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    Clinical Trial Results:
    A Phase II Study to Evaluate Safety and Efficacy to a Third Vaccination in Immunocompromised Patients with Inadequate Humoral Response after Primary mRNA SARS-CoV-2 (Covid-19) Vaccination

    Summary
    EudraCT number
    		 2021-002693-10
    Trial protocol
    		 AT  
    Global end of trial date
    21 Feb 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Apr 2026
    First version publication date
    17 Apr 2026
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    VAC3_SARS-CoV2_seroconversion_study
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Medical University of Vienna
    Sponsor organisation address
    Waehringer Guertel 18-20, Vienna, Austria,
    Public contact
    Clinical Trials Office , Medical University of Vienna, 0043 14040043010, daniela.sieghart@meduniwien.ac.at
    Scientific contact
    Clinical Trials Office , Medical University of Vienna, 0043 14040043010, daniela.sieghart@meduniwien.ac.at
    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
    23 Feb 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Feb 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Feb 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The study aims to investigate A) the humoral and cellular immune responses after a second boost vaccination against SARS-CoV-2 in adult patients treated with immunosuppressive therapy who did not show response to the first two vaccinations with an mRNA vaccine. To assess the immunogenicity to a third vaccination mRNA-SARS-CoV-2 vaccine (Biontech/Pfizer or Moderna) compared to a vector SARS-CoV-2 (AstraZeneca) vaccination as a second boost in patients with immunosuppressive therapy. B) To compare the immunogenicity to a third vaccination with a mRNA-SARS-CoV-2 vaccine as a second boost in immunocompromised patients and healthy controls who developed insufficient titres of antibodies (< 1500 U/ml) after the standard vaccination by measuring quantitative antibody levels by spike-protein-based assay. The level of antibody increase will be compared between the two groups.
    Protection of trial subjects
    As the intervention was minimal (one time vaccination), no specific measures were performed.
    Background therapy
    		 Patient groups were on their standard immunosuppressive treatment, NSAIDs were allowed wen required.
    Evidence for comparator
    		 Some evidence suggested that a heterologous vaccination strategy might be more efficient in nonimmunocompromised healthy volunteers (Munro et al Lancet 2021, Atmar et al NEJM, 2022), thus warranting a trial in a very difficult to vacciate patient cohort.
    Actual start date of recruitment
    21 Jun 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
    Austria: 218
    Worldwide total number of subjects
    218
    EEA total number of subjects
    218
    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)
    155
    From 65 to 84 years
    62
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 For A) The trial started on July 22, 2021, with the inclusion of the first patient. The last patient finalized the 4-week follow-up on October 8, 2021. For B) The first participant was enrolled on 28 September 2021 and the last completed the 4-week follow-up on 22 December 2021. For both parts: All recruitment was performed in Vienna, Austria.

    Pre-assignment
    Screening details
    		 For A) Adults (age ≥ 18 years) under immunosuppressive treatment without measurable SARS-CoV-2 spike protein-specific antibodies at least 4 weeks after their second COVID-19 vaccination were included. For B) Adults (age>18 years) with a diagnosis of an IMIDs and HCs, both with anti-RBD antibody levels<1500 BAU after primary vaccination.

    Period 1
    Period 1 title
    Vaccination
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor
    Blinding implementation details
    In this trial, laboratory assessors and patients were blinded to the type of vaccine used. Blinding of vaccines was ensured by the Central Pharmacy of the Vienna General Hospital, where dose aliquots were prearranged in syringes without reference to the vaccine type used.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 A) mRNA
    Arm description
    		 Vaccination with a third dose of mRNA vaccine without detectable antibodies.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    BNT162b2
    Investigational medicinal product code
    Other name
    Comirnaty
    Pharmaceutical forms
    Powder and solvent for suspension for injection in multidose container
    Routes of administration
    Intramuscular use
    Dosage and administration details
    BNT162b2 i.m. once.

    Investigational medicinal product name
    mRNA-1273
    Investigational medicinal product code
    Other name
    Elasomeran
    Pharmaceutical forms
    Powder and solvent for solution for injection in multidose container
    Routes of administration
    Intramuscular use
    Dosage and administration details
    mRNA-1273 containing 100 μg mRNA i.m. once.

    Arm title
    		 A) Vector
    Arm description
    		 Vaccination with a third dose of vector vaccine without detectable antibodies.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ChAdOx1 nCoV-19
    Investigational medicinal product code
    Other name
    AZD1222
    Pharmaceutical forms
    Solution for injection in multidose container
    Routes of administration
    Intramuscular use
    Dosage and administration details
    I.m. administration with the predefined dose per manfacturer.

    Arm title
    		 B) IMID
    Arm description
    		 Immunosuppressed patients with detectable antibodies received a third vaccination with an mRNA vaccine.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    BNT162b2
    Investigational medicinal product code
    Other name
    Comirnaty
    Pharmaceutical forms
    Powder and solvent for suspension for injection in multidose container
    Routes of administration
    Intramuscular use
    Dosage and administration details
    BNT162b2 i.m. once.

