<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/NCT02231281</url>
  </required_header>
  <id_info>
    <org_study_id>2014ZX10001002-001</org_study_id>
    <secondary_id>2014ZX10001002-001</secondary_id>
    <nct_id>NCT02231281</nct_id>
  </id_info>
  <brief_title>Early cART and cART in Combination With Autologous HIV-1 Specific Cytotoxic T Lymphocyte (CTL) Infusion in The Treatment of Acute HIV-1 Infected Adults</brief_title>
  <official_title>A Randomized, Open-label Trial to Compare the Efficacy and Safety of Early Initiation of cART With or Without Autologous HIV-1 Specific Cytotoxic T Lymphocyte (CTL) Infusion in Treatment-Naïve Acute HIV-1 Infected Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yongtao Sun, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Tang-Du Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for AIDS/STD Control and Prevention, China CDC</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing YouAn Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>China Medical University, China</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shandong Province Centers for Disease Control and Prevention</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First Affiliated Hospital of Guangxi Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tang-Du Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the ability of the early initiation of cART or cART in&#xD;
      combination with autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion to achieve a&#xD;
      post-treatment control among treatment-naïve acute HIV-infected adults.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Although combined antiretroviral therapy (cART) can suppress HIV-1 replication to a very low&#xD;
      level in the blood, but it cannot eliminate latent viral reservoirs, and need lifelong&#xD;
      adherence to expensive regimens that have potential side effects. Increasing evidence&#xD;
      indicates that early antiretroviral therapy for recently HIV-infected patients results in&#xD;
      slower progression of HIV disease and represent a unique opportunity to interfere with either&#xD;
      the quantities or qualities of persistent reservoirs of replication-competent virus. However,&#xD;
      the time course before the interruption of cART is unclear. This study will compare the&#xD;
      virological and immunological outcomes and HIV latency of recently infected adults who&#xD;
      receive cART or cART in combination with autologous HIV-1 CTL infusion for different periods.&#xD;
&#xD;
      The study will last 120 weeks. Participants will be randomly assigned to either the cART or&#xD;
      the cART plus autologous HIV-1 CTL infusion arm of one of three cohorts. The three cohorts&#xD;
      will differ in the period of cART given. Cohort 1, Cohort 2 or Cohort 3 will receive cART&#xD;
      (Zidovudine (AZT)/Tenofovir disoproxil fumarate (TDF) +Lamivudine (3TC） + Lopinavir /&#xD;
      Ritonavir （LPV/r)） for 48, 72 or 96 weeks, respectively. After 48, 72 or 96 weeks, cART will&#xD;
      be interrupted respectively. Study visits will occur at study entry, Week 4 and 12, and every&#xD;
      12 weeks thereafter through treatment interruption, then every 4 weeks through 12 weeks&#xD;
      later, then every 12 weeks through Week 120. At each study visit, a physical exam, blood&#xD;
      collection, and completion of an adherence questionnaire will occur. Clinical, virological,&#xD;
      and immunological evaluations and HIV latency examination will be performed at most study&#xD;
      visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">August 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in HIV DNA quantification at the interruption of cART</measure>
    <time_frame>48 weeks for Cohort 1, 72 weeks for Cohort 2, 96 weeks for Cohort 3</time_frame>
    <description>HIV DNA detection includes total HIV DNA, integrated HIV DNA , 2-long terminal repeat （LTR） HIV DNA in resting CD4+T cell subsets.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients who achieve virological remission</measure>
    <time_frame>72 weeks for Cohort 1, 96 weeks for Cohort 2, 120 weeks for Cohort 3</time_frame>
    <description>Virological remission is defined as undetectable of plasma HIV RNA for 24 weeks after the interruption of cART.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients who occur any grade 3 or 4 (clinical or laboratory) adverse events</measure>
    <time_frame>120 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients who need to initiate late treatment</measure>
    <time_frame>120 weeks</time_frame>
    <description>Late treatment is defined cART should be administered according to local HIV treatment guidelines.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from cART interruption to virological relapse (plasma viral load more than 50 copies/mL)</measure>
    <time_frame>120 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV-1 specific CD4+ and CD8+ T cell responses at week 120</measure>
    <time_frame>120 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">65</enrollment>
  <condition>Acute HIV Infection</condition>
  <arm_group>
    <arm_group_label>cART(TDF/AZT+3TC+LPV/r)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>cART(TDF/AZT+3TC+LPV/r)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CTL infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>cART plus autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cART(TDF/AZT+3TC+LPV/r)</intervention_name>
    <description>Standard antiretroviral therapy for HIV infection</description>
    <arm_group_label>CTL infusion</arm_group_label>
    <arm_group_label>cART(TDF/AZT+3TC+LPV/r)</arm_group_label>
    <other_name>Tenofovir Disoproxil Fumarate</other_name>
