<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/NCT03020524</url>
  </required_header>
  <id_info>
    <org_study_id>826035</org_study_id>
    <nct_id>NCT03020524</nct_id>
  </id_info>
  <brief_title>Autologous CD4 T-Cells in HIV (C34-CXCR4)</brief_title>
  <official_title>A Pilot Study to Evaluate the Safety and Tolerability of Escalating Doses of Autologous CD4 T-Cells Modified With Lentiviral Vector Expressing an HR2, C34-peptide Conjugated to the CXCR4 N-terminus in HIV-infected Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <brief_summary>
    <textblock>
      A single cohort, open-label pilot study of the safety and tolerability of a single infusion&#xD;
      of autologous CD4+ T-cells genetically modified with an HR2, C34-peptide conjugated to the&#xD;
      CXCR4 N-terminus using a lentiviral vector in HIV-infected subjects. This is a first in human&#xD;
      study of C34-CXCR4 T cells&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There will be a single cohort in this study, which consists of subjects with well-controlled&#xD;
      HIV replication on HAART. Within this cohort will be 3 escalating doses of T-cell infusions.&#xD;
      A modified 3+3+3 dose-escalation design will be followed, in which the standard&#xD;
      dose-escalation algorithm is stopped when a maximum of 9 evaluable subjects or a DLT stopping&#xD;
      point has been reached, whichever comes first. At each dose level, three patients are&#xD;
      treated. For dose levels 1 and 2, if 0/3 subjects have a dose limiting toxicity (DLT), then&#xD;
      the dose is escalated. If 1/3 has a DLT (grade 3 or higher unexpected, related adverse event&#xD;
      [AE]) at a dose level then 3 additional patients are treated at that dosage before&#xD;
      escalating, and if &lt;2/6 have DLT (i.e. no additional DLT is observed) then the dose is&#xD;
      escalated to the next planned dose level and patients treated until a maximum of 9 evaluable&#xD;
      subjects has been reached. The study will comprise of 5 steps:&#xD;
&#xD;
      Step 1, all participants will undergo leukapheresis to obtain CD4 positive T-cells that will&#xD;
      be genetically modified. A second leukapheresis and a rectal biopsy will provide baseline&#xD;
      specimens to evaluate the size of the HIV reservoir&#xD;
&#xD;
      Step 2, all participants will receive a single infusion of C34-CXCR4-modified CD4+ T-cells at&#xD;
      one of 3 dose levels. The first 3 subjects will receive dose level 1 of 0.8-1x109 transduced&#xD;
      CD4+T-cells. Provided no dose limiting toxicity (DLT) is seen at the first dose level, the&#xD;
      next 3 subjects will receive infusion at the 2nd dose level of 2.4-3x109 transduced CD4+&#xD;
      T-cells. If no DLT occurs at that dose, the final 3 subjects will receive the 3rd dose level&#xD;
      of 0.8-1x1010 transduced CD4+ T-cells. In the event of a DLT (grade 3 or higher unexpected,&#xD;
      related AE) recruitment will be paused pending DSMB decision.&#xD;
&#xD;
      Step 3 all participants will participate in a 16-week analytical treatment interruption&#xD;
      beginning 4 weeks after T-cell infusion.&#xD;
&#xD;
      At the end of step 3 all participants will undergo mini-leukapheresis and rectal biopsy&#xD;
&#xD;
      Step 4 all participants will be advised to resume antiretroviral therapy and will be followed&#xD;
      until plasma HIV RNA falls below the limit of detection.&#xD;
&#xD;
      In Step 5 all participants will undergo leukapheresis and rectal biopsy at 52 weeks post&#xD;
      infusion. At the completion of the study, participants will be asked to participate in a&#xD;
      long-term follow-up study as required by regulatory authorities.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">March 2020</completion_date>
  <primary_completion_date type="Actual">November 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Number of Subjects With Treatment Related Adverse Events</measure>
    <time_frame>one year</time_frame>
    <description>assessed by DAIDS AE grading table v2.0 November 2014</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare the Percentage of Enriched Modified Cells C34-CXCR4 Modifiec T- Cells</measure>
    <time_frame>2 weeks post infusion, prior to ARV reinitiation, weeks 12, 16 and 20</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the Change Between CD4 Count</measure>
    <time_frame>Baseline, week 2 post infusion, prior to ARV initiation, weeks 12, 16 20</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare Viral Set Point Log 10 HIV RNA Level</measure>
    <time_frame>week 2 post infusion, prior to ARV initiation, week 12, 16, 20</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate Cell Mediated Response (Immunogenicity) Using Flow Cytometry</measure>
    <time_frame>baseline through 1 year</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Hiv</condition>
  <arm_group>
    <arm_group_label>Dose level 1:</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous CD4 T-Cells0.8-1x10^9 transduced CD4+T-cells administered IV as a single dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose level 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Autologous CD4 T-Cells 2.4-3x10^9 transduced CD4+ T-cells administered IV as a single dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose level 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Autologous CD4 T-Cells 0.8-1x10^10 transduced CD4+ T-cells administered IV as a single dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Autologous CD4 T-Cells</intervention_name>
