<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/NCT04444674</url>
  </required_header>
  <id_info>
    <org_study_id>ChAdOx1 nCoV-19_ZA_phI/II v4.1</org_study_id>
    <nct_id>NCT04444674</nct_id>
  </id_info>
  <brief_title>COVID-19 Vaccine (ChAdOx1 nCoV-19) Trial in South African Adults With and Without HIV-infection</brief_title>
  <official_title>An Adaptive Phase I/II Randomized Placebo-controlled Trial to Determine Safety, Immunogenicity and Efficacy of Non-replicating ChAdOx1 SARS-CoV-2 Vaccine in South African Adults Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical Research Council, South Africa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bill and Melinda Gates Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wits Health Consortium (Pty) Ltd</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Witwatersrand, South Africa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oxford</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Phase I/II, double-blinded, placebo-controlled, individually randomized trial to assess&#xD;
      safety, immunogenicity and efficacy of the candidate Coronavirus disease (COVID-19) vaccine&#xD;
      ChAdOx1 nCoV-19 in adults aged 18-65 years living with and without HIV in South Africa. The&#xD;
      vaccine or placebo will be administered via an intramuscular injection into the deltoid&#xD;
      muscle of the non-dominant arm.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 2070 participants will be enrolled into the trial; 1970 HIV-uninfected and 100&#xD;
      people living with HIV. There will be 4 trial groups, group 1 (n=50; intensive safety &amp;&#xD;
      immunogenicity cohort, HIV negative), group 2a (n=250; safety, intense immunogenicity &amp;&#xD;
      efficacy), group 2b (n=1650; safety, immunogenicity &amp; vaccine efficacy) and group 3 (n=100,&#xD;
      intensive safety &amp; immunogenicity cohort, HIV positive).&#xD;
&#xD;
      Participants will be followed up for 12 months after enrollment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">June 24, 2020</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Four groups will be enrolled to receive either one or two doses of investigational vaccine or placebo. Follow up intensity and blood draws differ between groups</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blinded, placebo controlled. Pharmacist and vaccine administrators will be unblinded only. DSMB will be unblinded if required to assess safety signal</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Assess the incidence of adverse events (intervention-related and intervention-unrelated) in HIV-negative adults aged 18-65 year receiving candidate ChAdOx1 nCoV-19 vaccine or placebo (safety)</measure>
    <time_frame>Up to 12 months post enrollment</time_frame>
    <description>Number of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, and unsolicited adverse events for 28 days following vaccination.&#xD;
Assess occurrence of disease enhancement episodes and serious adverse events in year post vaccination</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determine if there is a reduction of severe and non-severe COVID-19 disease in HIV-negative adults who receive candidate vaccine ChAdOx1 nCoV-19 compared to placebo recipients (efficacy)</measure>
    <time_frame>Up to 12 months post enrollment</time_frame>
    <description>Virologically-confirmed COVID-19 clinical disease will be defined as an acute respiratory illness that is clinically consistent with COVID-19 disease, AND SARS-CoV-2 RT-PCR positivity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess the incidence of adverse events (intervention-related and intervention-unrelated) in HIV-positive adults aged 18-65 year receiving candidate ChAdOx1 nCoV-19 vaccine or placebo (safety)</measure>
    <time_frame>Up to 12 months post enrollment</time_frame>
    <description>Number of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, and unsolicited adverse events for 28 days following vaccination.&#xD;
Assess occurrence of disease enhancement episodes and serious adverse events in year post vaccination</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in people living with HIV (immunogenicity)</measure>
    <time_frame>Up to 12 months post enrollment</time_frame>
    <description>Assessing the Interferon-gamma (IFN-γ) enzyme- linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein and Th1 and Th2 cytokine response profile at 3-4 days after vaccination</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess humoral immunogenicity of ChAdOx1 nCoV-19 in people living with HIV</measure>
    <time_frame>Up to 12 months post enrollment</time_frame>
    <description>Assessing Enzyme-linked immunosorbent assay (ELISA) or fluorescence based micro-bead immunosorbent assay on luminex platform to quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) and Virus neutralising antibody (NAb) assays against live and/or pseudotyped SARS-CoV-2 virus</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess humoral Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)</measure>
