<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/NCT03758625</url>
  </required_header>
  <id_info>
    <org_study_id>DAIDS-ES 38541</org_study_id>
    <secondary_id>U01AI131285</secondary_id>
    <nct_id>NCT03758625</nct_id>
  </id_info>
  <brief_title>Comparison of Dendritic Cell-Based Therapeutic Vaccine Strategies for HIV Functional Cure</brief_title>
  <acronym>DC-HIV04</acronym>
  <official_title>A Phase I Study to Evaluate the Safety, Tolerability and Immunogenicity of a Therapeutic HIV Vaccine Composed of Autologous Dendritic Cells Loaded With Autologous Inactivated Whole Virus or Conserved Peptides in ART-treated HIV-infected Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sharon Riddler</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will be done in people living with HIV to see if an investigational vaccine made&#xD;
      from a person's own white blood cells is safe and tolerated. This study will also look at the&#xD;
      body's immune response to the vaccine and evaluate four different methods of making the&#xD;
      vaccine to see which method may result in better immune responses.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite the availability of strong medicines for HIV infection, there is no cure for the&#xD;
      infection. The current anti-HIV drugs, used in combination, are effective in slowing the&#xD;
      growth of the virus and delaying the progression of the infection. There is increasing&#xD;
      information to suggest that a vigorous immune response (a strong response of the body to&#xD;
      fight infection) to HIV may also result in improved control of the HIV infection. Such strong&#xD;
      immune responses are found in a small number of HIV-infected individuals, but not in the&#xD;
      majority.&#xD;
&#xD;
      Dendritic cells, or DCs, are a type of white blood cell that works together with other immune&#xD;
      cells to fight infection. The DCs role is to bring substances foreign to the body, such as&#xD;
      viruses including HIV or cancer cell proteins, to the body's immune system. Large numbers of&#xD;
      DCs can be made from blood samples and administered back to the same person as an&#xD;
      individualized vaccine. Vaccines made from DCs have been studied in HIV and numerous types of&#xD;
      cancer.&#xD;
&#xD;
      The vaccines will be created by two different laboratory methods, standard or improved, using&#xD;
      an individual's own DCs and either an individual's own inactive HIV that has been killed with&#xD;
      heat or manmade HIV proteins called peptides. The peptides have not been studied for this use&#xD;
      in humans, and these vaccines are not approved by the Food and Drug Administration (FDA) to&#xD;
      prevent or treat HIV infection.&#xD;
&#xD;
      This study will be done in two steps. During Step 1 (Entry-Week 12), participants will have 4&#xD;
      study visits for tests, procedures and exams. At Week 4, participants will be randomized by&#xD;
      chance into one of six study groups, like rolling dice. Four of the study groups will receive&#xD;
      a DC-HIV vaccine while two of the study groups will receive a &quot;control&quot; vaccine with only&#xD;
      DCs. Participants will have a 4:1 chance of receiving a DC-HIV study vaccine.&#xD;
&#xD;
        -  Group 1: enhanced DC-HIV vaccine with inactive HIV&#xD;
&#xD;
        -  Group 2: enhanced DC-HIV vaccine with HIV peptides&#xD;
&#xD;
        -  Group 3: enhanced DCs only (control)&#xD;
&#xD;
        -  Group 4: classic DC-HIV vaccine with inactive HIV&#xD;
&#xD;
        -  Group 5: classic DC-HIV vaccine with HIV peptides&#xD;
&#xD;
        -  Group 6: classic DCs only (control)&#xD;
&#xD;
      Each participant will receive 6 study vaccinations at 4-week intervals beginning at Week 12.&#xD;
      Researchers will compare the results from participants who get the active study vaccines with&#xD;
      results from participants who get the control vaccines. Participants, the researchers and the&#xD;
      clinic staff will not know which vaccine participants are getting.&#xD;
&#xD;
      In Step 2 (Weeks 12 - 80), participants will have 18 study visits to receive the 6 study&#xD;
      vaccinations and for tests to monitor health and safety and to see how the study vaccine&#xD;
      affects the immune system and the virus.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 30, 2018</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2023</primary_completion_date>
  <phase>Phase 1</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>
    <intervention_model_description>Randomized, double-blind, multi-arm</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of six immunizations (10e7 DCs per dose) of DC-whole virus and DC-peptide vaccines in HIV-1 infected participants on effective ART</measure>
    <time_frame>Step 2-Week 0 (overall Study Week 12) to overall Study Week 80</time_frame>
