<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/NCT02973802</url>
  </required_header>
  <id_info>
    <org_study_id>ATX-GD-59-001</org_study_id>
    <nct_id>NCT02973802</nct_id>
  </id_info>
  <brief_title>ATX-GD-59 in Patients With Graves Disease Not Treated With Anti-thyroid Therapy</brief_title>
  <official_title>Safety and Proof of Principle Study of ATX-GD-59 in Male and Female Subjects With Graves' Disease Not Currently Treated With Anti-thyroid Therapy: An Open Label Study, With an Upward Titration Over Five Dose Levels Administered by Intradermal Injection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Apitope International NV</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Quintiles, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>European Commission</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Apitope International NV</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 1 study to assess the safety and biological activity of ATX-GD-59 in patients with&#xD;
      Graves Disease not currently treated with anti-thyroid therapy. This will be an open label&#xD;
      dose titration involving injections on 10 occasions, each two weeks apart. After dosing is&#xD;
      complete there will be a 12 week follow up period. Blood samples will be drawn throughout the&#xD;
      study to monitor safety and the body's response to the injections. Thyroid function will be&#xD;
      measured throughout the trial to monitor Graves disease progression.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2016</start_date>
  <completion_date type="Actual">February 14, 2018</completion_date>
  <primary_completion_date type="Actual">February 14, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline.</measure>
    <time_frame>22 weeks</time_frame>
    <description>An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII)</measure>
    <time_frame>Weeks 18, 22 and 30</time_frame>
    <description>TSHR-binding inhibitory immunoglobulin (TBII) are autoantibodies directed against the TSH receptor. TBII is used clinically for the differential diagnosis and management of Graves' Disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb)</measure>
    <time_frame>Weeks 18, 22 and 30</time_frame>
    <description>Stimulatory TSHR antibodies (TSAb) assays were measured using cell-based methods described by Leschik et al.&#xD;
TSAb activity is measured by calculating percentage specimen-to-reference ratio (%SRR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb)</measure>
    <time_frame>Weeks 18, 22 and 30</time_frame>
    <description>Blocking TSHR antibodies (TBAb) assays were measured using cell-based methods described by Leschik et al.&#xD;
TBAb activity is measured by calculating percentage inhibition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22.</measure>
    <time_frame>Weeks 18, 22 and 30</time_frame>
    <description>Serum fT3 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT3 value at study day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Free Thyroxine (T4) From Baseline to Week 22.</measure>
    <time_frame>Weeks 18, 22 and 30</time_frame>
    <description>Serum fT4 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22.</measure>
    <time_frame>Weeks 18, 22 and 30</time_frame>
    <description>Serum TSH was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Peripheral Blood Mononuclear Cell (PBMC) T Cell Activity</measure>
    <time_frame>weeks 0, 18 and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in IL-10 mRNA Expression in PBMCs</measure>
    <time_frame>weeks 0, 18 and 22</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Biomarker Signature of PBMC Cells</measure>
    <time_frame>weeks 0, 18 and 22</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Graves Disease</condition>
  <arm_group>
    <arm_group_label>ATX-GD-59 treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 will be administered two weeks apart by intradermal injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ATX-GD-59</intervention_name>
    <description>Disease specific immune modulating treatment for Graves Disease</description>
    <arm_group_label>ATX-GD-59 treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. A diagnosis of Graves' disease as assessed by a physician from clinical and laboratory&#xD;
             findings and not receiving anti-thyroid therapy.&#xD;
&#xD;
          2. Quantifiable levels of TSHR antibodies.&#xD;
&#xD;
          3. Raised levels of free T3 and/or free T4 (not exceeding 15 pmol/L and 35 pmol/L&#xD;
             respectively) including undetectable levels of thyroid stimulating hormone.&#xD;
&#xD;
          4. HLA-DRB1*15, HLA DRB1*03 and or HLA DRB1*04 positive.&#xD;
&#xD;
          5. Age 18 - 65 years inclusive at the time of informed consent.&#xD;
&#xD;
          6. The subject must be willing and able to give written informed consent and must be&#xD;
             willing to comply with protocol assessments/procedures.&#xD;
&#xD;
          7. Male subjects must be sterile (biologically or surgically) or commit to the use of a&#xD;
             reliable method of birth control for the duration of the study until at least 90 days&#xD;
             after the last dose of ATX-GD-59.&#xD;
&#xD;
          8. Female subjects of child bearing potential must: - neither be pregnant nor&#xD;
             breast-feeding, nor attempting to conceive, and - use a highly effective method of&#xD;
             contraception as defined below, throughout the entire duration of the study and for at&#xD;
             least 90 days after the last dose of ATX-GD-59. A serum pregnancy test will be&#xD;
             performed at the screening visit in women of child bearing potential. Thereafter urine&#xD;
             pregnancy tests will be performed. A positive result will exclude the woman from the&#xD;
             study immediately. A highly effective method of contraception is defined as those&#xD;
             which result in a low failure rate when used consistently and correctly such as&#xD;
             implants, injectable, combined oral contraceptives, some Intrauterine Devices (IUDs),&#xD;
