<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/NCT01712425</url>
  </required_header>
  <id_info>
    <org_study_id>ChAd-MVA.HIVconsv-BCN01</org_study_id>
    <secondary_id>2011-000846-39</secondary_id>
    <nct_id>NCT01712425</nct_id>
  </id_info>
  <brief_title>Safety and Immunogenicity of ChAdV63.HIVconsv and MVA.HIVconsv Candidate HIV-1 Vaccines in Recently HIV-1 Infected Individuals</brief_title>
  <official_title>Safety and Immunogenicity of ChAdV63.HIVconsv and MVA.HIVconsv Candidate HIV-1 Vaccines in Recently HIV-1 Infected Individuals With Early Viral Suppression After Initiation of Antiretroviral Therapy (HAART)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IrsiCaixa</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Clinic of Barcelona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>HIVACAT</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>IrsiCaixa</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The HIVconsv gene was constructed by assembling the 14 most conserved regions of the HIV-1&#xD;
      proteome into one chimaeric protein. This gene has been inserted into 2 leading&#xD;
      non-replicating vaccine vectors: an attenuated chimpanzee adenovirus serotype 63 (ChAdV63)&#xD;
      and a modified vaccinia virus Ankara (MVA) to construct the ChAdV63.HIVconsv and MVA.HIVconsv&#xD;
      HIV-1 candidate vaccines. The present study is named ChAd-MVA.HIVconsv-BCN01 and it is a&#xD;
      phase I, multicenter primary/booster therapeutic vaccination study to evaluate the safety and&#xD;
      immunogenicity of ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly&#xD;
      according to a 0-8 weeks or a 0-24 weeks schedule to recently HIV-1 infected individuals with&#xD;
      early viral suppression 6 months after initiation of Tenofovir/Emtricitabine plus&#xD;
      Raltegravir.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is a Phase I, multicenter primary/booster therapeutic vaccination study to evaluate the&#xD;
      safety and immunogenicity of ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered&#xD;
      intramuscularly according to a 0-8 weeks or a 0-24 weeks schedule to recently HIV-1 infected&#xD;
      individuals with early viral suppression 6 months after initiation of Tenofovir/Emtricitabine&#xD;
      plus Raltegravir.&#xD;
&#xD;
      24 patients who meet all eligibility criteria will be enrolled, first 10 individuals will be&#xD;
      assigned in the 0-24 week prime/boost regimen (ARM A). The next 10 volunteers will be&#xD;
      assigned in the 0-8 week prime/boost regimen (ARM B).Four additional volunteers will be&#xD;
      included as 'back-up' and assigned 2 in ARM A and 2 in ARM B to cover a possible 10% of&#xD;
      patients who drop-off during the follow-up. Purpose of staging of 2 study arms is just to&#xD;
      shorten overall study duration (from screening of first volunteer to 6 months after last&#xD;
      immunisation of last volunteer).&#xD;
&#xD;
      Lastly, 24 patients who also meet all eligibility criteria will be enrolled as controls, will&#xD;
      also initiate promptly antiretroviral treatment with Tenofovir/Emtricitabine plus Raltegravir&#xD;
      but will not receive the investigational vaccines. Control patients will consecutively be&#xD;
      assigned to the 0-24w control arm (ARM C 'long control') or 0-8w control arm (ARM D 'short&#xD;
      control') until 12 patients per arm are reached. The purpose of the control arms is to have a&#xD;
      study population to compare the viral reservoir decay kinetics in the absence of vaccination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">October 2015</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>Grade 3 or 4 local reaction</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>The proportion of volunteers who develop a grade 3 or 4 local reaction</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Grade 3 or 4 systemic reaction</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>The proportion of volunteers who develop a grade 3 or 4 systemic reaction</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serious adverse event, including laboratory abnormalities.</measure>
    <time_frame>Up to 24 weeks</time_frame>
    <description>The proportion of volunteers who develop a serious adverse event, including laboratory abnormalities.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>HIV-specific CD8+ T cell responses</measure>
    <time_frame>Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.</time_frame>
    <description>Magnitude and phenotype of HIV-1-specific CD8+ T cell populations , in selected volunteers with appropriate human leukocyte antigen (HLA) class I alleles will be assessed according to first immunogenicity results.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Magnitude and phenotype of HIV-1-specific CD8+ T cell populations</measure>