    <description>Occurrence of Grade ≥ 3 AE including signs/symptoms, lab toxicities, and/or clinical events that are possibly, probably, or definitely related to study treatment (as judged by the site investigator, blinded to treatment arm) at any time from the initial dose of DC vaccine product to end of study follow-up.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy of six immunizations (10e7 DCs per dose) of DC-whole virus and DC-peptide vaccines in HIV-1 infected participants on effective ART</measure>
    <time_frame>Baseline to Step 2-Week 22 (overall Study Week 34)</time_frame>
    <description>Change in HIV-specific CD8 and T-cell immune response as measured by ELISPOT between the vaccine arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Relative efficacy of the DC-HIV vaccines in priming HIV-specific-CD8+ T cells</measure>
    <time_frame>Baseline to Step 2-Week 22 (overall Study Week 34)</time_frame>
    <description>Change in the ability of the DC-HIV vaccines to inhibit autologous HIV in an ex vivo virus inhibition assay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of DC-HIV vaccination on the level of persistent viremia in plasma</measure>
    <time_frame>Baseline to Step 2-Week 22 (overall Study Week 34)</time_frame>
    <description>Change in plasma HIV-1 RNA viral load as measured by single copy assay (SCA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of DC-HIV vaccination on HIV specific CD8 T-cell polyfunctional responses</measure>
    <time_frame>Baseline to Step 2-Week 22 (overall Study Week 34)</time_frame>
    <description>Change in HIV specific CD8 T-cell polyfunctional responses as measured by intracellular cytokine staining using flow cytometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the impact of DC-HIV vaccination on levels of cell-associated HIV-1 RNA and DNA</measure>
    <time_frame>Baseline to Step 2-Week 22 (overall Study Week 34)</time_frame>
    <description>Changes in cell-associated HIV-1 RNA and DNA levels and assessment of the differences between the vaccine arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of DC-HIV vaccination on the levels of immune activation</measure>
    <time_frame>Baseline to Step 2-Week 22 (overall Study Week 34)</time_frame>
    <description>Changes in markers of cellular immune cell activation and assessment of the differences between the vaccine arms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of DC-HIV vaccination on the levels of systemic inflammation</measure>
    <time_frame>Baseline to Step 2-Week 22 (overall Study Week 34)</time_frame>
    <description>Changes in soluble markers of systemic inflammation and assessment of the differences between the vaccine arms</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>ARM A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>a1DC + inactivated whole autologous HIV vaccine given as six monthly doses of approximately 10e7 DC per dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>a1DC + conserved HIV peptides vaccine given as six monthly doses of approximately 10e7 DC per dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM C</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>a1DC + no antigen vaccine given as six monthly doses of approximately 10e7 DC per dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>pgDC + inactivated whole autologous HIV vaccine given as six monthly doses of approximately 10e7 DC per dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>pgDC + conserved HIV peptides vaccine given as six monthly doses of approximately 10e7 DC per dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM F</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>pgDC + no antigen vaccine given as six monthly doses of approximately 10e7 DC per dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>a1DC + inactivated whole autologous HIV</intervention_name>
    <description>Investigational vaccine composed of autologous dendritic cells matured with an optimized cocktail (a1DC) and loaded with autologous -inactivated HIV</description>
    <arm_group_label>ARM A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>a1DC + conserved HIV peptides</intervention_name>
    <description>Investigational vaccine composed of autologous dendritic cells matured with an optimized cocktail (a1DC) and loaded with a conserved HIV gag and pol peptide pool</description>
    <arm_group_label>ARM B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>a1DC + no antigen</intervention_name>
    <description>Control vaccine composed of autologous dendritic cells matured with an optimized cocktail (a1DC) but without an antigen</description>
    <arm_group_label>ARM C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pgDC + inactivated whole autologous HIV</intervention_name>
    <description>Investigational vaccine composed of autologous dendritic cells matured with a standard prostaglandin E2 cocktail (pgDC) and loaded with autologous -inactivated HIV</description>
    <arm_group_label>ARM D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pgDC + conserved HIV peptides</intervention_name>
    <description>Investigational vaccine composed of autologous dendritic cells matured with a standard prostaglandin E2 cocktail (pgDC) and loaded with a conserved HIV gag and pol peptide pool</description>
    <arm_group_label>ARM E</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pgDC + no antigen</intervention_name>