    Investigational medicinal product name
    mRNA-1273
    Investigational medicinal product code
    Other name
    Elasomeran
    Pharmaceutical forms
    Powder and solvent for solution for injection in multidose container
    Routes of administration
    Intramuscular use
    Dosage and administration details
    mRNA-1273 containing 100 μg mRNA i.m. once.

    Arm title
    		 B) HC
    Arm description
    		 Healthy controls with detectable anti-RBD antibodies receiving a third mRNA vaccination
    Arm type
    		 Experimental

    Investigational medicinal product name
    BNT162b2
    Investigational medicinal product code
    Other name
    Comirnaty
    Pharmaceutical forms
    Powder and solvent for suspension for injection in multidose container
    Routes of administration
    Intramuscular use
    Dosage and administration details
    BNT162b2 i.m. once.

    Investigational medicinal product name
    mRNA-1273
    Investigational medicinal product code
    Other name
    Elasomeran
    Pharmaceutical forms
    Powder and solvent for solution for injection in multidose container
    Routes of administration
    Intramuscular use
    Dosage and administration details
    mRNA-1273 containing 100 μg mRNA i.m. once.

    Number of subjects in period 1 [1]
    		A) mRNA A) Vector B) IMID B) HC
    Started
    26
    25
    60
    48
    Completed
    24
    22
    56
    47
    Not completed
    2
    3
    4
    1
         Consent withdrawn by subject
    2
    3
    -
    -
         Development of COVID19
    -
    -
    1
    1
         Lost to follow-up
    -
    -
    3
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The difference is due to a relevant percentage of individuals being screen failures (most likely due to detectable antibodies at screening in part A) and thus no being vaccinated in the trial. These individuals would have skewed baseline characteristics and were thus not included.
    Period 2
    Period 2 title
    B) Follow-up
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 B) HC
    Arm description
    		 Follow-up period including Healthy controls
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 B) IMID Patients
    Arm description
    		 Follow-up of IMID patients
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2 [2]
    		B) HC B) IMID Patients
    Started
    47
    56
    Completed
    42
    50
    Not completed
    5
    6
         Consent withdrawn by subject
    -
    1
         Development of COVID19
    2
    2
         Lost to follow-up
    3
    3
    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: Only patients from Part B) were included into the B) Follow-up period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    A) mRNA
    Reporting group description
    		 Vaccination with a third dose of mRNA vaccine without detectable antibodies.

    Reporting group title
    A) Vector
    Reporting group description
    		 Vaccination with a third dose of vector vaccine without detectable antibodies.

    Reporting group title
    B) IMID
    Reporting group description
    		 Immunosuppressed patients with detectable antibodies received a third vaccination with an mRNA vaccine.

    Reporting group title
    B) HC
    Reporting group description
    		 Healthy controls with detectable anti-RBD antibodies receiving a third mRNA vaccination

    Reporting group values
    		 A) mRNA A) Vector B) IMID B) HC Total
    Number of subjects
    		 26 25 60 48 159
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 63.4 ( 11.4 ) 61.2 ( 14.9 ) 57.6 ( 16.2 ) 48.1 ( 14.3 ) -
    Gender categorical
    Units: Subjects
        Female
    		 11 8 45 26 90
        Male
    		 15 17 15 22 69

    End points

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    End points reporting groups
    Reporting group title
    A) mRNA
    Reporting group description
    		 Vaccination with a third dose of mRNA vaccine without detectable antibodies.

    Reporting group title
    A) Vector
    Reporting group description
    		 Vaccination with a third dose of vector vaccine without detectable antibodies.

    Reporting group title
    B) IMID
    Reporting group description
    		 Immunosuppressed patients with detectable antibodies received a third vaccination with an mRNA vaccine.

    Reporting group title
    B) HC
    Reporting group description
    		 Healthy controls with detectable anti-RBD antibodies receiving a third mRNA vaccination
    Reporting group title
    B) HC
    Reporting group description
    		 Follow-up period including Healthy controls

    Reporting group title
    B) IMID Patients
    Reporting group description
    		 Follow-up of IMID patients

    Primary: Seroconversion

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    End point title
    		 Seroconversion [1]
    End point description
    Rate of seroconversion after a third dose.
    End point type
    Primary
    End point timeframe
    After 4 weeks.
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study consists of two different arms representing different populations, with a different statistical primary outcome.
    End point values
    		 A) mRNA A) Vector
    Number of subjects analysed
    24
    22
    Units: Rate of Seroconverion
        Seroconversion
    15
    4
        No seroconversion
    9
    18
    Statistical analysis title
    		 Rate of seroconversion
    Comparison groups
    A) mRNA v A) Vector
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.006
    Method
    		 Chi-squared
    Confidence interval