    <time_frame>Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.</time_frame>
    <description>Magnitude and phenotype of HIV-1-specific CD8+ T cell populations , in selected volunteers with appropriate HLA class I alleles will be assessed according to first immunogenicity results.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lymphocyte activation marker HLADR+CD38+</measure>
    <time_frame>Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.</time_frame>
    <description>Lymphocyte activation marker HLA-DR+CD38+ will be assessed at selected timepoints according to first immunogenicity results</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrated and unintegrated viral HIV-1 DNA in PBMCs.</measure>
    <time_frame>Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.</time_frame>
    <description>Quantification of integrated and unintegrated viral HIV-1 DNA in peripheral blood mononucleated cells (PBMC)s will be determined at selected timepoints according to first immunogenicity results</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral suppressive capacity of CD8+ T cells in vitro</measure>
    <time_frame>Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.</time_frame>
    <description>Viral suppressive capacity of CD8+ T cells in vitro using a flow cytometric assay at selected timepoints according to first immunogenicity results</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>0-24 week prime/boost regimen (ARM A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly, 0-24 week prime/boost regimen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0-8 week prime/boost regimen (ARM B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly, 0-8 week prime/boost regimen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm A control (ARM C)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. Follow-up as in Arm A.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B control (ARM D)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. Follow-up as in Arm B.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>0-24 week prime/boost regimen</intervention_name>
    <description>ChAdV63.HIVcons (5x10^10 vp) and MVA.HIVconsv (2x10^8 pfu) HIV-1 vaccines, delivered intramuscularly</description>
    <arm_group_label>0-24 week prime/boost regimen (ARM A)</arm_group_label>
    <other_name>ARM A</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>0-8 week prime/boost regimen</intervention_name>
    <description>ChAdV63.HIVcons (5x10^10 vp) and MVA.HIVconsv (2x10^8 pfu) HIV-1 vaccines, delivered intramuscularly</description>
    <arm_group_label>0-8 week prime/boost regimen (ARM B)</arm_group_label>
    <other_name>ARM B</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, aged 18-60 years&#xD;
&#xD;
          2. Confirmed HIV-1 seropositive documented in the past 6 months (by acute antiretroviral&#xD;
             syndrome, p24 antigenemia and/or ELISA seroconversion)&#xD;
&#xD;
          3. Willing and able to give written informed consent for participation in the study&#xD;
&#xD;
          4. Willing and able to adhere to an effective HAART regimen for the duration of the study&#xD;
&#xD;
          5. Cluster of differentiation 4 (CD4)+ T cell count &gt; 350 cells/ml at screening and at&#xD;
             the preceding clinic visit&#xD;
&#xD;
          6. No new AIDS-defining diagnosis or progression of HIV-related disease.&#xD;
&#xD;
          7. Haematological and biochemical laboratory parameters as follows: Haemoglobin &gt; 10g/dl,&#xD;
             Platelets &gt; 100.000/dl, alanine aminotransferase (ALT) ≤ 2.5 x ULN, Creatinine ≤ 1.3 x&#xD;
             upper limit of normal (ULN)&#xD;
&#xD;
          8. Serology: negative for hepatitis B surface antigen OR HbsAg positive with Hepatitis B&#xD;
             Virus (HBV)-DNA &lt; 1000 copies/ml; negative for hepatitis C antibodies OR confirmed&#xD;
             clearance of Hepatitis C Virus (HCV) infection (spontaneous or following treatment);&#xD;
             negative syphilis serology or documented adequate treatment of syphilis if positive&#xD;
             enzimeimmunoassay (EIA) Immonoglobulin G (IgG) or Treponema pallidum hemagglutination&#xD;
             assay (TPHA)&#xD;
&#xD;
          9. Available for follow up for duration of study (screening + 72 weeks) and willing to&#xD;
             comply with the protocol requirements&#xD;
&#xD;
         10. Women of child-bearing age must not be pregnant, not be planning a pregnancy or&#xD;
             breast-feeding. Sexually active women must be willing to use an approved method of&#xD;
             contraception from screening until 4 months after the second immunisation. Sexually&#xD;