    <other_name>Zidovudine</other_name>
    <other_name>Lamivudine</other_name>
    <other_name>Lopinavir/ritonavir (Kaletra)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>CTL infusion</intervention_name>
    <description>cART(TDF/AZT+3TC+LPV/r) plus autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion</description>
    <arm_group_label>CTL infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of acute HIV infection (meets one of following criteria)&#xD;
&#xD;
               1. Negative for anti-HIV test formerly, but with an anti-HIV serological conversion&#xD;
                  within 6 months&#xD;
&#xD;
               2. Detection of plasma HIV RNA by RT-PCR in the absence of HIV antibody&#xD;
&#xD;
               3. Low-level of anti-HIV for BED HIV-1 capture enzyme immuno assay (BED-CEIA),&#xD;
                  optical density (OD)&lt;0.6, only for B subtype)&#xD;
&#xD;
               4. Uncertain for an anti-HIV test, with an increasing anti-HIV level for repeated&#xD;
                  test within two weeks&#xD;
&#xD;
               5. A patient with a report of recent risk behavior in association with symptoms and&#xD;
                  signs of the acute retroviral syndrome, as well as a positive for HIV antigen&#xD;
                  detection and less than 4 bands in a Western blot assay&#xD;
&#xD;
          2. Ability, willingness to give informed consent&#xD;
&#xD;
          3. Able, willing to adhere to therapy and adherent to ART&#xD;
&#xD;
          4. Able, willing to comply with time requirements for study visits and evaluations&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Chronic HIV - 1 infection&#xD;
&#xD;
          2. Any evidence of an active AIDS-defining opportunistic infection&#xD;
&#xD;
          3. Screening detects the following results:HGB&lt;90g/L、WBC&lt; 2 x 10E9/L、PLT&lt; 75 x&#xD;
             10E9/L、hemodiastase&gt;2 x ULN、Scr&gt;1.5 x ULN、ALT/AST/ALP&gt; 3 xULN、TbiL&gt;2 xULN、CK&gt;2&#xD;
             xULN、CCr&lt;60ml/min&#xD;
&#xD;
          4. A personal history of clinically significant cardiac disease, symptomatic or&#xD;
             asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades&#xD;
             de points&#xD;
&#xD;
          5. History of chronic kidney disease&#xD;
&#xD;
          6. History of malignancy or transplantation, including skin cancers or Kaposi sarcoma&#xD;
&#xD;
          7. History of Severe peptic ulcer&#xD;
&#xD;
          8. History of alcoholism and drug abuse&#xD;
&#xD;
          9. Receipt of immunomodulating agents, immunization or systemic chemotherapeutic agents&#xD;
             within 28 days prior to screening&#xD;
&#xD;
         10. Women who are pregnant or breastfeeding, or with a positive pregnancy test during&#xD;
             screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to&#xD;
             use an acceptable method of contraception to avoid pregnancy for the entire study&#xD;
             period&#xD;
&#xD;
         11. Have contraindications to cART&#xD;
&#xD;
         12. Other condition that does not fit to participate in this study&#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>Yongtao Sun, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing You'an Hospital, Capital Medical University</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Center for STD and AIDS Control and Prevention, Chinese Center for Disease Control and Prevention</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Guangxi Medical University</name>
      <address>
        <city>Nanning</city>
        <state>Guangxi</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China Medical University</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical Universit</name>
      <address>
        <city>Xi'an</city>
        <state>Shaanxi</state>
        <zip>710038</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shandong Center for Disease Control and Prevention</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>August 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <last_update_submitted>April 24, 2018</last_update_submitted>
  <last_update_submitted_qc>April 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Tang-Du Hospital</investigator_affiliation>
    <investigator_full_name>Yongtao Sun, MD, PhD</investigator_full_name>
    <investigator_title>Director of Department of Infectious Diseases</investigator_title>
  </responsible_party>
  <keyword>HIV Infections</keyword>
  <keyword>Acquired Immunodeficiency Syndrome</keyword>
  <keyword>Immunologic Deficiency Syndromes</keyword>
  <keyword>Immune System Diseases</keyword>
  <keyword>Lentivirus Infections</keyword>
  <keyword>Retroviridae Infections</keyword>
  <keyword>Virus Diseases</keyword>
  <keyword>RNA Virus Infections</keyword>
  <keyword>Sexually Transmitted Diseases, Viral</keyword>
  <keyword>Slow Virus Diseases</keyword>
  <keyword>Therapeutic Uses</keyword>
  <keyword>Pharmacologic Actions</keyword>
  <keyword>Antiretroviral therapy</keyword>
  <keyword>Early therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</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>Ritonavir</mesh_term>
    <mesh_term>Lopinavir</mesh_term>
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Lamivudine</mesh_term>
    <mesh_term>Zidovudine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02231281
org study id: 2014ZX10001002-001
secondary id: 2014ZX10001002-001
nct id: NCT02231281
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to assess the ability of the early initiation of cART or cART in
      combination with autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion to achieve a
      post-treatment control among treatment-naïve acute HIV-infected adults.
