<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/NCT04400838</url>
  </required_header>
  <id_info>
    <org_study_id>COV002</org_study_id>
    <nct_id>NCT04400838</nct_id>
  </id_info>
  <brief_title>Investigating a Vaccine Against COVID-19</brief_title>
  <official_title>A Phase 2/3 Study to Determine the Efficacy, Safety and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 nCoV-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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 2/3 study to determine the efficacy, safety and immunogenicity of the candidate&#xD;
      Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in healthy UK volunteers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There will be 12 study groups and it is anticipated that a total of 12,390 volunteers will be&#xD;
      enrolled. Groups 1, 7 &amp; 9 are adults aged 56-69 years; groups 2, 8 &amp; 10 are adults 70 years&#xD;
      and over; groups 4, 5 &amp; 6 are adults aged 18-55 years; group 11 is adults aged 18-55 years&#xD;
      who have previously received a ChAdOx vectored vaccine; group 12 is HIV positive adults aged&#xD;
      18-55 years.&#xD;
&#xD;
      The vaccine will be administered intramuscularly into the deltoid of the non-dominant arm&#xD;
      (preferably).&#xD;
&#xD;
      All subjects will undergo follow-up for a total of 1 year post last vaccination. Additional&#xD;
      visits or procedures may be performed at the discretion of the investigators, e.g., further&#xD;
      medical history and physical examination, or additional blood tests and other investigations&#xD;
      if clinically relevant&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 28, 2020</start_date>
  <completion_date type="Anticipated">March 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2024</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assess the efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older.</measure>
    <time_frame>Study duration (12 months from last vaccination)</time_frame>
    <description>Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in adults</measure>
    <time_frame>Study duration (12 months from last vaccination)</time_frame>
    <description>Occurrence of serious adverse events (SAEs) throughout the study duration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: occurrence of solicited local reactogenicity signs and symptoms for 7 days following</measure>
    <time_frame>7 days post vaccination</time_frame>
    <description>Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following</measure>
    <time_frame>7 days post vaccination</time_frame>
    <description>Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: occurrence of unsolicited adverse events (AEs) for 28 days following vaccination</measure>
    <time_frame>28 days post vaccination</time_frame>
    <description>Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19 through standard blood tests (full blood count, liver and kidney function tests)</measure>
    <time_frame>6 months</time_frame>
    <description>Frequency of participants with clinically significant changes from baseline for safety laboratory measures (haematology and biochemistry blood results; except groups 4, 6, 9 &amp; 10)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19 by measuring the number of disease enhancement episodes</measure>
    <time_frame>Study duration (12 months from last vaccination)</time_frame>
    <description>Occurrence of disease enhancement episodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: hospital admissions</measure>
    <time_frame>Study duration (12 months from last vaccination)</time_frame>
    <description>Number of hospital admissions associated with COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19</measure>
    <time_frame>6 months</time_frame>
    <description>Number of intensive care unit (ICU) admissions associated with COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: number of deaths</measure>
    <time_frame>6 months</time_frame>
    <description>Number of deaths associated with COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates</measure>
    <time_frame>6 months</time_frame>
    <description>Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring incidence of Covid-19</measure>
    <time_frame>Study duration (12 months from last vaccination)</time_frame>
    <description>Proportion of people diagnosed with severe Covid-19 disease (defined according to clinical severity scales)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess humoral immunogenicity of ChAdOx1 nCoV-19: antibody quantification</measure>
    <time_frame>28 days post vaccination</time_frame>
    <description>Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess humoral immunogenicity of ChAdOx1 nCoV-19: seroconversion</measure>
    <time_frame>28 days post vaccination</time_frame>
    <description>Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 28 post-vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays (groups 1, 2, 7 and 8 only)</measure>
    <time_frame>6 months</time_frame>
    <description>Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1, 2, 7 and 8 only): local reactogenicity</measure>
    <time_frame>7 days post vaccination</time_frame>
    <description>Occurrence of solicited local reactogenicity signs and symptoms for 7 days following booster vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only): systemic reactogenicity</measure>
    <time_frame>7 days post vaccination</time_frame>
    <description>Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following booster vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only)</measure>
    <time_frame>28 days post vaccination</time_frame>
    <description>Occurrence of unsolicited adverse events (AEs) for 28 days following booster vaccination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only) through standard blood tests (full blood count, liver and kidney function tests)</measure>
    <time_frame>6 months</time_frame>
    <description>Frequency of participants with clinically significant changes from baseline from pre-booster for safety laboratory measures (haematology and biochemistry blood results)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only) via seroconversion</measure>
    <time_frame>56 days post vaccination</time_frame>
