Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    SARS-CoV-2 vaccination strategies in previous hospitalised and recovered COVID-19 patients

    Summary
    EudraCT number
    		 2021-003386-35
    Trial protocol
    		 DK   ES  
    Global end of trial date
    21 Dec 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Jan 2024
    First version publication date
    19 Jan 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    INSIGHT-016
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04969250
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Regents of the University of Minnesota
    Sponsor organisation address
    Office of the Vice President for Research, 420 Johnston Hall, 101 Pleasant St SE, Minneapolis, United States, 55455
    Public contact
    Jens Lundgren, CHIP-Rigshospitalet, 45 3545 5757, jens.lundgren@regionh.dk
    Scientific contact
    Jens Lundgren, CHIP-Rigshospitalet, 45 3545 5757, jens.lundgren@regionh.dk
    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
    22 Nov 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Dec 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Dec 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    1. Among participants in TICO who were randomized to placebo, to estimate the difference in NAb levels at Week 48 to the Moderna mRNA-1273 vaccine or the Pfizer BNT162b2 vaccine among participants who are vaccinated early (i.e. at time of enrolment into this protocol, within 28 to 90 days of enrolment in TICO) versus deferred (i.e. 12 weeks after enrolment into this protocol). 2. Among participants in TICO who were randomized to placebo, to estimate the difference in neutralizing antibody levels at Week 48 to the Moderna mRNA-1273 vaccine or the Pfizer BNT162b2 vaccine among participants who are vaccinated once versus twice.
    Protection of trial subjects
    Informed consent was obtained from the participant before any trial-related procedures were conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jul 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Switzerland: 4
    Country: Number of subjects enrolled
    United States: 28
    Country: Number of subjects enrolled
    Uganda: 20
    Country: Number of subjects enrolled
    Spain: 14
    Worldwide total number of subjects
    66
    EEA total number of subjects
    14
    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)
    55
    From 65 to 84 years
    8
    85 years and over
    3

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants must be randomized to the TICO trial.

    Period 1
    Period 1 title
    Entire trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 One vaccine, immediate (I1)
    Arm description
    		 One vaccine dose, administered immediately following randomization
    Arm type
    		 Strategy

    Investigational medicinal product name
    Anti-SARS-CoV2 vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose of vaccine given upper arm

    Arm title
    		 Two vaccines, immediate (I2)
    Arm description
    		 Two vaccine doses, one administered immediately following randomization and one 4 weeks later
    Arm type
    		 Strategy

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 One vaccine, delayed (D1)
    Arm description
    		 One vaccine dose, administered 12 weeks following randomization
    Arm type
    		 strategy

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Two vaccines, delayed (D2)
    Arm description
    		 Two vaccine doses, one administered 12 weeks following randomization and the second 16 weeks following randomization (4 weeks after the first dose)
    Arm type
    		 Strategy

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		One vaccine, immediate (I1) Two vaccines, immediate (I2) One vaccine, delayed (D1) Two vaccines, delayed (D2)
    Started
    16
    18
    16
    16
    Completed
    16
    15
    13
    8
    Not completed
    0
    3
    3
    8
         Consent withdrawn by subject
    -
    1
    -
    -
         Protocol deviation
    -
    2
    3
    8

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    One vaccine, immediate (I1)
    Reporting group description
    		 One vaccine dose, administered immediately following randomization

    Reporting group title
    Two vaccines, immediate (I2)
    Reporting group description
    		 Two vaccine doses, one administered immediately following randomization and one 4 weeks later

    Reporting group title
    One vaccine, delayed (D1)
    Reporting group description
    		 One vaccine dose, administered 12 weeks following randomization

    Reporting group title
    Two vaccines, delayed (D2)
    Reporting group description
    		 Two vaccine doses, one administered 12 weeks following randomization and the second 16 weeks following randomization (4 weeks after the first dose)

    Reporting group values
    		 One vaccine, immediate (I1) Two vaccines, immediate (I2) One vaccine, delayed (D1) Two vaccines, delayed (D2) Total
    Number of subjects
    		 16 18 16 16 66
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 12 15 13 15 55
        From 65-84 years
    		 2 3 3 0 8
        85 years and over
    		 2 0 0 1 3
    Gender categorical
    Units: Subjects
        Female
    		 8 6 6 8 28
        Male
    		 8 12 10 8 38

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    One vaccine, immediate (I1)
    Reporting group description
    		 One vaccine dose, administered immediately following randomization

    Reporting group title
    Two vaccines, immediate (I2)
    Reporting group description
    		 Two vaccine doses, one administered immediately following randomization and one 4 weeks later

    Reporting group title
    One vaccine, delayed (D1)
    Reporting group description
    		 One vaccine dose, administered 12 weeks following randomization

    Reporting group title
    Two vaccines, delayed (D2)
    Reporting group description
    		 Two vaccine doses, one administered 12 weeks following randomization and the second 16 weeks following randomization (4 weeks after the first dose)

    Primary: Neutralizing antibody (NAb) levels following vaccination (change from baseline, log 10 scale)

