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    Clinical Trial Results:
    Monitoring immunogenicity of SARS-Cov-2 vaccination in Dutch middle-aged and older individuals (participating in the Doetinchem Cohort Study)

    Summary
    EudraCT number
    		 2021-001976-40
    Trial protocol
    		 NL  
    Global end of trial date
    12 Oct 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Nov 2025
    First version publication date
    08 Nov 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IIV-479
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 ABR number: NL76551.041.21
    Sponsors
    Sponsor organisation name
    RIVM
    Sponsor organisation address
    PO Box 1, Bilthoven, Netherlands, 3720BA
    Public contact
    Clinical Expertise Centre, RIVM , National Institute for Public Health and the Environment , mensgebonden-onderzoek@rivm.nl
    Scientific contact
    Clinical Expertise Centre, RIVM , National Institute for Public Health and the Environment , mensgebonden-onderzoek@rivm.nl
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Oct 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Oct 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Oct 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The overall aim is to address the magnitude, quality and persistence of the antibody responses to SARS-CoV-2-vaccinations in the Dutch population of above 50 years of age. • Assess the SARS-CoV-2 vaccine systemic antibody responses in 52+ years old male and female persons in the DC after SARS-CoV-2 (booster) vaccinations. • Determine the kinetics and longevity of SARS-CoV-2 antibody responses based on the data at all timepoints related to frailty in 52-90 years old male and female persons in the DC. • Assess the relation of age, frailty and specific co-morbidities in 52-90 years old male and female persons with antibody responses to SARS-CoV-2 and identifying subgroups of individuals more at risk for lower vaccine responsiveness
    Protection of trial subjects
    SARS-COV-2 vaccines have been granted a conditional marketing authorization. The products are routinely used in several countries in the same age groups and considered safe. It is therefore unlikely that serious side effects will occur that can lead to premature termination of the study. These vaccines are given by the participants’ own GP or the GGD as part of the routine immunization program for this age group, not as part of this study. Furthermore, the burden and risk of blood sampling is considered low. Collection of finger prick blood is regarded an adequate and safe alternative for full venousblood puncture. The applied lancet is easy to use, sterile and with a pricking needle which is designed to prevent exposure and re-use. Risk of infecting someone via the lancet is therefore very unlikely
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Mar 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 1273
    Worldwide total number of subjects
    1273
    EEA total number of subjects
    1273
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    580
    From 65 to 84 years
    669
    85 years and over
    24

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 DCS participants: All persons still participating in the DCS who have participated in round 6 of the DCS (n=3200) were invited for participation in the current study. Recruitment was done by a personal letter inviting the subjects to participate.

    Pre-assignment
    Screening details
    		 Inclusion: - participated in DCS round 6 - receive SARS-CoV-2 vaccine - Sign informed consent Exclusion: - received 2nd SARS-CoV-2 vaccine dose 1 months before signing ICF - Incapacitated

    Period 1
    Period 1 title
    SARS-CoV-2 primary immunization
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    No blinding

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 SARS-CoV-2 primary immunization comirnaty
    Arm description
    		 Participants that received their SARS-CoV-2 primary immunization with comirnaty, and participants that only received a single dose comirnaty as SARS-CoV-2 primary immunization.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Comirnaty
    Investigational medicinal product code
    EU/1/20/1528 - J07BN01 - Covid-19, RNA-based vacci
    Other name
    Pharmaceutical forms
    Concentrate for dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    "Comirnaty is administered intramuscularly after dilution as a single dose of 0.3 mL for individuals 12 years of age and older regardless of prior COVID-19 vaccination status. For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty should be administered at least 3 months after the most recent dose of a COVID-19 vaccine. Comirnaty 30 micrograms/dose concentrate for dispersion for injection should be administered intramuscularly after dilution. The preferred site is the deltoid muscle of the upper arm."

    Arm title
    		 SARS-CoV-2 primary immunization spikevax
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Spikevax
    Investigational medicinal product code
     EU/1/20/1507 - J07BN01 - Covid-19, RNA-based vacc
    Other name
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The primary series consists of 2 doses (0.5 ml each, containing 100 mincrograms mRNA). It is recommended to administer the seconde dose 28 days after the first dose. Spikevax may be used to boost individuals 12 years of age and older who have received a primary series with Spikevax or a primary series comprised of another mRNA vaccine or adenoviral vector vaccine at least 3 months after completion of the primary series. The booster dose consists of 1 dose of 0.25 ml, containing 50 micrograms mRNA. The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of the upper arm or in infants and young children, the anterolateral aspect of the thigh.

