<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/NCT02224820</url>
  </required_header>
  <id_info>
    <org_study_id>13-HMedIdeS-02</org_study_id>
    <secondary_id>2013-005417-13</secondary_id>
    <nct_id>NCT02224820</nct_id>
  </id_info>
  <brief_title>Phase II Study, Evaluation of Safety and Efficacy of IdeS in Chronic Kidney Disease</brief_title>
  <official_title>A Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous IdeS After Administration of Ascending Doses in Chronic Kidney Disease Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hansa Biopharma AB</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hansa Biopharma AB</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      IdeS is an immunoglobulin g (IgG) cleaving enzyme. It will given to patients with donor&#xD;
      specific antibodies to reduce the antibody load and thus enable kidney transplantation. IdeS&#xD;
      antibody reducing efficacy and its safety will be studied.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study 13-HMedIdeS-02 (EudraCT no. 2013-005417-13) is a single centre, single arm, dose&#xD;
      finding, Phase II study in sensitized CKD patients assessing safety, tolerability,&#xD;
      pharmacokinetics (PK) and efficacy of HMED-IdeS without intent to transplantation. However,&#xD;
      patients are not removed from the transplant waitlist during the study. Included patients has&#xD;
      a panel reactive antibody [PRA] &gt;70% (n=7).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy</measure>
    <time_frame>24 hours</time_frame>
    <description>Efficacy was defined as the IdeS dosing scheme in the majority of the patients resulting in human leucocyte antigen (HLA) antibody levels which are acceptable for transplantation, measured as mean fluorescent intensity (MFI) of less than 1100, within 24 hours from dosing. MFI was determined by single antigen bead (SAB) assay and detection of complement fixating ability (CIq Screen) in serum.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>9 weeks</time_frame>
    <description>Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics</measure>
    <time_frame>Up to day 64</time_frame>
    <description>IgG cleavage and regeneration measured by ELISA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>Up to 64 days</time_frame>
    <description>Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics</measure>
    <time_frame>Up to 21 days</time_frame>
    <description>IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Chronic Kidney Disease</condition>
  <arm_group>
    <arm_group_label>Intravenous IdeS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One or two doses of IdeS in ascending doses</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IdeS</intervention_name>
    <description>Doses are administered in ascending doses</description>
    <arm_group_label>Intravenous IdeS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with chronic kidney disease and in dialysis with identified antibodies&#xD;
             against at least two HLA antigens of which at least one is 3000 MFI or more as&#xD;
             measured by SAB assay on at least two occasions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior malignancy within 2 years excluding adequately treated basal cell or squamous&#xD;
             cell skin cancer, cervical carcinoma in situ and prostate cancer Gleason &lt;6 and&#xD;
             prostate-specific antigen (PSA) &lt;10 ng/mL.&#xD;
&#xD;
          -  Any positive result on screening for serum hepatitis B surface antigen, hepatitis C&#xD;
             antibody and human immunodeficiency virus (HIV&#xD;
&#xD;
          -  Clinical signs of ongoing infectious disease.&#xD;
&#xD;
          -  Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure&#xD;
             &gt; New York Heart Association (NYHA) grade 3, unstable coronary disease or oxygen&#xD;
             dependent chronic obstructive pulmonary disease (COPD)&#xD;
&#xD;
          -  History of any other clinically significant disease or disorder which, in the opinion&#xD;
             of the investigator, may either put the patient at increased risk because of&#xD;
             participation in the study, or influence the results or the patient's ability to&#xD;
             participate in the study&#xD;
&#xD;
          -  Hypogammaglobulinemia defined as any values of P-total IgG less than 3 g/L&#xD;
&#xD;
          -  History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as&#xD;
             judged by the investigator or history of hypersensitivity to drugs with a similar&#xD;
             chemical structure or class to IdeS (e. g streptokinase and/or staphylokinase)&#xD;
&#xD;
          -  Has received another new chemical entity (defined as a compound which has not been&#xD;
             approved for marketing) or has participated in any other clinical study that included&#xD;
             drug treatment within 4 months of the first administration of investigational product&#xD;
             in this study. Patients consented and screened but not dosed in previous studies are&#xD;
             not excluded&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tomas Lorant, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Uppsala University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dept. of Transplant Surgery, Uppsala University Hospital</name>
      <address>
        <city>Uppsala</city>
        <zip>75185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>August 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <results_first_submitted>February 18, 2016</results_first_submitted>
  <results_first_submitted_qc>April 19, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">May 23, 2016</results_first_posted>
  <last_update_submitted>January 18, 2017</last_update_submitted>
  <last_update_submitted_qc>January 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>transplantation</keyword>
  <keyword>sensitised patients</keyword>
  <keyword>HLA-antibodies</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was performed at a medical clinic, the Department of Transplantat Surgery, Uppsala, SE between 10 Jun 2014 and 13 Feb 2015. The patients had chronic kidney disease, were in dialysis and on the waiting list for transplantation. (Transplantation was not part of the protocol).</recruitment_details>
      <pre_assignment_details>In total, 10 patients were assessed for eligibility. One patient declined to participate and one patient was not available for recieving information about the study. Eight patients were enrolled and started treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Intravenous IdeS</title>
          <description>One or two doses of IdeS in ascending doses.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8">One patient did not receive full dose</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>0ne patient interrupted treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Intravenous IdeS</title>
          <description>One or two doses of IdeS in ascending doses&#xD;
IdeS</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50.5" spread="11.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight (kg)</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74.5" spread="14.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/mg^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.1" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="172.3" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Efficacy</title>
        <description>Efficacy was defined as the IdeS dosing scheme in the majority of the patients resulting in human leucocyte antigen (HLA) antibody levels which are acceptable for transplantation, measured as mean fluorescent intensity (MFI) of less than 1100, within 24 hours from dosing. MFI was determined by single antigen bead (SAB) assay and detection of complement fixating ability (CIq Screen) in serum.</description>
