<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/NCT02208167</url>
  </required_header>
  <id_info>
    <org_study_id>14-0741</org_study_id>
    <secondary_id>5U19AI096113-05</secondary_id>
    <nct_id>NCT02208167</nct_id>
  </id_info>
  <brief_title>Phase I Study of HIV 1 Antigen Expanded Specific T Cell Therapy</brief_title>
  <acronym>HXTC</acronym>
  <official_title>IGHID 1320 - A Phase I Study to Evaluate the Safety, Immunologic, and Virologic Responses of HIV-1 Antigen Expanded Specific T Cell Therapy (HXTC) as a Therapeutic Strategy in HIV-Infected Individuals Started on Antiretroviral Therapy During Acute and Chronic Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>CARE Collaboratory of AIDS Researchers for Eradication</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 1, single-site study is to evaluate the safety and immunologic and virologic&#xD;
      efficacy of ex vivo expanded HIV-1 multi-antigen specific T-cell (HXTC) therapy in&#xD;
      HIV-infected individuals with viral suppression on antiretroviral therapy (ART).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main hypothesis of this study is that the administration of autologous ex vivo expanded&#xD;
      HIV-specific T-cells (HXTCs) primed to recognize multiple HIV-1 antigens in HIV-infected&#xD;
      participants who initiated ART during acute and chronic HIV infection will be safe, increase&#xD;
      HIV-1 antigen specific T-cell immune responses and decrease low level viremia.&#xD;
&#xD;
      In addition, secondary objectives are to:&#xD;
&#xD;
        1. Determine the feasibility of manufacturing HXTC from participants who started cART&#xD;
           during acute and chronic HIV infection.&#xD;
&#xD;
        2. Explore the ability of autologous ex vivo expanded HIV-1 specific T-cells (HXTC) to&#xD;
           increase HIV-1 specific immune responses in participants initiated on cART during acute&#xD;
           and chronic HIV infection.&#xD;
&#xD;
        3. Explore the ability of autologous ex vivo expanded HIV-1 specific T-cells (HXTC) to&#xD;
           impact latent HIV infection as measured by a quantitative viral outgrowth assay (QVOA)&#xD;
           and integrated proviral DNA quantification, and low level viremia as measured by a&#xD;
           single copy assay (SCA) in participants initiated on cART during acute and chronic HIV&#xD;
           infection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 7, 2015</start_date>
  <completion_date type="Actual">November 27, 2017</completion_date>
  <primary_completion_date type="Actual">January 19, 2017</primary_completion_date>
  <phase>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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety</measure>
    <time_frame>1st day of study treatment until 28 days post last infusion</time_frame>
    <description>Occurrence of any ≥ Grade 3 AE including signs/symptoms, lab toxicities, and/or clinical events, that are: possibly, probably or definitely related to study treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Safety</measure>
    <time_frame>1st day of study treatment through Week 48</time_frame>
    <description>Occurrence of any ≥ Grade 3 AE including signs/symptoms, lab toxicities, and/or clinical events regardless of adjudicated relationship to study treatment.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Immune Response</measure>
    <time_frame>baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion</time_frame>
    <description>Frequency of HIV-1 antigen-specific (gag, pol, nef) CD8+ T-cells by ELIspot</description>
  </other_outcome>
  <other_outcome>
    <measure>Immune Response</measure>
    <time_frame>baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion</time_frame>
    <description>Change in T cell responses from baseline to post-infusion, measured by frequency of cells secreting IFN-γ by multimer analysis, intracellular cytokine staining and ELIspot.</description>
  </other_outcome>
  <other_outcome>
    <measure>Immune Response</measure>
    <time_frame>baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion</time_frame>
    <description>Change in cytokine release as measured by multi-color flow cytometry</description>
  </other_outcome>
  <other_outcome>
    <measure>Immune Response</measure>
    <time_frame>baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion</time_frame>
    <description>Change in polyfunctionality of HIV-1 specific CD8+ and CD4+ T-cells</description>
  </other_outcome>
  <other_outcome>
    <measure>Immune Response</measure>
    <time_frame>baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion</time_frame>
    <description>Change in proportion of total and HIV-1 specific CD8+ T-cells expressing markers of immune exhaustion</description>
  </other_outcome>
  <other_outcome>
    <measure>Immune Response</measure>
    <time_frame>baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion</time_frame>
    <description>Change in proportion of CD28+/CD45RA- CD8+ CTL that display effector function from baseline to post-infusion, measured by multi-color flow cytometry.</description>
  </other_outcome>
  <other_outcome>
    <measure>Immune Response</measure>
    <time_frame>baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion</time_frame>
    <description>Change in antiviral activity of CD8 cells as measured by a viral inhibition assay</description>
  </other_outcome>
  <other_outcome>
    <measure>Immune Response</measure>
    <time_frame>baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion</time_frame>