    <description>Antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination (seroconversion rates)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only)</measure>
    <time_frame>56 days post vaccination</time_frame>
    <description>Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory Immunology by virus neutralising antibody assays</measure>
    <time_frame>6 months</time_frame>
    <description>Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Immunology by flow cytometry</measure>
    <time_frame>6 months</time_frame>
    <description>Cell analysis by flow cytometry assays</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Immunology by functional antibody assays</measure>
    <time_frame>6 months</time_frame>
    <description>Functional antibody assays</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory Immunology: anti-vector immunity</measure>
    <time_frame>6 months</time_frame>
    <description>Anti-vector immunity induced by 1 or 2 doses of ChAdOx1 nCoV-19</description>
  </other_outcome>
  <other_outcome>
    <measure>Measure exposure to COVID-19</measure>
    <time_frame>6 months</time_frame>
    <description>Reported by weekly survey to collect information about cases amongst household contacts and friends, contact with the general public, infection control procedures</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory efficacy against infection: assess efficacy of the candidate ChAdOx1 nCoV-19 against SARS-CoV-2 infection by PCR or NAAT</measure>
    <time_frame>6 months</time_frame>
    <description>Number of PCR or NAAT positive cases of COVID-19 infection</description>
  </other_outcome>
  <other_outcome>
    <measure>Exploratory efficacy against infection: assess efficacy of the candidate ChAdOx1 nCoV-19 against SARS-CoV-2 infection</measure>
    <time_frame>6 months</time_frame>
    <description>Measure of differences in viral loads between those with severe, mild, and asymptomatic PCR+ SARS-CoV-2 infections</description>
  </other_outcome>
  <other_outcome>
    <measure>Compare safety, reactogenicity and immunogenicity between different manufacturing batches of ChAdOx1 nCoV-19 used in COV001 and COV002</measure>
    <time_frame>6 months</time_frame>
    <description>Differences in safety, reactogenicity and immunogenicity profiles between Group 1 in COV001 and Group 5 in COV002 (proportion of Grade 3 solicited AEs, occurrence of fevers, seroconversion rates at D28, neutralising antibody titres and differences in T-cell responses at D14).</description>
  </other_outcome>
  <other_outcome>
    <measure>Compare safety, reactogenicity and immunogenicity between different methods for measuring doses</measure>
    <time_frame>6 months</time_frame>
    <description>Differences in safety, reactogenicity and immunogenicity profiles between Groups 1, 2, and 5A compared with Groups, 7, 8, and 5B, C and D respectively (proportion of Grade 3 solicited AEs, occurrence of fevers, seroconversion rates at D28, neutralising antibody titres and differences in T-cell responses at D14).</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess vaccine induced mucosal immunity: Nasal mucosa IgA levels at D0 and D28 in a subset of individuals</measure>
    <time_frame>6 months</time_frame>
    <description>Nasal mucosa IgA levels at D0 and D28 in a subset of individuals</description>
  </other_outcome>
  <other_outcome>
    <measure>Compare viral shedding on stool samples of SARS-CoV-2 PCR or NAAT positive individuals</measure>
    <time_frame>6 months</time_frame>
    <description>Differences in viral shedding on stool at 7 days and beyond post SARS-CoV-2 PCR or NAAT positivity</description>
  </other_outcome>
  <other_outcome>
    <measure>Compare immunogenicity of ChAdOx1 nCoV-19 in participants receiving 1 or 2 doses in groups 1, 2, 7 and 8: differences in antibody titres</measure>
    <time_frame>6 months</time_frame>
    <description>Differences in antibody titres (ELISA and Neutralising antibodies) in participants who received 1 or 2 doses of ChAdOx1 nCoV-19 (groups 1, 2, 7 and 8)</description>
  </other_outcome>
  <other_outcome>
    <measure>Compare immunogenicity of ChAdOx1 nCoV-19 in participants receiving 1 or 2 doses in groups 1, 2, 7 and 8: longevity of immune responses</measure>
    <time_frame>6 months</time_frame>
    <description>Longevity of immune responses in participants who received 1 or 2 doses of ChAdOx1 nCoV-19</description>
  </other_outcome>
  <other_outcome>
    <measure>Describe the impact of previous vaccination with other ChAdOx1 vectored vaccines on safety and immune responses to ChAdOx1 nCoV-19</measure>
    <time_frame>6 months</time_frame>
    <description>Differences reactogenicity profile, antibody titres and T-cell responses between groups 5d and 11 and their relationship with anti-vector neutralising antibody titres.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess the cell-mediated and humoral immunogenicity profile of ChAdOx1 nCoV-19 vaccine in HIV infected adults</measure>
    <time_frame>6 months</time_frame>
    <description>Cell-mediated and humoral responses against SARS-Cov-2 These will be measured by the following:&#xD;
Proportion of seroconversion to antibodies (Ab) against SARS-CoV-2 spike protein measured by ELISA.&#xD;
Interferon-gamma enzyme linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein&#xD;
Intracellular Cytokine analyses of CD4 and CD8-specific SARS-CoV-2 spike protein responses&#xD;
Further exploratory immunology including immune responses to a further dose administered via the NHS national roll out</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults: CD4 count-vaccine immune responses</measure>
    <time_frame>6 months</time_frame>
    <description>Relationship between nadir CD4 count vs vaccine immune responses</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults: age vs vaccine immune responses</measure>
    <time_frame>6 months</time_frame>
    <description>Relationship between age at enrolment and vaccine immune response</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults</measure>
    <time_frame>6 months</time_frame>
    <description>Immune responses to ChAdOx1 nCoV-19 (assessed as described above)</description>
  </other_outcome>
  <other_outcome>
    <measure>Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in HIV infected adults</measure>
    <time_frame>Study duration (12 months from last vaccination)</time_frame>
