Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04400838
Other study ID # COV002
Secondary ID
Status Active, not recruiting
Phase Phase 2/Phase 3
First received
Last updated
Start date May 28, 2020
Est. completion date March 31, 2024

Study information

Verified date July 2023
Source University of Oxford
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 12390
Est. completion date March 31, 2024
Est. primary completion date March 31, 2024
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Adults aged 18 - 55 years (groups 4, 5, 6 and 11) - Adults aged 56-69 years (groups 1, 7, and 9) - Adults aged 70 years and older (groups 2, 8, and 10) - Able and willing (in the Investigator's opinion) to comply with all study requirements. - Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner and access all medical records when relevant to study procedures. - For females of childbearing potential only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination. - Agreement to refrain from blood donation during the course of the study. - Provide written informed consent. Additional Inclusion criteria to Group 12 (HIV sub-study): - HIV positive - Receiving antiretroviral therapy - Undetectable HIV viral load - CD4>350 cells/mL Exclusion Criteria: • Participation in COVID-19 prophylactic drug trials for the duration of the study. Note: Participation in COVID-19 treatment trials is allowed in the event of hospitalisation due to COVID-19. The COV002 study team should be informed as soon as possible. • Participation in SARS-CoV-2 serological surveys where participants are informed of their serostatus for the duration of the study. Note: Disclosure of serostatus post enrolment may accidently unblind participants to group allocation. Participation in COV002 can only be allowed if volunteers are kept blinded to their serology results from local/national serological surveys - Receipt of any vaccine (licensed or investigational) other than the study intervention within 30 days before and after each study vaccination, with the exception of the licensed seasonal influenza vaccination and the licensed pneumococcal vaccination. Participants will be encouraged to receive these vaccinations at least 7 days before or after their study vaccine. - Prior or planned receipt of an investigational or licensed vaccine or product likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines). This exclusion criteria will not apply to group 11, as recruitment will be targeted at those volunteers who previously received a ChAdOx1 vectored vaccine. - Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. - Any confirmed or suspected immunosuppressive or immunodeficient state (except group 12, where HIV infected participants are allowed); asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting =14 days) - History of allergic disease or reactions likely to be exacerbated by any component of ChAdOx1 nCoV-19 or MenACWY - Any history of angioedema. - Any history of anaphylaxis. - Pregnancy, lactation or willingness/intention to become pregnant during the study. - Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). - History of serious psychiatric condition likely to affect participation in the study. - Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture. - Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) - Suspected or known current alcohol or drug dependency. - Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data. - Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well controlled comorbidities are allowed) - History of laboratory confirmed COVID-19 (except groups 5d, 5e, 5f, 9, 10 and 11). - Seropositivity to SARS-CoV-2 before enrolment (except groups 5d, 5e, 5f, 9, 10 and 11) - NB: volunteers with previous NAAT positive results are also allowed in groups 9, 10 and 11 Additional Exclusion criteria to Groups 4, 6, 9 and 10 - History of allergic disease or reactions likely to be exacerbated by Paracetamol - Note: Caution should be taken when recommending paracetamol to adults who already take paracetamol chronically Re-vaccination exclusion criteria (two-dose groups only) - Anaphylactic reaction following administration of vaccine - Pregnancy. An exception to this will be prior to receipt of a booster dose at extra visit B. If a pregnant woman has discussed vaccination with their usual clinician (e.g. GP) and chooses to receive a COVID-19 vaccination, this may be administered by the trial team as part of extra visit B. (Protocol 19.0) or as part of the provision of treatment to controls. - Any AE that in the opinion of the Investigator may affect the safety of the participant or the interpretation of the study results

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
ChAdOx1 nCoV-19 (Abs 260)
A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260
MenACWY vaccine
Standard single dose of MenACWY vaccine
ChAdOx1 nCoV-19 (Abs 260) + 2.2x10^10vp (qPCR) boost
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
Two dose MenACWY vaccine
Two standard doses of MenACWY vaccine 4-6 weeks apart
ChAdOx1 nCoV-19 (qPCR)
A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR
ChAdOx1 nCoV-19 0.5mL prime plus boost
Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Two dose MenACWY vaccine min. 4 weeks apart
Two standard doses of MenACWY vaccine minimum 4 weeks apart
Two dose ChAdOx1 nCoV-19/Covishield 0.5mL
Two dose ChAdOx1 nCoV-19 0.5mL (Covishield 0.9 x 10^11 vp/mL), 4-6 weeks apart
Two dose ChAdOx1 nCoV-19/Covishield 0.25mL & 0.5mL
Two dose ChAdOx1 nCoV-19 (Covishield 0.9 x 10^11 vp/mL), 0.25mL prime and 0.5mL boost 4-6 weeks apart

