Covid-19 Living Data

Trial NCT04444674
Publication Voysey M (COV005), Lancet, 2020
Dates: 6/28/2020 to 11/4/2020
Funding: Mixed (UK Research and Innovation (For Vaccine supply only), The Bill and Melinda Gates Foundation and South African Medical Research Counci)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / South Africa Follow-up duration (days): Median=3.4

Inclusion criteria	1.Healthy adults aged 18-65 years. 2.Documented result of not being infected with HIV (including screening by a rapid HIV antibody test) within two weeks of randomization into the study for Group-1 and Group-2 participants only. 3.Able and willing (in the Investigator's opinion) to comply with all study requirements. 4.Willing to allow investigators review available medical records, and review all medical and laboratory records if participant is admitted to hospital with respiratory tract infection suspected or confirmed to be COVID-19. 5.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 (within 14 days of randomization) or vaccination. 6.For Group-3 only (i.e. HIV-infected), need to have been on anti-retroviral treatment for at least three months and HIV-1 viral load is <1,000 copies/ml within two weeks of randomization. 7.Agreement to refrain from blood donation during the course of the study. Provide written informed consent.
Exclusion criteria	1.Planned receipt of any vaccine other (licensed or investigational) than the study intervention within 30 days before and after each study vaccination. 2.Use of any unproven registered and unregistered treatments for COVID-19. 3.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). 4.Administration of immunoglobulins and/ or any blood products within the three months preceding the planned administration of the vaccine candidate. 5.HBSAg positivity on the screening sample. 6.Grade 2 or higher level of abnormality for FBC, U&E or LFT based on DAIDS Grading Criteria (Version 2.1, July 2017) 7.History of allergic disease or reactions likely to be exacerbated by any component of the ChAdOx1 nCoV-19 vaccine. 8.Any history of hereditary angioedema or idiopathic angioedema. 9.Any history of anaphylaxis in relation to vaccination. 10.Pregnancy, lactation or willingness/intention to become pregnant during the study. 11.History of 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 venipuncture. 14.Any other serious chronic illness requiring hospital specialist supervision. 15.Chronic respiratory diseases, including asthma 16.Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness 17.Seriously overweight (BMI ? 40 Kg/m2) 18.Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week. 19.Suspected or known injecting drug abuse in the 5 years preceding enrollment. 20.Any clinically significant abnormal finding on screening urinalysis. 21.Any other significant disease, disorder or finding which may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study or impair interpretation of the study data. 22.History of laboratory confirmed COVID-19 illness or known contact with a person that was infected with SARS-COV-2. 23.New onset of fever or a cough or shortness of breath in the 30 days preceding screening and/or enrollment 24.Travel history to any other country with widespread epidemic since January 2020 25.In addition to above, Group 1 & 2 participants need to fulfill the following exclusion criteria: Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within the past 6 months ( topical steroids are allowed). 26.Any confirmed or suspected immunosuppressive or immunodeficient state (except HIV infection for Group-3), asplenia, recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed).
Interventions
	Treatment ChAdOx1 std 2 doses (*)
	Control Saline
Participants
	Randomized 2013 participants
	Characteristics of participants Type of participants: Healthy volunteers N=2013 Adults: 2013 Children: 0 Pregnant women: 0 HIV patients: 0 Health care workers: 0 Participants close contacts to COVID-19 patients: 0 Mean age : NR 1136 males
	Description of participants Healthy adults from four studies in multiple centres in Brazil, South Africa, and the UK
Primary outcome
	In the register 1.Assess the incidence of adverse events (intervention-related and intervention-unrelated) in HIV-negative adults aged 18-65 year receiving candidate ChAdOx1 nCoV-19 vaccine or placebo (safety) [ Time Frame: Up to 12 months post enrollment ] 2.Determine if there is a reduction of severe and non-severe COVID-19 disease in HIV-negative adults who receive candidate vaccine ChAdOx1 nCoV-19 compared to placebo recipients (efficacy) [ Time Frame: Up to 12 months post enrollment ] 3.Assess the incidence of adverse events (in
	In the report Virologically confirmed, symptomatic COVID-19, defined as a NAAT-positive swab combined with at least one qualifying symptom (fever ?37·8°C, cough, shortness of breath, or anosmia or ageusia)
Documents avalaible	Protocol Yes Statistical plan Yes Data-sharing stated Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
General comment	In addition to the published article, the trial registry, study protocol and statistical analysis plan were used in data extraction and assessment of risk of bias. Interim efficacy was assessed by combining data from COV002 (UK) and COV003 (Brazil). The safety of the vaccine was assessed using data from four studies (COV001, COV002, COV003 and COV005). Three studies were single blind and one (COV005) was double blind, all of the which are ongoing. The statistical analysis plan was developed once the trials were underway but before data cutoff on Nov 4, 2020. COV001 and COV005 were not included in the efficacy assessment for the interim analysis due to having fewer than 5 cases eligible for inclusion in the primary outcome, however, according to the report COV001 included an efficacy cohort and COV005 expanded enrollment to a wider population with higher likelihood of exposure. This data (though small) was not reported, but "it is expected that they will be included in efficacy assessments in future analyses once more cases have accrued." There were several changes to the protocols after study initiation, notably: 1) a booster dose incorporated into the three trials that were initially designed to assess a single-dose of ChAdOx1 nCoV-19 compared with control (COV001, COV002, and COV003) after review of the antibody response data from COV001. 2) In COV002 a dose of 5 × 10¹⁰ viral particles was chosen but a 2·2 × 10¹⁰ viral particles dose was given for some of the participants future batches are all released with a specification dose of 3·5–6·5 × 10¹⁰ viral particles, and this was used for the booster doses in the efficacy and the protocol was amended resulting in enrolment of two distinct groups with different dosing regimens. Future batches are all released with a specification dose of 3·5–6·5 × 10¹⁰ viral particles, and this was used for the booster doses in the efficacy analysis presented here. Otherwise, there were no major differences in population, procedures or treatment between the published article and registry and protocol.