    <description>Measured by the following:&#xD;
Occurrence of serious adverse events (SAEs) throughout the study duration&#xD;
Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination&#xD;
Occurrence of solicited systemic signs and symptoms for 7 days following each vaccination&#xD;
Occurrence of unsolicited AEs for 28 days following each vaccination</description>
  </other_outcome>
  <other_outcome>
    <measure>To assess Impact of vaccination on HIV reservoirs</measure>
    <time_frame>Study duration (12 months from last vaccination)</time_frame>
    <description>Change in Total HIV DNA copies per million CD4 T cells</description>
  </other_outcome>
  <other_outcome>
    <measure>To assess immunological correlates of protection in relation to occurrence of COVID-19 disease in ChAdOx1 nCoV-19 recipients</measure>
    <time_frame>Throughout the study, average of 18 months]</time_frame>
    <description>Immunological endpoints (antibody &amp; cellular responses to SARS-COV2 spike protein) and COVID-19 disease endpoints (SARS-COV2 PCR positivity plus symptoms) in ChAdOx1 nCoV-19 recipients</description>
  </other_outcome>
  <number_of_arms>29</number_of_arms>
  <enrollment type="Anticipated">12390</enrollment>
  <condition>Coronavirus</condition>
  <arm_group>
    <arm_group_label>Group 1 a1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive a single dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1 a3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine: 5x10^10vp (Abs 260) prime and 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260) boost, minimum 4 weeks from prime</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1 b1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) prime and 2.2x10^10vp (qPCR) boost (4-6 weeks apart)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 a1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive a single dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 a3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine: 5x10^10vp (Abs 260) prime and 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260) boost, minimum 4 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 b1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>.Volunteers will receive two dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) prime and 2.2x10^10vp (qPCR) boost 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4 a1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp (Abs 260)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4 b1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) prime and 2.2x10^10vp (qPCR) boost 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4 c1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs260) prime and 2.2x10^10vp (qPCR) boost*, at least 4 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5 a1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp, (Abs 260)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5 a3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine: 5x10^10vp (Abs 260) prime and 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260) boost, minimum 4 weeks from prime</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5 b1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x1010vp, (qPCR)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5 c1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp, (qPCR)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5 d1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5 e1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two dose ChAdOx1 nCoV-19 0.5mL (Covishield 0.9 x 10^11 vp/mL), 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 5 f1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two dose ChAdOx1 nCoV-19 (Covishield 0.9 x 10^11 vp/mL), 0.25mL prime and 0.5mL boost 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 6 a1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive a single dose ofChAdOx1 nCoV19 vaccine, 5x1010vp (qPCR)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 6 b1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 5x1010vp (Abs260) prime and 0.5mL (3.5 - 6.5 × 1010 vp, Abs 260)* boost* at least 4 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 7 a1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive a single dose ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 7 b1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR)* 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 8 a1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive a single dose ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 8 b1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 9 a1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 10 a1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 11</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 12</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Single dose MenACWY</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Groups 1 a2, 2 a2, 4 a2, 5 a2, 5 b2, 5 c2, 6 a2, 7 a2 &amp; 8 a2 will receive a standard single dose of MenACWY vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Two dose MenACWY 4 - 6 weeks</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Groups 1 b2, 2 b2, 4 b2, 5 d2, 7 b2, 8 b2, 9 a2 &amp; 10 a2 will receive two doses of MenACWY 4-6 weeks apart</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Two dose MenACWY minimum 4 weeks</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Groups 1 a4, 2 a4, 4 c2, 5 a4, 6b2 will receive two doses of MenACWY at least 4 weeks apart</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ChAdOx1 nCoV-19 (Abs 260)</intervention_name>
    <description>A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260</description>
    <arm_group_label>Group 1 a1</arm_group_label>
    <arm_group_label>Group 2 a1</arm_group_label>
    <arm_group_label>Group 4 a1</arm_group_label>
    <arm_group_label>Group 5 a1</arm_group_label>
    <arm_group_label>Group 5 c1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MenACWY vaccine</intervention_name>
    <description>Standard single dose of MenACWY vaccine</description>
    <arm_group_label>Single dose MenACWY</arm_group_label>
    <other_name>Menveo</other_name>
    <other_name>Nimenrix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ChAdOx1 nCoV-19 (Abs 260) + 2.2x10^10vp (qPCR) boost</intervention_name>