             unless post-menopausal or surgically sterilized. Barrier forms of contraception are&#xD;
             considered appropriate when used in combination with one of the above methods.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects who are pregnant or breastfeeding and/or subjects in the post-partum period.&#xD;
&#xD;
          2. A known history of, or hypersensitivity reactions that in the opinion of the&#xD;
             investigator would exclude the subjects' participation in the study.&#xD;
&#xD;
          3. Treatment with any Anti-Thyroid Drugs eg carbimazole within the previous 3 months&#xD;
             prior to Study Day 1.&#xD;
&#xD;
          4. Previous treatment with radioiodine or (partial or complete) thyroidectomy.&#xD;
&#xD;
          5. Signs of moderate or severe orbitopathy including optic nerve compression requiring&#xD;
             steroids and/or a clinical activity score &gt;3.&#xD;
&#xD;
          6. Large and compressive goitres causing localised symptoms such as difficulty swallowing&#xD;
             or breathing.&#xD;
&#xD;
          7. Treatment with steroids (administered via the oral and/or parenteral routes) or&#xD;
             adrenocorticotropic hormone with the exception of inhaled steroids within the three&#xD;
             months prior to Study Day 1.&#xD;
&#xD;
          8. Symptoms and signs of thyroid storm such as confusion, pyrexia with no other cause&#xD;
             than hyperthyroidism.&#xD;
&#xD;
          9. Significant cardiac disease and/or atrial fibrillation that would require urgent&#xD;
             treatment of thyrotoxicosis.&#xD;
&#xD;
         10. Prior treatment with biological or peptide-based therapeutics including rituximab.&#xD;
&#xD;
         11. Prior use of disease related T cell vaccine or peptide-tolerising agent to treat&#xD;
             Graves' disease.&#xD;
&#xD;
         12. Detectable levels of antibodies in plasma specific for any of the peptides within&#xD;
             ATX-GD-59 at the screening visit.&#xD;
&#xD;
         13. A history of significant drug allergies.&#xD;
&#xD;
         14. The use of any investigational drug, or participation in any Clinical Trial within&#xD;
             three months prior to Study Day 1.&#xD;
&#xD;
         15. Treatment with any cytokine or anti-cytokine therapy within three months prior to&#xD;
             Study Day 1.&#xD;
&#xD;
         16. Inadequate liver function, defined by a total bilirubin, aspartate aminotransferase&#xD;
             (AST), alanine aminotransferase (ALT) or alkaline phosphatase &gt; 3 times the upper&#xD;
             limit of the normal values at Screening visit. 17. Subject with any significant&#xD;
             medical illness or psychiatric condition that in the opinion of the Investigator,&#xD;
             would preclude participation in the study or impair the ability to give informed&#xD;
             consent; any other clinically apparent autoimmune disease.&#xD;
&#xD;
        18. Clinically significant illness, as determined by the investigator, within 4 weeks prior&#xD;
        to the first dose (Study Day 1) of ATX-GD-59.&#xD;
&#xD;
        19. Known history of active or chronic infectious disease or any disease which compromises&#xD;
        immune function (e.g. HIV+, HTLV-1, Lyme disease, Latent or active TB, Hepatitis).&#xD;
&#xD;
        20. Major surgery in previous four weeks before screening visit. 21. Known osteoporosis or&#xD;
        metabolic bone disease.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Simon HS Pearce</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Victoria Infirmary</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Queen Elizabeth Hospital</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Wales</name>
      <address>
        <city>Cardiff</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Devon and Exeter Hospital</name>
      <address>
        <city>Exeter</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St James's University Hospital</name>
      <address>
        <city>Leeds</city>
        <zip>LS9 7TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hammersmith Hospital</name>
      <address>
        <city>London</city>
        <zip>W12 0HS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kings College Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Victoria Infirmary</name>
      <address>
        <city>Newcastle</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>November 14, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <results_first_submitted>October 11, 2018</results_first_submitted>
  <results_first_submitted_qc>March 14, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 14, 2019</results_first_posted>
  <last_update_submitted>March 14, 2019</last_update_submitted>
  <last_update_submitted_qc>March 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Graves Disease</keyword>
  <keyword>Phase 1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Graves Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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>January 6, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/02/NCT02973802/Prot_000.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>February 28, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/02/NCT02973802/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study enrolled patients diagnosed with Graves Disease from 8 hospital clinics located in the UK. The last patient enrolled completed dosing in February 2018.</recruitment_details>
      <pre_assignment_details>28 subjects were screened for the study, of which 12 were eligible, and commenced treatment with ATX-GD-59.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>ATX-GD-59 Treatment</title>
          <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>ATX-GD-59 Treatment</title>
          <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="42.7" spread="9.69"/>
                  </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="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline.</title>
        <description>An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug</description>
        <time_frame>22 weeks</time_frame>