             active men in heterosexual relationships must be willing to use an approved method of&#xD;
             contraception with their partners from screening until 4 months after the second&#xD;
             immunisation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Confirmed HIV-2 seropositive&#xD;
&#xD;
          2. Positive pregnancy test&#xD;
&#xD;
          3. Presence of Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTI) mutation in the&#xD;
             screening genotype&#xD;
&#xD;
          4. Participation in another clinical trial within 12 weeks of study entry&#xD;
&#xD;
          5. History of autoimmune disease other than HIV-related auto-immune disease.&#xD;
&#xD;
          6. History or clinical manifestations of any physical or psychiatric disorder which could&#xD;
             impair the subject's ability to complete the study&#xD;
&#xD;
          7. History of anaphylaxis or severe adverse reaction to vaccines&#xD;
&#xD;
          8. Previous immunisation with any experimental immunogens&#xD;
&#xD;
          9. Receipt of blood products within 6 months of study entry&#xD;
&#xD;
         10. Treatment for cancer or lymphoproliferative disease within 1 year of study entry&#xD;
&#xD;
         11. Receipt of vaccines other than Hepatitis B vaccine within 2 weeks of study entry or&#xD;
             planned receipt within 2 weeks of vaccination&#xD;
&#xD;
         12. Any other prior therapy which, in the opinion of the investigators, would make the&#xD;
             individual unsuitable for the study or influence the results of the study&#xD;
&#xD;
         13. Current or recent use (within last 3 months) of interferon or systemic corticosteroids&#xD;
             or other immunosuppressive agents&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christian Brander, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Institut de Recerca de la Sida IrsiCaixa-HIVACAT</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Beatriz Mothe, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut de Recerca de la Sida IrsiCaixa-HIVACAT</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Josep Maria Miró, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Clínic i Provincial de Barcelona, HIVACAT</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Germans Trias i Pujol Hospital</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinic de Barcelona Hospital</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 23, 2012</study_first_posted>
  <last_update_submitted>April 28, 2016</last_update_submitted>
  <last_update_submitted_qc>April 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>vaccine</keyword>
  <keyword>recently HIV-1 infected individuals</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/NCT01712425
org study id: ChAd-MVA.HIVconsv-BCN01
secondary id: 2011-000846-39
nct id: NCT01712425
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The HIVconsv gene was constructed by assembling the 14 most conserved regions of the HIV-1
      proteome into one chimaeric protein. This gene has been inserted into 2 leading
      non-replicating vaccine vectors: an attenuated chimpanzee adenovirus serotype 63 (ChAdV63)
      and a modified vaccinia virus Ankara (MVA) to construct the ChAdV63.HIVconsv and MVA.HIVconsv
      HIV-1 candidate vaccines. The present study is named ChAd-MVA.HIVconsv-BCN01 and it is a
      phase I, multicenter primary/booster therapeutic vaccination study to evaluate the safety and
      immunogenicity of ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly
      according to a 0-8 weeks or a 0-24 weeks schedule to recently HIV-1 infected individuals with
      early viral suppression 6 months after initiation of Tenofovir/Emtricitabine plus
      Raltegravir.
It is a Phase I, multicenter primary/booster therapeutic vaccination study to evaluate the
      safety and immunogenicity of ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered
      intramuscularly according to a 0-8 weeks or a 0-24 weeks schedule to recently HIV-1 infected
      individuals with early viral suppression 6 months after initiation of Tenofovir/Emtricitabine
      plus Raltegravir.

      24 patients who meet all eligibility criteria will be enrolled, first 10 individuals will be
      assigned in the 0-24 week prime/boost regimen (ARM A). The next 10 volunteers will be
      assigned in the 0-8 week prime/boost regimen (ARM B).Four additional volunteers will be
      included as 'back-up' and assigned 2 in ARM A and 2 in ARM B to cover a possible 10% of
      patients who drop-off during the follow-up. Purpose of staging of 2 study arms is just to
      shorten overall study duration (from screening of first volunteer to 6 months after last
      immunisation of last volunteer).