    <description>all participants will receive a single infusion of C34-CXCR4-modified CD4+ T-cells at one of 3 dose levels. The first 3 subjects will receive dose level 1 of 0.8-1x109 transduced CD4+T-cells. Provided no dose limiting toxicity (DLT) is seen at the first dose level, the next 3 subjects will receive infusion at the 2nd dose level of 2.4-3x109 transduced CD4+ T-cells. If no DLT occurs at that dose, the final 3 subjects will receive the 3rd dose level of 0.8-1x1010 transduced CD4+ T-cells. In the event of a DLT (grade 3 or higher unexpected, related AE) recruitment will be paused pending DSMB decision</description>
    <arm_group_label>Dose level 1:</arm_group_label>
    <arm_group_label>Dose level 2</arm_group_label>
    <arm_group_label>Dose level 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or&#xD;
             chemiluminescence immunoassay (E/CIA) test kit at any time prior to enrollment and&#xD;
             confirmed by a licensed Western blot or a second antibody test by a method other than&#xD;
             the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL.&#xD;
&#xD;
          -  Ability and willingness of subject to provide informed consent.&#xD;
&#xD;
          -  Men and women ages ≥18 years.&#xD;
&#xD;
          -  Clinically stable on their first or second HAART regimen. Changes while the patient&#xD;
             HIV viral load is undetectable does not count toward the number of ART regimens used,&#xD;
             only changes made for virologic failure (for example an individual switching from an&#xD;
             NNRTI-based regimen to an integrase inhibitor based regimen while the HIV viral load&#xD;
             is undetectable will still be in their first regimen). Site investigator anticipates&#xD;
             that a fully active alternative ART regimen could be constructed in the event of&#xD;
             virologic failure on the current ART regimen.The current regimen should have no&#xD;
             changes within 4 weeks of enrollment. Subjects must be willing to continue on current&#xD;
             antiretroviral therapy for the duration of the study except for the duration of the 16&#xD;
             week analytical treatment interruption. (NOTE: changes to safely begin the treatment&#xD;
             interruption are permitted).&#xD;
&#xD;
          -  Screening HIV-1 RNA that is ≤50 copies/mL using a FDA-approved assay performed by any&#xD;
             laboratory that has a CLIA certification or its equivalent within 30 days prior to&#xD;
             enrollment.&#xD;
&#xD;
          -  HIV-1 RNA ≤50 copies/mL using a FDA-approved assay for at least 24 weeks prior to&#xD;
             enrollment performed by any laboratory that has a CLIA certification or its&#xD;
             equivalent.&#xD;
&#xD;
               -  NOTE: HIV-RNA must be measured at least once in the last 24 weeks and at least 3&#xD;
                  days before the screening measure. Single determinations that are between &gt;50 and&#xD;
                  &lt;400 copies/mL (ie, blips) are allowed as long as the preceding and subsequent&#xD;
                  determinations are ≤50 copies/mL. The screening value may serve as the subsequent&#xD;
                  determination ≤50 copies/mL following a blip&#xD;
&#xD;
               -  NOTE: subjects who have participated in other trials using ATI's will be&#xD;
                  permitted since detectable virus during the interruption does not represent&#xD;
                  virologic failure. These subjects should have at least 24 weeks of VL &lt;50&#xD;
                  copies/mL.&#xD;
&#xD;
          -  Screening CD4+ T-cell count ≥450 cells/ mm3 within 30 days of enrollment.&#xD;
&#xD;
          -  Started ART with nadir CD4+ ≥200 cells/ mm3.&#xD;
&#xD;
          -  The following laboratory values obtained within 30 days prior to enrollment meeting&#xD;
             the following criteria:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥1000 cells/mm3&#xD;
&#xD;
               -  Hemoglobin:≥10.0(males); ≥9.5 (females) g/dL&#xD;
&#xD;
               -  Platelet count: 100,000/mm3&#xD;
&#xD;
               -  Calculated creatinine clearance ≥50 mL/min estimated by the Cockcroft-Gault&#xD;
                  equation&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) ≤ 2.0 x ULN&#xD;
&#xD;
          -  Negative HBsAg within 6 months prior to enrollment.&#xD;
&#xD;
          -  Negative HCV serology, or if positive, negative HCV RNA within 6 months prior to&#xD;
             enrollment&#xD;
&#xD;
          -  Adequate venous access and no other contraindications for leukapheresis.&#xD;
&#xD;
          -  Have a Karnofsky Performance Score of 70 or higher.&#xD;
&#xD;
          -  Have a recorded viral load set point prior to starting antiretroviral therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute or chronic hepatitis B or hepatitis C infection&#xD;
&#xD;
          -  Current or prior AIDS diagnosis.&#xD;
&#xD;
          -  History of cancer or malignancy, with the exception of successfully treated basal cell&#xD;
             or squamous cell carcinoma of the skin&#xD;
&#xD;
          -  History or any features on physical examination indicative of active or unstable&#xD;