        <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria. The Safety population was denoted as the 'Intention-to-treat population' for the summarisation of safety endpoints.</population>
        <group_list>
          <group group_id="O1">
            <title>ATX-GD-59 Treatment</title>
            <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
          </group>
        </group_list>
        <measure>
          <title>Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline.</title>
          <description>An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug</description>
          <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria. The Safety population was denoted as the 'Intention-to-treat population' for the summarisation of safety endpoints.</population>
          <units>Adverse Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="311"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mild Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="293"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Moderate Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Severe Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug Related Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="180"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Serious Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Drug Related Serious Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adverse Events leading to death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adverse Events leading to early study withdrawal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Events leading to dose interruption or suspension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment emergent injection related reaction</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="153"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII)</title>
        <description>TSHR-binding inhibitory immunoglobulin (TBII) are autoantibodies directed against the TSH receptor. TBII is used clinically for the differential diagnosis and management of Graves' Disease.</description>
        <time_frame>Weeks 18, 22 and 30</time_frame>
        <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.</population>
        <group_list>
          <group group_id="O1">
            <title>ATX-GD-59 Treatment</title>
            <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII)</title>
          <description>TSHR-binding inhibitory immunoglobulin (TBII) are autoantibodies directed against the TSH receptor. TBII is used clinically for the differential diagnosis and management of Graves' Disease.</description>
          <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.</population>
          <units>IU/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at week 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7737" spread="1.55475"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 22</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6602" spread="1.35220"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 30</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8971" spread="1.67639"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb)</title>
        <description>Stimulatory TSHR antibodies (TSAb) assays were measured using cell-based methods described by Leschik et al.&#xD;
TSAb activity is measured by calculating percentage specimen-to-reference ratio (%SRR).</description>
        <time_frame>Weeks 18, 22 and 30</time_frame>
        <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.</population>
        <group_list>
          <group group_id="O1">
            <title>ATX-GD-59 Treatment</title>
            <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb)</title>
          <description>Stimulatory TSHR antibodies (TSAb) assays were measured using cell-based methods described by Leschik et al.&#xD;
TSAb activity is measured by calculating percentage specimen-to-reference ratio (%SRR).</description>
          <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.</population>
          <units>%SRR</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at week 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-92.7" spread="145.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 22</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-54.0" spread="118.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 30</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-39.3" spread="125.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb)</title>
        <description>Blocking TSHR antibodies (TBAb) assays were measured using cell-based methods described by Leschik et al.&#xD;
TBAb activity is measured by calculating percentage inhibition.</description>
        <time_frame>Weeks 18, 22 and 30</time_frame>
        <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.</population>
        <group_list>
          <group group_id="O1">
            <title>ATX-GD-59 Treatment</title>
            <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb)</title>
          <description>Blocking TSHR antibodies (TBAb) assays were measured using cell-based methods described by Leschik et al.&#xD;
TBAb activity is measured by calculating percentage inhibition.</description>
          <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.</population>
          <units>% Inhibition</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at week 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.9" spread="46.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 22</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.0" spread="55.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 30</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="60.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22.</title>
        <description>Serum fT3 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT3 value at study day 1.</description>
        <time_frame>Weeks 18, 22 and 30</time_frame>
        <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.</population>
        <group_list>
          <group group_id="O1">
            <title>ATX-GD-59 Treatment</title>
            <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22.</title>