    <description>A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260 and 2.2x10^10vp ChAdOx1 nCoV-19 boost measured by qPCR 4-6 weeks later</description>
    <arm_group_label>Group 1 b1</arm_group_label>
    <arm_group_label>Group 2 b1</arm_group_label>
    <arm_group_label>Group 4 b1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Two dose MenACWY vaccine</intervention_name>
    <description>Two standard doses of MenACWY vaccine 4-6 weeks apart</description>
    <arm_group_label>Two dose MenACWY 4 - 6 weeks</arm_group_label>
    <other_name>Menveo</other_name>
    <other_name>Nimenrix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ChAdOx1 nCoV-19 (qPCR)</intervention_name>
    <description>A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR</description>
    <arm_group_label>Group 5 b1</arm_group_label>
    <arm_group_label>Group 6 a1</arm_group_label>
    <arm_group_label>Group 7 a1</arm_group_label>
    <arm_group_label>Group 8 a1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ChAdOx1 nCoV-19 0.5mL prime plus boost</intervention_name>
    <description>Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)</description>
    <arm_group_label>Group 1 a3</arm_group_label>
    <arm_group_label>Group 10 a1</arm_group_label>
    <arm_group_label>Group 11</arm_group_label>
    <arm_group_label>Group 12</arm_group_label>
    <arm_group_label>Group 2 a3</arm_group_label>
    <arm_group_label>Group 4 c1</arm_group_label>
    <arm_group_label>Group 5 a3</arm_group_label>
    <arm_group_label>Group 5 d1</arm_group_label>
    <arm_group_label>Group 6 b1</arm_group_label>
    <arm_group_label>Group 7 b1</arm_group_label>
    <arm_group_label>Group 8 b1</arm_group_label>
    <arm_group_label>Group 9 a1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Two dose MenACWY vaccine min. 4 weeks apart</intervention_name>
    <description>Two standard doses of MenACWY vaccine minimum 4 weeks apart</description>
    <arm_group_label>Two dose MenACWY minimum 4 weeks</arm_group_label>
    <other_name>Menveo</other_name>
    <other_name>Nimenrix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Two dose ChAdOx1 nCoV-19/Covishield 0.5mL</intervention_name>
    <description>Two dose ChAdOx1 nCoV-19 0.5mL (Covishield 0.9 x 10^11 vp/mL), 4-6 weeks apart</description>
    <arm_group_label>Group 5 e1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Two dose ChAdOx1 nCoV-19/Covishield 0.25mL &amp; 0.5mL</intervention_name>
    <description>Two dose ChAdOx1 nCoV-19 (Covishield 0.9 x 10^11 vp/mL), 0.25mL prime and 0.5mL boost 4-6 weeks apart</description>
    <arm_group_label>Group 5 f1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults aged 18 - 55 years (groups 4, 5, 6 and 11)&#xD;
&#xD;
          -  Adults aged 56-69 years (groups 1, 7, and 9)&#xD;
&#xD;
          -  Adults aged 70 years and older (groups 2, 8, and 10)&#xD;
&#xD;
          -  Able and willing (in the Investigator's opinion) to comply with all study&#xD;
             requirements.&#xD;
&#xD;
          -  Willing to allow the investigators to discuss the volunteer's medical history with&#xD;
             their General Practitioner and access all medical records when relevant to study&#xD;
             procedures.&#xD;
&#xD;
          -  For females of childbearing potential only, willingness to practice continuous&#xD;
             effective contraception (see below) during the study and a negative pregnancy test on&#xD;
             the day(s) of screening and vaccination.&#xD;
&#xD;
          -  Agreement to refrain from blood donation during the course of the study.&#xD;
&#xD;
          -  Provide written informed consent.&#xD;
&#xD;
        Additional Inclusion criteria to Group 12 (HIV sub-study):&#xD;
&#xD;
          -  HIV positive&#xD;
&#xD;
          -  Receiving antiretroviral therapy&#xD;
&#xD;
          -  Undetectable HIV viral load&#xD;
&#xD;
          -  CD4&gt;350 cells/mL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        • Participation in COVID-19 prophylactic drug trials for the duration of the study.&#xD;
&#xD;
        Note: Participation in COVID-19 treatment trials is allowed in the event of hospitalisation&#xD;
        due to COVID-19. The COV002 study team should be informed as soon as possible.&#xD;
&#xD;
        • Participation in SARS-CoV-2 serological surveys where participants are informed of their&#xD;
        serostatus for the duration of the study.&#xD;
&#xD;
        Note: Disclosure of serostatus post enrolment may accidently unblind participants to group&#xD;
        allocation. Participation in COV002 can only be allowed if volunteers are kept blinded to&#xD;
        their serology results from local/national serological surveys&#xD;
&#xD;
          -  Receipt of any vaccine (licensed or investigational) other than the study intervention&#xD;
             within 30 days before and after each study vaccination, with the exception of the&#xD;
             licensed seasonal influenza vaccination and the licensed pneumococcal vaccination.&#xD;
             Participants will be encouraged to receive these vaccinations at least 7 days before&#xD;
             or after their study vaccine.&#xD;
&#xD;
          -  Prior or planned receipt of an investigational or licensed vaccine or product likely&#xD;
             to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any&#xD;
             coronavirus vaccines). This exclusion criteria will not apply to group 11, as&#xD;
             recruitment will be targeted at those volunteers who previously received a ChAdOx1&#xD;
             vectored vaccine.&#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;
          -  Any confirmed or suspected immunosuppressive or immunodeficient state (except group&#xD;
             12, where HIV infected participants are allowed); asplenia; recurrent severe&#xD;
             infections and use of immunosuppressant medication within the past 6 months, except&#xD;
             topical steroids or short-term oral steroids (course lasting ≤14 days)&#xD;
&#xD;
          -  History of allergic disease or reactions likely to be exacerbated by any component of&#xD;
             ChAdOx1 nCoV-19 or MenACWY&#xD;
&#xD;
          -  Any history of angioedema.&#xD;
&#xD;
          -  Any history of anaphylaxis.&#xD;
&#xD;
          -  Pregnancy, lactation or willingness/intention to become pregnant during the study.&#xD;
&#xD;
          -  Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin&#xD;
