Investigating a Vaccine Against COVID-19

Coronavirus Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04400838
• Other study ID #: COV002
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• 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
• 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

Related Conditions & MeSH terms

• Coronavirus
• Coronavirus Infections
• COVID-19

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