    <description>Control vaccine composed of autologous dendritic cells matured with a standard prostaglandin E2 cocktail (pgDC) but without an antigen</description>
    <arm_group_label>ARM F</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. HIV-1 infection, documented by any FDA-approved assay. NOTE: The term 'licensed'&#xD;
             refers to a US FDA approved kit, which is required for all investigational new drug&#xD;
             (IND) studies.&#xD;
&#xD;
          2. Receiving continuous ART for at least 24 months (defined as no interruptions longer&#xD;
             than 14 consecutive days) and with no changes in the components of the ART for at&#xD;
             least 8 weeks prior to study entry. A change in formulation (for example tenofovir&#xD;
             disaproxil fumarate to tenofovir alafenamide) will not be considered a change in ART.&#xD;
&#xD;
          3. Screening CD4+ cell count ≥350cells/mm3 obtained within 60 days prior to study entry&#xD;
             by any US laboratory that has a CLIA certification or its equivalent.&#xD;
&#xD;
          4. Plasma HIV-1 RNA levels &lt; 50 copies/ml for at least 24 months prior to study entry&#xD;
             using a FDA-approved assay performed by any laboratory that has a CLIA certification&#xD;
             or its equivalent. Participants must have at least one documented HIV-1 RNA less than&#xD;
             50 copies/ml &gt;24 months prior to study entry and at least one HIV-1 RNA less than 50&#xD;
             copies/ml within 12 months prior to study entry. All available HIV-1 RNA measurements&#xD;
             must be &lt; 50 copies/ml during the 24 months prior to study entry except as allowed by&#xD;
             the following note.&#xD;
&#xD;
             NOTE: Unconfirmed plasma HIV-1 RNA &gt; 50 copies/ml but &lt;200 copies/mL is allowed if&#xD;
             followed by a subsequent value &lt; 50 copies/ml.&#xD;
&#xD;
          5. Screening HIV-1 RNA levels &lt;50 copies/mL using a FDA-approved assay performed by any&#xD;
             laboratory that has a CLIA certification or its equivalent within 60 days prior to&#xD;
             entry.&#xD;
&#xD;
          6. Men and women age 18 to 70 years, inclusive.&#xD;
&#xD;
          7. The following laboratory values obtained within 60 days prior to entry:&#xD;
&#xD;
             Hemoglobin ≥10 g/dL Absolute neutrophil count (ANC) ≥1000/mm3 Platelet count&#xD;
             ≥100,000/mm3 Creatinine ≤ 1.5x upper limit of normal (ULN) Aspartate aminotransferase&#xD;
             (AST) and alanine aminotransferase (ALT) (SGPT) ≤2.5x ULN&#xD;
&#xD;
          8. Ability and willingness of participant to provide informed consent.&#xD;
&#xD;
          9. In the opinion of the investigator, no medical, mental health or other condition that&#xD;
             precludes participation.&#xD;
&#xD;
         10. For females of reproductive potential, negative serum or urine pregnancy test within&#xD;
             48 hours prior to entry by any US clinic or laboratory that has a CLIA certification&#xD;
             or its equivalent, or is using a point-of-care (POC)/ CLIA-waived test. Females of&#xD;
             reproductive potential include women who have not been post-menopausal for at least 12&#xD;
             consecutive months, (i.e., who have had menses within the preceding 12 months) or&#xD;
             women who have not undergone surgical sterilization (e.g. hysterectomy, bilateral&#xD;
             oophorectomy, bilateral tubal ligation or salpingectomy). Self- report is acceptable&#xD;
             documentation of menopause and sterilization.&#xD;
&#xD;
         11. All participants must agree not to participate in the conception process (eg, active&#xD;
             attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization),&#xD;
             and if participating in sexual activity that could lead to pregnancy, the&#xD;
             participant/partner must use at least one reliable form of contraception (condoms,&#xD;
             with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an&#xD;
             IUD; or hormone-based contraceptive), while receiving study treatment and for 12 weeks&#xD;
             following the final study vaccine.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Currently breastfeeding or pregnant&#xD;
&#xD;
          2. Known allergy/sensitivity or any hypersensitivity to components of study vaccine or&#xD;
             their formulation.&#xD;
&#xD;
          3. Known chronic inflammatory conditions such as, but not limited to, rheumatoid&#xD;
             arthritis, systemic lupus erythematosus, sarcoidosis, inflammatory bowel disease&#xD;
             (i.e., Crohn's disease or ulcerative colitis), chronic pancreatitis, or autoimmune&#xD;
             hepatitis, myositis, or myopathy.&#xD;
&#xD;
          4. 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;
          5. Serious medical illness that requires systemic treatment and/or hospitalization within&#xD;
             30 days prior to entry.&#xD;
&#xD;
          6. Use of systemic immunomodulators (eg, interleukins, interferons, cyclosporine),&#xD;
             systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to&#xD;
             study entry.&#xD;
&#xD;
             NOTE: Participants receiving stable physiologic doses of glucocorticoids, defined as&#xD;
             the equivalent of prednisone ≤10 mg/day, will not be excluded. Stable physiologic&#xD;
             glucocorticoid doses should not be discontinued for the duration of the study. In&#xD;
             addition, participants receiving inhaled or topical corticosteroids, or topical&#xD;
             imiquimod will not be excluded.&#xD;
&#xD;
          7. Participation on any HIV immunotherapy or therapeutic vaccination trials within 6&#xD;
             months prior to study entry.&#xD;
&#xD;
          8. History of positive HCV antibody with detectable HCV RNA in plasma within 48 weeks&#xD;
             prior to study entry.&#xD;
&#xD;
             NOTE: Persons with positive HCV Ab but negative plasma HCV RNA are allowed to&#xD;
             participate. Sites must document negative HCV RNA within 24 weeks of study entry.&#xD;
&#xD;
          9. History of positive HBsAg within 48 weeks prior to study entry.&#xD;
&#xD;
         10. Treatment for hepatitis C within 6 months prior to study entry.&#xD;
&#xD;
         11. Initiation of ART during acute HIV-1 infection (as determined by the site investigator&#xD;
             by history and/or available medical records).&#xD;
&#xD;
         12. Lack of adequate venous access that, in the opinion of the investigator, would&#xD;
             interfere with study requirements.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sharon Riddler, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bernard Macatangay, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John Mellors, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jamie Fullerton, MPPM</last_name>
    <phone>412-383-1675</phone>
    <email>idelucaj@upmc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sherri Karas, MEd</last_name>
    <phone>412-383-1313</phone>
    <email>schesx@upmc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>AIDS Clinical Trials Unit/The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lindsay Summers, MPH</last_name>
      <phone>614-293-8529</phone>
      <email>Lindsay.Summers@osumc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Keiichi Koshino, BSN, RN</last_name>
      <phone>614-293-4855</phone>
      <email>Keiichi.Koshino@osumc.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Susan Koletar, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Carlos Malvestutto, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>HIV/AIDS Clinical Research Unit / University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jamie Fullerton</last_name>
      <phone>412-383-1675</phone>
      <email>idelucaj@upmc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Sherri Karas</last_name>
      <phone>412-383-1313</phone>
      <email>schesx@upmc.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Sharon Riddler, MD, MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bernard Macatangay, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kaleab Abebe, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ken Ho, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Deborah McMahon, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Madhu Choudhary, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Joshua Cyktor, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>John Mellors, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yen-Michael Hsu, MD, PhD, FCAP</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>May 2, 2023</last_update_submitted>
  <last_update_submitted_qc>May 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Sharon Riddler</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>dendritic cell</keyword>
  <keyword>vaccine</keyword>
  <keyword>immunogenicity</keyword>
  <keyword>HIV</keyword>
  <keyword>vaccination</keyword>
  <keyword>immune system</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
  </condition_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/NCT03758625
org study id: DAIDS-ES 38541
secondary id: U01AI131285
nct id: NCT03758625
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will be done in people living with HIV to see if an investigational vaccine made
      from a person's own white blood cells is safe and tolerated. This study will also look at the
      body's immune response to the vaccine and evaluate four different methods of making the
      vaccine to see which method may result in better immune responses.
Despite the availability of strong medicines for HIV infection, there is no cure for the
      infection. The current anti-HIV drugs, used in combination, are effective in slowing the
      growth of the virus and delaying the progression of the infection. There is increasing
      information to suggest that a vigorous immune response (a strong response of the body to
      fight infection) to HIV may also result in improved control of the HIV infection. Such strong
      immune responses are found in a small number of HIV-infected individuals, but not in the
      majority.

