<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/NCT02215200</url>
  </required_header>
  <id_info>
    <org_study_id>ATG-GCSF (IND)</org_study_id>
    <secondary_id>Type 1 Diabetes TrialNet</secondary_id>
    <secondary_id>TN19</secondary_id>
    <secondary_id>UC4DK106993</secondary_id>
    <secondary_id>UC4DK117009</secondary_id>
    <nct_id>NCT02215200</nct_id>
  </id_info>
  <brief_title>ATG-GCSF in New Onset Type 1 Diabetes</brief_title>
  <acronym>ATG-GCSF</acronym>
  <official_title>Antithymocyte Globulin (ATG) and Pegylated Granulocyte Colony Stimulating Factor (GCSF) in New Onset Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Research Resources (NCRR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Juvenile Diabetes Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>American Diabetes Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Leona M. and Harry B. Helmsley Charitable Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a three-arm, 1:1:1 randomized, placebo controlled, double- blinded trial in which at&#xD;
      least 28 subjects will receive active Anti-Thymocyte Globulin and Granulocyte&#xD;
      colony-stimulating factor (ATG-GCSF), at least 28 subjects will receive ATG alone and at&#xD;
      least 28 subjects will receive placebo alone within 100 days from diagnosis of Type 1&#xD;
      Diabetes (T1D).&#xD;
&#xD;
      The primary objective of the study will be to determine the safety and ability of low dose&#xD;
      ATG plus GCSF and low dose ATG alone to retain/enhance C-peptide production in new onset T1D&#xD;
      patients demonstrating residual beta cell function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary statistical hypothesis to be assessed in the study is whether the 2 hour area&#xD;
      under the curve (change in baseline to 12 months) in residual beta cell function (C-peptide)&#xD;
      will differ between those treated with ATG and GCSF or ATG alone as compared with placebo.&#xD;
&#xD;
      The study will also examine the effect of the proposed treatments on surrogate markers for&#xD;
      immunologic and metabolic outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">August 2018</completion_date>
  <primary_completion_date type="Actual">August 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Area Under the Stimulated C-peptide Curve From Baseline to 12 Months.</measure>
    <time_frame>-10, 0 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months</time_frame>
    <description>The C-peptide 2 hour area under the curve (AUC) mean is calculated at baseline and 12 months and measured in nmol/L. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the &quot;AUC mean&quot; and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis&quot;).</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">89</enrollment>
  <condition>Diabetes Mellitus, Type 1</condition>
  <arm_group>
    <arm_group_label>Anti-Thymocyte Globulin (ATG) and Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose.&#xD;
Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ATG plus Granulocyte colony stimulating factor (GCSF)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg.&#xD;
GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-Thymocyte Globulin (ATG)</intervention_name>
    <description>Thymoglobulin</description>
    <arm_group_label>ATG plus Granulocyte colony stimulating factor (GCSF)</arm_group_label>
    <arm_group_label>Anti-Thymocyte Globulin (ATG) and Placebo</arm_group_label>
    <other_name>Thymoglobulin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Granulocyte colony stimulating factor (GCSF)</intervention_name>
    <description>Granulocyte colony stimulating factor (GCSF)</description>
    <arm_group_label>ATG plus Granulocyte colony stimulating factor (GCSF)</arm_group_label>
    <other_name>Neulasta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for ATG)</intervention_name>
    <description>Normal saline administered by IV infusion to mimic ATG</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for GCSF)</intervention_name>
    <description>Placebo prepared to mimic 6mg subcutaneous injection of GCSF</description>
    <arm_group_label>Anti-Thymocyte Globulin (ATG) and Placebo</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be &gt; 12 years &lt; 46&#xD;
&#xD;
          -  Must have a diagnosis of T1D for less than 100 days at randomization&#xD;
&#xD;
          -  Willing to provide Informed Consent or have a parent or legal guardian provide&#xD;
             informed consent if the subject is &lt;18 years of age&#xD;
&#xD;
          -  Positive for at least one islet cell autoantibody; glutamic acid decarboxylase 65&#xD;
             (GAD65A), Insulin micro IAA (mIAA), if obtained within 10 days of the onset of insulin&#xD;
             therapy, islet antigen 2 (IA-2A), Islet Cell Antigen (ICA), or zinc transporter 8&#xD;
             (ZnT8A)&#xD;
&#xD;
          -  Must have stimulated C-peptide levels = 0.2 pmol/ml measured during a mixed meal&#xD;
             tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes and within&#xD;
             one month (37 days) of randomization&#xD;
&#xD;
          -  Must be Epstein-Barr virus (EBV PCR) negative within two weeks of randomization if EBV&#xD;
             seronegative at screening&#xD;
&#xD;
          -  Be at least 6 weeks from last live immunization&#xD;
&#xD;
          -  Participants are required to receive killed influenza vaccination at least 2 weeks&#xD;
             prior to randomization when vaccine for the current or upcoming flu season is&#xD;
             available&#xD;
&#xD;
          -  Be willing to forgo vaccines during the treatment period and for 3 months following&#xD;
             last dose of study drug&#xD;
&#xD;
          -  Be willing to comply with intensive diabetes management&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Be immunodeficient or have clinically significant chronic lymphopenia: (Leukopenia (&lt;&#xD;
             3,000 leukocytes /µL), neutropenia (&lt;1,500 neutrophils/µL), lymphopenia (&lt;800&#xD;
             lymphocytes/µL), or thrombocytopenia (&lt;100,000 platelets/µL).&#xD;
&#xD;