    Arm title
    		 SARS-CoV-2 primary immunization Vaxzevria
    Arm description
    		 Participants that received their SARS-CoV-2 primary immunization with Vaxzevria, and participants that received a single dose of Vaxzevria and a single dose of comirnaty as SARS-CoV-2 primary immunization.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vaxzevria
    Investigational medicinal product code
    EU/1/21/1529 - J07BN02 - Covid-19, viral vector, n
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The Vaxzevria primary vaccination course consists of two separate doses of 0.5 ml each. The second dose should be administered between 4 and 12 weeks (28 to 84 days) after the first dose. Vaxzevria is for intramuscular injection only, preferably in the deltoid muscle of the upper arm.

    Arm title
    		 SARS-CoV-2 primary immunization JCOVDEN
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    JCOVDEN
    Investigational medicinal product code
    EU/1/20/1525 - J07BN02 - Covid-19, viral vector, n
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    "JCOVDEN is administered as a single-dose of 0.5 mL by intramuscular injection only. A booster dose (second dose) of 0.5 mL of JCOVDEN may be administered intramuscularly at least 2 months after the primary vaccination in individuals 18 years of age and older. JCOVDEN is for intramuscular injection only, preferably in the deltoid muscle of the upper arm."

    Arm title
    		 Vaccination unknown
    Arm description
    		 It is unknown what product this participant has received since the participant has not informed the study team about this.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Comirnaty
    Investigational medicinal product code
    EU/1/20/1528 - J07BN01 - Covid-19, RNA-based vacci
    Other name
    Pharmaceutical forms
    Concentrate for dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    "Comirnaty is administered intramuscularly after dilution as a single dose of 0.3 mL for individuals 12 years of age and older regardless of prior COVID-19 vaccination status. For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty should be administered at least 3 months after the most recent dose of a COVID-19 vaccine. Comirnaty 30 micrograms/dose concentrate for dispersion for injection should be administered intramuscularly after dilution. The preferred site is the deltoid muscle of the upper arm."

    Investigational medicinal product name
    Spikevax
    Investigational medicinal product code
     EU/1/20/1507 - J07BN01 - Covid-19, RNA-based vacc
    Other name
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The primary series consists of 2 doses (0.5 ml each, containing 100 mincrograms mRNA). It is recommended to administer the seconde dose 28 days after the first dose. Spikevax may be used to boost individuals 12 years of age and older who have received a primary series with Spikevax or a primary series comprised of another mRNA vaccine or adenoviral vector vaccine at least 3 months after completion of the primary series. The booster dose consists of 1 dose of 0.25 ml, containing 50 micrograms mRNA. The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of the upper arm or in infants and young children, the anterolateral aspect of the thigh.

    Investigational medicinal product name
    Vaxzevria
    Investigational medicinal product code
    EU/1/21/1529 - J07BN02 - Covid-19, viral vector, n
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The Vaxzevria primary vaccination course consists of two separate doses of 0.5 ml each. The second dose should be administered between 4 and 12 weeks (28 to 84 days) after the first dose. Vaxzevria is for intramuscular injection only, preferably in the deltoid muscle of the upper arm.

    Investigational medicinal product name
    JCOVDEN
    Investigational medicinal product code
    EU/1/20/1525 - J07BN02 - Covid-19, viral vector, n
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    "JCOVDEN is administered as a single-dose of 0.5 mL by intramuscular injection only. A booster dose (second dose) of 0.5 mL of JCOVDEN may be administered intramuscularly at least 2 months after the primary vaccination in individuals 18 years of age and older. JCOVDEN is for intramuscular injection only, preferably in the deltoid muscle of the upper arm."

    Number of subjects in period 1
    		SARS-CoV-2 primary immunization comirnaty SARS-CoV-2 primary immunization spikevax SARS-CoV-2 primary immunization Vaxzevria SARS-CoV-2 primary immunization JCOVDEN Vaccination unknown
    Started
    880
    20
    333
    37
    3
    Pre 1st primary SARS-CoV-2 immunization
    878
    20
    332
    37
    3
    1 month post 1st primary SARS-CoV-2 immu
    869
    20
    325
    35
    2
    1 month post 2nd primary SARS-CoV-2 immu
    850
    20
    312
    35
    2
    3 months post 2nd primary SARS-CoV-2 imm
    828
    20
    297
    35
    2
    6 months post 2nd primary SARS-CoV-2 imm
    806
    20
    289
    35
    0
    9 months post 2nd primary SARS-CoV-2 imm
    762
    19
    273
    34
    0
    1 year post 2nd primary SARS-CoV-2 immun
    748
    18
    270
    34
    0
    Completed
    748
    18
    270
    34
    0
    Not completed
    132
    2
    63
    3
    3
         Deceased
    6
    -
    -
    -
    -
         unknown
    1
    -
    2
    -
    -
         emigration
    2
    -
    1
    -
    -
         Participant decided to end participation
    57
    2
    26
    1
    -
         Lost to follow-up
    66
    -
    34
    2
    3
    Period 2
    Period 2 title
    SARS-CoV-2 1st booster immunization
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    No blinding

