A multinational, phase 2, randomised, adaptive protocol to assess immune response and side effects of different COVID-19 vaccines given in older adults (75 years and older) already vaccinated against SARS-CoV-2

INTERVENTION: Trade Name: Comirnaty Pharmaceutical Form: Concentrate for dispersion for injection Trade Name: Spikevax Product Name: Spikevax Pharmaceutical Form: Dispersion for injection CONDITION: Prevention of COVID‐19 infection ; MedDRA version: 23.1 Level: LLT Classification code 10084464 Term: COVID‐19 immunization System Organ Class: 100000004865 ; MedDRA version: 23.1 Level: LLT Classification code 10084465 Term: COVID‐19 vaccination System Organ Class: 100000004865 ; MedDRA version: 24.0 Level: LLT Classification code 10085559 Term: Revaccination with different COVID‐19 vaccine System Organ Class: 100000004865 ; MedDRA version: 23.0 Level: LLT Classification code 10084462 Term: SARS‐CoV‐2 vaccination System Organ Class: 100000004865 ; MedDRA version: 23.0 Level: LLT Classification code 10084463 Term: SARS‐CoV‐2 immunisation System Organ Class: 100000004865 ; MedDRA version: 23.0 Level: LLT Classification code 10084466 Term: SARS‐CoV‐2 immunization System Organ Class: 100000004865 Therapeutic area: Body processes [G] ‐ Immune system processes [G12] PRIMARY OUTCOME: Main Objective: To evaluate immune response against wild‐type SARS‐CoV‐2 of different booster strategies in elderly subjects (=75 years old) already fully vaccinated against SARS‐CoV‐2. Primary end point(s): • Rate of 2‐fold antibody titre increase following 3rd dose vaccination measured by quantitative enzyme‐linked immunosorbent assay (Anti‐RBD‐ELISA) against wildtype virus 14 days after 3rd dose. Secondary Objective: • To compare the humoral immune response against wild‐type SARS‐CoV‐2 between treatment arms within each cohort following 3rd vaccination dose in elderly individuals (=75 years) already vaccinated against SARS‐CoV‐2.; • To compare the humoral immune response against wild‐type SARS‐CoV‐2 between cohorts following 3rd vaccination dose in elderly individuals (=75 years) already vaccinated against SARS‐CoV‐2.; • To evaluate immune response against variants of concern of SARS‐CoV‐2 of different booster strategies in elderly individuals (=75 years) already fully vaccinated against SARS‐CoV‐2.; • To assess the CD4+ and CD8+ T cell response of different booster strategies in elderly individuals (=75 years) already vaccinated against SARS‐CoV‐2.; • To evaluate the long‐term humoral immune response of different booster strategies in individuals already fully vaccinated against SARS‐CoV‐2.; Timepoint(s) of evaluation of this end point: 14 days after IMP administration INCLUSION CRITERIA: • Elderly (=75 years old). • Already fully vaccinated adults. • Primary vaccination (1st and 2nd dose) using BNT162b2, mRNA‐1273 or ChAdOx‐1‐S). • No contra‐indication against any of the vaccine products in the trial at time of enrolment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 600 SECONDARY OUTCOME: Secondary end point(s): Safety:; • Unsolicited AEs until the end of trial.; • Solicited AEs for 7 days after 3rd dose.; • Rate of serious adverse events (SAEs) Grade =3 according to the National Cancer Institute Common Toxicity Criteria up to three months after 3rd dose.; Immunogenicity:; • Antibody titre increase following 3rd dose measured by neutralising activity against wildtype virus (Virus Neutralisation Assay) in a subgroup 14 days after 3rd dose.; Immunogenicity against variants:; • Change in neutralising capacity measured by neutralising activity against variants of concern (Virus Neutralisation Assay) in a subgroup 14 days after 3rd dose.; Long‐term immunity:; • Antibody titre level following 3rd dose measured by a quantitative enzyme‐linked immunosorbent assay (anti‐RBD‐ELISA assay) 12 months after 3rd dose.; • Antibody titre level following 3rd dose measured by neutralising activity against wildtype virus (Virus Neutralisation Assay) in a subgroup 12 months after 3rd dose.; • Change in neutralising capacity 12 months after 3rd dose measured by neutralising activity against variants of concern (Virus Neutralisation Assay) in a subgroup of subjects.; ; Timepoint(s) of evaluation of this end point: at 7 days, 14 days and/or 12 months after IMP administration