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   44335   clinical trials with a EudraCT protocol, of which   7366   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:
    Double blinded, randomized, Priorix®- and placebo-controlled, trial to evaluate the optimal dose of MV-CHIK vaccine (against Chikungunya virus) in regard to immunogenicity, safety and tolerability in healthy volunteers

    Summary
    EudraCT number
    		 2015-004037-26
    Trial protocol
    		 DE   AT  
    Global end of trial date
    16 Apr 2018

    Results information
    Results version number
    		 v1
    This version publication date
    09 Feb 2020
    First version publication date
    09 Feb 2020
    Other versions
    		 v2

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MV-CHIK-202
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02861586
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Themis Bioscience GmbH
    Sponsor organisation address
    Muthgasse 11/2, Vienna, Austria, 1190
    Public contact
    Andrea Pfeiffer, MSc Clinica Project Officer, Themis Bioscience GmbH, +43 6765102835, andrea.pfeiffer@themisbio.com
    Scientific contact
    Dr. Katrin Ramsauer Chief Scientific Officer, Themis Bioscience GmbH, +43 676843496418, katrin.ramsauer@themisbio.com
    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
    17 Jul 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Apr 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Apr 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the immunogenicity and safety of MV-CHIK 28 days after primary immunization regime, comprising one or two vaccinations.
    Protection of trial subjects
    Subjects’ safety was an essential concern in this clinical study MV-CHIK-202 and was addressed in the clinical study protocol: -Physical examination: During each study visit subjects underwent a symptom-directed physical examination and the assessment of vital signs like systolic and diastolic blood pressure, pulse and body temperature, allowed to detect and record adverse conditions. -Post vaccination reactogenicity assessment: All subjects were observed for 1 hour after each vaccination in order to investigate local and systemic tolerability and to ensure the subjects wellbeing before discharge. -AEs: For general safety reasons, all subjects that at least received one vaccination were followed up for at least 28 days after the last vaccination. -Body temperature: All subjects received a thermometer and were asked to note their daily body temperature in a diary for 7 days after each vaccination to perceive side effects. -Subject diary: Solicited AEs were recorded by the subjects by checking the presence of listed symptoms in a subject’s diary. The diary provided also space for noting unsolicited AEs and concomitant medication. This enabled the subjects to better remember AEs and the investigator to gather and assess AEs in more detail. -Laboratory parameters: were regularly measured to reveal clinically relevant lab values on hematology, blood chemistry, coagulation parameters and urinalysis. All lab results were evaluated carefully by the investigator to identify adverse conditions. -Safety stopping rules: An independent DSMB was installed to review safety information, and if necessary, to determine whether study or individual subject stopping rules have been met. -Data Safety Monitoring Board (DSMB): In close cooperation with the DSMB and the investigators the protection of study participants was assured.
    Background therapy
    		 n.a.
    Evidence for comparator
    		 Priorix® (Glaxo Smith Kline GSK) a measles, mumps, rubella vaccine was used as a control-vaccine because the contained attenuated Schwarz measles virus strain is the same strain, used as backbone in MV-CHIK.
    Actual start date of recruitment
    17 Aug 2016
    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
    Austria: 168
    Country: Number of subjects enrolled
    Germany: 95
    Worldwide total number of subjects
    263
    EEA total number of subjects
    263
    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)
    263
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 First subject in, Austria: 17-Aug-2016 Last subjec out, Austria: 11-Jan-2018 First subject in, Germany: 04-May-2017 Last subjec out, Germany: 16-Apr-2018

    Pre-assignment
    Screening details
    		 To confirm the health status of volunteers the following data and parameters were assessed during screening: Medical/vacination history, physical examination, hematology, coagulation parameters, HIV, hepatitis B/C, urinalysis

    Period 1
    Period 1 title
    overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Assessor
    Blinding implementation details
    This study was conducted in a double-blind manner in regard to assignment to Treatment Groups A, B, C or D. An assignment to the measles booster groups M1 and M2 was apparent to both, subject and study personnel, but the vaccination sequence was kept double-blind (allocation to M1 or to M2 was unknown). Vaccine was prepared by authorized unblinded personnel otherwise not involved in the conduct of the study. Readyly prepared syringes were blinded.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Treatment Group A
    Arm description
    		 Treatment group A received i.m. vaccinations with MV-CHIK low dose (5x10E4 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MV-CHIK low dose 5x10E4 (± 0.5 log) TCID50/dose
    Investigational medicinal product code
    MV-CHIK
    Other name
    Chikungunya vaccine
    Pharmaceutical forms
    Powder for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Treatment group A received i.m. vaccinations with 0.3 ml MV-CHIK low dose on study day 0 and 28, and 0.3 ml placebo on day 196.