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 SARS-CoV-2 1st booster immunization comirnaty
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Comirnaty
    Investigational medicinal product code
    EU/1/20/1528 - J07BN01 - Covid-19, RNA-based vacci
    Other name
    Pharmaceutical forms
    Concentrate for dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    "Comirnaty is administered intramuscularly after dilution as a single dose of 0.3 mL for individuals 12 years of age and older regardless of prior COVID-19 vaccination status. For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty should be administered at least 3 months after the most recent dose of a COVID-19 vaccine. Comirnaty 30 micrograms/dose concentrate for dispersion for injection should be administered intramuscularly after dilution. The preferred site is the deltoid muscle of the upper arm."

    Arm title
    		 SARS-CoV-2 1st booster immunization spikevax
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Spikevax
    Investigational medicinal product code
     EU/1/20/1507 - J07BN01 - Covid-19, RNA-based vacc
    Other name
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The primary series consists of 2 doses (0.5 ml each, containing 100 mincrograms mRNA). It is recommended to administer the seconde dose 28 days after the first dose. Spikevax may be used to boost individuals 12 years of age and older who have received a primary series with Spikevax or a primary series comprised of another mRNA vaccine or adenoviral vector vaccine at least 3 months after completion of the primary series. The booster dose consists of 1 dose of 0.25 ml, containing 50 micrograms mRNA. The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of the upper arm or in infants and young children, the anterolateral aspect of the thigh.

    Arm title
    		 Vaccination unknown
    Arm description
    		 It is unknown what product this participant has received since the participant has not informed the study team about this.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Comirnaty
    Investigational medicinal product code
    EU/1/20/1528 - J07BN01 - Covid-19, RNA-based vacci
    Other name
    Pharmaceutical forms
    Concentrate for dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    "Comirnaty is administered intramuscularly after dilution as a single dose of 0.3 mL for individuals 12 years of age and older regardless of prior COVID-19 vaccination status. For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty should be administered at least 3 months after the most recent dose of a COVID-19 vaccine. Comirnaty 30 micrograms/dose concentrate for dispersion for injection should be administered intramuscularly after dilution. The preferred site is the deltoid muscle of the upper arm."

    Investigational medicinal product name
    Spikevax
    Investigational medicinal product code
     EU/1/20/1507 - J07BN01 - Covid-19, RNA-based vacc
    Other name
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The primary series consists of 2 doses (0.5 ml each, containing 100 mincrograms mRNA). It is recommended to administer the seconde dose 28 days after the first dose. Spikevax may be used to boost individuals 12 years of age and older who have received a primary series with Spikevax or a primary series comprised of another mRNA vaccine or adenoviral vector vaccine at least 3 months after completion of the primary series. The booster dose consists of 1 dose of 0.25 ml, containing 50 micrograms mRNA. The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of the upper arm or in infants and young children, the anterolateral aspect of the thigh.

    Number of subjects in period 2 [1]
    		SARS-CoV-2 1st booster immunization comirnaty SARS-CoV-2 1st booster immunization spikevax Vaccination unknown
    Started
    239
    791
    1
    pre 1st SARS-CoV-2 booster immunization
    238
    773
    1
    1 month post 1st SARS-CoV-2 booster immu
    238
    769
    1
    6 months post 1st SARS-CoV-2 booster im
    227
    732
    0
    1 year post 1st SARS-CoV-2 booster immun
    223
    712
    0
    Completed
    223
    712
    0
    Not completed
    16
    79
    1
         Deceased
    1
    1
    -
         unknown
    -
    1
    -
         Participant decided to end participation
    9
    41
    1
         Lost to follow-up
    6
    36
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Not all subjects received the 1ts booster immunization. Then they completed period 1 (primary immunization) but did not start period 2 (1st booster) because they did not have the 1st booster immunization.
    Period 3
    Period 3 title
    SARS-CoV-2 2nd booster immunization
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    No blinding

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 SARS-CoV-2 2nd booster immunization comirnaty
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Comirnaty
    Investigational medicinal product code
    EU/1/20/1528 - J07BN01 - Covid-19, RNA-based vacci
    Other name
    Pharmaceutical forms
    Concentrate for dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    "Comirnaty is administered intramuscularly after dilution as a single dose of 0.3 mL for individuals 12 years of age and older regardless of prior COVID-19 vaccination status. For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty should be administered at least 3 months after the most recent dose of a COVID-19 vaccine. Comirnaty 30 micrograms/dose concentrate for dispersion for injection should be administered intramuscularly after dilution. The preferred site is the deltoid muscle of the upper arm."