             cardiac disease or hemodynamic instability.&#xD;
&#xD;
               -  NOTE: Subjects with a history of cardiac disease may participate with a&#xD;
                  physician's approval.&#xD;
&#xD;
          -  History or any features on physical examination indicative of a bleeding diathesis&#xD;
&#xD;
          -  Have been previously treated with any HIV experimental vaccine within 6 months prior&#xD;
             to enrollment, or any previous gene therapy using an integrating vector.&#xD;
&#xD;
               -  NOTE: Subjects treated with placebo in an HIV vaccine study will not be excluded&#xD;
                  if documentation that they received placebo is provided.&#xD;
&#xD;
          -  Use of chronic systemic corticosteroids, hydroxyurea, or immunomodulating agents&#xD;
             (e.g., interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating&#xD;
             factors, etc.) within 30 days prior to enrollment.&#xD;
&#xD;
               -  NOTE: Recent or current use of inhaled steroids is not exclusionary. If subjects&#xD;
                  are prescribed a brief course of oral corticosteroids, the use should be limited&#xD;
                  to less than 7 days. Use of steroids before apheresis and immune assessment blood&#xD;
                  draws should be discouraged as it will affect white blood cell function.&#xD;
&#xD;
          -  Breast-feeding, pregnant, or unwilling to use acceptable methods of birth control.&#xD;
&#xD;
          -  Anticipated use of aspirin, dipyridamole, warfarin or any other medication that is&#xD;
             likely to affect platelet function or other aspects of blood coagulation during the&#xD;
             2-week period prior to leukapheresis&#xD;
&#xD;
          -  Active drug or alcohol use or dependence that, in the opinion of the site&#xD;
             investigator, would interfere with adherence to study requirements.&#xD;
&#xD;
          -  Serious illness requiring systemic treatment and/or hospitalization within 30 days&#xD;
             prior to enrollment&#xD;
&#xD;
          -  Asymptomatic baseline serum chemistry elevations in LFTs, bilirubin, and serum&#xD;
             creatinine due to HAART medication are not exclusionary, when in the opinion of the&#xD;
             investigator, the abnormalities are not attributable to intrinsic hepatorenal disease.&#xD;
             Such baseline elevations must be due to HAART.&#xD;
&#xD;
          -  Receipt of vaccination within 30 days prior to enrollment.&#xD;
&#xD;
               -  NOTE: It is recommended that subjects enrolling into this study should have&#xD;
                  completed their routine vaccinations (hepatitis A, hepatitis B, pneumococcus, and&#xD;
                  tetanus diphtheria booster) at least 30 days prior to enrollment&#xD;
&#xD;
          -  Have an allergy or hypersensitivity to study product excipients (human serum albumin,&#xD;
             DMSO and Dextran 40).&#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>Pablo Tebas, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennaylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <results_first_submitted>October 14, 2020</results_first_submitted>
  <results_first_submitted_qc>November 5, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 9, 2020</results_first_posted>
  <last_update_submitted>November 13, 2022</last_update_submitted>
  <last_update_submitted_qc>November 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/24/NCT03020524/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/24/NCT03020524/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Dose Level 1</title>
          <description>Autologous CD4 T-Cells0.8-1x10^9 transduced CD4+T-cells administered IV as a single dose</description>
        </group>
        <group group_id="P2">
          <title>Dose Level 2</title>
          <description>Autologous CD4 T-Cells 2.4-3x10^9 transduced CD4+ T-cells administered IV as a single dose</description>
        </group>
        <group group_id="P3">
          <title>Dose Level 3</title>
          <description>Autologous CD4 T-Cells 0.8-1x10^10 transduced CD4+ T-cells administered IV as a single dose</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="3"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Dose Level 1</title>
          <description>Autologous CD4 T-Cells0.8-1x10^9 transduced CD4+T-cells administered IV as a single dose</description>
        </group>
        <group group_id="B2">
          <title>Dose Level 2</title>
          <description>Autologous CD4 T-Cells 2.4-3x10^9 transduced CD4+ T-cells administered IV as a single dose</description>
        </group>
        <group group_id="B3">
          <title>Dose Level 3</title>
          <description>Autologous CD4 T-Cells 0.8-1x10^10 transduced CD4+ T-cells administered IV as a single dose</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="9"/>
          </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="38.0" spread="8.9"/>
                    <measurement group_id="B2" value="40.7" spread="5.5"/>
                    <measurement group_id="B3" value="33.3" spread="10.2"/>
                    <measurement group_id="B4" value="37.3" spread="8.0"/>
                  </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="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Number of Subjects With Treatment Related Adverse Events</title>
