Randomised Phase II Study to Assess the Immunogenicity and Safety of Heterologous SARS-CoV-2 Vaccine Schedules (rAd26-rAd5, rAd26-rAd26, rAd26-ChAdOx1 and rAd26-mRNA-1273).

Descripción detallada

The Covid-19 disease caused by the SARS-COV 2 virus has caused a pandemic with more than 180 million cases worldwide and more than 4 million deaths. In Argentina, this pandemic has had a significant impact, with about 4.5 million cases and about 95,000 deaths. In no more than nine months, medical science developed different vaccines to prevent new cases and mitigate this pandemic. At the time of the presentation of this research protocol, there are four vaccines for the prevention of COVID-19 approved for emergency use by the National Administration of Medicines, Food and Medical Technology (ANMAT). Argentina recently received a donation of 3.2 million doses of Moderna (mRNA-1273) vaccine from the US government. This vaccine was approved for emergency use in the context of the pandemic. All require the administration of two doses with an administration interval of at least 21 days. All these vaccines were designed to be used with a homologous two-dose regimen. However, for both logistical and biomedical reasons, the need to use vaccines in heterologous regimens (one dose of one vaccine and a second dose of another vaccine) is emerging worldwide. The efficacy and safety of this type of regimen has not yet been demonstrated. In Argentina, there are a large number of people who currently have one dose of Gam-COVID-Vac vaccine and who - even after a period of ≥21 days - have not received the second component. At the same time, the provision of the second component of the Gam-COVID-Vac vaccine is delayed due to production and distribution logistics. As of 08/02/2021, among the universe of people vaccinated with Gam-COVID, residents of CABA, vaccinated in establishments in the City of Buenos Aires - and excluding deceased and infected people - there were a total of 332,291 people with one dose and ≥22 days since the first dose was administered. In a context of high viral circulation, it is desirable to try to vaccinate as much of the population as possible with a full schedule in the shortest possible time. In addition, new variants of SARS-COV2 virus possessing the E384K genomic variant such as the gamma strain (formerly Manaus), the beta strain (known as South African) and the Delta strain (also known as Indian) have the ability to evade the immune system and therefore most laboratories that have developed vaccines recognise that the efficacy of the vaccines requires two doses. This study will attempt to determine whether administration of a heterologous regimen combining a first dose of Gam-COVID-Vac the repetition of the first component of the Gam-COVID-Vac vaccine (rAd26) or the administration of an RNA vaccine (mRNA-1273) resulted in a non inferiority result that the classic and recomended protocol based on two dosis of Gam-COVID-Vac (rAd26-rAd5) . The present protocol is therefore oriented to respond to a practical management need and to guarantee the best possible protection to the population through two doses, which is what is considered worldwide as "complete vaccination" according to WHO for the vaccines used by Argentina. The proposed protocol is a pragmatic and public health oriented clinical trial, whose primary objective is to establish whether there are indicators that allow the implementation of a heterologous vaccination scheme. For this, a surrogate endpoint will be used, which is immunogenicity measured by the presence of antibodies against protein S. In addition, the safety of the combination will be evaluated in terms of monitoring self-reported and non-self-reported clinical events by patients.