Although combined antiretroviral therapy (cART) can suppress HIV-1 replication to a very low
      level in the blood, but it cannot eliminate latent viral reservoirs, and need lifelong
      adherence to expensive regimens that have potential side effects. Increasing evidence
      indicates that early antiretroviral therapy for recently HIV-infected patients results in
      slower progression of HIV disease and represent a unique opportunity to interfere with either
      the quantities or qualities of persistent reservoirs of replication-competent virus. However,
      the time course before the interruption of cART is unclear. This study will compare the
      virological and immunological outcomes and HIV latency of recently infected adults who
      receive cART or cART in combination with autologous HIV-1 CTL infusion for different periods.

      The study will last 120 weeks. Participants will be randomly assigned to either the cART or
      the cART plus autologous HIV-1 CTL infusion arm of one of three cohorts. The three cohorts
      will differ in the period of cART given. Cohort 1, Cohort 2 or Cohort 3 will receive cART
      (Zidovudine (AZT)/Tenofovir disoproxil fumarate (TDF) +Lamivudine (3TC） + Lopinavir /
      Ritonavir （LPV/r)） for 48, 72 or 96 weeks, respectively. After 48, 72 or 96 weeks, cART will
      be interrupted respectively. Study visits will occur at study entry, Week 4 and 12, and every
      12 weeks thereafter through treatment interruption, then every 4 weeks through 12 weeks
      later, then every 12 weeks through Week 120. At each study visit, a physical exam, blood
      collection, and completion of an adherence questionnaire will occur. Clinical, virological,
      and immunological evaluations and HIV latency examination will be performed at most study
      visit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in HIV DNA quantification at the interruption of cART
time frame: 48 weeks for Cohort 1, 72 weeks for Cohort 2, 96 weeks for Cohort 3
description: HIV DNA detection includes total HIV DNA, integrated HIV DNA , 2-long terminal repeat （LTR） HIV DNA in resting CD4+T cell subsets.
measure: Number of patients who achieve virological remission
time frame: 72 weeks for Cohort 1, 96 weeks for Cohort 2, 120 weeks for Cohort 3
description: Virological remission is defined as undetectable of plasma HIV RNA for 24 weeks after the interruption of cART.
measure: Number of patients who occur any grade 3 or 4 (clinical or laboratory) adverse events
time frame: 120 weeks
measure: Number of patients who need to initiate late treatment
time frame: 120 weeks
description: Late treatment is defined cART should be administered according to local HIV treatment guidelines.
measure: Time from cART interruption to virological relapse (plasma viral load more than 50 copies/mL)
time frame: 120 weeks
measure: HIV-1 specific CD4+ and CD8+ T cell responses at week 120
time frame: 120 weeks
arm group label: cART(TDF/AZT+3TC+LPV/r)
arm group type: Experimental
description: cART(TDF/AZT+3TC+LPV/r)
arm group label: CTL infusion
arm group type: Experimental
description: cART plus autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion
intervention type: Drug
intervention name: cART(TDF/AZT+3TC+LPV/r)
description: Standard antiretroviral therapy for HIV infection
arm group label: CTL infusion
arm group label: cART(TDF/AZT+3TC+LPV/r)
other name: Tenofovir Disoproxil Fumarate
other name: Zidovudine
other name: Lamivudine
other name: Lopinavir/ritonavir (Kaletra)
intervention type: Procedure
intervention name: CTL infusion
description: cART(TDF/AZT+3TC+LPV/r) plus autologous HIV-1 specific cytotoxic T lymphocyte (CTL) infusion
arm group label: CTL infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Yongtao Sun, M.D., Ph.D.
role: Principal Investigator
affiliation: Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor-Investigator
investigator affiliation: Tang-Du Hospital
investigator full name: Yongtao Sun, MD, PhD
investigator title: Director of Department of Infectious Diseases
mesh term: Infections
mesh term: HIV Infections
mesh term: Ritonavir
mesh term: Lopinavir
mesh term: Tenofovir
mesh term: Lamivudine
mesh term: Zidovudine