        <description>assessed by DAIDS AE grading table v2.0 November 2014</description>
        <time_frame>one year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 1</title>
            <description>Autologous CD4 T-Cells0.8-1x10^9 transduced CD4+T-cells administered IV as a single dose</description>
          </group>
          <group group_id="O2">
            <title>Dose Level 2</title>
            <description>Autologous CD4 T-Cells 2.4-3x10^9 transduced CD4+ T-cells administered IV as a single dose</description>
          </group>
          <group group_id="O3">
            <title>Dose Level 3</title>
            <description>Autologous CD4 T-Cells 0.8-1x10^10 transduced CD4+ T-cells administered IV as a single dose</description>
          </group>
        </group_list>
        <measure>
          <title>The Number of Subjects With Treatment Related Adverse Events</title>
          <description>assessed by DAIDS AE grading table v2.0 November 2014</description>
          <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="3"/>
                <count group_id="O3" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Compare the Percentage of Enriched Modified Cells C34-CXCR4 Modifiec T- Cells</title>
        <time_frame>2 weeks post infusion, prior to ARV reinitiation, weeks 12, 16 and 20</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Compare the Change Between CD4 Count</title>
        <time_frame>Baseline, week 2 post infusion, prior to ARV initiation, weeks 12, 16 20</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Compare Viral Set Point Log 10 HIV RNA Level</title>
        <time_frame>week 2 post infusion, prior to ARV initiation, week 12, 16, 20</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Evaluate Cell Mediated Response (Immunogenicity) Using Flow Cytometry</title>
        <time_frame>baseline through 1 year</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>One year - Adverse events were collected from the time of informed consent to the completion of the scheduled study visits following the administration of study treatment.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Dose Level 1</title>
          <description>Autologous CD4 T-Cells0.8-1x10^9 transduced CD4+T-cells administered IV as a single dose</description>
        </group>
        <group group_id="E2">
          <title>Dose Level 2</title>
          <description>Autologous CD4 T-Cells 2.4-3x10^9 transduced CD4+ T-cells administered IV as a single dose</description>
        </group>
        <group group_id="E3">
          <title>Dose Level 3</title>
          <description>Autologous CD4 T-Cells 0.8-1x10^10 transduced CD4+ T-cells administered IV as a single dose</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="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </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="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </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="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>lymphadenopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>anal fissure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>rectal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <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="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>vaccination site lymphadenopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>bronchial infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>gum infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>lymph gland infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>penile infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>pyuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </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="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>strange smell sensation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>dysuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>testicular mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>vaginal discharge</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>chest congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>sneezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>sore throat</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>body odor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>night sweats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>skin mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>skin rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>tooth extraction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Regulatory Lead</name_or_title>
      <organization>University of Pennsylvania</organization>
      <phone>215.662.4484</phone>
      <email>psom-ind-ide@pobox.upenn.edu</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/NCT03020524
org study id: 826035
nct id: NCT03020524
lead sponsor: 
A single cohort, open-label pilot study of the safety and tolerability of a single infusion
      of autologous CD4+ T-cells genetically modified with an HR2, C34-peptide conjugated to the
      CXCR4 N-terminus using a lentiviral vector in HIV-infected subjects. This is a first in human
      study of C34-CXCR4 T cells
There will be a single cohort in this study, which consists of subjects with well-controlled
      HIV replication on HAART. Within this cohort will be 3 escalating doses of T-cell infusions.
