The highly anticipated vaccine (AZD1222) produced by a collaboration between Oxford University and AstraZeneca has become the first to have its interim study data published and appears to be as effective as reported in various media outlets.
AZD1222 is a viral vector based on an adenovirus derived from chimpanzees and subsequently modified so that it would induce a strong immune response against COVID-19. An interim analysis of the data has now been published by the Oxford Vaccine Group, based on four ongoing, and randomised controlled trials done across three countries. The trials include a Phase I/II (COV001) and Phase II/III (COV002), both from the UK, together with a Phase III trial (COV003) conducted in Brazil and a Phase I/II study (COV005) in South Africa, although three of these trials are single blind and only the South African study is double-blind. The interim data comes from all patients in the trials who received two doses of AZD1222. In COV001 patients are aged between 18 and 55 and randomised 1:1 to the test vaccine or a control vaccine (meningococcal group A, C W and Y). In COV002, participants (also aged 18 to 55) have received two doses of the vaccine, with the first being a lower dose which was boosted by the second, standard dose. However, subsequent enrolment to this arm occurred with patients aged 56 – 69 years of age and at a later stage patients aged 70 years and over and this later cohort received two standard doses of the vaccine.
The authors also reported that while COV002 was originally designed as a single dose study, this was amended to include a second booster dose. COV003 recruited individuals at high risk e.g., healthcare workers, 18 years and older and received a different dose again of the test vaccine administered up to 12 weeks apart. Finally, COV005 included healthy adults (18 – 65 years of age) who received the same two doses received in COV003. For the interim analysis, all studies were required to have at least 5 cases eligible for inclusion but neither COV001 or COV005 met these criteria and hence the interim analysis was based on only two studies. Vaccine efficacy was calculated 1 – adjusted relative risk and the primary outcome was set as virologically confirmed COVID-19 (via a swab test) combined with at least one qualifying symptom (e.g. fever, cough, shortness of breath or anosmia or ageusia.
A total of 23,848 patients were recruited across the 4 trials and 11,636 were included in the interim analysis. The majority of patients (86%) were aged between 18 and 55 and 12.2% were older than 56 years (those recruited later in the trial). In the trial with an initial lower dose, there were 33 cases of COVID-19, 3 (0.2%) in the test vaccine group and 30 (2.2%) in the control arm, which gave a vaccine efficacy of 90%. among those who received two standard doses, vaccine efficacy was 62.1%.
The authors were unable to explain why a lower followed by a standard dose resulted in higher vaccine efficacy and this is the subject of further work.
Voysey M et al. 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. Lancet 2020 doi.org/10.1016/ S0140-6736(20)32661-1