<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/NCT02225665</url>
  </required_header>
  <id_info>
    <org_study_id>SB-728mR-1401</org_study_id>
    <nct_id>NCT02225665</nct_id>
  </id_info>
  <brief_title>Repeat Doses of SB-728mR-T After Cyclophosphamide Conditioning in HIV-Infected Subjects on HAART</brief_title>
  <official_title>A Phase 1/2, Open-Label Study to Assess the Safety and Tolerability of Repeat Doses of Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Subjects Following Cyclophosphamide Conditioning</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sangamo Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sangamo Therapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and tolerability of repeat doses of&#xD;
      T-cell immunotherapy (SB-728mR-T) following cyclophosphamide conditioning.&#xD;
&#xD;
      CCR5 is a major co-receptor for HIV entry into T-cells. Disruption of CCR5 by zinc finger&#xD;
      nuclease (SB-728mR), blocks HIV entry into the T-cells, therefore, protects the T-cells from&#xD;
      HIV infection. Safety (primary outcome) and anti-viral effect (secondary outcome) of zinc&#xD;
      finger nuclease-mediated CCR5 disrupted autologous T-cells (SB-728mR-T) will be evaluated in&#xD;
      the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">June 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Outcome Measure</measure>
    <time_frame>12 months</time_frame>
    <description>Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728mR-T infusion</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Outcome Measure</measure>
    <time_frame>12 months</time_frame>
    <description>Effect of repeat doses of SB-728mR-T on engraftment following cyclophosphamide conditioning as measured by CCR5 Modified CD4 Cells at Month 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Outcome Measure</measure>
    <time_frame>12 months</time_frame>
    <description>Effect of SB-728mR-T on plasma HIV-1 RNA levels following HAART interruption</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary Outcome Measure</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Change from baseline to month 12 in CD4+ T-cell counts in peripheral blood after repeat treatments with SB-728mR-T. (i.e. month 12 value - baseline value)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Human Immunodeficiency Virus (HIV)</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>SB-728mR-T</intervention_name>
    <description>-SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)</description>
    <arm_group_label>Cohort 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>SB-728mR-T</intervention_name>
    <description>- SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)</description>
    <arm_group_label>Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>- IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, 18 years of age or older with documented HIV diagnosis.&#xD;
&#xD;
          -  Must be willing to comply with study-mandated evaluations; including discontinuation&#xD;
             of current antiretroviral therapy during the treatment interruption.&#xD;
&#xD;
          -  Initiated HAART therapy within (≤) 1 year of HIV diagnosis or suspected infection.&#xD;
&#xD;
          -  Undetectable HIV-1 RNA for at least 2 months prior to screening and at screening.&#xD;
&#xD;
          -  CD4+ T-cell count ≥500 cells/µL.&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) ≥ 2500/mm3.&#xD;
&#xD;
          -  Platelet count ≥ 200,000/mm3.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute or chronic hepatitis B or hepatitis C infection.&#xD;
&#xD;
          -  Active or recent (in prior 6 months) AIDS defining complication.&#xD;
&#xD;
          -  Any cancer or malignancy within the past 5 years, with the exception of successfully&#xD;
             treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal&#xD;
             or cervical dysplasia.&#xD;
&#xD;
          -  Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or uncontrolled&#xD;
             arrhythmias.&#xD;
&#xD;
          -  History or any features on physical examination indicative of a bleeding diathesis.&#xD;
&#xD;
          -  Received HIV experimental vaccine within 6 months prior to screening, or any previous&#xD;
             gene therapy using an integrating vector.&#xD;
&#xD;
          -  Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents within 30 days&#xD;
             prior to screening.&#xD;
&#xD;
          -  Use of Aspirin, dipyridamole, warfarin or any other medication that is likely to&#xD;
             affect platelet function or other aspects of blood coagulation during the 2 week&#xD;
             period prior to leukapheresis.&#xD;
&#xD;
          -  Currently participating in another clinical trial or participation in such a trial&#xD;
             within 30 days prior to screening visit.&#xD;
&#xD;
          -  Currently taking maraviroc or have received maraviroc within 6 months prior to&#xD;
             screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Norwalk</city>
        <state>Connecticut</state>
        <zip>06850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>August 22, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 26, 2014</study_first_posted>
  <results_first_submitted>December 22, 2020</results_first_submitted>
  <results_first_submitted_qc>January 21, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 9, 2021</results_first_posted>
  <last_update_submitted>March 17, 2021</last_update_submitted>
  <last_update_submitted_qc>March 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol: Protocol Amendment 2 Signature page</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>October 15, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT02225665/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: Protocol Amendment 2</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>October 10, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT02225665/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 21, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT02225665/SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Cohort 1</title>
          <description>SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
        </group>
        <group group_id="P2">
          <title>Cohort 2</title>
          <description>SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Subject moved from area and finds it difficult to return for visits.</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject restarted HAART prior to month 18.</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Cohort 1</title>
          <description>SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
        </group>
        <group group_id="B2">
          <title>Cohort 2</title>
          <description>SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" 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="59.0" spread="8.19"/>
                    <measurement group_id="B2" value="39.6" spread="10.09"/>
                    <measurement group_id="B3" value="46.9" spread="13.35"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Primary Outcome Measure</title>
