Randomized Controlled Trial
Study population and setting
This study was a phase 3 trial of the Novavax NVX-CoV2373 recombinant SARS-CoV-2 nanoparticle vaccine. NVX-CoV2373 is comprised of a trimeric full-length SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant. The trial assessed safety and efficacy of NVX-CoC2373 in preventing COVID-19 in participants in the UK, at a time when the UK variant (B.1.1.7) was beginning to circulate more widely. Individuals with a history of documented COVID-19 were excluded from participation. 14,039 participants meeting criteria for the per-protocol efficacy population, were randomized 1:1, with 7020 in the vaccine group and 7019 in the placebo group. Participants at the 33 sites across the UK were between the ages of 18-84 years, and received two 5 ug intramuscular doses, 21 days apart. Solicited adverse events were recorded for 8 days after each dose, and unsolicited adverse events were recorded through 28 days after the second dose. The primary endpoint was symptomatic COVID-19 confirmed by qPCR, with onset at least 7 days after the second vaccination in serologically negative patients. At symptom onset, respiratory specimens were collected daily f or 3 days in order to confirm infection.
Summary of Main Findings
The most commonly reported adverse events were injection site pain, headache, muscle pain, and fatigue. These were all mild and of short duration. Adverse events were more commonly reported in the vaccine group compared to the placebo group, and more common after the second dose compared to the first dose. Additionally, they were more common among younger vaccine recipients (18-64 years) compared to older recipients (>64 years). Fever was only reported in 2% and 4.8% of participants after the first and second dose of vaccine, respectively. Out of 14,039 participants, there were few cases of virologically confirmed, symptomatic, mild, moderate or severe COVID-19 with onset at least 7 days after the second dose. There were 10 cases in the vaccinated group and 96 cases in the placebo group, resulting in an estimated 89.7% vaccine efficiency. Vaccine efficacy among patients >64 years was 88.9%. Post-hoc analysis of patient respiratory swab samples collected identified 29 cases of COVID-19 where the isolated strain was the prototype strain, 66 cases where it was the UK variant, and 11 cases where the strain was unknown, respectively. Based on these identifications, vaccine efficacy against the prototype strain was 96.4%, while efficacy against UK variant was 86.3%.
6% of participants in the study had at least one co-morbid condition, which is an important variable to include in SARS-CoV-2 vaccine trials due to the fact that COVID-19 can be particularly dangerous for individuals with co-morbidities.
Over 94% of participants in this trial where white, and this vaccine should be tested in a more diverse population of individuals in future trials. Next, the viral strains from patient samples were sequenced and identified post-hoc, so the trial was not powered to assess efficacy of the vaccine against individual strains of SARS-CoV-2. The trial began in September 2020, while the UK (B.1.1.7) variant was not identified and sequenced until October 2020. Also, vaccine efficacy estimates were derived from a short duration of observation time (~ 3 months). Therefore, this study requires ongoing follow-up to determine the durability of the effectiveness. Interestingly, in a previous analysis in South Africa from the same group, serologically positive individuals were excluded from analysis, but that was not done here.
This was a report of a recombinant vaccine that demonstrated high efficacy against the UK variant in a phase 3 clinical trial.
This review was posted on: 28 May 2021