Interim Efficacy Results
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised control trials in Brazil, South Africa and the UK
Summary
An interim analysis of the University of Oxford’s vaccine, ChAdOx1 nCoV-19, shows that it prevents symptomatic COVID-19 with 70.4% efficacy across all cohorts.
Two different dose regimes were assessed. In one, a low dose was followed by a standard dose, and this prevented 9 out of 10 symptomatic COVID-19 cases. When two standard doses of the vaccine were used, 6 out of 10 symptomatic COVID-19 cases were prevented.
Importantly, there were no hospitalised or severe cases of COVID-19 in any participants who received the vaccine. The study also showed that the vaccine has an acceptable safety profile.
Aims
The outcomes reported at this stage include the safety of the vaccine and the protection provided against symptomatic COVID-19. This analysis includes 23,848 participants across four clinical trials: two in the UK, one in Brazil and one in South Africa.
We previously reported on safety and the immune response associated with the vaccine in people aged 18-55 years and in older adults.
This report is the first publication showing efficacy of a vaccine against SARS-CoV-2 and provides evidence of protection in this subset of participants included in the interim analysis.
The Trial
Between 23rd April and 4th November 2020, a total of 23,848 participants were enrolled in trials in the UK, Brazil and South Africa. The efficacy analysis included 11,636 participants from the UK and Brazil study sites, who were randomly allocated to receive either the ChAdOx1 nCoV-19 vaccine or a ‘control’ vaccine for comparison. The safety analysis was pooled across the four trials, which include participants of different ages, healthcare workers and people with stable pre-existing health conditions.
Two dose regimes were tested as part of this study: a standard dose of the vaccine (the same dose used in the Phase I and II studies), followed by a booster of the standard dose; and a lower dose of the vaccine, followed by a standard dose booster. The doses used in this trial were chosen based on previous experiences with other ChAdOx1 based vaccines.
During the COV002 trial in the UK, two methods of dose measurement were used, which provided different readings of the vaccine dose. Following discussion with the regulators, a reading was used, which resulted in a lower dose being given to a subset of participants. Although the lower dose was unplanned, following further discussion with regulators, the trial continued to recruit participants into this group to receive the low-dose, standard-dose regime. It was agreed with the regulators that a new group of participants were recruited who received the standard-dose, standard-dose regime, allowing for data to be collected on both regimens.
Study participants remained blinded throughout and will not know whether they received the ChAdOx1 nCoV-19 vaccine or the control vaccine until the participants are unblinded.
The Results:
Safety
The report shows an acceptable safety profile for the ChAdOx1 nCoV-19, similar to that of other vaccines of this type. Across all four studies, three adverse events were classified as possibly linked to a vaccine, one in the control group, one in the ChAdOx1 nCoV-19 group and one which remains blinded. In total, 168 serious adverse events were reported, 84 who received the ChAdOx1 nCoV-19 vaccine and 91 in the control groups. The majority of these were classified as not related to the vaccine.
The safety profile was reported in our previous studies, and includes pain and tenderness at the injection site, and flu-like symptoms such as headache, fever and muscle aches.
Efficacy
In our previous studies, we reported that following a single vaccination all participants produced good immune responses against the spike protein of the coronavirus in both the younger (18-55) and older (56-69, 70 and over) age groups. Here, we show that the immune response initiated provides protection against symptomatic COVID-19. Results were consistent across the UK and Brazil trials, indicating that the efficacy is similar in two diverse settings.
The efficacy results observed are below:
| Dose regime |
Cases in ChAdOx1 nCoV-19 group |
Cases in control group | Efficacy |
|---|---|---|---|
| Low-dose, standard-dose | 3 of 1367 0.2% | 30 of 1374 2.2% | 90.0% |
|
Standard-dose, standard-dose |
27 of 4440 0.6% | 71 of 4455 1.6% | 62.1% |
| All participants | 30 of 5807 0.5% | 101 of 5829 1.7% | 70.4% |
This means that in the low-dose, standard-dose group, every 9 in 10 cases of symptomatic COVID-19 would be prevented by the vaccine. In the standard-dose, standard-dose group, every 6 in 10 cases would be prevented.
Importantly, no participants who received the vaccine were hospitalised with COVID-19 and no severe cases of COVID-19 were seen in the vaccinated groups. In the control group, 10 participants were hospitalised with COVID-19 and two cases were classified as severe COVID-19.
What’s next?
Modelling studies have shown that a vaccine with 60-80% efficacy could allow a reduction of physical distancing measures, and the World Health Organisation set a target of 50% efficacy for deployable COVID-19 vaccines. Our data exceed these target thresholds, providing potential for a significant impact on public health.
The University of Oxford and AstraZeneca teams have submitted data to the regulatory agencies for full review and consideration for licensing.
We have completed recruitment of over 23,000 people in our clinical trials and all participants continue to be followed up. Further analyses will be undertaken to assess efficacy in older adults, as the majority of cases observed so far were in those aged 18-55 years, as the older adults were recruited later. Future analyses will also seek to understand whether the vaccine can prevent asymptomatic COVID-19, which could provide a considerable reduction in community transmission.