    Primary: Anti-RBD antibody levels >1500 BAU/mL

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    End point title
    		 Anti-RBD antibody levels >1500 BAU/mL [2]
    End point description
    he primary endpoint was defined as the presence of antibody levels against the receptor-binding domain (RBD)>1500 BAU/mL in patients with IMIDs versus HCs.
    End point type
    Primary
    End point timeframe
    4 weeks
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The study consists of two different arms representing different populations, with a different statistical primary outcome.
    End point values
    		 B) IMID B) HC
    Number of subjects analysed
    56
    47
    Units: AB level over threshold
        AB < 1500 BAU/ml
    5
    0
        AB > 1500 BAU/ml
    51
    47
    Statistical analysis title
    		 Rate of individuals with anti-RBD antibodies>1500
    Comparison groups
    B) IMID v B) HC
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.101
    Method
    		 Chi-squared
    Confidence interval

    Post-hoc: Relative antibody reduction

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    End point title
    		 Relative antibody reduction
    End point description
    End point type
    Post-hoc
    End point timeframe
    After 12 weeks of vaccination.
    End point values
    		 B) HC B) IMID Patients
    Number of subjects analysed
    42
    50
    Units: Relative reduction
        number (confidence interval 95%)
    42 (33 to 52)
    59 (43 to 69)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 12 week in Group B, up to 4 weeks in group A.
    Adverse event reporting additional description
    Paper based diary for vaccine related AEs.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 ICD
    Dictionary version
    10
    Reporting groups
    Reporting group title
    A) mRNA
    Reporting group description
    		 Vaccination with a third dose of mRNA vaccine without detectable antibodies.

    Reporting group title
    A) Vector
    Reporting group description
    		 Vaccination with a third dose of vector vaccine without detectable antibodies.

    Reporting group title
    B) IMID
    Reporting group description
    		 Immunosuppressed patients with detectable antibodies received a third vaccination with an mRNA vaccine.

    Reporting group title
    B) HC
    Reporting group description
    		 Healthy controls with detectable anti-RBD antibodies receiving a third mRNA vaccination

    Serious adverse events
    		 A) mRNA A) Vector B) IMID B) HC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 25 (4.00%)
    1 / 60 (1.67%)
    0 / 48 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Gastrointestinal disorders
    Diarrhoea
    Additional description: Patients hospitalized because of diarrhea after the inital 4 weeks observational period.
    alternative assessment type: Non-systematic
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 25 (0.00%)
    0 / 60 (0.00%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary tract infection
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 25 (4.00%)
    1 / 60 (1.67%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
    Additional description: Hospitalization after ERCP due to elevated serum Potassium after the inital 4 weeks observational period.
    alternative assessment type: Non-systematic
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 25 (4.00%)
    0 / 60 (0.00%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 A) mRNA A) Vector B) IMID B) HC
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    23 / 26 (88.46%)
    17 / 25 (68.00%)
    51 / 60 (85.00%)
    42 / 48 (87.50%)
    Nervous system disorders
    Fatigue
         subjects affected / exposed
    10 / 26 (38.46%)
    11 / 25 (44.00%)
    33 / 60 (55.00%)
    24 / 48 (50.00%)
         occurrences all number
    10
    11
    33
    24
    Headache
         subjects affected / exposed
    8 / 26 (30.77%)
    9 / 25 (36.00%)
    20 / 60 (33.33%)
    16 / 48 (33.33%)
         occurrences all number
    8
    9
    20
    16
    General disorders and administration site conditions
    Pain at injection site
         subjects affected / exposed
    9 / 26 (34.62%)
    5 / 25 (20.00%)
    43 / 60 (71.67%)
    36 / 48 (75.00%)
         occurrences all number
    9
    5
    43
    36
    Redness at vaccination site
         subjects affected / exposed
    9 / 26 (34.62%)
    5 / 25 (20.00%)
    11 / 60 (18.33%)
    3 / 48 (6.25%)
         occurrences all number
    9
    5
    11
    3
    Swelling at vaccination site
         subjects affected / exposed
    9 / 26 (34.62%)
    5 / 25 (20.00%)
    8 / 60 (13.33%)
    2 / 48 (4.17%)
         occurrences all number
    9
    5
    8
    2
    Itching at vaccination site
         subjects affected / exposed
    4 / 26 (15.38%)
    3 / 25 (12.00%)
    6 / 60 (10.00%)
    4 / 48 (8.33%)
         occurrences all number
    4
    3
    6
    4
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 25 (8.00%)
    5 / 60 (8.33%)
    5 / 48 (10.42%)
         occurrences all number
    3
    2
    5
    5
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    9 / 26 (34.62%)
    7 / 25 (28.00%)
    19 / 60 (31.67%)
    19 / 48 (39.58%)
         occurrences all number
    9
    7
    19
    19
    Arthralgia
         subjects affected / exposed
    4 / 26 (15.38%)
    7 / 25 (28.00%)
    12 / 60 (20.00%)
    7 / 48 (14.58%)
         occurrences all number
    4
    7
    12
    7

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/36097029
    http://www.ncbi.nlm.nih.gov/pubmed/36109141
    http://www.ncbi.nlm.nih.gov/pubmed/36706534
    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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