    Investigational medicinal product name
    Placebo NaCl 0.9%
    Investigational medicinal product code
    Placebo
    Other name
    Physiological saline solution
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Treatment group A received i.m. vaccinations with 0.3 ml MV-CHIK low dose on study day 0 and 28, and 0.3 ml placebo on day 196.

    Arm title
    		 Treatment Group B
    Arm description
    		 Group B subjects received i.m. vaccinations with placebo on study day 0; MV-CHIK low dose (5x10E4 (± 0.5 log) TCID50 per 0.3 mL) on day 28 and MV-CHIK boosting dose on day 196.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MV-CHIK low dose 5x10E4 (± 0.5 log) TCID50/ dose
    Investigational medicinal product code
    MV-CHIK
    Other name
    Chikungunya vaccine
    Pharmaceutical forms
    Powder for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Group B subjects received i.m. vaccinations with 0.3 ml placebo on study day 0, and 0.3 ml MV-CHIK low dose on day 28 and on day 196.

    Investigational medicinal product name
    Placebo NaCl 0.9%
    Investigational medicinal product code
    Placebo
    Other name
    physiological saline solution
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Group B subjects received i.m. vaccinations with 0.3 ml placebo on study day 0, and 0.3 ml MV-CHIK low dose on day 28 and on day 196.

    Arm title
    		 Treatment Group C
    Arm description
    		 Group C received i.m. vaccinations with MV-CHIK high dose (5x10E5 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MV-CHIK high dose 5x10E5 (± 0.5 log) TCID50/ dose
    Investigational medicinal product code
    MV-CHIK
    Other name
    Chikungunya vaccine
    Pharmaceutical forms
    Powder for suspension for injection
    Routes of administration
    Intranasal use
    Dosage and administration details
    Group C received i.m. vaccinations with 0.3 ml MV-CHIK high dose on study day 0 and 28, and 0.3 ml placebo on day 196.

    Investigational medicinal product name
    Placebo NaCl 0.9%
    Investigational medicinal product code
    Placebo
    Other name
    Physiological saline solution
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Group C received i.m. vaccinations with 0.3 ml MV-CHIK high dose on study day 0 and 28, and 0.3 ml placebo on day 196.

    Arm title
    		 Treatment Group D
    Arm description
    		 Group D received i.m. vaccinations with placebo on study day 0, MV-CHIK high dose (5x10E5 (± 0.5 log) TCID50 per 0.3 mL) on study day 28 and MV-CHIK boosting dose on day 196.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MV-CHIK high dose 5x10E5 (± 0.5 log) TCID50/ dose
    Investigational medicinal product code
    MV-CHIK
    Other name
    Chikungunya vaccine
    Pharmaceutical forms
    Powder for suspension for injection
    Routes of administration
    Intranasal use
    Dosage and administration details
    Group D received i.m. vaccinations with 0.3 ml placebo on study day 0, and 0.3 ml MV-CHIK high dose on study day 28 and on day 196.

    Investigational medicinal product name
    Placebo NaCl 0.9%
    Investigational medicinal product code
    Placebo
    Other name
    Physiological saline solution
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Group D received i.m. vaccinations with 0.3 ml placebo on study day 0, and 0.3 ml MV-CHIK high dose on study day 28 and on day 196.

    Arm title
    		 Treatment Group M1
    Arm description
    		 Measles Booster Group 1, M1: received i.m. vaccinations with Priorix® 28 days prior to vaccination with MV-CHIK on day 0 and 28, and placebo on day 168 and 196.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Priorix® measles, mumps rubella vaccine
    Investigational medicinal product code
    Priorix® controll vaccine
    Other name
    comperator
    Pharmaceutical forms
    Powder for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects of group M1 received the control vaccine (Priorix®) 28 days prior to two MV-CHIK vaccinations on day 0 and 28, followed by two placebo injections on day 168 and 196.