    <description>Change in CTL killing of resting CD4+ T cells via a novel latency clearance assay from baseline to week 13 following administration of HXTC</description>
  </other_outcome>
  <other_outcome>
    <measure>Virologic Measures</measure>
    <time_frame>baseline, 4 and 13 weeks</time_frame>
    <description>Change in plasma HIV-1 RNA by single copy assay (SCA)</description>
  </other_outcome>
  <other_outcome>
    <measure>Virologic Measures</measure>
    <time_frame>baseline, 4 and 13 weeks</time_frame>
    <description>Change in frequency of HIV-1 infection of resting CD4+ T cells using the viral outgrowth assay</description>
  </other_outcome>
  <other_outcome>
    <measure>Virologic Measures</measure>
    <time_frame>baseline, 4 and 13 weeks</time_frame>
    <description>Change in T-cell associated HIV-1 DNA</description>
  </other_outcome>
  <other_outcome>
    <measure>Virologic Measures</measure>
    <time_frame>baseline, 4 and 13 weeks</time_frame>
    <description>Change in 2LTR circles in CD4+ T cells</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Chronic HIV infection</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>HXTC infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Acute HIV infection</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>HXTC infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>HXTC infusion</intervention_name>
    <arm_group_label>Acute HIV infection</arm_group_label>
    <arm_group_label>Chronic HIV infection</arm_group_label>
    <other_name>HIV 1 antigen expanded specific T cell</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ≥ 18 years and ≤65 years of age&#xD;
&#xD;
          2. Confirmation of HIV 1 infection&#xD;
&#xD;
               -  Chronic HIV infection (CHI) is defined as documentation of a positive HIV test&#xD;
                  result by any licensed ELISA test kit and confirmed by Western blot or Multispot&#xD;
                  HIV 1/HIV 2 assay prior to screening. HIV culture, HIV antigen, plasma HIV RNA,&#xD;
                  or a second antibody test by a method other than ELISA is acceptable as an&#xD;
                  alternative confirmatory test.&#xD;
&#xD;
               -  Acute HIV infection (AHI) is defined as: 1) a negative or indeterminate enzyme&#xD;
                  immunoassay (EIA) plus a reproducibly detectable HIV by amplification methods, or&#xD;
                  2) a positive 4th generation HIV Ag/Ab Combination assay and either a&#xD;
                  negative/indeterminate HIV rapid test or a negative/indeterminate Western blot,&#xD;
                  or 3) a negative HIV RNA test within 45 days of a positive EIA and ART&#xD;
                  initiation.&#xD;
&#xD;
             Note: the HIV definitions above are pertinent to the time of diagnosis and treatment&#xD;
             initiation.&#xD;
&#xD;
          3. AHI participants are defined as HIV infected patients on suppressive ART that was&#xD;
             initiated within 45 days of AHI diagnosis as defined in protocol section 5.1.2.&#xD;
&#xD;
          4. CHI participants are defined as HIV infected patients who initiated ART with chronic&#xD;
             HIV as defined in protocol section 5.1.2.&#xD;
&#xD;
          5. On potent antiretroviral therapy, defined as at least 2 nucleoside/nucleotide reverse&#xD;
             transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor,&#xD;
             integrase inhibitor, or a protease inhibitor without interruption (defined as missing&#xD;
             doses for more than two (2) consecutive days or more than four (4) cumulative days) in&#xD;
             the 12 weeks prior to entry.&#xD;
&#xD;
             Other potent fully suppressive antiretroviral combinations will be considered on a&#xD;
             case by case basis. Prior changes in or elimination of medications for easier dosing&#xD;
             schedule, intolerance, toxicity, or other reasons are permitted if an alternative&#xD;
             suppressive regimen was maintained.&#xD;
&#xD;
          6. Stable ART regimen for minimum of 3 months. NOTE: The ART regimen is defined by&#xD;
             current treatment guidelines. Participants may have had one or more changes in their&#xD;
             ART regimen for tolerance, change of guidelines, or dosing simplification.&#xD;
&#xD;
          7. Ability and willingness of participant to continue cART throughout the study.&#xD;
&#xD;
          8. Plasma HIV 1 RNA below detected limit by conventional assays (limit of detection: 75,&#xD;
             50, 40, or 20 copies/mL) for ˃1 year.&#xD;
&#xD;
             A single unconfirmed plasma HIV RNA ˃ limit of detection but ˂ 1000 c/mL allowed&#xD;
             within the prior 12 months; but none in the preceding 6 months.&#xD;
&#xD;
          9. Plasma HIV 1 RNA ˂ 50 copies/mL at screening.&#xD;
&#xD;
         10. CD4+ cell count ˃ 350 cells/mm3 at screening.&#xD;
&#xD;
         11. No active HCV infection (measureable HCV RNA) within 90 days of enrollment.&#xD;
&#xD;
         12. No active HBV infection (measureable HBV DNA or HBVsAg+) within 90 days of enrollment.&#xD;
&#xD;
         13. All female participants participating in sexual activity that could lead to pregnancy&#xD;
             must agree to use at least two of the following reliable methods of birth control (at&#xD;
             least one of which is a barrier method) for at least 21 days prior to study entry and&#xD;
             until 12 weeks after the last dose of the study product: condoms (male or female) with&#xD;
