Trial NCT04400838
Publication Voysey M, Lancet, 2020
Dates: 28/05/2020 to 04/11/2020
Funding: Mixed (United Kingdom National Institute for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca)
Conflict of interest: Yes
| Methods | |
| RCT | |
| Location :
Multicenter / United Kingdom 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 and access all medical records when relevant to study procedures; For females of childbearing potential only, willingness to practice continuous effective contraception 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 | 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; 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); 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 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) |
| Interventions | |
| Intervention
1 IM low-dose (2.2 × 10^10 vp)D0, 1 IM standard-dose (3.5-6.5 x 10^10 vp) ChAdOx1 nCoV-19 vaccine D28 2 IM standard-doses (3.5-6.5 x 10^10 vp) ChAdOx1 nCoV-19 vaccine on Days 0/28 |
|
| Control
2 IM doses of MenACWY control vaccine on Days 0/28 2 IM doses of MenACWY control vaccine on Days 0/28 | |
| Participants | |
| Randomized * participants | |
| Characteristics of participants Type of participants: Healthy volunteers N=* 2920 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: NR Age range: 18-55 | |
| Description of participants Healthy adults in 18 centres in the UK | |
| Primary outcome | |
| In the register Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19; Occurrence of serious adverse events (SAEs) throughout the study duration | |
| 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) | |
| Variants description | |
| Variants | |
| Description | |
| Documents avalaible |
Protocol Yes. In English Statistical plan Yes Data-sharing stated:
Yes, when the trials are
complete |
| 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. |