             and cervical carcinoma in 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;
             venepuncture.&#xD;
&#xD;
          -  Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e.&#xD;
             warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and&#xD;
             edoxaban)&#xD;
&#xD;
          -  Suspected or known current alcohol or drug dependency.&#xD;
&#xD;
          -  Any other significant disease, disorder or finding which may significantly increase&#xD;
             the risk to the volunteer because of participation in the study, affect the ability of&#xD;
             the volunteer to participate in the study or impair interpretation of the study data.&#xD;
&#xD;
          -  Severe and/or uncontrolled cardiovascular disease, respiratory disease,&#xD;
             gastrointestinal disease, liver disease, renal disease, endocrine disorder and&#xD;
             neurological illness (mild/moderate well controlled comorbidities are allowed)&#xD;
&#xD;
          -  History of laboratory confirmed COVID-19 (except groups 5d, 5e, 5f, 9, 10 and 11).&#xD;
&#xD;
          -  Seropositivity to SARS-CoV-2 before enrolment (except groups 5d, 5e, 5f, 9, 10 and 11)&#xD;
&#xD;
          -  NB: volunteers with previous NAAT positive results are also allowed in groups 9, 10&#xD;
             and 11&#xD;
&#xD;
        Additional Exclusion criteria to Groups 4, 6, 9 and 10&#xD;
&#xD;
          -  History of allergic disease or reactions likely to be exacerbated by Paracetamol&#xD;
&#xD;
          -  Note: Caution should be taken when recommending paracetamol to adults who already take&#xD;
             paracetamol chronically&#xD;
&#xD;
        Re-vaccination exclusion criteria (two-dose groups only)&#xD;
&#xD;
          -  Anaphylactic reaction following administration of vaccine&#xD;
&#xD;
          -  Pregnancy. An exception to this will be prior to receipt of a booster dose at extra&#xD;
             visit B. If a pregnant woman has discussed vaccination with their usual clinician&#xD;
             (e.g. GP) and chooses to receive a COVID-19 vaccination, this may be administered by&#xD;
             the trial team as part of extra visit B. (Protocol 19.0) or as part of the provision&#xD;
             of treatment to controls.&#xD;
&#xD;
          -  Any AE that in the opinion of the Investigator may affect the safety of the&#xD;
             participant or the interpretation of the study results&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew Pollard, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Oxford</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Southampton NHS Foundation Trust</name>
      <address>
        <city>Southampton</city>
        <state>Hampshire</state>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Castle Hill Hospital</name>
      <address>
        <city>Cottingham</city>
        <state>Hull</state>
        <zip>HU16 5JQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Georges University Hospital NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <state>Tooting</state>
        <zip>SW17 0QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Birmingham NHS Foundation Trust</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Bristol and Weston NHS Foundation Trust</name>
      <address>
        <city>Bristol</city>
        <zip>BS1 3NU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Bristol NHS Trust</name>
      <address>
        <city>Bristol</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NIHR Cambridge Clinical Research Facility</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Lothian, Western General Hospital</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH4 2XU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Glasgow University and NHS Greater Glasgow &amp; Clyde, New Lister Building, Glasgow Royal Infirmary &amp; Queen Elizabeth University Hospital</name>
      <address>
        <city>Glasgow</city>
        <zip>G31 2ER</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Liverpool School of Tropical Medicine (LSTM), Accelerator Research Clinic. Clinical Sciences Accelerator</name>
      <address>
        <city>LIverpool</city>
        <zip>L7 8XZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London North West University Healthcare Trust (LNWUH), Northwick Park Hospital</name>
      <address>
        <city>London</city>
        <zip>HA1 3UJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospitals NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>NW1 2PG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's and St Thomas' NHS Foundation Trust, Department of Infection, St Thomas Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 7EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <zip>W12 0HS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary</name>
      <address>
        <city>Newcastle upon Tyne</city>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Public Health Wales</name>
      <address>
        <city>Newport</city>
        <zip>NP18 3XQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nottingham Health Service, Cripps Health Centre, University Park</name>
      <address>
        <city>Nottingham</city>
        <zip>NG7 2QW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CCVTM, University of Oxford, Churchill Hospital</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 7LE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Radcliffe Hospital</name>
      <address>
        <city>Oxford</city>
        <zip>OX3 9DU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheffield Teaching Hospitals, Royal Hallamshire Hospital</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2RX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>May 12, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>July 31, 2023</last_update_submitted>
  <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Covid-19</keyword>
  <keyword>ChAdOx1 nCov19</keyword>
  <keyword>sars-cov-2</keyword>
  <keyword>vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccines</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04400838
org study id: COV002
nct id: NCT04400838
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A phase 2/3 study to determine the efficacy, safety and immunogenicity of the candidate
      Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in healthy UK volunteers.