Locations

Country Name City State
United Kingdom University Hospitals Birmingham NHS Foundation Trust Birmingham
United Kingdom North Bristol NHS Trust Bristol
United Kingdom University Hospitals Bristol and Weston NHS Foundation Trust Bristol
United Kingdom NIHR Cambridge Clinical Research Facility Cambridge
United Kingdom Castle Hill Hospital Cottingham Hull
United Kingdom NHS Lothian, Western General Hospital Edinburgh
United Kingdom Glasgow University and NHS Greater Glasgow & Clyde, New Lister Building, Glasgow Royal Infirmary & Queen Elizabeth University Hospital Glasgow
United Kingdom Liverpool School of Tropical Medicine (LSTM), Accelerator Research Clinic. Clinical Sciences Accelerator LIverpool
United Kingdom Guy's and St Thomas' NHS Foundation Trust, Department of Infection, St Thomas Hospital London
United Kingdom Imperial College Healthcare NHS Trust London
United Kingdom London North West University Healthcare Trust (LNWUH), Northwick Park Hospital London
United Kingdom St Georges University Hospital NHS Foundation Trust London Tooting
United Kingdom University College London Hospitals NHS Foundation Trust London
United Kingdom The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary Newcastle upon Tyne
United Kingdom Public Health Wales Newport
United Kingdom University of Nottingham Health Service, Cripps Health Centre, University Park Nottingham
United Kingdom CCVTM, University of Oxford, Churchill Hospital Oxford
United Kingdom John Radcliffe Hospital Oxford
United Kingdom Sheffield Teaching Hospitals, Royal Hallamshire Hospital Sheffield
United Kingdom University Hospital Southampton NHS Foundation Trust Southampton Hampshire

Sponsors (1)