    <time_frame>Up to 12 months post enrollment</time_frame>
    <description>Assessing Enzyme-linked immunosorbent assay (ELISA) or fluorescence based micro-bead immunosorbent assay on luminex platform to quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) and Virus neutralising antibody (NAb) assays against live and/or pseudotyped SARS-CoV-2 virus</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)</measure>
    <time_frame>Up to 12 months post enrollment</time_frame>
    <description>Assessing the Interferon-gamma (IFN-γ) enzyme- linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein and Th1 and Th2 cytokine response profile at 3-4 days after vaccination</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Assess Fc effector functionality in participants who receive ChAdOx1 nCoV-19 vaccine or placebo</measure>
    <time_frame>Up to 12 months post enrollment</time_frame>
    <description>Cellular Fc effector functionality assays to measure the ability of vaccine elicited antibodies to mediate cellular cytotoxicity, complement deposition, and phagocytosis.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess B cell responses to SARS-CoV-2 spike trimer and/or the receptor binding domain in participants who receive ChAdOx1 nCoV-19 vaccine or placebo</measure>
    <time_frame>Up to 12 months post enrollment</time_frame>
    <description>Flow cytometric sorting of plasmablasts and memory B cells to using spike and receptor binding domain &quot;baits&quot; to isolate SARS-CoV-2 specific B cells, sequence their immunoglobulin genes and define their epitope specificity.</description>
  </other_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">2130</enrollment>
  <condition>Coronavirus</condition>
  <arm_group>
    <arm_group_label>Group 1- IP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants (HIV-negative) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1- placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants (HIV-negative) will receive two doses of Normal saline (0.9%) in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2a- IP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants (HIV-negative) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 7 (1-dose) or 9 (2 doses) routine visits over a 12 month period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2a- placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants (HIV-negative) will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 7 (1-dose) or 9 (2 doses) routine visits over a 12 month period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2b- IP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 5 (1-dose) or 6 (2 doses) routine visits over a 12 month period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2b- placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 5 (1-dose) or 6 (2 doses) routine visits over a 12 month period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3- IP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants (HIV-positive) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3- placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants (HIV-positive) will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ChAdOx1 nCoV-19</intervention_name>
    <description>Dose of 5-7.5x10^10vp of ChAdOx1 nCoV-19</description>
    <arm_group_label>Group 1- IP</arm_group_label>
    <arm_group_label>Group 2a- IP</arm_group_label>
    <arm_group_label>Group 2b- IP</arm_group_label>
    <arm_group_label>Group 3- IP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Normal saline 0.9%</intervention_name>
    <description>Normal saline 0.9% as placebo</description>
    <arm_group_label>Group 1- placebo</arm_group_label>
    <arm_group_label>Group 2a- placebo</arm_group_label>
    <arm_group_label>Group 2b- placebo</arm_group_label>
    <arm_group_label>Group 3- placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adults aged 18-65 years.&#xD;
&#xD;
          -  Documented result of not being infected with HIV (including screening by a rapid HIV&#xD;
             antibody test) within two weeks of randomization into the study for Group-1 and&#xD;
             Group-2 participants only.&#xD;
&#xD;
          -  Able and willing (in the Investigator's opinion) to comply with all study&#xD;
             requirements.&#xD;
&#xD;
          -  Willing to allow investigators review available medical records, and review all&#xD;
             medical and laboratory records if participant is admitted to hospital with respiratory&#xD;
             tract infection suspected or confirmed to be COVID-19.&#xD;
&#xD;
          -  For females only, willingness to practice continuous effective contraception (see&#xD;