There will be 12 study groups and it is anticipated that a total of 12,390 volunteers will be
      enrolled. Groups 1, 7 & 9 are adults aged 56-69 years; groups 2, 8 & 10 are adults 70 years
      and over; groups 4, 5 & 6 are adults aged 18-55 years; group 11 is adults aged 18-55 years
      who have previously received a ChAdOx vectored vaccine; group 12 is HIV positive adults aged
      18-55 years.

      The vaccine will be administered intramuscularly into the deltoid of the non-dominant arm
      (preferably).

      All subjects will undergo follow-up for a total of 1 year post last vaccination. Additional
      visits or procedures may be performed at the discretion of the investigators, e.g., further
      medical history and physical examination, or additional blood tests and other investigations
      if clinically relevant
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Prevention
masking: Single (Participant)
measure: Assess the efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older.
time frame: Study duration (12 months from last vaccination)
description: Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19
measure: Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in adults
time frame: Study duration (12 months from last vaccination)
description: Occurrence of serious adverse events (SAEs) throughout the study duration.
measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: occurrence of solicited local reactogenicity signs and symptoms for 7 days following
time frame: 7 days post vaccination
description: Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination
measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following
time frame: 7 days post vaccination
description: Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination
measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: occurrence of unsolicited adverse events (AEs) for 28 days following vaccination
time frame: 28 days post vaccination
description: Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination
measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19 through standard blood tests (full blood count, liver and kidney function tests)
time frame: 6 months
description: Frequency of participants with clinically significant changes from baseline for safety laboratory measures (haematology and biochemistry blood results; except groups 4, 6, 9 & 10)
measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19 by measuring the number of disease enhancement episodes
time frame: Study duration (12 months from last vaccination)
description: Occurrence of disease enhancement episodes
measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: hospital admissions
time frame: Study duration (12 months from last vaccination)
description: Number of hospital admissions associated with COVID-19
measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19
time frame: 6 months
description: Number of intensive care unit (ICU) admissions associated with COVID-19
measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: number of deaths
time frame: 6 months
description: Number of deaths associated with COVID-19
measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates
time frame: 6 months
description: Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study
measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring incidence of Covid-19
time frame: Study duration (12 months from last vaccination)
description: Proportion of people diagnosed with severe Covid-19 disease (defined according to clinical severity scales)
measure: Assess humoral immunogenicity of ChAdOx1 nCoV-19: antibody quantification
time frame: 28 days post vaccination
description: Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates)
measure: Assess humoral immunogenicity of ChAdOx1 nCoV-19: seroconversion
time frame: 28 days post vaccination
description: Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 28 post-vaccination
measure: Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays (groups 1, 2, 7 and 8 only)
time frame: 6 months
description: Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein
measure: Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1, 2, 7 and 8 only): local reactogenicity
time frame: 7 days post vaccination
description: Occurrence of solicited local reactogenicity signs and symptoms for 7 days following booster vaccination
measure: Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only): systemic reactogenicity
time frame: 7 days post vaccination
description: Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following booster vaccination
measure: Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only)
time frame: 28 days post vaccination
description: Occurrence of unsolicited adverse events (AEs) for 28 days following booster vaccination
measure: Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only) through standard blood tests (full blood count, liver and kidney function tests)
time frame: 6 months
description: Frequency of participants with clinically significant changes from baseline from pre-booster for safety laboratory measures (haematology and biochemistry blood results)
measure: Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only) via seroconversion
time frame: 56 days post vaccination
description: Antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination (seroconversion rates)
measure: Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only)
time frame: 56 days post vaccination
description: Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination
measure: Exploratory Immunology by virus neutralising antibody assays
time frame: 6 months
description: Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus
measure: Exploratory Immunology by flow cytometry
time frame: 6 months
description: Cell analysis by flow cytometry assays
measure: Exploratory Immunology by functional antibody assays
time frame: 6 months
description: Functional antibody assays
measure: Exploratory Immunology: anti-vector immunity
time frame: 6 months
description: Anti-vector immunity induced by 1 or 2 doses of ChAdOx1 nCoV-19
measure: Measure exposure to COVID-19
time frame: 6 months
description: Reported by weekly survey to collect information about cases amongst household contacts and friends, contact with the general public, infection control procedures
measure: Exploratory efficacy against infection: assess efficacy of the candidate ChAdOx1 nCoV-19 against SARS-CoV-2 infection by PCR or NAAT
time frame: 6 months
description: Number of PCR or NAAT positive cases of COVID-19 infection
measure: Exploratory efficacy against infection: assess efficacy of the candidate ChAdOx1 nCoV-19 against SARS-CoV-2 infection
time frame: 6 months
description: Measure of differences in viral loads between those with severe, mild, and asymptomatic PCR+ SARS-CoV-2 infections
measure: Compare safety, reactogenicity and immunogenicity between different manufacturing batches of ChAdOx1 nCoV-19 used in COV001 and COV002
time frame: 6 months
description: Differences in safety, reactogenicity and immunogenicity profiles between Group 1 in COV001 and Group 5 in COV002 (proportion of Grade 3 solicited AEs, occurrence of fevers, seroconversion rates at D28, neutralising antibody titres and differences in T-cell responses at D14).
