A Study of a Candidate COVID-19 Vaccine (COV001)

Conditions

Coronavirus

Keywords

COVID-19, Vaccine

Brief summary

A phase I/II single-blinded, randomised, multi-centre study to determine efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in UK healthy adult volunteers aged 18-55 years. The vaccine will be administered intramuscularly (IM) into the deltoid region of the arm

Detailed description

There will be 4 study groups and it is anticipated that a total of 1090 volunteers will be enrolled. Volunteers will participate in the study for approximately 12 months from last vaccination visit (approximately 15 months from enrolment for participants receiving 2 doses)

Ruth Drury, Susana Camara, Irina Chelysheva, Sagida Bibi, Katherine Sanders et al. (15 authors)

Nature Communications2024-04-2223 citations

10.1038/s41467-024-47463-6

Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.

Liu Z, Le K, Zhou X, Alexander JL, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald TJ, Lamb CA, Sebastian S, Kok K, Lees CW, Hart AL, Pollok RC, Boyton RJ, Altmann DM, Pollock KM, Goodhand JR, Kennedy NA, Ahmad T, Powell N, CLARITY study investigators.

2022-12-0532 citations

10.1016/s2468-1253(22)00389-2

Comparison of blood and lymph node cells after intramuscular injection with HIV envelope immunogens

Suzanne Day, Charandeep Kaur, Hannah M. Cheeseman, Emily de Groot, Leon R. McFarlane et al. (14 authors)

Frontiers in Immunology2022-10-0515 citations

10.3389/fimmu.2022.991509

Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002).

Flaxman A, Marchevsky NG, Jenkin D, Aboagye J, Aley PK, Angus B, Belij-Rammerstorfer S, Bibi S, Bittaye M, Cappuccini F, Cicconi P, Clutterbuck EA, Davies S, Dejnirattisai W, Dold C, Ewer KJ, Folegatti PM, Fowler J, Hill AVS, Kerridge S, Minassian AM, Mongkolsapaya J, Mujadidi YF, Plested E, Ramasamy MN, Robinson H, Sanders H, Sheehan E, Smith H, Snape MD, Song R, Woods D, Screaton G, Gilbert SC, Voysey M, Pollard AJ, Lambe T, Oxford COVID Vaccine Trial group.

2021-09-01208 citations

10.1016/s0140-6736(21)01699-8

A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial

Pedro M. Folegatti, Kate Harrison, Lorena Preciado‐Llanes, Fernando Ramos Lopez, Mustapha Bittaye et al. (23 authors)

Nature Communications2021-07-3057 citations

10.1038/s41467-021-24906-y

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bhorat QE, Bibi S, Briner C, Cicconi P, Clutterbuck EA, Collins AM, Cutland CL, Darton TC, Dheda K, Dold C, Duncan CJA, Emary KRW, Ewer KJ, Flaxman A, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hill C, Hill HC, Hirsch I, Izu A, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Libri V, Lillie PJ, Marchevsky NG, Marshall RP, Mendes AVA, Milan EP, Minassian AM, McGregor A, Mujadidi YF, Nana A, Padayachee SD, Phillips DJ, Pittella A, Plested E, Pollock KM, Ramasamy MN, Ritchie AJ, Robinson H, Schwarzbold AV, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Thomson EC, Török ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, White T, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ, Oxford COVID Vaccine Trial Group.

2021-02-19903 citations

10.1016/s0140-6736(21)00432-3

Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses.

Barrett JR, Belij-Rammerstorfer S, Dold C, Ewer KJ, Folegatti PM, Gilbride C, Halkerston R, Hill J, Jenkin D, Stockdale L, Verheul MK, Aley PK, Angus B, Bellamy D, Berrie E, Bibi S, Bittaye M, Carroll MW, Cavell B, Clutterbuck EA, Edwards N, Flaxman A, Fuskova M, Gorringe A, Hallis B, Kerridge S, Lawrie AM, Linder A, Liu X, Madhavan M, Makinson R, Mellors J, Minassian A, Moore M, Mujadidi Y, Plested E, Poulton I, Ramasamy MN, Robinson H, Rollier CS, Song R, Snape MD, Tarrant R, Taylor S, Thomas KM, Voysey M, Watson MEE, Wright D, Douglas AD, Green CM, Hill AVS, Lambe T, Gilbert S, Pollard AJ, Oxford COVID Vaccine Trial Group.

2020-12-17264 citations

10.1038/s41591-020-01179-4

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Collins AM, Colin-Jones R, Cutland CL, Darton TC, Dheda K, Duncan CJA, Emary KRW, Ewer KJ, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Goodman AL, Green CM, Green CA, Heath PT, Hill C, Hill H, Hirsch I, Hodgson SHC, Izu A, Jackson S, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Lawrie AM, Lelliott A, Libri V, Lillie PJ, Mallory R, Mendes AVA, Milan EP, Minassian AM, McGregor A, Morrison H, Mujadidi YF, Nana A, O'Reilly PJ, Padayachee SD, Pittella A, Plested E, Pollock KM, Ramasamy MN, Rhead S, Schwarzbold AV, Singh N, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Tarrant R, Thomson EC, Török ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Watson MEE, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ, Oxford COVID Vaccine Trial Group.

2020-12-083,647 citations

10.1016/s0140-6736(20)32661-1

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, Bellamy D, Bibi S, Bittaye M, Clutterbuck EA, Dold C, Faust SN, Finn A, Flaxman AL, Hallis B, Heath P, Jenkin D, Lazarus R, Makinson R, Minassian AM, Pollock KM, Ramasamy M, Robinson H, Snape M, Tarrant R, Voysey M, Green C, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ, Oxford COVID Vaccine Trial Group.

2020-07-201,868 citations

10.1016/s0140-6736(20)31604-4

Are Genetic Vaccines the Right Weapon against COVID-19?

Antonella Conforti, Emanuele Marra, Giuseppe Roscilli, Fabio Palombo, Gennaro Ciliberto et al. (6 authors)

Molecular Therapy2020-06-0921 citations

10.1016/j.ymthe.2020.06.007

Interventions

BIOLOGICALChAdOx1 nCoV-19

A single dose of 5x10\^10vp of ChAdOx1 nCoV-19

BIOLOGICALMenACWY

Standard single dose of MenACWY vaccine delivered intramuscularly

BIOLOGICALChAdOx1 nCoV-19 full boost

A single dose of 5x10\^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 5x10\^10vp of ChAdOx1 nCoV-19

BIOLOGICALChAdOx1 nCoV-19 half boost

A single dose of 5x10\^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 2.5x10\^10vp of ChAdOx1 nCoV-19

BIOLOGICALMenACWY boost

A standard dose of MenACWY followed by a boost dose of MenACWY

DRUGParacetamol

1g every 6 hours for 24 hours

BIOLOGICALChAdOx1 nCoV-19 0.5mL boost

A single dose of 5x10\^10vp of ChAdOx1 nCoV-19 followed by a boost dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10\^10vp)

BIOLOGICALChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine (LV)

A dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10\^10vp) 9 months after receiving a single or double dose of 5x10\^10vp of ChAdOx1 nCoV-19

BIOLOGICALChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine two (LVT)

A dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10\^10vp) 9 months after receiving a single or double dose of MenACWY, then a boost 4-12 weeks later

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

The volunteer must satisfy all the following criteria to be eligible for the study: * Healthy adults aged 18-55 years. * Able and willing (in the Investigator's opinion) to comply with all study requirements (participants must not rely on public transport or taxis). * 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 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.

Exclusion criteria

The volunteer may not enter the study if any of the following apply: * Planned receipt of any vaccine 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 vaccine. Participants will be encouraged to receive this vaccination at least 7 days before or after their study vaccine. * Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines). * 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, including HIV infection; 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) . * Any autoimmune conditions, except mild psoriasis, well-controlled autoimmune thyroid disease, vitiligo or stable coeliac disease not requiring immunosuppressive or immunomodulatory therapy. * History of allergic disease or reactions likely to be exacerbated by any component of the ChAdOx1 nCoV-19 or MenACWY vaccines. * Any history of angioedema . * Any history of anaphylaxis . * Pregnancy, lactation or willingness/intention to become pregnant during the study. * History of 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 (e.g. ongoing severe depression, history of admission to an in-patient psychiatric facility, recent suicidal ideation, history of suicide attempt, bipolar disorder, personality disorder, alcohol and drug dependency, severe eating disorder, psychosis, use of mood stabilisers or antipsychotic medication). * Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture. * Any other serious chronic illness requiring hospital specialist supervision. * Chronic respiratory diseases, including mild asthma (resolved childhood asthma is allowed) * Chronic cardiovascular disease (including hypertension), gastrointestinal disease, liver disease (except Gilberts Syndrome), renal disease, endocrine disorder (including diabetes) and neurological illness (excluding migraine) * Seriously overweight (BMI≥40 Kg/m2) or underweight (BMI≤18 Kg/m2) * Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week. * Suspected or known injecting drug abuse in the 5 years preceding enrolment. * Any clinically significant abnormal finding on screening biochemistry, haematology blood tests or urinalysis. * 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. * History of laboratory confirmed COVID-19. * New onset of fever or a cough or shortness of breath or anosmia/ageusia since February 2020. Should a reliable test become available, this

Design outcomes

Primary

Measure	Time frame	Description
Assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19: Number of virologically confirmed (PCR positive) symptomatic cases	6 months	Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19
Assess the safety of the candidate vaccine ChAdOx1 nCoV: Occurrence of serious adverse events (SAEs)	Throughout the study, average of 18 months	Occurrence of serious adverse events (SAEs) throughout the study until a cutoff date of 1st July 2021 or 6 months post late vaccination visit, whichever is latest

Secondary

Measure	Time frame	Description
Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV by measuring the number of disease enhancement episodes	6 months	Occurrence of disease enhancement episodes
Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by ICU admissions	6 months	Number of intensive care unit admissions associated with COVID-19
Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by COVID-19 related deaths	6 months	Number of deaths associated with COVID-19
Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19	6 months	Occurrence of severe COVID-19 disease (defined according to clinical severity scales)
Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates	6 months	Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study
Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays	6 months	Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein
Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19	6 months	Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates)
Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited local reactogenicity signs and symptoms	7 days following vaccination	Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination
Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited systemic reactogenicity signs and symptoms	7 days following vaccination	Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination
Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of unsolicited adverse events (AEs)	7 or 28 days following vaccination	Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination (7 days following vaccination for groups 1c, 1d, 5a & 5b)
Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV through standard blood tests	6 months	Change from baseline for safety laboratory measures (haematology and biochemistry blood results)
Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by hospital admissions	6 months	Number of hospital admissions associated with COVID-19

Other

Measure	Time frame	Description
Compare viral shedding on stool samples of SARS-CoV-2 PCR or NAAT positive individuals	6 months	Differences in viral shedding on stool between vaccine and comparator arms at 7 days and beyond post SARS-CoV-2 PCR or NAAT positivity
Assess immunogenicity of a delayed three dose ChAdOx1 nCoV-19 schedule	Blood samples drawn at LV14, LV28 and LV182	Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) post boost
assess immunological correlates of protection in relation to occurrence of COVID-19 disease in ChAdOx1 nCoV-19 recipients	Throughout the study, average of 18 months	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
Assess immunogenicity of ChAdOx1 nCoV-19 given as homologous prime-boost	6 months	Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) post boost
Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through Virus neutralising antibody assays	6 months	Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus
Assess safety, reactogenicity, immunogenicity and efficacy endpoints, for participants receiving prophylactic paracetamol	6 months	All safety, reactogenicity, immunogenicity and efficacy endpoints

Countries

United Kingdom

Outcome results

None listed