      Dendritic cells, or DCs, are a type of white blood cell that works together with other immune
      cells to fight infection. The DCs role is to bring substances foreign to the body, such as
      viruses including HIV or cancer cell proteins, to the body's immune system. Large numbers of
      DCs can be made from blood samples and administered back to the same person as an
      individualized vaccine. Vaccines made from DCs have been studied in HIV and numerous types of
      cancer.

      The vaccines will be created by two different laboratory methods, standard or improved, using
      an individual's own DCs and either an individual's own inactive HIV that has been killed with
      heat or manmade HIV proteins called peptides. The peptides have not been studied for this use
      in humans, and these vaccines are not approved by the Food and Drug Administration (FDA) to
      prevent or treat HIV infection.

      This study will be done in two steps. During Step 1 (Entry-Week 12), participants will have 4
      study visits for tests, procedures and exams. At Week 4, participants will be randomized by
      chance into one of six study groups, like rolling dice. Four of the study groups will receive
      a DC-HIV vaccine while two of the study groups will receive a "control" vaccine with only
      DCs. Participants will have a 4:1 chance of receiving a DC-HIV study vaccine.

        -  Group 1: enhanced DC-HIV vaccine with inactive HIV

        -  Group 2: enhanced DC-HIV vaccine with HIV peptides

        -  Group 3: enhanced DCs only (control)

        -  Group 4: classic DC-HIV vaccine with inactive HIV

        -  Group 5: classic DC-HIV vaccine with HIV peptides

        -  Group 6: classic DCs only (control)

      Each participant will receive 6 study vaccinations at 4-week intervals beginning at Week 12.
      Researchers will compare the results from participants who get the active study vaccines with
      results from participants who get the control vaccines. Participants, the researchers and the
      clinic staff will not know which vaccine participants are getting.