          -  Have active signs or symptoms of acute infection at the time of randomization&#xD;
&#xD;
          -  Have evidence of prior or current tuberculosis infection as assessed by purified&#xD;
             protein derivative (PPD), interferon gamma release assay (IGRA) or by history&#xD;
&#xD;
          -  Be currently pregnant or lactating, or anticipate getting pregnant within the two year&#xD;
             study period&#xD;
&#xD;
          -  Require use of other immunosuppressive agents including chronic use of systemic&#xD;
             steroids&#xD;
&#xD;
          -  Have evidence of current or past human immunodeficiency virus (HIV), Hepatitis B or&#xD;
             Hepatitis C infection&#xD;
&#xD;
          -  Have any complicating medical issues or abnormal clinical laboratory results that may&#xD;
             interfere with study conduct, or cause increased risk to include pre-existing cardiac&#xD;
             disease, chronic obstructive pulmonary disease (COPD), sickle cell disease,&#xD;
             neurological, or blood count abnormalities&#xD;
&#xD;
          -  Have a history of malignancies other than skin&#xD;
&#xD;
          -  Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine&#xD;
             transaminase (ALT) greater than 3 times the upper limits of normal&#xD;
&#xD;
          -  Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit&#xD;
             of normal&#xD;
&#xD;
          -  Vaccination with a live virus within the last 6 weeks&#xD;
&#xD;
          -  Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control&#xD;
             within prior 7 days of screening&#xD;
&#xD;
          -  Active participation in another T1D treatment study in the previous 30 days&#xD;
&#xD;
          -  Prior treatment with abatacept or anti-cd3&#xD;
&#xD;
          -  Known allergy to GCSF or ATG&#xD;
&#xD;
          -  Prior treatment with ATG or known allergy to rabbit derived products&#xD;
&#xD;
          -  Any condition that in the investigator's opinion may adversely affect study&#xD;
             participation or may compromise the study results&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael J Haller, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California - San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158-2549</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Davis Center</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06519</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of South Florida Diabetes Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University-Riley Hospital for Children</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University-Naomi Berrie Diabetes Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt Eskind Diabetes Clinic</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Benaroya Research Institute</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.diabetestrialnet.org</url>
    <description>Type 1 Diabetes TrialNet</description>
  </link>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 11, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <results_first_submitted>May 30, 2019</results_first_submitted>
  <results_first_submitted_qc>February 28, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 2, 2020</results_first_posted>
  <last_update_submitted>February 28, 2020</last_update_submitted>
  <last_update_submitted_qc>February 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Type 1 Diabetes TrialNet</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>Lenograstim</mesh_term>
    <mesh_term>Thymoglobulin</mesh_term>
    <mesh_term>Antilymphocyte Serum</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data are available at the NIDDK Central Repository</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_url>https://repository.niddk.nih.gov/studies/TN19_ATG_GCSF/?query=tn19</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 30, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT02215200/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 30, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT02215200/ICF_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 30, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT02215200/SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Anti-Thymocyte Globulin (ATG) and Placebo</title>
          <description>Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose.&#xD;
Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses&#xD;
Anti-Thymocyte Globulin (ATG): Thymoglobulin&#xD;
Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF</description>
        </group>
        <group group_id="P2">
          <title>ATG Plus Granulocyte Colony Stimulating Factor (GCSF)</title>
          <description>Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg.&#xD;
GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses&#xD;
Anti-Thymocyte Globulin (ATG): Thymoglobulin&#xD;
Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses&#xD;
Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG&#xD;
Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="29"/>
                <participants group_id="P3" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="28"/>
                <participants group_id="P3" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Anti-Thymocyte Globulin (ATG) and Placebo</title>
          <description>Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose.&#xD;
Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses&#xD;
Anti-Thymocyte Globulin (ATG): Thymoglobulin&#xD;
Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF</description>
        </group>
        <group group_id="B2">
          <title>ATG Plus Granulocyte Colony Stimulating Factor (GCSF)</title>
          <description>Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg.&#xD;
GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses&#xD;
Anti-Thymocyte Globulin (ATG): Thymoglobulin&#xD;
Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses&#xD;
Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG&#xD;
Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="29"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="31"/>