    Arm title
    		 Treatment Group M2
    Arm description
    		 Measles Booster Group 2, M2: received i.m. vaccinations with Priorix® 28 days prior to placebo on day 0 and 28, and MV-CHIK on day 168 and 196.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Priorix® measles, mumps, rubella vaccine
    Investigational medicinal product code
    Priorix®controll vaccine
    Other name
    comperator
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Group M2 received the control vaccine (Priorix®) 28 days prior to two placebo injections on day 0 and 28, followed by two MV-CHIK vaccinations on day 168 and 196.

    Arm title
    		 Control Group CV1, A/C
    Arm description
    		 Control Group CV1, A/C received i.m. vaccinations with Priorix® on study day 0 and 28, and placebo on day 196.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Priorix® measles, mumps, rubella vaccine
    Investigational medicinal product code
    Priorix® control vaccine
    Other name
    comperator
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Control Group CV1, A/C received i.m. vaccinations with Priorix® on study day 0 and 28, and placebo on day 196.

    Investigational medicinal product name
    Placebo NaCl 0.9%
    Investigational medicinal product code
    Placebo
    Other name
    Physiological saline solution
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Control Group CV1, A/C received i.m. vaccinations with Priorix® on study day 0 and 28, and placebo on day 196.

    Arm title
    		 Control Group CV2, B/D
    Arm description
    		 Control Group CV2, B/D received i.m. vaccinations with placebo on study day 0, Priorix® on day 28 and one boosting dose with Priorix® on day 196.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Priorix® measles, mumps, rubella vaccine
    Investigational medicinal product code
    Priorix® control vaccine
    Other name
    comperator
    Pharmaceutical forms
    Powder and solvent for solution for injection/skin-prick test
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Control Group CV2, B/D received i.m. vaccinations with placebo on study day 0, and Priorix® on day 28 and day 196.

    Investigational medicinal product name
    Placebo NaCl 0.9%
    Investigational medicinal product code
    Placebo
    Other name
    Physiological saline solution
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Control Group CV2, B/D received i.m. vaccinations with placebo on study day 0, and Priorix® on day 28 and day 196.

    Number of subjects in period 1
    		Treatment Group A Treatment Group B Treatment Group C Treatment Group D Treatment Group M1 Treatment Group M2 Control Group CV1, A/C Control Group CV2, B/D
    Started
    51
    47
    47
    50
    18
    16
    18
    16
    Completed
    49
    44
    47
    44
    16
    15
    16
    16
    Not completed
    2
    3
    0
    6
    2
    1
    2
    0
         Consent withdrawn by subject
    1
    2
    -
    2
    1
    -
    -
    -
         Adverse event, non-fatal
    -
    -
    -
    1
    -
    -
    -
    -
         Lost to follow-up
    1
    1
    -
    3
    1
    1
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    overall trial
    Reporting group description
    		 -

    Reporting group values
    		 overall trial Total
    Number of subjects
    		 263 263
    Age categorical
    study population: healthy male and female voluntees aged 18 -55 years
    Units: Subjects
        18-55
    		 263 263
    Gender categorical
    Units: Subjects
        Female
    		 140 140
        Male
    		 123 123

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Treatment Group A
    Reporting group description
    		 Treatment group A received i.m. vaccinations with MV-CHIK low dose (5x10E4 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

    Reporting group title
    Treatment Group B
    Reporting group description
    		 Group B subjects received i.m. vaccinations with placebo on study day 0; MV-CHIK low dose (5x10E4 (± 0.5 log) TCID50 per 0.3 mL) on day 28 and MV-CHIK boosting dose on day 196.

    Reporting group title
    Treatment Group C
    Reporting group description
    		 Group C received i.m. vaccinations with MV-CHIK high dose (5x10E5 (± 0.5 log) TCID50 per 0.3 mL) on study day 0 and 28, placebo on day 196.

    Reporting group title
    Treatment Group D
    Reporting group description
    		 Group D received i.m. vaccinations with placebo on study day 0, MV-CHIK high dose (5x10E5 (± 0.5 log) TCID50 per 0.3 mL) on study day 28 and MV-CHIK boosting dose on day 196.

    Reporting group title
    Treatment Group M1
    Reporting group description
    		 Measles Booster Group 1, M1: received i.m. vaccinations with Priorix® 28 days prior to vaccination with MV-CHIK on day 0 and 28, and placebo on day 168 and 196.

