by Reynald Castaneda in London
The University of Oxford is drawing up trial plans to investigate the safety and immunogenicity of combining different Covid-19 vaccines once more than one is authorised in the UK, a source familiar with the trial said.
Pfizer/BioNTech’s BNT162b2 vaccine locked in temporary authorization from the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) on 2 December. This means it is likely to be the first vaccine to be included in the combination study, the source added. On 1 October, the EMA started a rolling review of the university’s AZD1222 vaccine, which is being developed in collaboration with AstraZeneca. One rationale behind the combination is the recent AZD1222 trial data showing the vaccine could have an even better shot at efficacy if used only as a primer vaccine in a primer-booster approach, the source explained.
The combination trial would investigate if using one authorised vaccine as a primer and another as a booster would yield improved efficacy, the source noted. The study would have a primary endpoint involving reactogenicity and other safety signals, as well as humoral and cellular immunogenicity data, he added.
The trial would be designed pragmatically, with each arm having volunteer numbers in the low hundreds, the source added, noting the trial would not recruit enough volunteers to investigate the difference in protection efficacy between arms. Other design elements would depend on the data supporting each vaccine’s authorisation, such as the duration between jabs, he added.
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Rolling EMA review processes were also initiated for Moderna’s mRNA-1273 and Johnson & Johnson’s JNJ-78436735 on 16 November and 1 December, respectively. BNT162b2 and mRNA-1273 are mRNA vaccines, whereas AZD1222 uses a chimpanzee adenovirus vector and JNJ-78436735 features the human adenovirus type 26 (AD26). While JNJ-78436735 is the only vaccine candidate under investigation as a single-dose vaccine, it is also in a two-dose trial.
So far, only the Russia-developed Sputnik V vaccine has data featuring a prime-boost approach comprising a vector mixture, specifically of AD26 and AD5. On 11 December, the Russian Direct Investment Fund announced investigations of Sputnik V’s AD26 component, in combination with AstraZeneca’s AZD1222, will begin by the end of 2020. Sputnik V is registered for use outside clinical trials in Russia and is in various trials in other parts of the world.
Various sites in the UK are likely be involved in the combination trial, particularly the main centers that are running the various Covid-19 stand-alone vaccine trials, the source added. One of the late-phase trials investigating AZD1222, a 12,390-volunteer Phase II/III trial (NCT04400838), is only recruiting in the UK. On 30 November, Novavax announced it had completed recruitment of its UK-based, 15,000-particiant Phase III trial (NCT04583995) for its protein subunit vaccine NVX-CoV2373, with event-driven interim data expected in 1Q21. Moderna’s 30,000-participant Phase III (NCT04470427) and J&J’s single-dose, 60,000-volunteer Phase III (NCT04505722) are not recruiting in the UK, although the latter’s double-dose, 30,000-participant Phase III trial (NCT04614948) has UK sites.
According to recent AZD1222 pooled data published by the Lancet online on 8 December, vaccine efficacy was 62.1% in participants who received two standard doses, and 90% in volunteers who received a low-dose primer and a standard-dose booster. One of the reasons for this efficacy data difference could be due to lower levels of antivector immunity with lower dosing in the first jab, but further work is needed to understand the mechanism fully, according to the article. The University of Oxford did not respond to a comment request.
Reynald Castaneda is an Associate Editor for Clinical Trials Arena parent company GlobalData’s investigative journalism team. A version of this article originally appeared on the Insights module of GlobalData’s Pharmaceutical Intelligence Center. To access more articles like this, visit GlobalData.