             below) during the study and a negative pregnancy test on the day(s) of screening&#xD;
             (within 14 days of randomization) or vaccination.&#xD;
&#xD;
          -  For Group-3 only (i.e. HIV-infected), need to have been on anti-retroviral treatment&#xD;
             for at least three months and HIV-1 viral load is &lt;1,000 copies/ml within two weeks of&#xD;
             randomization.&#xD;
&#xD;
          -  Agreement to refrain from blood donation during the course of the study.&#xD;
&#xD;
          -  Provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Planned receipt of any vaccine other (licensed or investigational) than the study&#xD;
             intervention within 30 days before and after each study vaccination.&#xD;
&#xD;
          -  Use of any unproven registered and unregistered treatments for COVID-19.&#xD;
&#xD;
          -  Prior receipt of an investigational or licensed vaccine likely to impact on&#xD;
             interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus&#xD;
             vaccines).&#xD;
&#xD;
          -  Administration of immunoglobulins and/ or any blood products within the three months&#xD;
             preceding the planned administration of the vaccine candidate.&#xD;
&#xD;
          -  HBSAg positivity on the screening sample.&#xD;
&#xD;
          -  Grade 2 or higher level of abnormality for FBC, U&amp;E or LFT based on DAIDS Grading&#xD;
             Criteria (Version 2.1, July 2017)&#xD;
&#xD;
          -  History of allergic disease or reactions likely to be exacerbated by any component of&#xD;
             the ChAdOx1 nCoV-19 vaccine.&#xD;
&#xD;
          -  Any history of hereditary angioedema or idiopathic angioedema.&#xD;
&#xD;
          -  Any history of anaphylaxis in relation to vaccination.&#xD;
&#xD;
          -  Pregnancy, lactation or willingness/intention to become pregnant during the study.&#xD;
&#xD;
          -  History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in&#xD;
             situ).&#xD;
&#xD;
          -  History of serious psychiatric condition likely to affect participation in the study.&#xD;
&#xD;
          -  Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or&#xD;
             prior history of significant bleeding or bruising following IM injections or&#xD;
             venipuncture.&#xD;
&#xD;
          -  Any other serious chronic illness requiring hospital specialist supervision.&#xD;
&#xD;
          -  Chronic respiratory diseases, including asthma&#xD;
&#xD;
          -  Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal&#xD;
             disease, endocrine disorder and neurological illness&#xD;
&#xD;
          -  Seriously overweight (BMI ≥ 40 Kg/m2)&#xD;
&#xD;
          -  Suspected or known current alcohol abuse as defined by an alcohol intake of greater&#xD;
             than 42 units every week.&#xD;
&#xD;
          -  Suspected or known injecting drug abuse in the 5 years preceding enrollment.&#xD;
&#xD;
          -  Any clinically significant abnormal finding on screening urinalysis.&#xD;
&#xD;
          -  Any other significant disease, disorder or finding which may significantly increase&#xD;
             the risk to the participant because of participation in the study, affect the ability&#xD;
             of the participant to participate in the study or impair interpretation of the study&#xD;
             data.&#xD;
&#xD;
          -  History of laboratory confirmed COVID-19 illness or known contact with a person that&#xD;
             was infected with SARS-COV-2.&#xD;
&#xD;
          -  New onset of fever or a cough or shortness of breath in the 30 days preceding&#xD;
             screening and/or enrollment&#xD;
&#xD;
          -  Travel history to any other country with widespread epidemic since January 2020&#xD;
&#xD;
          -  In addition to above, Group 1 &amp; 2 participants need to fulfill the following exclusion&#xD;
             criteria: Any confirmed or suspected immunosuppressive or immunodeficient state,&#xD;
             including HIV infection; asplenia; recurrent severe infections and chronic use (more&#xD;
             than 14 days) immunosuppressant medication within the past 6 months ( topical steroids&#xD;
             are allowed).&#xD;
&#xD;
          -  Any confirmed or suspected immunosuppressive or immunodeficient state (except HIV&#xD;
             infection for Group-3), asplenia, recurrent severe infections and chronic use (more&#xD;
             than 14 days) immunosuppressant medication within the past 6 months (topical steroids&#xD;
             are allowed).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shabir A Madhi, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Witwatersrand, South Africa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PHRU Kliptown</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>1811</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Soweto Clinical Trials Centre</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>1818</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wits RHI Shandukani Research Centre</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2001</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Setshaba Research Centre (SRC)</name>