        <time_frame>24 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intravenous IdeS</title>
            <description>One or two doses of IdeS in ascending doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy</title>
          <description>Efficacy was defined as the IdeS dosing scheme in the majority of the patients resulting in human leucocyte antigen (HLA) antibody levels which are acceptable for transplantation, measured as mean fluorescent intensity (MFI) of less than 1100, within 24 hours from dosing. MFI was determined by single antigen bead (SAB) assay and detection of complement fixating ability (CIq Screen) in serum.</description>
          <units>MFI</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="372" lower_limit="83" upper_limit="978"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Safety</title>
        <description>Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs)</description>
        <time_frame>9 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intravenous IdeS</title>
            <description>One or two doses of IdeS in ascending doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety</title>
          <description>Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs)</description>
          <units>Adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacodynamics</title>
        <description>IgG cleavage and regeneration measured by ELISA</description>
        <time_frame>Up to day 64</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intravenous IdeS</title>
            <description>One or two doses of IdeS in ascending doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacodynamics</title>
          <description>IgG cleavage and regeneration measured by ELISA</description>
          <units>µg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Immunogenicity</title>
        <description>Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period</description>
        <time_frame>Up to 64 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intravenous IdeS</title>
            <description>One or two doses of IdeS in ascending doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Immunogenicity</title>
          <description>Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pharmacokinetics</title>
        <description>IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded.</description>
        <time_frame>Up to 21 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intravenous IdeS</title>
            <description>One or two doses of IdeS in ascending doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics</title>
          <description>IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded.</description>
          <units>h</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="2" upper_limit="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time of admission until last visit, 64 days after treatment.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Intravenous IdeS</title>
          <description>One or two doses of IdeS in ascending doses.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (10.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Suspected upper respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Increased mucos production</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (10.0)</default_vocab>
        <default_assessment>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="8" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (18.6)">Anaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Leucocytosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Leucopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Scleral haemorrage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Visual impairment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Dyspesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Infusion site pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Feeling cold</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Feeling hot</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Kidney transplant rejection</sub_title>
                <description>Dose was interrupted for this patient due to infusion reaction.The pat was transplanted (not defined as SAE in protocol) 4 days after dosing. Pat remained in the study for safety follow-up. A number of AEs related to the transplantation are reported.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Clostridium difficile infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Herpes simplex infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Hordeolum</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Infusion related reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferas increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferas increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Blood phosphorus increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">C-reactive proteine increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Donor specific antibody present</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Weight increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Iron deficiency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dizziness postural</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Dysgeuisa</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (18.6)">Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (18.6)">Thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Tomas Lorant</name_or_title>
      <organization>Dept of Transplant Surgery, Uppsala University Hospital</organization>
      <phone>+46 70 677 29 01</phone>
      <email>tomas.lorant@surgsci.uu.se</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/NCT02224820
org study id: 13-HMedIdeS-02
secondary id: 2013-005417-13
nct id: NCT02224820
lead sponsor: 
has dmc: Yes
IdeS is an immunoglobulin g (IgG) cleaving enzyme. It will given to patients with donor
      specific antibodies to reduce the antibody load and thus enable kidney transplantation. IdeS
      antibody reducing efficacy and its safety will be studied.
Study 13-HMedIdeS-02 (EudraCT no. 2013-005417-13) is a single centre, single arm, dose
      finding, Phase II study in sensitized CKD patients assessing safety, tolerability,
      pharmacokinetics (PK) and efficacy of HMED-IdeS without intent to transplantation. However,
      patients are not removed from the transplant waitlist during the study. Included patients has
      a panel reactive antibody [PRA] >70% (n=7).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy
time frame: 24 hours
description: Efficacy was defined as the IdeS dosing scheme in the majority of the patients resulting in human leucocyte antigen (HLA) antibody levels which are acceptable for transplantation, measured as mean fluorescent intensity (MFI) of less than 1100, within 24 hours from dosing. MFI was determined by single antigen bead (SAB) assay and detection of complement fixating ability (CIq Screen) in serum.
measure: Safety
time frame: 9 weeks
description: Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs)
measure: Pharmacodynamics
time frame: Up to day 64
description: IgG cleavage and regeneration measured by ELISA
measure: Immunogenicity
time frame: Up to 64 days
description: Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period
measure: Pharmacokinetics
time frame: Up to 21 days
description: IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded.
arm group label: Intravenous IdeS
arm group type: Experimental
description: One or two doses of IdeS in ascending doses
intervention type: Biological
intervention name: IdeS
description: Doses are administered in ascending doses
arm group label: Intravenous IdeS
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tomas Lorant, MD, PhD
role: Principal Investigator
affiliation: Uppsala University Hospital
facility: 
country: Sweden
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 