      A modified 3+3+3 dose-escalation design will be followed, in which the standard
      dose-escalation algorithm is stopped when a maximum of 9 evaluable subjects or a DLT stopping
      point has been reached, whichever comes first. At each dose level, three patients are
      treated. For dose levels 1 and 2, if 0/3 subjects have a dose limiting toxicity (DLT), then
      the dose is escalated. If 1/3 has a DLT (grade 3 or higher unexpected, related adverse event
      [AE]) at a dose level then 3 additional patients are treated at that dosage before
      escalating, and if <2/6 have DLT (i.e. no additional DLT is observed) then the dose is
      escalated to the next planned dose level and patients treated until a maximum of 9 evaluable
      subjects has been reached. The study will comprise of 5 steps:

      Step 1, all participants will undergo leukapheresis to obtain CD4 positive T-cells that will
      be genetically modified. A second leukapheresis and a rectal biopsy will provide baseline
      specimens to evaluate the size of the HIV reservoir

      Step 2, all participants will receive a single infusion of C34-CXCR4-modified CD4+ T-cells at
      one of 3 dose levels. The first 3 subjects will receive dose level 1 of 0.8-1x109 transduced
      CD4+T-cells. Provided no dose limiting toxicity (DLT) is seen at the first dose level, the
      next 3 subjects will receive infusion at the 2nd dose level of 2.4-3x109 transduced CD4+
      T-cells. If no DLT occurs at that dose, the final 3 subjects will receive the 3rd dose level
      of 0.8-1x1010 transduced CD4+ T-cells. In the event of a DLT (grade 3 or higher unexpected,
      related AE) recruitment will be paused pending DSMB decision.

      Step 3 all participants will participate in a 16-week analytical treatment interruption
      beginning 4 weeks after T-cell infusion.

      At the end of step 3 all participants will undergo mini-leukapheresis and rectal biopsy

      Step 4 all participants will be advised to resume antiretroviral therapy and will be followed
      until plasma HIV RNA falls below the limit of detection.

      In Step 5 all participants will undergo leukapheresis and rectal biopsy at 52 weeks post
      infusion. At the completion of the study, participants will be asked to participate in a
      long-term follow-up study as required by regulatory authorities.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: The Number of Subjects With Treatment Related Adverse Events
time frame: one year
description: assessed by DAIDS AE grading table v2.0 November 2014
measure: Compare the Percentage of Enriched Modified Cells C34-CXCR4 Modifiec T- Cells
time frame: 2 weeks post infusion, prior to ARV reinitiation, weeks 12, 16 and 20
measure: Compare the Change Between CD4 Count
time frame: Baseline, week 2 post infusion, prior to ARV initiation, weeks 12, 16 20
measure: Compare Viral Set Point Log 10 HIV RNA Level
time frame: week 2 post infusion, prior to ARV initiation, week 12, 16, 20
measure: Evaluate Cell Mediated Response (Immunogenicity) Using Flow Cytometry
time frame: baseline through 1 year
arm group label: Dose level 1:
arm group type: Experimental
description: Autologous CD4 T-Cells0.8-1x10^9 transduced CD4+T-cells administered IV as a single dose
arm group label: Dose level 2
arm group type: Active Comparator
description: Autologous CD4 T-Cells 2.4-3x10^9 transduced CD4+ T-cells administered IV as a single dose
arm group label: Dose level 3
arm group type: Active Comparator
description: Autologous CD4 T-Cells 0.8-1x10^10 transduced CD4+ T-cells administered IV as a single dose
intervention type: Biological
intervention name: Autologous CD4 T-Cells
description: all participants will receive a single infusion of C34-CXCR4-modified CD4+ T-cells at one of 3 dose levels. The first 3 subjects will receive dose level 1 of 0.8-1x109 transduced CD4+T-cells. Provided no dose limiting toxicity (DLT) is seen at the first dose level, the next 3 subjects will receive infusion at the 2nd dose level of 2.4-3x109 transduced CD4+ T-cells. If no DLT occurs at that dose, the final 3 subjects will receive the 3rd dose level of 0.8-1x1010 transduced CD4+ T-cells. In the event of a DLT (grade 3 or higher unexpected, related AE) recruitment will be paused pending DSMB decision
arm group label: Dose level 1:
arm group label: Dose level 2
arm group label: Dose level 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pablo Tebas, MD
role: Principal Investigator
affiliation: University of Pennaylvania
facility: 
country: United States
responsible party type: Sponsor
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 