            <count group_id="B4" value="89"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17.2" spread="5"/>
                    <measurement group_id="B2" value="18.1" spread="6.9"/>
                    <measurement group_id="B3" value="16.9" spread="4.6"/>
                    <measurement group_id="B4" value="17.4" spread="5.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="30"/>
                    <measurement group_id="B4" value="85"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="29"/>
                    <measurement group_id="B4" value="86"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="31"/>
                    <measurement group_id="B4" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Area Under the Stimulated C-peptide Curve From Baseline to 12 Months.</title>
        <description>The C-peptide 2 hour area under the curve (AUC) mean is calculated at baseline and 12 months and measured in nmol/L. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the &quot;AUC mean&quot; and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis&quot;).</description>
        <time_frame>-10, 0 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Anti-Thymocyte Globulin (ATG) and Placebo</title>
            <description>Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose.&#xD;
Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses&#xD;
Anti-Thymocyte Globulin (ATG): Thymoglobulin&#xD;
Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF</description>
          </group>
          <group group_id="O2">
            <title>ATG Plus Granulocyte Colony Stimulating Factor (GCSF)</title>
            <description>Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg.&#xD;
GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses&#xD;
Anti-Thymocyte Globulin (ATG): Thymoglobulin&#xD;
Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses&#xD;
Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG&#xD;
Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Area Under the Stimulated C-peptide Curve From Baseline to 12 Months.</title>
          <description>The C-peptide 2 hour area under the curve (AUC) mean is calculated at baseline and 12 months and measured in nmol/L. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the &quot;AUC mean&quot; and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis&quot;).</description>
          <units>nmol/L</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
                <count group_id="O3" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.528" lower_limit="0.435" upper_limit="0.627"/>
                    <measurement group_id="O2" value="0.646" lower_limit="0.547" upper_limit="0.750"/>
                    <measurement group_id="O3" value="0.406" lower_limit="0.324" upper_limit="0.494"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected over 1 year.</time_frame>
      <desc>Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.</desc>
      <group_list>
        <group group_id="E1">
          <title>Anti-Thymocyte Globulin (ATG) and Placebo</title>
          <description>Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose.&#xD;
Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses&#xD;
Anti-Thymocyte Globulin (ATG): Thymoglobulin&#xD;
Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF</description>
        </group>
        <group group_id="E2">
          <title>ATG Plus Granulocyte Colony Stimulating Factor (GCSF)</title>
          <description>Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg.&#xD;
GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses&#xD;
Anti-Thymocyte Globulin (ATG): Thymoglobulin&#xD;
Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses&#xD;
Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG&#xD;
Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>CD4 lymphocyte decrease or other</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="24" subjects_affected="18" subjects_at_risk="29"/>
                <counts group_id="E2" events="23" subjects_affected="17" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorder</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Endocrine Disorders</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="5" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal Disorders</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General Disorders and administration</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>All immune system disorders</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="14" subjects_affected="12" subjects_at_risk="29"/>
                <counts group_id="E2" events="15" subjects_affected="15" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury, poisoning, and procedural complications</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Metabolism and nutrition disorders</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms: benign, malignant, and unspecified</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous system disorders</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychiatric Disorders</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="29"/>
                <counts group_id="E3" subjects_affected="31" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>CD4 lymphocyte decrease or other</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="42" subjects_affected="21" subjects_at_risk="29"/>
                <counts group_id="E2" events="43" subjects_affected="22" subjects_at_risk="29"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Blood and lymphatic system disorder</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac Disorders</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear and labyrinth disorders</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Endocrine Disorders</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="7" subjects_affected="3" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal Disorders</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General Disorders and administration</sub_title>
                <counts group_id="E1" events="16" subjects_affected="7" subjects_at_risk="29"/>