             or without a spermicidal agent, diaphragm or cervical cap with spermicide,&#xD;
             Intrauterine Device, hormone-based contraceptive, tubal ligation, NuvaRing.&#xD;
&#xD;
         14. All male participants participating in sexual activity that could lead to pregnancy&#xD;
             must agree to use condoms for at least 21 days prior to study entry and until 12 weeks&#xD;
             after the last dose of the study product.&#xD;
&#xD;
         15. Ability and willingness of subject to give written informed consent.&#xD;
&#xD;
         16. Ability and willingness to provide adequate locator information.&#xD;
&#xD;
         17. Ability and willingness to communicate effectively with study personnel; considered&#xD;
             reliable, willing, and cooperative in terms of compliance with the Protocol&#xD;
             requirements.&#xD;
&#xD;
         18. Adequate vascular access for HXTC infusion and leukapheresis.&#xD;
&#xD;
         19. Potential participant must have adequate organ function as indicated by the following&#xD;
             laboratory values:&#xD;
&#xD;
        Absolute neutrophil count (ANC): ≥ 1,500 /mcL Platelets: ≥ 125,000 / mcL Hemoglobin: ≥ 12&#xD;
        g/dL&#xD;
&#xD;
        Coagulation:&#xD;
&#xD;
        Prothrombin Time or INR: ≤ 1.5 times upper limit of normal (ULN)&#xD;
&#xD;
        Chemistry K+ levels: Within normal limits&#xD;
&#xD;
        Renal:&#xD;
&#xD;
        Serum creatinine (or calculated creatinine clearance* for those with creatinine &gt; 1.3 ULN):&#xD;
        ≤ 1.3 times upper limit of normal (ULN); OR Creatinine clearance* ≥ 60 mL/min for potential&#xD;
        participants with creatinine levels &gt; 1.3 times institutional ULN&#xD;
&#xD;
        Hepatic Serum total bilirubin: Total bilirubin &lt; 1.5 times the upper limit of the normal&#xD;
        range. If total bilirubin is elevated, direct bilirubin must be &lt; 2 times the ULN range.&#xD;
&#xD;
        NOTE: If participant is on an atazanavir containing therapy then a direct bilirubin should&#xD;
        be measured instead of the total bilirubin and must be ≤ 1.0mg/dL.&#xD;
&#xD;
        AST (SGOT) and ALT (SGPT): ≤ 2.0 times ULN Alkaline Phosphatase: ≤ 2.5 times ULN&#xD;
&#xD;
        *Creatinine clearance should be calculated per institutional standard.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior use of any HIV immunotherapy or vaccine within 12 months prior to Screening.&#xD;
&#xD;
          2. Use of any of the following within 90 days prior to entry: immunomodulatory, cytokine,&#xD;
             or growth stimulating factors such as systemic corticosteroids, cyclosporine,&#xD;
             methotrexate, azathioprine, anti-CD25 antibody, IFN, interleukin 2 (IL 2), Coumadin,&#xD;
             warfarin, or other Coumadin derivative anticoagulants.&#xD;
&#xD;
          3. Received any infusion blood product, immune globulin, or hematopoietic growth factors&#xD;
             within 90 days prior to study entry.&#xD;
&#xD;
          4. Pregnancy or breast-feeding.&#xD;
&#xD;
          5. History or other evidence of severe illness, malignancy, immunodeficiency other than&#xD;
             HIV, or any other condition that would make the subject unsuitable for the study in&#xD;
             the opinion of the investigator.&#xD;
&#xD;
          6. Use of topical steroids over a total area exceeding 0.5mg/kg/day within 30 days prior&#xD;
             to Screening.&#xD;
&#xD;
          7. Any active malignancy that may require chemotherapy or radiation therapy.&#xD;
&#xD;
          8. Compulsorily detained (involuntarily incarcerated) for treatment of either a&#xD;
             psychiatric illness or a physical illness, e.g., infectious disease. Prisoner&#xD;
             recruitment and participation is not permitted.&#xD;
&#xD;
          9. Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza,&#xD;
             pneumococcal polysaccharide) within 4 weeks prior to study entry.&#xD;
&#xD;
         10. Unable to have a person available to drive participant home at infusion visits.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cynthia Gay, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David Margolis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of North Carolina</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599-7030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.unc.edu</url>
    <description>University of North Carolina</description>
  </link>
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  <verification_date>February 2018</verification_date>
  <study_first_submitted>July 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <last_update_submitted>October 2, 2019</last_update_submitted>
  <last_update_submitted_qc>October 2, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Antigen Expanded Specific T Cell Therapy</keyword>
  <keyword>HXTC</keyword>
  <keyword>Antiretroviral Therapy</keyword>
  <keyword>Acute HIV infection</keyword>
  <keyword>Chronic HIV infection</keyword>
  <keyword>Leukapheresis</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02208167
org study id: 14-0741
secondary id: 5U19AI096113-05
nct id: NCT02208167
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
This is a phase 1, single-site study is to evaluate the safety and immunologic and virologic
      efficacy of ex vivo expanded HIV-1 multi-antigen specific T-cell (HXTC) therapy in
      HIV-infected individuals with viral suppression on antiretroviral therapy (ART).
