Study to Evaluate the Immunogenicity and Safety of Heterologous SARS-CoV-2 Vaccine Schemes
Condition: COVID-19 Vaccines
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 2

Summary: 
      To determine whether a heterologous vaccination regimen in individuals with no known previous
      history of COVID-19 is non-inferior to that observed with counterpart regimens currently in
      use in Argentina.
    

Detailed description: 
      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). Of these, three (1-3) are currently available
      and are part of the vaccination campaign. Of these three vaccines, two use a non-replicating
      viral vector platform (Gam-COVID-Vac and ChAdOx1 nCoV-19) while one uses an inactivated virus
      platform (BBIBP-CorV). 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 June 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 325,788 people with one dose and ≥22 and ≤90 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.

      The use of heterologous schedules is a source of active research in various parts of the
      world (4-6). However, most of this research is testing the combination of a combination
      schedule that includes an mRNA vaccine. There is an ongoing study sponsored by the Gamaleya
      Institute and AstraZeneca that is evaluating the immunogenicity of a scheme similar to the
      one proposed in this trial. Results from this joint trial would not be available until
      mid-October (7). No trials have evaluated the combination of rAd26-rAd5 and BBIBP-CorV.

      This study will attempt to determine whether administration of a heterologous regimen
      combining a first dose of Gam-COVID-Vac with a second dose of ChAdOx1 nCoV-19 or BBIBP-CorV
      results in non-inferior immunogenicity to the homologous regimen used.

      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.
    

Intervention name(s): Gam-COVID-Vac / Gam-COVID-Vac
Intervention type(s): Drug
Intervention description(s): A comparison of antibody levels against protein S will be performed using the Gam-COVID-Vac / Gam-COVID-Vac group as a control group and the Gam-COVID-Vac / ChAdOx1 nCoV-19 and Gam-COVID-Vac / BBIBP-CorV groups as comparators.
Other intervention name(s): Gam-COVID-Vac / ChAdOx1 nCoV-19; Gam-COVID-Vac / BBIBP-CorV
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Health Services Research
Keywords: COVID-19 Serological Testing