                <counts group_id="E2" events="18" subjects_affected="8" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>All Immune system disorders</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="33" subjects_affected="21" subjects_at_risk="29"/>
                <counts group_id="E2" events="38" subjects_affected="23" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations</sub_title>
                <counts group_id="E1" events="14" subjects_affected="9" subjects_at_risk="29"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="29"/>
                <counts group_id="E3" events="16" subjects_affected="9" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury, poisoning, and procedural complications</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Metabolism and nutrition disorders</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="4" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal and connective tissue</sub_title>
                <counts group_id="E1" events="14" subjects_affected="10" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="29"/>
                <counts group_id="E3" events="6" subjects_affected="5" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms: benign, malignant, and unspecified</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Nervous system disorders</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E2" events="11" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E3" events="5" subjects_affected="2" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychiatric Disorders</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory, thoracic, and mediastinal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and subcutaneous tissue disorder</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="29"/>
                <counts group_id="E2" events="10" subjects_affected="7" subjects_at_risk="29"/>
                <counts group_id="E3" events="7" subjects_affected="4" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Vascular Disorders</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Carla Greenbaum, MD</name_or_title>
      <organization>Benaroya Research Institute</organization>
      <phone>1-800-425-8361</phone>
      <email>cjgreen@benaroyaresearch.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02215200
org study id: ATG-GCSF (IND)
secondary id: Type 1 Diabetes TrialNet
secondary id: TN19
secondary id: UC4DK106993
secondary id: UC4DK117009
nct id: NCT02215200
lead sponsor: 
collaborator: 
collaborator: 
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has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a three-arm, 1:1:1 randomized, placebo controlled, double- blinded trial in which at
      least 28 subjects will receive active Anti-Thymocyte Globulin and Granulocyte
      colony-stimulating factor (ATG-GCSF), at least 28 subjects will receive ATG alone and at
      least 28 subjects will receive placebo alone within 100 days from diagnosis of Type 1
      Diabetes (T1D).

      The primary objective of the study will be to determine the safety and ability of low dose
      ATG plus GCSF and low dose ATG alone to retain/enhance C-peptide production in new onset T1D
      patients demonstrating residual beta cell function.
The primary statistical hypothesis to be assessed in the study is whether the 2 hour area
      under the curve (change in baseline to 12 months) in residual beta cell function (C-peptide)
      will differ between those treated with ATG and GCSF or ATG alone as compared with placebo.

      The study will also examine the effect of the proposed treatments on surrogate markers for
      immunologic and metabolic outcomes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in Area Under the Stimulated C-peptide Curve From Baseline to 12 Months.
time frame: -10, 0 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months
description: The C-peptide 2 hour area under the curve (AUC) mean is calculated at baseline and 12 months and measured in nmol/L. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis").
arm group label: Anti-Thymocyte Globulin (ATG) and Placebo
arm group type: Experimental
description: Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose.
Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses
arm group label: ATG plus Granulocyte colony stimulating factor (GCSF)
arm group type: Experimental
description: Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg.
GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses
intervention type: Drug
intervention name: Anti-Thymocyte Globulin (ATG)
description: Thymoglobulin
arm group label: ATG plus Granulocyte colony stimulating factor (GCSF)
arm group label: Anti-Thymocyte Globulin (ATG) and Placebo
other name: Thymoglobulin
intervention type: Drug
intervention name: Granulocyte colony stimulating factor (GCSF)
description: Granulocyte colony stimulating factor (GCSF)
arm group label: ATG plus Granulocyte colony stimulating factor (GCSF)
other name: Neulasta
intervention type: Drug
intervention name: Placebo (for ATG)
description: Normal saline administered by IV infusion to mimic ATG
arm group label: Placebo
intervention type: Drug
intervention name: Placebo (for GCSF)
description: Placebo prepared to mimic 6mg subcutaneous injection of GCSF
arm group label: Anti-Thymocyte Globulin (ATG) and Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 12 Years
maximum age: 45 Years
healthy volunteers: No
last name: Michael J Haller, M.D.
role: Principal Investigator
affiliation: University of Florida
facility: 
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country: United States
url: http://www.diabetestrialnet.org
description: Type 1 Diabetes TrialNet
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Lenograstim
mesh term: Thymoglobulin
mesh term: Antilymphocyte Serum
sharing ipd: Yes
ipd description: Data are available at the NIDDK Central Repository
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd url: https://repository.niddk.nih.gov/studies/TN19_ATG_GCSF/?query=tn19
provided document: 
provided document: 
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participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 