    Reporting group title
    Treatment Group M2
    Reporting group description
    		 Measles Booster Group 2, M2: received i.m. vaccinations with Priorix® 28 days prior to placebo on day 0 and 28, and MV-CHIK on day 168 and 196.

    Reporting group title
    Control Group CV1, A/C
    Reporting group description
    		 Control Group CV1, A/C received i.m. vaccinations with Priorix® on study day 0 and 28, and placebo on day 196.

    Reporting group title
    Control Group CV2, B/D
    Reporting group description
    		 Control Group CV2, B/D received i.m. vaccinations with placebo on study day 0, Priorix® on day 28 and one boosting dose with Priorix® on day 196.

    Subject analysis set title
    Modified Intent-to-Treat Population
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The exploratory immunogenicity analyses were based on the modified Intent-to-treat (mITT) population. The mITT population included all randomized subjects who received at least one vaccination. Subjects were analyzed according to the treatment group they were randomized to, rather than by the actual treatment they received.

    Subject analysis set title
    Per Protocol Population
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The Per-Protocol (PP) population was defined as the mITT population minus subjects with at least one major protocol deviation. The PP population excluded an enrolled subject if one of the following criteria was met:  Immunosuppressive drugs: Use of corticosteroids (excluding topical preparations) or immunosuppressive drugs within 30 days prior to vaccination, or anticipated use during the trial  Subjects with any confirmed immunosuppressive or immunodeficient condition, including HIV, hepatitis A, B or C infection or a family history of congenital or hereditary immunodeficiency  Subjects who received the wrong or no study medication  Subjects with other major protocol deviations

    Primary: Immunogenicity on day 56 by PRNT50

    		 Close Top of page
    End point title
    		 Immunogenicity on day 56 by PRNT50
    End point description
    Immunogenicity on study day 56 confirmed by the presence of functional anti-chikungunya antibodies as determined by the plaque reduction neutralization test (PRNT50)
    End point type
    Primary
    End point timeframe
    Functional anti-chikungunya antibodies measured by the plaque reduction neutralization test (PRNT50) on study day 56
    End point values
    		 Treatment Group A Treatment Group B Treatment Group C Treatment Group D Treatment Group M1 Treatment Group M2 Control Group CV1, A/C Control Group CV2, B/D
    Number of subjects analysed
    49
    44
    47
    44
    16
    15
    16
    16
    Units: Titer
        geometric mean (standard deviation)
    50.2 ( 127.69 )
    12.9 ( 100.47 )
    174.8 ( 436.11 )
    33.6 ( 59.38 )
    80.0 ( 233.80 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
    Statistical analysis title
    		 ANOVA PRNT50 at Day 56
    Statistical analysis description
    ANOVA with fixed factor treatment group for GMT of functional antibodies by PRNT50 at day 56.
    Comparison groups
    Treatment Group A v Treatment Group B v Treatment Group C v Treatment Group D v Treatment Group M1 v Treatment Group M2 v Control Group CV1, A/C v Control Group CV2, B/D
    Number of subjects included in analysis
    247
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 ≤ 0.05
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -
    Variability estimate
    Standard deviation

    Secondary: Anti-measles antibodies by ELISA

    		 Close Top of page
    End point title
    		 Anti-measles antibodies by ELISA
    End point description
    Measurement of anti-measles antibody titers on day 0, 28, and 56 and additionally for group M1 and M2 on day -28 as determined by ELISA. Please note that for some timepoints testing has not been done. "Not done" cannot be entered but only numerical values. "9999" should serve as indicator of a test which was not performed.
    End point type
    Secondary
    End point timeframe
    Anti-measles antibodies on day 0, 28, and 56 and additionally for group M1 and M2 on day -28 as determined by ELISA
    End point values
    		 Treatment Group A Treatment Group B Treatment Group C Treatment Group D Treatment Group M1 Treatment Group M2 Control Group CV1, A/C Control Group CV2, B/D
    Number of subjects analysed
    49
    44
    47
    44
    16
    15
    16
    16
    Units: Titer
    geometric mean (standard deviation)
        Day -28
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    542.6 ( 1118.52 )
    304.5 ( 343.53 )
    9999 ( 9999 )
    9999 ( 9999 )
        Day 0
    456.2 ( 1398.54 )
    398.1 ( 1267.55 )
    495.0 ( 1181.36 )
    401.8 ( 1073.54 )
    785.6 ( 1149.47 )
    645.9 ( 850.56 )
    693.9 ( 1307.42 )
    390.4 ( 1106.86 )
        Day 28
    1509.4 ( 1360.83 )
    396.9 ( 1183.04 )
    2343.9 ( 1357.29 )
    2343.9 ( 1357.29 )
    1761.5 ( 1578.85 )
    561.2 ( 385.36 )
    1200.6 ( 1129.77 )
    447.5 ( 1139.37 )
        Day 56
    1651.8 ( 1384.39 )
    1255.0 ( 1279.28 )
    2750.5 ( 1284.23 )
    2750.5 ( 1284.23 )
    1825.2 ( 1459.93 )
    521.4 ( 455.37 )
    1129.4 ( 1168.63 )
    673.8 ( 917.52 )
    No statistical analyses for this end point