      In Step 2 (Weeks 12 - 80), participants will have 18 study visits to receive the 6 study
      vaccinations and for tests to monitor health and safety and to see how the study vaccine
      affects the immune system and the virus.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, double-blind, multi-arm
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety and tolerability of six immunizations (10e7 DCs per dose) of DC-whole virus and DC-peptide vaccines in HIV-1 infected participants on effective ART
time frame: Step 2-Week 0 (overall Study Week 12) to overall Study Week 80
description: Occurrence of Grade ≥ 3 AE including signs/symptoms, lab toxicities, and/or clinical events that are possibly, probably, or definitely related to study treatment (as judged by the site investigator, blinded to treatment arm) at any time from the initial dose of DC vaccine product to end of study follow-up.
measure: Efficacy of six immunizations (10e7 DCs per dose) of DC-whole virus and DC-peptide vaccines in HIV-1 infected participants on effective ART
time frame: Baseline to Step 2-Week 22 (overall Study Week 34)
description: Change in HIV-specific CD8 and T-cell immune response as measured by ELISPOT between the vaccine arms.
measure: Relative efficacy of the DC-HIV vaccines in priming HIV-specific-CD8+ T cells
time frame: Baseline to Step 2-Week 22 (overall Study Week 34)
description: Change in the ability of the DC-HIV vaccines to inhibit autologous HIV in an ex vivo virus inhibition assay.
measure: Effect of DC-HIV vaccination on the level of persistent viremia in plasma
time frame: Baseline to Step 2-Week 22 (overall Study Week 34)
description: Change in plasma HIV-1 RNA viral load as measured by single copy assay (SCA)
measure: Effect of DC-HIV vaccination on HIV specific CD8 T-cell polyfunctional responses
time frame: Baseline to Step 2-Week 22 (overall Study Week 34)
description: Change in HIV specific CD8 T-cell polyfunctional responses as measured by intracellular cytokine staining using flow cytometry.
measure: Assess the impact of DC-HIV vaccination on levels of cell-associated HIV-1 RNA and DNA
time frame: Baseline to Step 2-Week 22 (overall Study Week 34)
description: Changes in cell-associated HIV-1 RNA and DNA levels and assessment of the differences between the vaccine arms
measure: Effect of DC-HIV vaccination on the levels of immune activation
time frame: Baseline to Step 2-Week 22 (overall Study Week 34)
description: Changes in markers of cellular immune cell activation and assessment of the differences between the vaccine arms
measure: Effect of DC-HIV vaccination on the levels of systemic inflammation
time frame: Baseline to Step 2-Week 22 (overall Study Week 34)
description: Changes in soluble markers of systemic inflammation and assessment of the differences between the vaccine arms
arm group label: ARM A
arm group type: Experimental
description: a1DC + inactivated whole autologous HIV vaccine given as six monthly doses of approximately 10e7 DC per dose
arm group label: ARM B
arm group type: Experimental
description: a1DC + conserved HIV peptides vaccine given as six monthly doses of approximately 10e7 DC per dose
arm group label: ARM C
arm group type: Active Comparator
description: a1DC + no antigen vaccine given as six monthly doses of approximately 10e7 DC per dose
arm group label: ARM D
arm group type: Experimental
description: pgDC + inactivated whole autologous HIV vaccine given as six monthly doses of approximately 10e7 DC per dose
arm group label: ARM E
arm group type: Experimental
description: pgDC + conserved HIV peptides vaccine given as six monthly doses of approximately 10e7 DC per dose
arm group label: ARM F
arm group type: Active Comparator
description: pgDC + no antigen vaccine given as six monthly doses of approximately 10e7 DC per dose
intervention type: Biological
intervention name: a1DC + inactivated whole autologous HIV
description: Investigational vaccine composed of autologous dendritic cells matured with an optimized cocktail (a1DC) and loaded with autologous -inactivated HIV
arm group label: ARM A
intervention type: Biological
intervention name: a1DC + conserved HIV peptides
description: Investigational vaccine composed of autologous dendritic cells matured with an optimized cocktail (a1DC) and loaded with a conserved HIV gag and pol peptide pool
arm group label: ARM B
intervention type: Biological
intervention name: a1DC + no antigen
description: Control vaccine composed of autologous dendritic cells matured with an optimized cocktail (a1DC) but without an antigen
arm group label: ARM C
intervention type: Biological
intervention name: pgDC + inactivated whole autologous HIV
description: Investigational vaccine composed of autologous dendritic cells matured with a standard prostaglandin E2 cocktail (pgDC) and loaded with autologous -inactivated HIV
arm group label: ARM D
intervention type: Biological
intervention name: pgDC + conserved HIV peptides
description: Investigational vaccine composed of autologous dendritic cells matured with a standard prostaglandin E2 cocktail (pgDC) and loaded with a conserved HIV gag and pol peptide pool
arm group label: ARM E
intervention type: Biological
intervention name: pgDC + no antigen
description: Control vaccine composed of autologous dendritic cells matured with a standard prostaglandin E2 cocktail (pgDC) but without an antigen
arm group label: ARM F
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Sharon Riddler, MD
role: Study Chair
affiliation: University of Pittsburgh
last name: Bernard Macatangay, MD
role: Study Chair
affiliation: University of Pittsburgh
last name: John Mellors, MD
role: Study Chair
affiliation: University of Pittsburgh
last name: Jamie Fullerton, MPPM
phone: 412-383-1675
email: idelucaj@upmc.edu
last name: Sherri Karas, MEd
phone: 412-383-1313
email: schesx@upmc.edu
facility: 
status: Recruiting
contact: 
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country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Sharon Riddler
investigator title: Professor
mesh term: HIV Infections