        <description>Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728mR-T infusion</description>
        <time_frame>12 months</time_frame>
        <population>Safety Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Primary Outcome Measure</title>
          <description>Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728mR-T infusion</description>
          <population>Safety Analysis Set</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Outcome Measure</title>
        <description>Effect of repeat doses of SB-728mR-T on engraftment following cyclophosphamide conditioning as measured by CCR5 Modified CD4 Cells at Month 12.</description>
        <time_frame>12 months</time_frame>
        <population>Safety analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Outcome Measure</title>
          <description>Effect of repeat doses of SB-728mR-T on engraftment following cyclophosphamide conditioning as measured by CCR5 Modified CD4 Cells at Month 12.</description>
          <population>Safety analysis set</population>
          <units>cells 10^9/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="2"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.090" spread="0.0015"/>
                    <measurement group_id="O2" value="0.162" spread="0.0818"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Outcome Measure</title>
        <description>Effect of SB-728mR-T on plasma HIV-1 RNA levels following HAART interruption</description>
        <time_frame>12 months</time_frame>
        <population>Safety analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Outcome Measure</title>
          <description>Effect of SB-728mR-T on plasma HIV-1 RNA levels following HAART interruption</description>
          <population>Safety analysis set</population>
          <units>log copies/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="2"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.218" spread="1.9243"/>
                    <measurement group_id="O2" value="1.228" spread="1.7029"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Secondary Outcome Measure</title>
        <description>Change from baseline to month 12 in CD4+ T-cell counts in peripheral blood after repeat treatments with SB-728mR-T. (i.e. month 12 value - baseline value)</description>
        <time_frame>Baseline and 12 months</time_frame>
        <population>Safety analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Cohort 1</title>
            <description>SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
          </group>
          <group group_id="O2">
            <title>Cohort 2</title>
            <description>SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
          </group>
        </group_list>
        <measure>
          <title>Secondary Outcome Measure</title>
          <description>Change from baseline to month 12 in CD4+ T-cell counts in peripheral blood after repeat treatments with SB-728mR-T. (i.e. month 12 value - baseline value)</description>
          <population>Safety analysis set</population>
          <units>cells 10^9/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="2"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.178" spread="0.0445"/>
                    <measurement group_id="O2" value="0.078" spread="0.2796"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Cohort 1</title>
          <description>SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
        </group>
        <group group_id="E2">
          <title>Cohort 2</title>
          <description>SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)&#xD;
Cyclophosphamide: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion</description>
        </group>
      </group_list>
      <serious_events>
        <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="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Chlamydial infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Pharyngitis streptococcal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Cachexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Skin odour abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Rosacea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </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>All proposed written materials related to the study or an outline of any proposed oral presentations, shall be submitted to Sangamo for approval at least 45 days prior to submission of materials for publication or any oral disclosure to a third party. If Sangamo determines that a description of patentable subject matter is contained in such written material or outline, it shall notify the clinical site within 1 month after receipt and Sangamo will have an additional 90 days for review.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Monitor</name_or_title>
      <organization>Sangamo Therapeutics</organization>
      <phone>510-970-6000</phone>
      <email>clinicaltrials@sangamo.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/NCT02225665
org study id: SB-728mR-1401
nct id: NCT02225665
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the safety and tolerability of repeat doses of
      T-cell immunotherapy (SB-728mR-T) following cyclophosphamide conditioning.

      CCR5 is a major co-receptor for HIV entry into T-cells. Disruption of CCR5 by zinc finger
      nuclease (SB-728mR), blocks HIV entry into the T-cells, therefore, protects the T-cells from
      HIV infection. Safety (primary outcome) and anti-viral effect (secondary outcome) of zinc
      finger nuclease-mediated CCR5 disrupted autologous T-cells (SB-728mR-T) will be evaluated in
      the study.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Primary Outcome Measure
time frame: 12 months
description: Number of Participants with Treatment related Adverse Events in subjects who received any portion of the SB-728mR-T infusion
measure: Secondary Outcome Measure
time frame: 12 months
description: Effect of repeat doses of SB-728mR-T on engraftment following cyclophosphamide conditioning as measured by CCR5 Modified CD4 Cells at Month 12.
measure: Secondary Outcome Measure
time frame: 12 months
description: Effect of SB-728mR-T on plasma HIV-1 RNA levels following HAART interruption
measure: Secondary Outcome Measure
time frame: Baseline and 12 months
description: Change from baseline to month 12 in CD4+ T-cell counts in peripheral blood after repeat treatments with SB-728mR-T. (i.e. month 12 value - baseline value)
arm group label: Cohort 1
arm group type: Experimental
arm group label: Cohort 2
arm group type: Experimental
intervention type: Genetic
intervention name: SB-728mR-T
description: -SB-728mR-T infusions of 2 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)
arm group label: Cohort 1
intervention type: Genetic
intervention name: SB-728mR-T
description: - SB-728mR-T infusions of 3 equal doses 14 days apart (total of up to 40 billion ZFN modified T-cells)
arm group label: Cohort 2
intervention type: Drug
intervention name: Cyclophosphamide
description: - IV cyclophosphamide 1 g/m2 two days prior to the first SB-728mR-T infusion
arm group label: Cohort 1
arm group label: Cohort 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Cyclophosphamide
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 