          <description>Serum fT3 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT3 value at study day 1.</description>
          <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.</population>
          <units>Percent change</units>
          <param>Geometric Least Squares Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at week 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.75" spread="26.513"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 22</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.19" spread="25.549"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 30</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.79" spread="27.367"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Serum Free Thyroxine (T4) From Baseline to Week 22.</title>
        <description>Serum fT4 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.</description>
        <time_frame>Weeks 18, 22 and 30</time_frame>
        <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.</population>
        <group_list>
          <group group_id="O1">
            <title>ATX-GD-59 Treatment</title>
            <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Free Thyroxine (T4) From Baseline to Week 22.</title>
          <description>Serum fT4 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.</description>
          <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria.</population>
          <units>Percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at week 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.80" spread="24.622"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 22</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.54" spread="20.011"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 30</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.24" spread="27.368"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22.</title>
        <description>Serum TSH was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.</description>
        <time_frame>Weeks 18, 22 and 30</time_frame>
        <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol</population>
        <group_list>
          <group group_id="O1">
            <title>ATX-GD-59 Treatment</title>
            <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22.</title>
          <description>Serum TSH was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.</description>
          <population>The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol</population>
          <units>mIU/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change from baseline at week 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.267" spread="0.8028"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 22</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.309" spread="0.8398"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from baseline at week 30</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.473" spread="1.1915"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Peripheral Blood Mononuclear Cell (PBMC) T Cell Activity</title>
        <time_frame>weeks 0, 18 and 22</time_frame>
        <population>No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.</population>
        <group_list>
          <group group_id="O1">
            <title>ATX-GD-59 Treatment</title>
            <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Peripheral Blood Mononuclear Cell (PBMC) T Cell Activity</title>
          <population>No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in IL-10 mRNA Expression in PBMCs</title>
        <time_frame>weeks 0, 18 and 22</time_frame>
        <population>No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.</population>
        <group_list>
          <group group_id="O1">
            <title>ATX-GD-59 Treatment</title>
            <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in IL-10 mRNA Expression in PBMCs</title>
          <population>No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Biomarker Signature of PBMC Cells</title>
        <time_frame>weeks 0, 18 and 22</time_frame>
        <population>No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.</population>
        <group_list>
          <group group_id="O1">
            <title>ATX-GD-59 Treatment</title>
            <description>An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 administered two weeks apart by intradermal injection.&#xD;
ATX-GD-59: Disease specific immune modulating treatment for Graves Disease</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Biomarker Signature of PBMC Cells</title>
          <population>No clear treatment effects could be determined possibly due to technical issues with the preparation and assay of the PBMCs. In addition, the 2 week post dose time point of blood sampling, meant that the induced Treg cells or cytokine changes were no longer detectable in peripheral blood.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were recorded from screening through to the final follow up visit at week 30.</time_frame>
      <desc>Adverse events were defined as per clinicaltrials.gov definitions. Adverse events were recorded by investigators and subjects in diaries which were reviewed at each visit. All SAEs and treatment emergent AEs are listed here.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment Emergent Adverse Events</title>
          <description>Treatment emergent adverse events were any adverse events that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of ATX-GD-59</description>
        </group>
        <group group_id="E2">
          <title>Non Treatment Emergent Adverse Events</title>
          <description>Any non-treatment emergent adverse events.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (20.1)</default_vocab>
        <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="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Paroxysmal Atrial Fibrillationion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Mild Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (20.1)</default_vocab>