      Lastly, 24 patients who also meet all eligibility criteria will be enrolled as controls, will
      also initiate promptly antiretroviral treatment with Tenofovir/Emtricitabine plus Raltegravir
      but will not receive the investigational vaccines. Control patients will consecutively be
      assigned to the 0-24w control arm (ARM C 'long control') or 0-8w control arm (ARM D 'short
      control') until 12 patients per arm are reached. The purpose of the control arms is to have a
      study population to compare the viral reservoir decay kinetics in the absence of vaccination.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Grade 3 or 4 local reaction
time frame: Up to 24 weeks
description: The proportion of volunteers who develop a grade 3 or 4 local reaction
measure: Grade 3 or 4 systemic reaction
time frame: Up to 24 weeks
description: The proportion of volunteers who develop a grade 3 or 4 systemic reaction
measure: Serious adverse event, including laboratory abnormalities.
time frame: Up to 24 weeks
description: The proportion of volunteers who develop a serious adverse event, including laboratory abnormalities.
measure: HIV-specific CD8+ T cell responses
time frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.
description: Magnitude and phenotype of HIV-1-specific CD8+ T cell populations , in selected volunteers with appropriate human leukocyte antigen (HLA) class I alleles will be assessed according to first immunogenicity results.
measure: Magnitude and phenotype of HIV-1-specific CD8+ T cell populations
time frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.
description: Magnitude and phenotype of HIV-1-specific CD8+ T cell populations , in selected volunteers with appropriate HLA class I alleles will be assessed according to first immunogenicity results.
measure: Lymphocyte activation marker HLADR+CD38+
time frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.
description: Lymphocyte activation marker HLA-DR+CD38+ will be assessed at selected timepoints according to first immunogenicity results
measure: Integrated and unintegrated viral HIV-1 DNA in PBMCs.
time frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.
description: Quantification of integrated and unintegrated viral HIV-1 DNA in peripheral blood mononucleated cells (PBMC)s will be determined at selected timepoints according to first immunogenicity results
measure: Viral suppressive capacity of CD8+ T cells in vitro
time frame: Change from baseline (pre-HAART) and w24, to +1week, +4weeks, +12weeks and +24weeks post vaccination.
description: Viral suppressive capacity of CD8+ T cells in vitro using a flow cytometric assay at selected timepoints according to first immunogenicity results
arm group label: 0-24 week prime/boost regimen (ARM A)
arm group type: Experimental
description: Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly, 0-24 week prime/boost regimen
arm group label: 0-8 week prime/boost regimen (ARM B)
arm group type: Experimental
description: Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. ChAdV63.HIVcons and MVA.HIVconsv HIV-1 vaccines, delivered intramuscularly, 0-8 week prime/boost regimen
arm group label: Arm A control (ARM C)
arm group type: No Intervention
description: Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. Follow-up as in Arm A.
arm group label: Arm B control (ARM D)
arm group type: No Intervention
description: Start antiretroviral treatment raltegravir + tenofovir/emtricitabine. Follow-up as in Arm B.
intervention type: Biological
intervention name: 0-24 week prime/boost regimen
description: ChAdV63.HIVcons (5x10^10 vp) and MVA.HIVconsv (2x10^8 pfu) HIV-1 vaccines, delivered intramuscularly
arm group label: 0-24 week prime/boost regimen (ARM A)
other name: ARM A
intervention type: Biological
intervention name: 0-8 week prime/boost regimen
description: ChAdV63.HIVcons (5x10^10 vp) and MVA.HIVconsv (2x10^8 pfu) HIV-1 vaccines, delivered intramuscularly
arm group label: 0-8 week prime/boost regimen (ARM B)
other name: ARM B
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Christian Brander, PhD
role: Study Chair
affiliation: Institut de Recerca de la Sida IrsiCaixa-HIVACAT
last name: Beatriz Mothe, MD,PhD
role: Principal Investigator
affiliation: Institut de Recerca de la Sida IrsiCaixa-HIVACAT
last name: Josep Maria Miró, MD,PhD
role: Principal Investigator
affiliation: Hospital Clínic i Provincial de Barcelona, HIVACAT
facility: 
facility: 
country: Spain
responsible party type: Sponsor