Clinical trial NCT04400838: Investigating a Vaccine Against COVID-19
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Coronavirus
Keywords: Covid-19
ChAdOx1 nCov19
sars-cov-2
vaccine
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2020-05-26
Enrollment: 12390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Assess the efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older.
timeFrame: Study duration (12 months from last vaccination)
measure: Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in adults
timeFrame: Study duration (12 months from last vaccination)
Secondary outcomes:
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
timeFrame: 7 days post 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
timeFrame: 7 days post 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
timeFrame: 28 days post 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)
timeFrame: 6 months
measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19 by measuring the number of disease enhancement episodes
timeFrame: Study duration (12 months from last vaccination)
measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: hospital admissions
timeFrame: Study duration (12 months from last vaccination)
measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19
timeFrame: 6 months
measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: number of deaths
timeFrame: 6 months
measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates
timeFrame: 6 months
measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring incidence of Covid-19
timeFrame: Study duration (12 months from last vaccination)
measure: Assess humoral immunogenicity of ChAdOx1 nCoV-19: antibody quantification
timeFrame: 28 days post vaccination
measure: Assess humoral immunogenicity of ChAdOx1 nCoV-19: seroconversion
timeFrame: 28 days post vaccination
measure: Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays (groups 1, 2, 7 and 8 only)
timeFrame: 6 months
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
timeFrame: 7 days post 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
timeFrame: 7 days post 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)
timeFrame: 28 days post 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)
timeFrame: 6 months
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
timeFrame: 56 days post 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)
timeFrame: 56 days post vaccination
Other outcomes:
measure: Exploratory Immunology by virus neutralising antibody assays
timeFrame: 6 months
measure: Exploratory Immunology by flow cytometry
timeFrame: 6 months
measure: Exploratory Immunology by functional antibody assays
timeFrame: 6 months
measure: Exploratory Immunology: anti-vector immunity
timeFrame: 6 months
measure: Measure exposure to COVID-19
timeFrame: 6 months
measure: Exploratory efficacy against infection: assess efficacy of the candidate ChAdOx1 nCoV-19 against SARS-CoV-2 infection by PCR or NAAT
timeFrame: 6 months
measure: Exploratory efficacy against infection: assess efficacy of the candidate ChAdOx1 nCoV-19 against SARS-CoV-2 infection
timeFrame: 6 months
measure: Compare safety, reactogenicity and immunogenicity between different manufacturing batches of ChAdOx1 nCoV-19 used in COV001 and COV002
timeFrame: 6 months
measure: Compare safety, reactogenicity and immunogenicity between different methods for measuring doses
timeFrame: 6 months
measure: Assess vaccine induced mucosal immunity: Nasal mucosa IgA levels at D0 and D28 in a subset of individuals
timeFrame: 6 months
measure: Compare viral shedding on stool samples of SARS-CoV-2 PCR or NAAT positive individuals
timeFrame: 6 months
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
timeFrame: 6 months
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
timeFrame: 6 months
measure: Describe the impact of previous vaccination with other ChAdOx1 vectored vaccines on safety and immune responses to ChAdOx1 nCoV-19
timeFrame: 6 months
measure: Assess the cell-mediated and humoral immunogenicity profile of ChAdOx1 nCoV-19 vaccine in HIV infected adults
timeFrame: 6 months
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
timeFrame: 6 months
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
timeFrame: 6 months
measure: Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults
timeFrame: 6 months
measure: Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in HIV infected adults
timeFrame: Study duration (12 months from last vaccination)
measure: To assess Impact of vaccination on HIV reservoirs
timeFrame: Study duration (12 months from last vaccination)
measure: To assess immunological correlates of protection in relation to occurrence of COVID-19 disease in ChAdOx1 nCoV-19 recipients
timeFrame: Throughout the study, average of 18 months]
Locations:
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
state: Hull
city: London
country: United Kingdom
facility: St Georges University Hospital NHS Foundation Trust
state: Tooting
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
city: Cambridge
country: United Kingdom
facility: NIHR Cambridge Clinical Research Facility
city: Edinburgh
country: United Kingdom
facility: NHS Lothian, Western General Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow University and NHS Greater Glasgow & Clyde, New Lister Building, Glasgow Royal Infirmary & Queen Elizabeth University Hospital
city: LIverpool
country: United Kingdom
facility: Liverpool School of Tropical Medicine (LSTM), Accelerator Research Clinic. Clinical Sciences Accelerator
city: London
country: United Kingdom
facility: London North West University Healthcare Trust (LNWUH), Northwick Park Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust, Department of Infection, St Thomas Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary
city: Newport
country: United Kingdom
facility: Public Health Wales
city: Nottingham
country: United Kingdom
facility: University of Nottingham Health Service, Cripps Health Centre, University Park
city: Oxford
country: United Kingdom
facility: CCVTM, University of Oxford, Churchill Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals, Royal Hallamshire Hospital
Study officials:
affiliation: University of Oxford
name: Andrew Pollard, Prof
role: PRINCIPAL_INVESTIGATOR
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