BACKGROUND AND PURPOSE:

• AstraZeneca Oxford’s ChAdOx1 nCoV-19 vaccine uses an adenoviral vector ChAdOx1 that contains the SARS-CoV-2 structural surface glycoprotein antigen
• Voysey et al. (Lancet, 2020) evaluated the safety and efficacy of the AstraZeneca Oxford’s ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials

METHODS:

• Pooled data from four ongoing blinded, randomized, controlled trials (COV001-3 are single blind | COV005 is double blind)
  • COV001: Phase 1/2; UK
  • COV002: Phase 2/3; UK
  • COV003: Phase 3; Brazil
  • COV005: Phase 1/2; South Africa
• Participants
  • ≥18 years and older
• Interventions
  • ChAdOx1 nCoV-19 vaccine
    • Standard dose/Standard dose (SD/SD) cohort: 2 doses containing 5 × 10¹⁰ viral particles
    • Low dose/Standard dose (LD/SD) cohort: Subset in the UK trial received a half dose as their first dose and a standard dose as their second dose
  • Control
    • Meningococcal group A, C, W, and Y conjugate vaccine OR saline

Note: The lower dose (LD) was noted during quality control procedures (for COV002 trial) and the protocol was amended following review and approval

• Study design
  • Analysis was according to treatment received, with a data cutoff on Nov 4, 2020
  • Vaccine efficacy was calculated as 1-relative risk derived from a robust Poisson regression model adjusted for age
• Primary outcomes
  • Primary efficacy analysis: symptomatic COVID-19 in seronegative participants with a positive PCR test >14 days after a second dose of vaccine

RESULTS:

• 23,848 participants enrolled | 11,636 were included in the interim primary efficacy analysis

Efficacy

• SD/SD vaccine efficacy: 62.1% (95% CI, 41.0 to 75.7%)
  • ChAdOx1 nCoV-19 group: 0.6% developed COVID-19
  • Control: 1.6% developed COVID-19
• LD/SD vaccine efficacy: 90.0% (95% CI, 67.4 to 97.0%)
  • ChAdOx1 nCoV-19 group: 0.2% developed COVID-19
  • Control group: 2.2% developed COVID-19
• Overall vaccine efficacy across both groups was: 70.4% (95% CI, 54.8 to 80.6%)
  • ChAdOx1 nCoV-19 group: 0.5% developed COVID-19
  • Control group: 1.7% developed COVID-19

Safety

• From 21 days after the first dose, there were 10 people hospitalized for COVID-19, all of which were in the control arm
  • Severe COVID-19: 2 participants
  • Deaths: 1 participant
• During 74,341 person-months of safety follow-up (median follow-up 3.4 months, IQR 1.3 to 4.8 months) there were 175 severe adverse events among 168 participants
  • ChAdOx1 nCoV-19 group: 84 events
  • Control group: 91 events
• 3 adverse events were classified as possibly related to the vaccine
  • ChAdOx1 nCoV-19 group: 1 participant
  • Control group: 1 participant
  • Still masked: 1 participant

CONCLUSION:

• The AstraZeneca Oxford SARS-CoV-2 vaccine, the first peer-review study of a viral-vectored coronavirus, is safe and efficacious for the prevention of symptomatic COVID-19
  • Overall efficacy was 70.4%
  • Results were generalizable across diverse settings
  • Additional benefit of a viral-vectored vaccine is the use of routine refrigerated cold chain vs ultra-low temperature freezers required for mRNA vaccines
• The authors address the increased efficacy of LD/SD dosing vs SD/SD and state

Efficacy of 90.0% seen in those who received a low dose as prime in the UK was intriguingly high compared with the other findings in the study

Although there is a possibility that chance might play a part in such divergent results, a similar contrast in efficacy between the LD/SD and SD/SD recipients with asymptomatic infections provides support for the observation

Learn More – Primary Sources:

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

Comment: Oxford–AstraZeneca COVID-19 vaccine efficacy