      <address>
        <city>Soshanguve</city>
        <state>Gauteng</state>
        <zip>0152</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chris Hani Baragwanath Academic Hospital - DST/NRF VPD RMPRU</name>
      <address>
        <city>Soweto</city>
        <state>Gauteng</state>
        <zip>2013</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FAMCRU</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <zip>7505</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groote Schuur hospital, Lung infection and immunity unit, UCT</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <zip>7925</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>South Africa</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>November 23, 2020</last_update_submitted>
  <last_update_submitted_qc>November 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronavirus Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data accumulated from this study will be stored at RMPRU/ Wits. In collaboration with UK collaborators, we aim to make the data available, within one year of completion of the study to any investigators who wish to use the data to address any specific questions not directly addressed under the study objectives and which the data would lend itself to.&#xD;
De-identified data will be shared. Related trial documents will be available (protocol, ICFs, statistical analysis plan)</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>within 1 year of trial completion</ipd_time_frame>
    <ipd_access_criteria>Any investigators who wish to use the data to address any specific questions not directly addressed under the study objectives and which the data would lend itself to.</ipd_access_criteria>
  </patient_data>
  <!-- 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/NCT04444674
org study id: ChAdOx1 nCoV-19_ZA_phI/II v4.1
nct id: NCT04444674
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A Phase I/II, double-blinded, placebo-controlled, individually randomized trial to assess
      safety, immunogenicity and efficacy of the candidate Coronavirus disease (COVID-19) vaccine
      ChAdOx1 nCoV-19 in adults aged 18-65 years living with and without HIV in South Africa. The
      vaccine or placebo will be administered via an intramuscular injection into the deltoid
      muscle of the non-dominant arm.
A total of 2070 participants will be enrolled into the trial; 1970 HIV-uninfected and 100
      people living with HIV. There will be 4 trial groups, group 1 (n=50; intensive safety &
      immunogenicity cohort, HIV negative), group 2a (n=250; safety, intense immunogenicity &
      efficacy), group 2b (n=1650; safety, immunogenicity & vaccine efficacy) and group 3 (n=100,
      intensive safety & immunogenicity cohort, HIV positive).

      Participants will be followed up for 12 months after enrollment.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Four groups will be enrolled to receive either one or two doses of investigational vaccine or placebo. Follow up intensity and blood draws differ between groups
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blinded, placebo controlled. Pharmacist and vaccine administrators will be unblinded only. DSMB will be unblinded if required to assess safety signal
measure: Assess the incidence of adverse events (intervention-related and intervention-unrelated) in HIV-negative adults aged 18-65 year receiving candidate ChAdOx1 nCoV-19 vaccine or placebo (safety)
time frame: Up to 12 months post enrollment
description: Number of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, and unsolicited adverse events for 28 days following vaccination.
Assess occurrence of disease enhancement episodes and serious adverse events in year post vaccination
measure: Determine if there is a reduction of severe and non-severe COVID-19 disease in HIV-negative adults who receive candidate vaccine ChAdOx1 nCoV-19 compared to placebo recipients (efficacy)
time frame: Up to 12 months post enrollment
description: Virologically-confirmed COVID-19 clinical disease will be defined as an acute respiratory illness that is clinically consistent with COVID-19 disease, AND SARS-CoV-2 RT-PCR positivity.
measure: Assess the incidence of adverse events (intervention-related and intervention-unrelated) in HIV-positive adults aged 18-65 year receiving candidate ChAdOx1 nCoV-19 vaccine or placebo (safety)
time frame: Up to 12 months post enrollment
description: Number of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, and unsolicited adverse events for 28 days following vaccination.