Lead Sponsor Collaborator
University of Oxford

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Exploratory Immunology by virus neutralising antibody assays Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus 6 months
Other Exploratory Immunology by flow cytometry Cell analysis by flow cytometry assays 6 months
Other Exploratory Immunology by functional antibody assays Functional antibody assays 6 months
Other Exploratory Immunology: anti-vector immunity Anti-vector immunity induced by 1 or 2 doses of ChAdOx1 nCoV-19 6 months
Other Measure exposure to COVID-19 Reported by weekly survey to collect information about cases amongst household contacts and friends, contact with the general public, infection control procedures 6 months
Other Exploratory efficacy against infection: assess efficacy of the candidate ChAdOx1 nCoV-19 against SARS-CoV-2 infection by PCR or NAAT Number of PCR or NAAT positive cases of COVID-19 infection 6 months
Other Exploratory efficacy against infection: assess efficacy of the candidate ChAdOx1 nCoV-19 against SARS-CoV-2 infection Measure of differences in viral loads between those with severe, mild, and asymptomatic PCR+ SARS-CoV-2 infections 6 months
Other Compare safety, reactogenicity and immunogenicity between different manufacturing batches of ChAdOx1 nCoV-19 used in COV001 and COV002 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). 6 months
Other Compare safety, reactogenicity and immunogenicity between different methods for measuring doses 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). 6 months
Other Assess vaccine induced mucosal immunity: Nasal mucosa IgA levels at D0 and D28 in a subset of individuals Nasal mucosa IgA levels at D0 and D28 in a subset of individuals 6 months
Other Compare viral shedding on stool samples of SARS-CoV-2 PCR or NAAT positive individuals Differences in viral shedding on stool at 7 days and beyond post SARS-CoV-2 PCR or NAAT positivity 6 months
Other Compare immunogenicity of ChAdOx1 nCoV-19 in participants receiving 1 or 2 doses in groups 1, 2, 7 and 8: differences in antibody titres 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) 6 months
Other Compare immunogenicity of ChAdOx1 nCoV-19 in participants receiving 1 or 2 doses in groups 1, 2, 7 and 8: longevity of immune responses Longevity of immune responses in participants who received 1 or 2 doses of ChAdOx1 nCoV-19 6 months
Other Describe the impact of previous vaccination with other ChAdOx1 vectored vaccines on safety and immune responses to ChAdOx1 nCoV-19 Differences reactogenicity profile, antibody titres and T-cell responses between groups 5d and 11 and their relationship with anti-vector neutralising antibody titres. 6 months
Other Assess the cell-mediated and humoral immunogenicity profile of ChAdOx1 nCoV-19 vaccine in HIV infected adults 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
6 months
Other 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 Relationship between nadir CD4 count vs vaccine immune responses 6 months
Other 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 Relationship between age at enrolment and vaccine immune response 6 months
Other Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults Immune responses to ChAdOx1 nCoV-19 (assessed as described above) 6 months
Other Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in HIV infected adults 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
Study duration (12 months from last vaccination)
Other To assess Impact of vaccination on HIV reservoirs Change in Total HIV DNA copies per million CD4 T cells Study duration (12 months from last vaccination)
Other To assess immunological correlates of protection in relation to occurrence of COVID-19 disease in ChAdOx1 nCoV-19 recipients 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 Throughout the study, average of 18 months]
Primary Assess the efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older. Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19 Study duration (12 months from last vaccination)
Primary Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in adults Occurrence of serious adverse events (SAEs) throughout the study duration. Study duration (12 months from last vaccination)
Secondary 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 Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination 7 days post vaccination
Secondary 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 Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination 7 days post vaccination
Secondary 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 Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination 28 days post vaccination
Secondary 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) Frequency of participants with clinically significant changes from baseline for safety laboratory measures (haematology and biochemistry blood results; except groups 4, 6, 9 & 10) 6 months
Secondary Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19 by measuring the number of disease enhancement episodes Occurrence of disease enhancement episodes Study duration (12 months from last vaccination)
Secondary Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: hospital admissions Number of hospital admissions associated with COVID-19 Study duration (12 months from last vaccination)
Secondary Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 Number of intensive care unit (ICU) admissions associated with COVID-19 6 months
Secondary Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: number of deaths Number of deaths associated with COVID-19 6 months
Secondary Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study 6 months
Secondary Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring incidence of Covid-19 Proportion of people diagnosed with severe Covid-19 disease (defined according to clinical severity scales) Study duration (12 months from last vaccination)
Secondary Assess humoral immunogenicity of ChAdOx1 nCoV-19: antibody quantification Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) 28 days post vaccination
Secondary Assess humoral immunogenicity of ChAdOx1 nCoV-19: seroconversion Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 28 post-vaccination 28 days post vaccination
Secondary Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays (groups 1, 2, 7 and 8 only) Interferon-gamma (IFN-?) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein 6 months
Secondary 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 Occurrence of solicited local reactogenicity signs and symptoms for 7 days following booster vaccination 7 days post vaccination
Secondary 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 Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following booster vaccination 7 days post vaccination
Secondary 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) Occurrence of unsolicited adverse events (AEs) for 28 days following booster vaccination 28 days post vaccination
Secondary 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) Frequency of participants with clinically significant changes from baseline from pre-booster for safety laboratory measures (haematology and biochemistry blood results) 6 months
Secondary 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 Antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination (seroconversion rates) 56 days post vaccination
Secondary 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) Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination 56 days post vaccination
See also
  Status Clinical Trial Phase
Completed NCT05065827 - Lung Ultrasound Findings in Patients With COVID-19 in a UK ED
Recruiting NCT05359770 - Association of Inspiratory Muscle Training With HD-tDCS for Assistance to Patients With Long Covid-19 N/A
Completed NCT04515147 - A Dose-Confirmation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Vaccine CVnCoV in Healthy Adults for COVID-19 Phase 2
Not yet recruiting NCT06025812 - Clinical Study of Omicron BA.4/5-Delta Strain Recombinant Novel Coronavirus Protein Vaccine (CHO Cells) N/A
Recruiting NCT05289115 - Protocol for Assistance to Patients With Long Covid-19 Undergoing Treatment With HD-tDCS N/A
Completed NCT04953078 - A Study to Evaluate Safety, Tolerability, and Reactogenicity of an RBD-Fc-based Vaccine to Prevent COVID-19 Phase 1
Completed NCT04779138 - Increasing Vaccine Uptake in Underresourced Public Housing Areas N/A
Not yet recruiting NCT05868239 - Impact of Aerosol Box Use During Cardiopulmonary Arrest: A Multicenter Study N/A
Completed NCT04818164 - Prone Position Improves End-Expiratory Lung Volumes in COVID-19 Acute Respiratory Distress Syndrome
Completed NCT04690413 - NOWDx Test for the Detection of Antibodies to COVID-19 N/A
Terminated NCT04530448 - Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization Phase 4
Completed NCT04572399 - UVA Light Device to Treat COVID-19 N/A
Recruiting NCT04610567 - Treatment of Patients With Mild Coronavirus-19 (COVID-19) Disease With Methotrexate Associated to LDL Like Nanoparticles (Nano-COVID19) Phase 1/Phase 2
Recruiting NCT04772170 - Observational Digital Biomarker Discovery in Respiratory Virus Challenge Studies
Recruiting NCT04581954 - Inflammatory Signal Inhibitors for COVID-19 (MATIS) Phase 1/Phase 2
Completed NCT04405934 - COG-UK Project Hospital-Onset COVID-19 Infections Study N/A
Enrolling by invitation NCT04484025 - SPI-1005 Treatment in Moderate COVID-19 Patients Phase 2
Completed NCT05572840 - Wear Your Mask, Wash Your Hands, Don't Get COVID-19 N/A
Withdrawn NCT04838847 - A Study to Evaluate the Immunogenicity and Safety of the SARS-CoV-2 mRNA Vaccine CVnCoV in Elderly Adults Compared to Younger Adults for COVID-19 Phase 3
Terminated NCT04371978 - Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19 Phase 3