Covid-19 Living Data

Trial ISRCTN89951424
Publication Voysey M, Lancet, 2020
Dates: 23/06/2020 to 04/11/2020
Funding: Mixed (University of Oxford, Fundação Lemann, Fundação Brava, Fundação Telles, Instituto D’or de Ensino e Pesquisa and AstraZeneca Brasil)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / Brazil Follow-up duration (months): 2.95
	*
Inclusion criteria	Adults aged ?18 years 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/personal doctor 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 Health professionals and/or adults at high risk of exposure to SARS-CoV-2
Exclusion criteria	Participation in COVID-19 prophylactic drug trials for the duration of the study Participation in SARS-CoV-2 serological surveys where participants are informed of their serostatus for the duration of the study Planned receipt of any vaccine (licensed or investigational), other than the study intervention, within 30 days before and after study vaccination 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, 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) History of allergic disease or reactions likely to be exacerbated by any component of ChAdOx1 nCoV-19 or MenACWY or paracetamol 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 Suspected or known current alcohol or drug dependency 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 Seropositive for SARS-CoV-2 antibodies before enrolment 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 Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) 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
Interventions
	Intervention 2 IM standard-doses (3.5-6.5 x 10^10 vp) ChAdOx1 nCoV-19 vaccine on Days 0/28
	Control 1 IM dose of MenACWY control vaccine on Day 0, 1 IM dose normal saline Day 28
Participants
	Randomized * participants
	Characteristics of participants Type of participants: Healthy volunteers N=* 1671 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: NR Age range: 18+
	Description of participants Healthy SARS-CoV-2 serology/DNA negative adults in six centres in Brazil
Primary outcome
	In the register Virologically confirmed (PCV positive) symptomatic cases of COVID-19 over the course of 12 months
	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 available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes, when the trials are complete Data accessibility: data can be shared through a secure online platform after signing a data access agreement
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	Some concerns
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 × 10¹? viral particles was chosen but a 2·2 × 10¹? viral particles dose was given for some of the participants future batches are all released with a specification dose of 3·5–6·5 × 10¹? 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 × 10¹? 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.