This morning, the Carlos III Institute of Health (ISCIII) has announced the launch of the CombivacS clinical trial that will analyse the possible protective effect and safety of delivering a dose of the messenger RNA vaccine for Covid-19 (BioNtech/Pfizer) to people who have already received a first dose of the AstraZeneca laboratory vaccine after a minimum of 8 weeks have elapsed since that dose.
CombivacS will be promoted, coordinated and funded by ISCIII, managed by its Clinical Research Platform and will be developed in five hospitals: Vall d'Hebron and Clínic, in Barcelona; La Paz and Clínico San Carlos in Madrid and Cruces in Bizkaia. In Vall d'Hebron it is coordinated by Dra. Magda Campins, head of the Preventive Medicine and Epidemiology Service and head of the research group in Epidemiology and Public Health of the Vall d'Hebron Research Institute (VHIR).
The clinical trial, which starts following the announcement of the cessation of AstraZeneca serum vaccination in people under 60, aims to provide scientific evidence to support decision-making regarding a possible alternative to complete immunization in these people. The aim is to clarify whether people who have received the first dose of AstraZeneca, have generated enough antibodies or need a booster dose with another vaccine, in this case, Pfizer Comirnaty. The CombivacS study is one of the first clinical trials to analyse the safety and immunogenicity of such combined guidelines.
The National Center for Microbiology (CNM) of the ISCIII will act as the central laboratory of the trial, which has had the scientific advice of the Spanish Agency for Medicines and Health Products (AEMPS). The AEMPS, following the approval of the protocol by the Drug Research Ethics Committee (CEIM) of the La Paz University Hospital in Madrid, has issued the relevant authorizations for its implementation.
Development and characteristics of the test
This is a phase 2 clinical trial, comparative, randomized and adaptive, to assess the safety and immunogenicity (ability of the immune system to respond successfully to an infection) of a dose of the Comirnaty vaccine (Pfizer) in humans who have previously received a dose of the Vaxcevria (AstraZeneca) vaccine. Thus, the study analyses the possible combination of more than one vaccine (heterologous vaccination pattern), with different mechanisms of action, to complete the desired immunization. The starting hypothesis is that said immunogenicity will be greater in the group receiving two different doses of vaccines compared to the single dose.
The primary objective of the trial is therefore to check whether in people who have already received a dose of the Vaxzevria vaccine (AstraZeneca) there is a significant increase at 14 days in their antibody figures against SARS- CoV-2 after receiving a dose of Comirnaty (Pfizer). To evaluate this possible increase in antibodies, the number of antibodies in a group of people who have previously been vaccinated with a single dose of Vaxzevria (AstraZeneca) but will not initially receive the dose of Comirnaty (Pfizer) will be analysed simultaneously.
600 people selected at random
CombivacS will involve 600 randomly selected people who have received a dose of the Vaxzevria vaccine (AstraZeneca), provided that a minimum of 8 weeks have elapsed since that dose until the start of the trial and are under 60 years of age. For logistical reasons, only people resident in the provinces where the five participating hospitals are located will be eligible.
In any case, the first results are expected to be available 5 weeks after the start of the trial. If these results were favourable in safety and efficacy to the sequential vaccination scheme, a dose of Comirnaty will be offered to all participants in the control group. Therefore, volunteers will participate in the trial divided into two groups, to which they will be randomly assigned. On the one hand, group 1 or intervention group, consisting of 400 people, will receive a dose of the Comirnaty vaccine (Pfizer), followed by 28 days of clinical observation and antibody analysis for one year. For its part, group 2, which will consist of 200 people, will not initially receive any vaccine. This group 2 will act as a control group, all monitoring, safety and analysis procedures being identical to those of the experimental group.
The comparison of immune response between the two groups will be performed on analyses obtained within 14 days of the inclusion of each volunteer, without prejudice to other very exhaustive analyses that will be performed over a year. Consequently, and given that the 600 participants will need a minimum of 7 days to join the study and that thousands of samples must be analysed, it cannot be expected to get results within 4 weeks of the first person receiving a dose of Comirnaty (Pfizer). If the results suggest this, 28 days after the start of the study, the Pfizer vaccine will be offered to all patients who did not initially receive it (group 2).
The National Center for Microbiology-ISCIII will act as the central laboratory for the assay and responsible for the analysis and interpretation of antibody figures. Thus, the biological samples from the participants will be sent to this center to proceed to the determination of antibodies and neutralizing antibodies against SARS-CoV-2 as an indicator of protection against Covid-19.
Additionally, this study will answer other scientifically relevant questions. Therefore, among the secondary objectives, the researchers seek to obtain knowledge about the immune response conferred by the sequential combination of the two vaccines over a year, as well as protection against SARS-CoV-2 variants at 14 and 28 days after completion of vaccination, among other issues.