The main hypothesis of this study is that the administration of autologous ex vivo expanded
      HIV-specific T-cells (HXTCs) primed to recognize multiple HIV-1 antigens in HIV-infected
      participants who initiated ART during acute and chronic HIV infection will be safe, increase
      HIV-1 antigen specific T-cell immune responses and decrease low level viremia.

      In addition, secondary objectives are to:

        1. Determine the feasibility of manufacturing HXTC from participants who started cART
           during acute and chronic HIV infection.

        2. Explore the ability of autologous ex vivo expanded HIV-1 specific T-cells (HXTC) to
           increase HIV-1 specific immune responses in participants initiated on cART during acute
           and chronic HIV infection.

        3. Explore the ability of autologous ex vivo expanded HIV-1 specific T-cells (HXTC) to
           impact latent HIV infection as measured by a quantitative viral outgrowth assay (QVOA)
           and integrated proviral DNA quantification, and low level viremia as measured by a
           single copy assay (SCA) in participants initiated on cART during acute and chronic HIV
           infection.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety
time frame: 1st day of study treatment until 28 days post last infusion
description: Occurrence of any ≥ Grade 3 AE including signs/symptoms, lab toxicities, and/or clinical events, that are: possibly, probably or definitely related to study treatment.
measure: Secondary Safety
time frame: 1st day of study treatment through Week 48
description: Occurrence of any ≥ Grade 3 AE including signs/symptoms, lab toxicities, and/or clinical events regardless of adjudicated relationship to study treatment.
measure: Immune Response
time frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion
description: Frequency of HIV-1 antigen-specific (gag, pol, nef) CD8+ T-cells by ELIspot
measure: Immune Response
time frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion
description: Change in T cell responses from baseline to post-infusion, measured by frequency of cells secreting IFN-γ by multimer analysis, intracellular cytokine staining and ELIspot.
measure: Immune Response
time frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion
description: Change in cytokine release as measured by multi-color flow cytometry
measure: Immune Response
time frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion
description: Change in polyfunctionality of HIV-1 specific CD8+ and CD4+ T-cells
measure: Immune Response
time frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion
description: Change in proportion of total and HIV-1 specific CD8+ T-cells expressing markers of immune exhaustion
measure: Immune Response
time frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion
description: Change in proportion of CD28+/CD45RA- CD8+ CTL that display effector function from baseline to post-infusion, measured by multi-color flow cytometry.
measure: Immune Response
time frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion
description: Change in antiviral activity of CD8 cells as measured by a viral inhibition assay
measure: Immune Response
time frame: baseline, weeks 1, 2, 4, 6, 8, 13, 24, 36, and 48 post-infusion
description: Change in CTL killing of resting CD4+ T cells via a novel latency clearance assay from baseline to week 13 following administration of HXTC
measure: Virologic Measures
time frame: baseline, 4 and 13 weeks
description: Change in plasma HIV-1 RNA by single copy assay (SCA)
measure: Virologic Measures
time frame: baseline, 4 and 13 weeks
description: Change in frequency of HIV-1 infection of resting CD4+ T cells using the viral outgrowth assay
measure: Virologic Measures
time frame: baseline, 4 and 13 weeks
description: Change in T-cell associated HIV-1 DNA
measure: Virologic Measures
time frame: baseline, 4 and 13 weeks
description: Change in 2LTR circles in CD4+ T cells
arm group label: Chronic HIV infection
arm group type: Other
description: HXTC infusion
arm group label: Acute HIV infection
arm group type: Other
description: HXTC infusion
intervention type: Biological
intervention name: HXTC infusion
arm group label: Acute HIV infection
arm group label: Chronic HIV infection
other name: HIV 1 antigen expanded specific T cell
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Cynthia Gay, MD, MPH
role: Principal Investigator
affiliation: University of North Carolina
last name: David Margolis, MD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
country: United States
url: http://www.unc.edu
description: University of North Carolina
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