    		 Close Top of page
    End point title
    		 Neutralizing antibody (NAb) levels following vaccination (change from baseline, log 10 scale)
    End point description
    End point type
    Primary
    End point timeframe
    48 weeks after enrollment
    End point values
    		 One vaccine, immediate (I1) Two vaccines, immediate (I2) One vaccine, delayed (D1) Two vaccines, delayed (D2)
    Number of subjects analysed
    12
    15
    13
    11
    Units: concentration
        geometric mean (confidence interval 95%)
    0.3722 (-.0566 to .8012)
    .5883 (.1366 to 1.0399)
    .2088 (-.1758 to .5935)
    .3073 (-.1479 to .7624)
    Statistical analysis title
    		 48 Week GMR in NAb level, by timing
    Statistical analysis description
    Use ANCOVA to compare GMR of 48 week NAb, by timing group (immediate vs. deferred), adjusted for baseline level.
    Comparison groups
    One vaccine, immediate (I1) v One vaccine, delayed (D1) v Two vaccines, immediate (I2) v Two vaccines, delayed (D2)
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.268
    Method
    		 ANCOVA
    Parameter type
    		 Relative change (GMR)
    Point estimate
    1.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 4.2
    Variability estimate
    Standard error of the mean
    Statistical analysis title
    		 48 Week GMR in NAb level, by number of doses
    Statistical analysis description
    Use ANCOVA to compare GMR of 48 week NAb, by number of doses (1 vs. 2), adjusted for baseline level.
    Comparison groups
    One vaccine, immediate (I1) v Two vaccines, immediate (I2) v One vaccine, delayed (D1) v Two vaccines, delayed (D2)
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.4524
    Method
    		 ANCOVA
    Parameter type
    		 Relative change (GMR)
    Point estimate
    0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.26
         upper limit
    		 1.83
    Variability estimate
    Standard error of the mean

    Secondary: Antibody levels 12 weeks after enrollment (change from baseline, log 10 scale)

    		 Close Top of page
    End point title
    		 Antibody levels 12 weeks after enrollment (change from baseline, log 10 scale)
    End point description
    End point type
    Secondary
    End point timeframe
    12 weeks after enrollment
    End point values
    		 One vaccine, immediate (I1) Two vaccines, immediate (I2) One vaccine, delayed (D1) Two vaccines, delayed (D2)
    Number of subjects analysed
    13
    15
    14
    13
    Units: concentration
        geometric mean (confidence interval 95%)
    .4827 (.0641 to .914)
    .9206 (.4938 to 1.3474)
    .2418 (-.1329 to .6165)
    .6533 (.1554 to 1.1513)
    No statistical analyses for this end point

    Secondary: % with >= 4-fold difference in NAb

    		 Close Top of page
    End point title
    		 % with >= 4-fold difference in NAb
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to 48 weeks
    End point values
    		 One vaccine, immediate (I1) Two vaccines, immediate (I2) One vaccine, delayed (D1) Two vaccines, delayed (D2)
    Number of subjects analysed
    12
    15
    13
    11
    Units: percent
        number (not applicable)
    5
    8
    4
    3
    No statistical analyses for this end point

    Secondary: Antibody levels 12 weeks after enrollment (change from baseline, log 10 scale)

    		 Close Top of page
    End point title
    		 Antibody levels 12 weeks after enrollment (change from baseline, log 10 scale)
    End point description
    End point type
    Secondary
    End point timeframe
    12 weeks after enrollment
    End point values
    		 One vaccine, immediate (I1) Two vaccines, immediate (I2) One vaccine, delayed (D1) Two vaccines, delayed (D2)
    Number of subjects analysed
    13
    15
    14
    13
    Units: concentration
        geometric mean (confidence interval 95%)
    .4827 (.0641 to .914)
    .9206 (.4938 to 1.3474)
    .2418 (-.1329 to .6165)
    .6533 (.1554 to 1.1513)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    Entire trial
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    One vaccine, immediate (I1)
    Reporting group description
    		 One vaccine dose, administered immediately following randomization

    Reporting group title
    Two vaccines, immediate (I2)
    Reporting group description
    		 Two vaccine doses, one administered immediately following randomization and one 4 weeks later

    Reporting group title
    One vaccine, delayed (D1)
    Reporting group description
    		 One vaccine dose, administered 12 weeks following randomization

    Reporting group title
    Two vaccines, delayed (D2)
    Reporting group description
    		 Two vaccine doses, one administered 12 weeks following randomization and the second 16 weeks following randomization (4 weeks after the first dose)

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: Grade 3 and 4 adverse events were assessed at weeks 12, 24 and 48 of the study. None were reported. Only 66 participants enrolled; study eligibility criteria required that they be recovered from COVID-19, so they were in better health than many intervention studies.
    Serious adverse events
    		 One vaccine, immediate (I1) Two vaccines, immediate (I2) One vaccine, delayed (D1) Two vaccines, delayed (D2)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
         number of deaths (all causes)
    1
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Bicytopenia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
    Additional description: Re-infection
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 One vaccine, immediate (I1) Two vaccines, immediate (I2) One vaccine, delayed (D1) Two vaccines, delayed (D2)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)

    More information

    		 Close Top of page

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

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    21 Feb 2022
    Individuals were eligible for VATICO within a given time period after enrollment into TICO. TICO closed to enrollment, and thus VATICO closed after there were no longer potentially eligible participants coming from TICO.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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.

    European Medicines Agency © 1995-Fri May 03 08:34:15 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA