A phase III study to investigate a vaccine against COVID-19

Conditions

COVID-19 (SARS-CoV-2 infection) Infections and Infestations

Clemens SAC, Folegatti PM, Emary KRW, Weckx LY, Ratcliff J, Bibi S, De Almeida Mendes AV, Milan EP, Pittella A, Schwarzbold AV, Sprinz E, Aley PK, Bonsall D, Fraser C, Fuskova M, Gilbert SC, Jenkin D, Kelly S, Kerridge S, Lambe T, Marchevsky NG, Mujadidi YF, Plested E, Ramasamy MN, Simmonds P, Golubchik T, Voysey M, Pollard AJ, AMPHEUS Project, Oxford COVID Vaccine Trial Team.

2021-10-0642 citations

10.1038/s41467-021-25982-w

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

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

Interventions

Current interventions as of 25/11/2020: Volunteers will initially be invited for a screening visit. Prior to attending they will have received written information about the study and had time to consi

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Current inclusion criteria as of 25/11/2020: 1. Adults aged 18 to 55 years of age 2. Adults aged 56-69 years old (after review of safety data by DSMB in this age group in the UK trial) 3. Adults aged 70 and above years old (after review of safety data by DSMB in this age group in the UK trial) 4. Able and willing (in the Investigator’s opinion) to comply with all study requirements 5. Willing to allow the investigators to discuss the volunteer’s medical history with their General Practitioner/personal doctor and access all medical records when relevant to study procedures 4. 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 5. Agreement to refrain from blood donation during the course of the study 6. Provide written informed consent 7. Health professionals and/or adults at high risk of exposure to SARS-CoV-2 Previous inclusion criteria: 1. Adults aged 18 to 55 years of age. Upper age can be extended upon the availability of additional safety data in an older population 2. Able and willing (in the Investigator’s opinion) to comply with all study requirements 3. Willing to allow the investigators to discuss the volunteer’s medical history with their General Practitioner/personal doctor and access all medical records when relevant to study procedures 4. 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 5. Agreement to refrain from blood donation during the course of the study 6. Provide written informed consent

Exclusion criteria

Exclusion criteria: 1. 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 study team should be informed as soon as possible 2. 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 accidentally unblind participants to group allocation. Participation in COV003 can only be allowed if volunteers are kept blinded to their serology results from local/national serological surveys 3. Planned receipt of any vaccine (licensed or investigational), other than the study intervention, within 30 days before and after study vaccination 4. 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) 5. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate 6. Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent severe infections and chronic use (more than 14 days) of immunosuppressant medication within the past 6 months except topical steroids or short-term oral steroids (course lasting =14 days) 7. History of allergic disease or reactions likely to be exacerbated by any component of ChAdOx1 nCoV-19 or MenACWY or paracetamol 8. Any history of angioedema 9. Any history of anaphylaxis 10. Pregnancy, lactation or willingness/intention to become pregnant during the study 11. Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ) 12. History of serious psychiatric condition likely to affect participation in the study 13. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture 14. Suspected or known current alcohol or drug dependency 15. 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) 16. History of laboratory-confirmed COVID-19 17. Seropositive for SARS-CoV-2 antibodies before enrolment 18. New onset of fever or a cough or shortness of breath or anosmia/ageusia since February 2020, unless seronegative for SARS-CoV-2 antibodies at screening 19. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) 20. 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

Design outcomes

Primary

Measure	Time frame
Current primary outcome measure as of 25/11/2020: Virologically confirmed (PCV positive) symptomatic cases of COVID-19 over the course of 12 months Previous primary outcome measure: Virologically confirmed (PCR positive) symptomatic cases of COVID-19 over the course of 12 months	—

Secondary

Measure	Time frame
1. Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, recorded in an electronic diary (in a subset of 200 participants only) 2. Occurrence of serious adverse events reported by participant/documented in an electronic diary over the course of 12 months 3. Occurrence of disease enhancement episodes reported by participant/documented in hospital records over the course of 12 months 4. Hospitalization due to PCR-confirmed COVID-19 disease, reported by participants, over the course of 12 months 5. Severe PCR confirmed COVID-19 disease, parameters recorded from hospital records/participant interview, over the course of 12 months 6. Death associated with COVID-19 disease over the course of 12 months 7. Antibodies against SARS-CoV-2 non-spike protein (sero-efficacy rates) measured by ELISA over the course of 12 months 8. Antibodies against SARS-CoV-2 spike protein (sero-conversion rates) measured by ELISA at 28 days post vaccination 9. Virus neutralising antibody (NAb) assays against live and/or pseudotyped SARS-CoV-2 virus at 28 days post vaccination All participants will be invited to follow-up visits at day 28, 90, 182 and 364 following their last vaccination. Participants will be asked to contact the study team if they develop symptoms suggestive of COVID-19 at any point during the trial. Symptomatic participants will be asked to present for a visit to test for SARS-CoV-2 PCR.	—

Measure

Time frame

1. Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, recorded in an electronic diary (in a subset of 200 participants only) 2. Occurrence of serious adverse events reported by participant/documented in an electronic diary over the course of 12 months 3. Occurrence of disease enhancement episodes reported by participant/documented in hospital records over the course of 12 months 4. Hospitalization due to PCR-confirmed COVID-19 disease, reported by participants, over the course of 12 months 5. Severe PCR confirmed COVID-19 disease, parameters recorded from hospital records/participant interview, over the course of 12 months 6. Death associated with COVID-19 disease over the course of 12 months 7. Antibodies against SARS-CoV-2 non-spike protein (sero-efficacy rates) measured by ELISA over the course of 12 months 8. Antibodies against SARS-CoV-2 spike protein (sero-conversion rates) measured by ELISA at 28 days post vaccination 9. Virus neutralising antibody (NAb) assays against live and/or pseudotyped SARS-CoV-2 virus at 28 days post vaccination All participants will be invited to follow-up visits at day 28, 90, 182 and 364 following their last vaccination. Participants will be asked to contact the study team if they develop symptoms suggestive of COVID-19 at any point during the trial. Symptomatic participants will be asked to present for a visit to test for SARS-CoV-2 PCR.

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Countries

Brazil

Outcome results

None listed