    Arm title
    		 SARS-CoV-2 2nd booster immunization spikevax
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Spikevax
    Investigational medicinal product code
     EU/1/20/1507 - J07BN01 - Covid-19, RNA-based vacc
    Other name
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The primary series consists of 2 doses (0.5 ml each, containing 100 mincrograms mRNA). It is recommended to administer the seconde dose 28 days after the first dose. Spikevax may be used to boost individuals 12 years of age and older who have received a primary series with Spikevax or a primary series comprised of another mRNA vaccine or adenoviral vector vaccine at least 3 months after completion of the primary series. The booster dose consists of 1 dose of 0.25 ml, containing 50 micrograms mRNA. The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of the upper arm or in infants and young children, the anterolateral aspect of the thigh.

    Arm title
    		 SARS-CoV-2 2nd booster immunization unknown vaccine
    Arm description
    		 It is unknown what product this participant has received since the participant has not informed the study team about this.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Comirnaty
    Investigational medicinal product code
    EU/1/20/1528 - J07BN01 - Covid-19, RNA-based vacci
    Other name
    Pharmaceutical forms
    Concentrate for dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    "Comirnaty is administered intramuscularly after dilution as a single dose of 0.3 mL for individuals 12 years of age and older regardless of prior COVID-19 vaccination status. For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty should be administered at least 3 months after the most recent dose of a COVID-19 vaccine. Comirnaty 30 micrograms/dose concentrate for dispersion for injection should be administered intramuscularly after dilution. The preferred site is the deltoid muscle of the upper arm."

    Investigational medicinal product name
    Spikevax
    Investigational medicinal product code
     EU/1/20/1507 - J07BN01 - Covid-19, RNA-based vacc
    Other name
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The primary series consists of 2 doses (0.5 ml each, containing 100 mincrograms mRNA). It is recommended to administer the seconde dose 28 days after the first dose. Spikevax may be used to boost individuals 12 years of age and older who have received a primary series with Spikevax or a primary series comprised of another mRNA vaccine or adenoviral vector vaccine at least 3 months after completion of the primary series. The booster dose consists of 1 dose of 0.25 ml, containing 50 micrograms mRNA. The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of the upper arm or in infants and young children, the anterolateral aspect of the thigh.

    Number of subjects in period 3 [2]
    		SARS-CoV-2 2nd booster immunization comirnaty SARS-CoV-2 2nd booster immunization spikevax SARS-CoV-2 2nd booster immunization unknown vaccine
    Started
    200
    475
    3
    1 month post 2nd SARS-CoV-2 booster immu
    196
    447
    3
    6 months post 2nd SARS-CoV-2 booster imm
    188
    436
    1
    1 year post 2nd SARS-CoV-2 booster immun
    183
    431
    1
    Completed
    183
    431
    1
    Not completed
    17
    44
    2
         Deceased
    -
    1
    -
         unknown
    5
    1
    1
         Participant decided to end participation
    8
    26
    -
         Lost to follow-up
    4
    16
    1
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Not all subjects received the 2nd booster immunization. Then they completed period 2 (primary immunization) but did not start period 3 (2nd booster) because they did not have the 2nd booster immunization.
    Period 4
    Period 4 title
    SARS-CoV-2 3rd booster immunization
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    No blinding

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 SARS-CoV-2 3nd booster immunization comirnaty
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Comirnaty
    Investigational medicinal product code
    EU/1/20/1528 - J07BN01 - Covid-19, RNA-based vacci
    Other name
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Comirnaty Original/Omicron BA.1 is administered intramuscularly as a single dose of 0.3 mL for individuals 12 years of age and older who have previously received at least a primary vaccination course against COVID-19. It should be administered at least 3 months after the most recent dose of a COVID-19 vaccine. Comirnaty Original/Omicron BA.1 (15/15 micrograms)/dose dispersion for injection should be administered intramuscularly.

    Arm title
    		 SARS-CoV-2 3nd booster immunization spikevax
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Spikevax
    Investigational medicinal product code
     EU/1/20/1507 - J07BN01 - Covid-19, RNA-based vacc
    Other name
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The booster consists of 1 dose (0.5 ml, containing 125 micrograms of elasomeran and 25 micrograms of imelasomeran, a COVID-19 mRNA Vaccine (nucleoside modified) (embedded in lipid nanoparticles)). There should be an interval of at least 3 months between administration of Spikevax bivalent Original/Omicron BA.1 and the last prior dose of a COVID-19 vaccine. Spikevax bivalent Original/Omicron BA.1 is only indicated for individuals who have previously received at least a primary vaccination course against COVID-19. The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of the upper arm.

    Arm title
    		 SARS-CoV-2 3nd booster immunization unknown vaccine
    Arm description
    		 It is unknown what product this participant has received since the participant has not informed the study team about this.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Comirnaty
    Investigational medicinal product code
    EU/1/20/1528 - J07BN01 - Covid-19, RNA-based vacci
    Other name
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Comirnaty Original/Omicron BA.1 is administered intramuscularly as a single dose of 0.3 mL for individuals 12 years of age and older who have previously received at least a primary vaccination course against COVID-19. It should be administered at least 3 months after the most recent dose of a COVID-19 vaccine. Comirnaty Original/Omicron BA.1 (15/15 micrograms)/dose dispersion for injection should be administered intramuscularly.

    Investigational medicinal product name
    Spikevax
    Investigational medicinal product code
     EU/1/20/1507 - J07BN01 - Covid-19, RNA-based vacc
    Other name
    Pharmaceutical forms
    Dispersion for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The booster consists of 1 dose (0.5 ml, containing 125 micrograms of elasomeran and 25 micrograms of imelasomeran, a COVID-19 mRNA Vaccine (nucleoside modified) (embedded in lipid nanoparticles)). There should be an interval of at least 3 months between administration of Spikevax bivalent Original/Omicron BA.1 and the last prior dose of a COVID-19 vaccine. Spikevax bivalent Original/Omicron BA.1 is only indicated for individuals who have previously received at least a primary vaccination course against COVID-19. The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of the upper arm.

    Number of subjects in period 4 [3]
    		SARS-CoV-2 3nd booster immunization comirnaty SARS-CoV-2 3nd booster immunization spikevax SARS-CoV-2 3nd booster immunization unknown vaccine
    Started
    33
    529
    1
    pre 3rd SARS-CoV-2 booster immunization
    44
    607
    5
    1 month post 3rd SARS-CoV-2 booster immu
    44
    604
    3
    6 months post 3rd SARS-CoV-2 booster imm
    44
    592
    3
    1 year post 3rd SARS-CoV-2 booster immun
    37
    537
    2
    Completed
    37
    537
    2
    Not completed
    7
    70
    3
         Deceased
    -
    3
    -
         Participant decided to end participation
    -
    18
    1
         Withdrawn from study by PI
    7
    49
    1
         Lost to follow-up
    -
    -
    1
    Joined
    11
    78
    4
         Did not participate in 2nd booster immu
    11
    78
    4
    Notes
    [3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Not all subjects participated in the 3rd period because they did not get a 2nd booster immunization. These participants skipped the timepoints for 2nd booster immunization and rejoined for the 3rd booster immunization. Therefore the number of participants at the end of period 3 (2nd booster) is lower than at the start of period 4 (3rd booster).

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    SARS-CoV-2 primary immunization
    Reporting group description
    		 -

    Reporting group values
    		 SARS-CoV-2 primary immunization Total
    Number of subjects
    		 1273 1273
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 580 580
        From 65-84 years
    		 669 669
        85 years and over
    		 24 24
    Gender categorical
    Units: Subjects
        Female
    		 679 679
        Male
    		 594 594
    Subject analysis sets

    Subject analysis set title
    T0
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Pre 1st primary SARS-CoV-2 immunization

    Subject analysis set title
    T1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 month post 1st primary SARS-CoV-2 immunization

    Subject analysis set title
    T2
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 month post 2nd primary SARS-CoV-2 immunization

    Subject analysis set title
    T3
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    3 months post 2nd primary SARS-CoV-2 immunization

    Subject analysis set title
    T4
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    6 months post 2nd primary SARS-CoV-2 immunization

    Subject analysis set title
    T5
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    9 months post 2nd primary SARS-CoV-2 immunization

    Subject analysis set title
    T6
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 year post 2nd primary SARS-CoV-2 immunization

    Subject analysis set title
    B0
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    pre 1st SARS-CoV-2 booster immunization

    Subject analysis set title
    B1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 month post 1st SARS-CoV-2 booster immunization

    Subject analysis set title
    B2
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    6 months post 1st SARS-CoV-2 booster immunization

    Subject analysis set title
    B3
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 year post 1st SARS-CoV-2 booster immunization

    Subject analysis set title
    C1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 month post 2nd SARS-CoV-2 booster immunization

    Subject analysis set title
    C2
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    6 months post 2nd SARS-CoV-2 booster immunization

    Subject analysis set title
    C3
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 year post 2nd SARS-CoV-2 booster immunization

    Subject analysis set title
    D0
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    pre 3rd SARS-CoV-2 booster immunization

    Subject analysis set title
    D1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 month post 3rd SARS-CoV-2 booster immunization

    Subject analysis set title
    D2
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    6 months post 3rd SARS-CoV-2 booster immunization

    Subject analysis set title
    D3
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 year post 3rd SARS-CoV-2 booster immunization

    Subject analysis sets values
    		 T0 T1 T2 T3 T4 T5 T6 B0 B1 B2 B3 C1 C2 C3 D0 D1 D2 D3
    Number of subjects
    1270
    1251
    1220
    1183
    1150
    1088
    1070
    1011
    1008
    959
    936
    646
    625
    615
    656
    651
    639
    576
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
    580
    562
    535
    508
    471
    439
    412
    417
    403
    353
    307
    145
    127
    105
    141
    134
    116
    78
        From 65-84 years
    667
    666
    660
    648
    651
    625
    634
    572
    583
    582
    602
    478
    476
    486
    494
    496
    501
    470
        85 years and over
    23
    23
    25
    27
    28
    24
    24
    22
    22
    24
    27
    23
    22
    24
    21
    21
    22
    28
    Age continuous
    Units:
        
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    478
    669
    658
    641
    628
    592
    586
    548
    548
    519
    508
    326
    318
    313
    339
    335
    327
    294
        Male
    593
    582
    562
    542
    522
    496
    485
    463
    460
    440
    428
    320
    307
    302
    317
    316
    312
    282

    End points

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    End points reporting groups
    Reporting group title
    SARS-CoV-2 primary immunization comirnaty
    Reporting group description
    		 Participants that received their SARS-CoV-2 primary immunization with comirnaty, and participants that only received a single dose comirnaty as SARS-CoV-2 primary immunization.

    Reporting group title
    SARS-CoV-2 primary immunization spikevax
    Reporting group description
    		 -

    Reporting group title
    SARS-CoV-2 primary immunization Vaxzevria
    Reporting group description
    		 Participants that received their SARS-CoV-2 primary immunization with Vaxzevria, and participants that received a single dose of Vaxzevria and a single dose of comirnaty as SARS-CoV-2 primary immunization.

    Reporting group title
    SARS-CoV-2 primary immunization JCOVDEN
    Reporting group description
    		 -

    Reporting group title
    Vaccination unknown
    Reporting group description
    		 It is unknown what product this participant has received since the participant has not informed the study team about this.
    Reporting group title
    SARS-CoV-2 1st booster immunization comirnaty
    Reporting group description
    		 -

    Reporting group title
    SARS-CoV-2 1st booster immunization spikevax
    Reporting group description
    		 -

    Reporting group title
    Vaccination unknown
    Reporting group description
    		 It is unknown what product this participant has received since the participant has not informed the study team about this.
    Reporting group title
    SARS-CoV-2 2nd booster immunization comirnaty
    Reporting group description
    		 -

    Reporting group title
    SARS-CoV-2 2nd booster immunization spikevax
    Reporting group description
    		 -

    Reporting group title
    SARS-CoV-2 2nd booster immunization unknown vaccine
    Reporting group description
    		 It is unknown what product this participant has received since the participant has not informed the study team about this.
    Reporting group title
    SARS-CoV-2 3nd booster immunization comirnaty
    Reporting group description
    		 -

    Reporting group title
    SARS-CoV-2 3nd booster immunization spikevax
    Reporting group description
    		 -

    Reporting group title
    SARS-CoV-2 3nd booster immunization unknown vaccine
    Reporting group description
    		 It is unknown what product this participant has received since the participant has not informed the study team about this.

    Subject analysis set title
    T0
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Pre 1st primary SARS-CoV-2 immunization

    Subject analysis set title
    T1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 month post 1st primary SARS-CoV-2 immunization

    Subject analysis set title
    T2
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 month post 2nd primary SARS-CoV-2 immunization

    Subject analysis set title
    T3
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    3 months post 2nd primary SARS-CoV-2 immunization

    Subject analysis set title
    T4
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    6 months post 2nd primary SARS-CoV-2 immunization

    Subject analysis set title
    T5
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    9 months post 2nd primary SARS-CoV-2 immunization

    Subject analysis set title
    T6
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 year post 2nd primary SARS-CoV-2 immunization

    Subject analysis set title
    B0
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    pre 1st SARS-CoV-2 booster immunization

    Subject analysis set title
    B1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 month post 1st SARS-CoV-2 booster immunization

    Subject analysis set title
    B2
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    6 months post 1st SARS-CoV-2 booster immunization

    Subject analysis set title
    B3
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 year post 1st SARS-CoV-2 booster immunization

    Subject analysis set title
    C1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 month post 2nd SARS-CoV-2 booster immunization

    Subject analysis set title
    C2
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    6 months post 2nd SARS-CoV-2 booster immunization

    Subject analysis set title
    C3
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 year post 2nd SARS-CoV-2 booster immunization

    Subject analysis set title
    D0
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    pre 3rd SARS-CoV-2 booster immunization

    Subject analysis set title
    D1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 month post 3rd SARS-CoV-2 booster immunization

    Subject analysis set title
    D2
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    6 months post 3rd SARS-CoV-2 booster immunization

    Subject analysis set title
    D3
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    1 year post 3rd SARS-CoV-2 booster immunization

    Primary: Circulating IgG antibodies concentrations for SARS-CoV-2 spike protein

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    End point title
    		 Circulating IgG antibodies concentrations for SARS-CoV-2 spike protein
    End point description
    End point type
    Primary
    End point timeframe
    all timepoints after the second or last primary vaccination (T2-T6) and at all time points after the booster vaccination(s) (B1-E3)
    End point values
    		 T2 T3 T4 T5 T6 B1 B2 B3 C1 C2 C3 D0 D1 D2 D3
    Number of subjects analysed
    1151
    1101
    647
    24
    11
    841
    313
    119
    505
    138
    36
    550
    600
    481
    360
    Units: BAU/ml
        geometric mean (confidence interval 95%)
    936.6825152 (867.72113 to 1011.12455)
    366.6477934 (340.67271 to 394.60338)
    183.2185913 (163.10807 to 205.80865)
    775.5095921 (284.88872 to 2111.05277)
    4828.52767 (2695.92256 to 8648.12655)
    4607.030342 (4361.76712 to 4866.08477)
    4110.210571 (3607.80893 to 4682.57363)
    2806.339551 (2296.39836 to 3429.51894)
    8633.215234 (7985.96131 to 9332.92842)
    3967.120399 (3225.08525 to 4879.88474)
    3643.358957 (2749.30249 to 4828.15716)
    3544.112801 (3226.22004 to 3893.32885)
    9954.809062 (9351.14418 to 10597.44365)
    4768.882863 (4339.66077 to 5240.55795)
    3230.29749 (2884.64069 to 3617.37319)
    Statistical analysis title
    		 Vaccine-specific serum IgG at T2 until D3
    Statistical analysis description
    Circulating IgG antibodies concentrations for SARS-CoV-2 spike protein at all timepoints after the second or last primary vaccination (T2-T6) and at all time points after the booster vaccination(s) (B1-E3). Geometric mean IgG concentrations with 95% confidence interval.
    Comparison groups
    T2 v T3 v T4 v T5 v T6 v B1 v B2 v B3 v C1 v C2 v C3 v D0 v D1 v D2 v D3
    Number of subjects included in analysis
    6877
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.05
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Circulating IgG antibodies concentrations for SARS-CoV-2 spike protein

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    End point title
    		 Circulating IgG antibodies concentrations for SARS-CoV-2 spike protein
    End point description
    End point type
    Secondary
    End point timeframe
    pre vaccination (T0) and at 1 month after the first vaccination (T1)
    End point values
    		 T0 T1
    Number of subjects analysed
    858
    997
    Units: BAU/ml
        geometric mean (confidence interval 95%)
    0.6664 (0.58246 to 0.76253)
    104.1130489 (94.30589 to 114.94009)
    No statistical analyses for this end point

    Secondary: Self-reported experiences with possible SARS-CoV-2 infection from answers to a short questionnaire.