Assess occurrence of disease enhancement episodes and serious adverse events in year post vaccination
measure: Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in people living with HIV (immunogenicity)
time frame: Up to 12 months post enrollment
description: Assessing the Interferon-gamma (IFN-γ) enzyme- linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein and Th1 and Th2 cytokine response profile at 3-4 days after vaccination
measure: Assess humoral immunogenicity of ChAdOx1 nCoV-19 in people living with HIV
time frame: Up to 12 months post enrollment
description: Assessing Enzyme-linked immunosorbent assay (ELISA) or fluorescence based micro-bead immunosorbent assay on luminex platform to quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) and Virus neutralising antibody (NAb) assays against live and/or pseudotyped SARS-CoV-2 virus
measure: Assess humoral Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)
time frame: Up to 12 months post enrollment
description: Assessing Enzyme-linked immunosorbent assay (ELISA) or fluorescence based micro-bead immunosorbent assay on luminex platform to quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) and Virus neutralising antibody (NAb) assays against live and/or pseudotyped SARS-CoV-2 virus
measure: Assess cellular Immunogenicity of ChAdOx1 nCoV-19 in HIV-negative adults (immunogenicity)
time frame: Up to 12 months post enrollment
description: Assessing the Interferon-gamma (IFN-γ) enzyme- linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein and Th1 and Th2 cytokine response profile at 3-4 days after vaccination
measure: Assess Fc effector functionality in participants who receive ChAdOx1 nCoV-19 vaccine or placebo
time frame: Up to 12 months post enrollment
description: Cellular Fc effector functionality assays to measure the ability of vaccine elicited antibodies to mediate cellular cytotoxicity, complement deposition, and phagocytosis.
measure: Assess B cell responses to SARS-CoV-2 spike trimer and/or the receptor binding domain in participants who receive ChAdOx1 nCoV-19 vaccine or placebo
time frame: Up to 12 months post enrollment
description: Flow cytometric sorting of plasmablasts and memory B cells to using spike and receptor binding domain "baits" to isolate SARS-CoV-2 specific B cells, sequence their immunoglobulin genes and define their epitope specificity.
arm group label: Group 1- IP
arm group type: Experimental
description: Participants (HIV-negative) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period.
arm group label: Group 1- placebo
arm group type: Placebo Comparator
description: Participants (HIV-negative) will receive two doses of Normal saline (0.9%) in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period.
arm group label: Group 2a- IP
arm group type: Experimental
description: Participants (HIV-negative) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 7 (1-dose) or 9 (2 doses) routine visits over a 12 month period.
arm group label: Group 2a- placebo
arm group type: Placebo Comparator
description: Participants (HIV-negative) will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 7 (1-dose) or 9 (2 doses) routine visits over a 12 month period.
arm group label: Group 2b- IP
arm group type: Experimental
description: Participants will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 5 (1-dose) or 6 (2 doses) routine visits over a 12 month period.
arm group label: Group 2b- placebo
arm group type: Placebo Comparator
description: Participants will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 5 (1-dose) or 6 (2 doses) routine visits over a 12 month period.
arm group label: Group 3- IP
arm group type: Experimental
description: Participants (HIV-positive) will receive two doses of 5-7.5x10^10 vp ChAdOx1 nCoV-19 vaccine in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period.
arm group label: Group 3- placebo
arm group type: Placebo Comparator
description: Participants (HIV-positive) will receive two doses of placebo in deltoid of non-dominant arm, 28 days apart. Participants, investigators and outcome assessors will be blinded to intervention. Participants will have 11 routine visits over a 12 month period.
intervention type: Biological
intervention name: ChAdOx1 nCoV-19
description: Dose of 5-7.5x10^10vp of ChAdOx1 nCoV-19
arm group label: Group 1- IP
arm group label: Group 2a- IP
arm group label: Group 2b- IP
arm group label: Group 3- IP
intervention type: Biological
intervention name: Normal saline 0.9%
description: Normal saline 0.9% as placebo
arm group label: Group 1- placebo
arm group label: Group 2a- placebo
arm group label: Group 2b- placebo
arm group label: Group 3- placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Shabir A Madhi, MD, PhD
role: Principal Investigator
affiliation: University of Witwatersrand, South Africa
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: South Africa
responsible party type: Sponsor
mesh term: Coronavirus Infections
sharing ipd: Yes
ipd description: The data accumulated from this study will be stored at RMPRU/ Wits. In collaboration with UK collaborators, we aim to make the data available, within one year of completion of the study to any investigators who wish to use the data to address any specific questions not directly addressed under the study objectives and which the data would lend itself to.
De-identified data will be shared. Related trial documents will be available (protocol, ICFs, statistical analysis plan)
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: within 1 year of trial completion
ipd access criteria: Any investigators who wish to use the data to address any specific questions not directly addressed under the study objectives and which the data would lend itself to.