        <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="11" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Atrial fibulation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Atrioventricular block first degree</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eyelid oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Ocular hyperaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="10" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="13" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Abdominal tenderness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site erythema</sub_title>
                <counts group_id="E1" events="61" subjects_affected="10" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Injection site swelling</sub_title>
                <counts group_id="E1" events="46" subjects_affected="8" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" events="27" subjects_affected="6" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Injection site pruritus</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Injection site rash</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Injection site urticaria</sub_title>
                <counts group_id="E1" events="9" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Feeling hot</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Injection site discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="9" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Suprapubic Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Thirst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic steatosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Onychomycosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary tract infection bacterial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vulvovaginal candidiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injection related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Wrist fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood uric acid increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Eosinophil count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Lymph node palpable</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Respiratory rate increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Muscle twitching</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Benign neoplasm of skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="19" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="10" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Possible Loss of Consciousness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Throat tightness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Increased bronchial secretion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermal cyst</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </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 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>CEO</name_or_title>
      <organization>Apitope International</organization>
      <phone>+44(0)1291 635511</phone>
      <email>info@apitope.com</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/NCT02973802
org study id: ATX-GD-59-001
nct id: NCT02973802
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Phase 1 study to assess the safety and biological activity of ATX-GD-59 in patients with
      Graves Disease not currently treated with anti-thyroid therapy. This will be an open label
      dose titration involving injections on 10 occasions, each two weeks apart. After dosing is
      complete there will be a 12 week follow up period. Blood samples will be drawn throughout the
      study to monitor safety and the body's response to the injections. Thyroid function will be
      measured throughout the trial to monitor Graves disease progression.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline.
time frame: 22 weeks
description: An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug
measure: Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII)
time frame: Weeks 18, 22 and 30
description: TSHR-binding inhibitory immunoglobulin (TBII) are autoantibodies directed against the TSH receptor. TBII is used clinically for the differential diagnosis and management of Graves' Disease.
measure: Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb)
time frame: Weeks 18, 22 and 30
description: Stimulatory TSHR antibodies (TSAb) assays were measured using cell-based methods described by Leschik et al.
TSAb activity is measured by calculating percentage specimen-to-reference ratio (%SRR).
measure: Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb)
time frame: Weeks 18, 22 and 30
description: Blocking TSHR antibodies (TBAb) assays were measured using cell-based methods described by Leschik et al.
TBAb activity is measured by calculating percentage inhibition.
measure: Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22.
time frame: Weeks 18, 22 and 30
description: Serum fT3 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT3 value at study day 1.
measure: Change in Serum Free Thyroxine (T4) From Baseline to Week 22.
time frame: Weeks 18, 22 and 30
description: Serum fT4 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.
measure: Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22.
time frame: Weeks 18, 22 and 30
description: Serum TSH was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.
measure: Change From Baseline in Peripheral Blood Mononuclear Cell (PBMC) T Cell Activity
time frame: weeks 0, 18 and 22
measure: Change From Baseline in IL-10 mRNA Expression in PBMCs
time frame: weeks 0, 18 and 22
measure: Change From Baseline in Biomarker Signature of PBMC Cells
time frame: weeks 0, 18 and 22
arm group label: ATX-GD-59 treatment
arm group type: Experimental
description: An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 will be administered two weeks apart by intradermal injection.
intervention type: Biological
intervention name: ATX-GD-59
description: Disease specific immune modulating treatment for Graves Disease
arm group label: ATX-GD-59 treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Simon HS Pearce
role: Principal Investigator
affiliation: Royal Victoria Infirmary
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Graves Disease
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 