measure: Compare safety, reactogenicity and immunogenicity between different methods for measuring doses
time frame: 6 months
description: Differences in safety, reactogenicity and immunogenicity profiles between Groups 1, 2, and 5A compared with Groups, 7, 8, and 5B, C and D respectively (proportion of Grade 3 solicited AEs, occurrence of fevers, seroconversion rates at D28, neutralising antibody titres and differences in T-cell responses at D14).
measure: Assess vaccine induced mucosal immunity: Nasal mucosa IgA levels at D0 and D28 in a subset of individuals
time frame: 6 months
description: Nasal mucosa IgA levels at D0 and D28 in a subset of individuals
measure: Compare viral shedding on stool samples of SARS-CoV-2 PCR or NAAT positive individuals
time frame: 6 months
description: Differences in viral shedding on stool at 7 days and beyond post SARS-CoV-2 PCR or NAAT positivity
measure: Compare immunogenicity of ChAdOx1 nCoV-19 in participants receiving 1 or 2 doses in groups 1, 2, 7 and 8: differences in antibody titres
time frame: 6 months
description: Differences in antibody titres (ELISA and Neutralising antibodies) in participants who received 1 or 2 doses of ChAdOx1 nCoV-19 (groups 1, 2, 7 and 8)
measure: Compare immunogenicity of ChAdOx1 nCoV-19 in participants receiving 1 or 2 doses in groups 1, 2, 7 and 8: longevity of immune responses
time frame: 6 months
description: Longevity of immune responses in participants who received 1 or 2 doses of ChAdOx1 nCoV-19
measure: Describe the impact of previous vaccination with other ChAdOx1 vectored vaccines on safety and immune responses to ChAdOx1 nCoV-19
time frame: 6 months
description: Differences reactogenicity profile, antibody titres and T-cell responses between groups 5d and 11 and their relationship with anti-vector neutralising antibody titres.
measure: Assess the cell-mediated and humoral immunogenicity profile of ChAdOx1 nCoV-19 vaccine in HIV infected adults
time frame: 6 months
description: Cell-mediated and humoral responses against SARS-Cov-2 These will be measured by the following:
Proportion of seroconversion to antibodies (Ab) against SARS-CoV-2 spike protein measured by ELISA.
Interferon-gamma enzyme linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein
Intracellular Cytokine analyses of CD4 and CD8-specific SARS-CoV-2 spike protein responses
Further exploratory immunology including immune responses to a further dose administered via the NHS national roll out
measure: Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults: CD4 count-vaccine immune responses
time frame: 6 months
description: Relationship between nadir CD4 count vs vaccine immune responses
measure: Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults: age vs vaccine immune responses
time frame: 6 months
description: Relationship between age at enrolment and vaccine immune response
measure: Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults
time frame: 6 months
description: Immune responses to ChAdOx1 nCoV-19 (assessed as described above)
measure: Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in HIV infected adults
time frame: Study duration (12 months from last vaccination)
description: Measured by the following:
Occurrence of serious adverse events (SAEs) throughout the study duration
Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination
Occurrence of solicited systemic signs and symptoms for 7 days following each vaccination
Occurrence of unsolicited AEs for 28 days following each vaccination
measure: To assess Impact of vaccination on HIV reservoirs
time frame: Study duration (12 months from last vaccination)
description: Change in Total HIV DNA copies per million CD4 T cells
measure: To assess immunological correlates of protection in relation to occurrence of COVID-19 disease in ChAdOx1 nCoV-19 recipients
time frame: Throughout the study, average of 18 months]
description: Immunological endpoints (antibody & cellular responses to SARS-COV2 spike protein) and COVID-19 disease endpoints (SARS-COV2 PCR positivity plus symptoms) in ChAdOx1 nCoV-19 recipients
arm group label: Group 1 a1
arm group type: Experimental
description: Volunteers will receive a single dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260)
arm group label: Group 1 a3
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine: 5x10^10vp (Abs 260) prime and 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260) boost, minimum 4 weeks from prime
arm group label: Group 1 b1
arm group type: Experimental
description: Volunteers will receive two dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) prime and 2.2x10^10vp (qPCR) boost (4-6 weeks apart)
arm group label: Group 2 a1
arm group type: Experimental
description: Volunteers will receive a single dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260)
arm group label: Group 2 a3
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine: 5x10^10vp (Abs 260) prime and 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260) boost, minimum 4 weeks apart
arm group label: Group 2 b1
arm group type: Experimental
description: .Volunteers will receive two dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) prime and 2.2x10^10vp (qPCR) boost 4-6 weeks apart
arm group label: Group 4 a1
arm group type: Experimental
description: Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp (Abs 260)
arm group label: Group 4 b1
arm group type: Experimental
description: Volunteers will receive two dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) prime and 2.2x10^10vp (qPCR) boost 4-6 weeks apart
arm group label: Group 4 c1
