin Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mariana Rachmiel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assaf Haroffe Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Schneider Children's Medical Center</name>
      <address>
        <city>Petah-Tikva</city>
        <zip>49202</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Assaf Haroffeh Medical Center</name>
      <address>
        <city>Zerifin</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>January 10, 2017</last_update_submitted>
  <last_update_submitted_qc>January 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Type 1 Diabetes</keyword>
  <keyword>newly diagnosed</keyword>
  <keyword>Beta cell preservation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alpha 1-Antitrypsin</mesh_term>
    <mesh_term>Protein C Inhibitor</mesh_term>
  </intervention_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/NCT01661192
org study id: 006971ctil
nct id: NCT01661192
lead sponsor: 
collaborator: 
has dmc: No
At a previous study the investigators have assessed the safety and efficacy of treatment with
      AAT(Alpha 1 Antitrypsin)in newly diagnosed type 1 diabetes subjects aiming at beta cells
      preservation .

      Since treatment with AAT is expected to be a chronic treatment; stopping treatment will
      probably result in eventual loss of the preserved beta-cell function. Indeed, other
      investigational drugs aiming at beta cells preservation have shown that patients who were
      initially treated and maintained their initial beta-cell function, required continuation of
      treatment or they lost the beta-cell function.

      Therefore, in this extension study, patients who were previously treated with AAT and
      maintained clinically significant beta-cell function are offered a continuation of treatment,
      since they are likely to benefit from use of the medication.

      The proposed study is aimed to assess the long term effect of AAT in subjects with type 1
      diabetes mellitus: safety and tolerability of treatment, and effect on beta-cell function.

      Subjects who have completed all visits of the 008 study will be offered to participate in the
      extension study.

      The study will be consist off two main arms as following:

      Arm 1: Subjects who maintained peak stimulated C-peptide secretion ≥ 0.2 nmol/L will continue
      treatment with AAT for up to 18 treatments according to the dosage group they were allocated
      to in the 008 study.

      Arm 2:

      Subjects who have not maintained peak stimulated C-peptide secretion ≥ 0.2nmol/L and subjects
      with peak stimulated C -peptide secretion ≥ 0.2 nmol/L who are reluctant to receive
      additional study drug.

      Clinical follow up for all subjects in both arms will be for 3 years
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Safety and tolerability of AAT in terms of adverse events and serious adverse events
time frame: At month 36
description: We will assess at each visit until final visit (month 36)the safety and tolerability of study drug in terms of adverse events and serious adverse events
measure: Safety and tolerability of the AAT in terms of laboratory values
time frame: At month 36
description: We will assess at each visit until final visit (month 36)the safety and tolerability of study drug in terms of laboratory values
measure: Beta cell function-AUC (Area Under the Curve) of stimulated C-Peptide from stimulated MMTT (mixed meal tolerance test)
time frame: at month 36
measure: Percentage of patients that maintain stimulated peak C-peptide >=0.2 nmol/L
time frame: at month 36
measure: Percentage of patients that achieve glycemic target of HbA1c <=7.5%
time frame: At month 36
measure: Daily insulin dose adjusted to body weight
time frame: At month 36
arm group label: AAT( Alpha 1 Antitrypsin)
arm group type: Experimental
description: Subjects who maintained peak stimulated C-peptide secretion ≥ 0.2nmol/L will continue treatment with AAT according to the dosage group they were allocated to at the previous study(40mg/kg or 60mg/kg or 80mg/kg), intravenously, once a week for 6 consecutive weeks, at 24-week intervals for a duration of ~54 weeks.
arm group label: Follow up group
arm group type: No Intervention
description: Subjects who have not maintained peak stimulated C-peptide secretion ≥ 0.2nmol/L or subjects with peak stimulated C -peptide secretion ≥ 0.2nmol/L who are reluctant to receive additional study drug, will be followed up only with no administration of investigational product
intervention type: Drug
intervention name: AAT( Alpha 1 Antitrypsin)
arm group label: AAT( Alpha 1 Antitrypsin)
criteria: 
gender: All
minimum age: 10 Years
maximum age: 25 Years
healthy volunteers: No
last name: Yael Lebenthal, MD
role: Principal Investigator
affiliation: Rabin Medical Center
last name: Mariana Rachmiel, MD
role: Principal Investigator
affiliation: Assaf Haroffe Medical Center
facility: 
facility: 
country: Israel
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Alpha 1-Antitrypsin
mesh term: Protein C Inhibitor