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    End point title
    		 Self-reported experiences with possible SARS-CoV-2 infection from answers to a short questionnaire.
    End point description
    End point type
    Secondary
    End point timeframe
    all timepoints (T0-D3)
    End point values
    		 T0 T1 T2 T3 T4 T5 T6 B0 B1 B2 B3 C1 C2 C3 D0 D1 D2 D3
    Number of subjects analysed
    858
    997
    1151
    1101
    647
    24
    11
    596
    841
    313
    119
    505
    138
    36
    550
    600
    481
    360
    Units: number of participants
    68
    4
    6
    1
    39
    19
    4
    0
    29
    192
    49
    26
    98
    24
    1
    33
    107
    17
    No statistical analyses for this end point

    Secondary: Virus-specific serum IgG antibody levels to SARS-CoV-2 Core N protein.

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    End point title
    		 Virus-specific serum IgG antibody levels to SARS-CoV-2 Core N protein.
    End point description
    End point type
    Secondary
    End point timeframe
    all timepoints (T0-D3)
    End point values
    		 T0 T1 T2 T3 T4 T5 T6 B0 B1 B2 B3 C1 C2 C3 D0 D1 D2 D3
    Number of subjects analysed
    858
    997
    1151
    1101
    647
    24
    11
    596
    841
    313
    119
    505
    138
    36
    550
    600
    481
    360
    Units: BAU/ml
        geometric mean (confidence interval 95%)
    1.78705821 (1.61448 to 1.97808)
    1.865683561 (1.70904 to 2.03668)
    4.365313604 (4.00216 to 4.76142)
    1.79855 (1.67105 to 1.93579)
    2.527670365 (2.2879 to 2.79256)
    11.47558387 (5.0749 to 25.94909)
    52.57177896 (21.09453 to 131.01938)
    2.232999312 (2.04067 to 2.44346)
    3.250543742 (3.02299 to 3.49523)
    12.42411729 (10.35664 to 14.90433)
    21.85940877 (15.05957 to 31.72959)
    6.009452832 (5.36653 to 6.7294)
    10.12417126 (7.52352 to 13.62378)
    36.31566196 (21.03002 to 62.71164)
    7.971602286 (6.95399 to 9.13812)
    9.422161452 (8.31914 to 10.67142)
    17.66520259 (14.86832 to 20.98821)
    11.94481629 (9.92612 to 14.37406)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    within one week after blood sampling for every timepoint.
    Adverse event reporting additional description
    The adverse events are reported by the subject.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.0
    Reporting groups
    Reporting group title
    SARS-CoV-2 primary immunization
    Reporting group description
    		 Participants that received their SARS-CoV-2 primary immunization

    Serious adverse events
    		 SARS-CoV-2 primary immunization
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 1270 (0.00%)
         number of deaths (all causes)
    24
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 0.02%
    Non-serious adverse events
    		 SARS-CoV-2 primary immunization
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 1270 (0.16%)
    Skin and subcutaneous tissue disorders
    Puncture site pain
    Additional description: Medra code: 10065599 participant had painful finger after the finger prick.
         subjects affected / exposed
    1 / 1270 (0.08%)
         occurrences all number
    1
    Wound healing delayed
    Additional description: Meddra code: 10048036 punture site after finger prick healed slowly
         subjects affected / exposed
    1 / 1270 (0.08%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Aug 2021
    The submission of the trail as drug research.
    12 Aug 2021
    additional sample collection from nursing homes
    29 Oct 2021
    Follow the immune responses after SARS-CoV-2 booster vaccination
    09 Mar 2022
    Follow the immune responses after the second and following SARS-CoV-2 booster vaccination
    16 May 2023
    1) Changes in the primary and secondary outcome measures due to the relevance and feasibility 2) change in informed consent procedure 3) adding questions about post-COVID complaints to questionnaire D3, 4) addition of questionnaires, covering letters, newsletters, and result letters
    19 Sep 2023
    Follow the immune responses in the nursing home participants after the fourth SARS-CoV-2 booster vaccination given in the autumn of 2023, with 2 extra fingerprick samples (E1 and E3)
    08 Oct 2024
    Corrections to make the protocol fully accurate and up to date.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Results on the secondary endpoint 'Integrated endpoint analysis of all antibody analysis with frailty data and data of specific co-morbidities (subgroups)' can be found in the pubmed article 39407293 and will not be added to this EudraCT report.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/39407293
    http://www.ncbi.nlm.nih.gov/pubmed/36146557
    http://www.ncbi.nlm.nih.gov/pubmed/37880758
    http://www.ncbi.nlm.nih.gov/pubmed/39748353
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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