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs260) prime and 2.2x10^10vp (qPCR) boost*, at least 4 weeks apart
arm group label: Group 5 a1
arm group type: Experimental
description: Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp, (Abs 260)
arm group label: Group 5 a3
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine: 5x10^10vp (Abs 260) prime and 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260) boost, minimum 4 weeks from prime
arm group label: Group 5 b1
arm group type: Experimental
description: Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x1010vp, (qPCR)
arm group label: Group 5 c1
arm group type: Experimental
description: Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp, (qPCR)
arm group label: Group 5 d1
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart
arm group label: Group 5 e1
arm group type: Experimental
description: Two dose ChAdOx1 nCoV-19 0.5mL (Covishield 0.9 x 10^11 vp/mL), 4-6 weeks apart
arm group label: Group 5 f1
arm group type: Experimental
description: Two dose ChAdOx1 nCoV-19 (Covishield 0.9 x 10^11 vp/mL), 0.25mL prime and 0.5mL boost 4-6 weeks apart
arm group label: Group 6 a1
arm group type: Experimental
description: Volunteers will receive a single dose ofChAdOx1 nCoV19 vaccine, 5x1010vp (qPCR)
arm group label: Group 6 b1
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 5x1010vp (Abs260) prime and 0.5mL (3.5 - 6.5 × 1010 vp, Abs 260)* boost* at least 4 weeks apart
arm group label: Group 7 a1
arm group type: Experimental
description: Volunteers will receive a single dose ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR)
arm group label: Group 7 b1
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR)* 4-6 weeks apart
arm group label: Group 8 a1
arm group type: Experimental
description: Volunteers will receive a single dose ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR)
arm group label: Group 8 b1
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart
arm group label: Group 9 a1
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart
arm group label: Group 10 a1
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart
arm group label: Group 11
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart
arm group label: Group 12
arm group type: Experimental
description: Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart
arm group label: Single dose MenACWY
arm group type: Active Comparator
description: Groups 1 a2, 2 a2, 4 a2, 5 a2, 5 b2, 5 c2, 6 a2, 7 a2 & 8 a2 will receive a standard single dose of MenACWY vaccine
arm group label: Two dose MenACWY 4 - 6 weeks
arm group type: Active Comparator
description: Groups 1 b2, 2 b2, 4 b2, 5 d2, 7 b2, 8 b2, 9 a2 & 10 a2 will receive two doses of MenACWY 4-6 weeks apart
arm group label: Two dose MenACWY minimum 4 weeks
arm group type: Active Comparator
description: Groups 1 a4, 2 a4, 4 c2, 5 a4, 6b2 will receive two doses of MenACWY at least 4 weeks apart
intervention type: Biological
intervention name: ChAdOx1 nCoV-19 (Abs 260)
description: A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260
arm group label: Group 1 a1
arm group label: Group 2 a1
arm group label: Group 4 a1
arm group label: Group 5 a1
arm group label: Group 5 c1
intervention type: Biological
intervention name: MenACWY vaccine
description: Standard single dose of MenACWY vaccine
arm group label: Single dose MenACWY
other name: Menveo
other name: Nimenrix
intervention type: Biological
intervention name: ChAdOx1 nCoV-19 (Abs 260) + 2.2x10^10vp (qPCR) boost
description: A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260 and 2.2x10^10vp ChAdOx1 nCoV-19 boost measured by qPCR 4-6 weeks later
arm group label: Group 1 b1
arm group label: Group 2 b1
arm group label: Group 4 b1
intervention type: Biological
intervention name: Two dose MenACWY vaccine
description: Two standard doses of MenACWY vaccine 4-6 weeks apart
arm group label: Two dose MenACWY 4 - 6 weeks
other name: Menveo
other name: Nimenrix
intervention type: Biological
intervention name: ChAdOx1 nCoV-19 (qPCR)
description: A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR
arm group label: Group 5 b1
arm group label: Group 6 a1
arm group label: Group 7 a1
arm group label: Group 8 a1
intervention type: Biological
intervention name: ChAdOx1 nCoV-19 0.5mL prime plus boost
description: Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
arm group label: Group 1 a3
arm group label: Group 10 a1
arm group label: Group 11
arm group label: Group 12
arm group label: Group 2 a3
arm group label: Group 4 c1
arm group label: Group 5 a3
arm group label: Group 5 d1
arm group label: Group 6 b1
arm group label: Group 7 b1
arm group label: Group 8 b1
arm group label: Group 9 a1
intervention type: Biological
intervention name: Two dose MenACWY vaccine min. 4 weeks apart
description: Two standard doses of MenACWY vaccine minimum 4 weeks apart
arm group label: Two dose MenACWY minimum 4 weeks
other name: Menveo
other name: Nimenrix
intervention type: Biological
intervention name: Two dose ChAdOx1 nCoV-19/Covishield 0.5mL
description: Two dose ChAdOx1 nCoV-19 0.5mL (Covishield 0.9 x 10^11 vp/mL), 4-6 weeks apart
arm group label: Group 5 e1
intervention type: Biological
intervention name: Two dose ChAdOx1 nCoV-19/Covishield 0.25mL & 0.5mL
description: Two dose ChAdOx1 nCoV-19 (Covishield 0.9 x 10^11 vp/mL), 0.25mL prime and 0.5mL boost 4-6 weeks apart
arm group label: Group 5 f1
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Andrew Pollard, Prof
role: Principal Investigator
affiliation: University of Oxford
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country: United Kingdom
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Vaccines