    Secondary: Shedding (Urine)

    		 Close Top of page
    End point title
    		 Shedding (Urine) [1]
    End point description
    Shedding of live recombinant virus until day 196 (in a subset of subjects at one site)
    End point type
    Secondary
    End point timeframe
    Shedding of live recombinant virus on day 0, 7, 10, 14, 28 and day 196 after the first injection
    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: No statistic calculations were planned or performed - not one case of sheeding was observed. Shedding analysis relies on PCR methods amplifying measles sequences. As M1 and M2 groups receive a measles vaccination and the study vaccination (modified measles virus), a potential positive result would not be indicative of the reason and therefore these groups were not tested for shedding.
    End point values
    		 Treatment Group A Treatment Group B Treatment Group C Treatment Group D Control Group CV1, A/C Control Group CV2, B/D
    Number of subjects analysed
    7
    3
    8
    4
    4
    2
    Units: Subjects shedding measles virus
        Day 0
    0
    0
    0
    0
    0
    0
        Day 7
    0
    0
    0
    0
    0
    0
        Day 10
    0
    0
    0
    0
    0
    0
        Day 14
    0
    0
    0
    0
    0
    0
        Day 28
    0
    0
    0
    0
    0
    0
        Day 196
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Immunogenicity on days 0, 28, 196, and 224 (and 168 for M1 and M2) by PRNT50

    		 Close Top of page
    End point title
    		 Immunogenicity on days 0, 28, 196, and 224 (and 168 for M1 and M2) by PRNT50
    End point description
    Immunogenicity on days 0, 28, 196 and 224; additionally, for group M1 and M2 on day 168 as confirmed by the presence of functional anti-chikungunya antibodies as determined by the plaque reduction neutralization test (PRNT50) and by ELISA. - please note that in the protocol the timepoint "day -28" for M1 and M2 groups is also mentioned; however that timepoint was used for testing pre-existing measles titer but has no additional value for the chikungunya-PRNTs as it would be only an additional pre-vaccination value. Please note that for some timepoints testing has not been done. "Not done" cannot be entered but only numerical values. "9999" should serve as indicator of a test which was not performed.
    End point type
    Secondary
    End point timeframe
    Study day 0 to day 224
    End point values
    		 Treatment Group A Treatment Group B Treatment Group C Treatment Group D Treatment Group M1 Treatment Group M2 Control Group CV1, A/C Control Group CV2, B/D
    Number of subjects analysed
    49
    44
    47
    44
    16
    15
    16
    16
    Units: Titer
    geometric mean (standard deviation)
        Day 0
    5.1 ( 0.71 )
    5.3 ( 3.16 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
        Day 28
    63.4 ( 10.0 )
    5.5 ( 3.82 )
    25.7 ( 52.22 )
    5.1 ( 0.75 )
    13.5 ( 40.52 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
        Day 168
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    9999 ( 9999 )
    28.9 ( 52.25 )
    5.0 ( 0.00 )
    9999 ( 9999 )
    9999 ( 9999 )
        Day 196
    13.5 ( 33.46 )
    6.4 ( 8.29 )
    38.8 ( 70.59 )
    24.1 ( 106.25 )
    24.1 ( 106.25 )
    11.5 ( 26.04 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
        Day 224
    14.6 ( 37.87 )
    70.5 ( 174.57 )
    41.8 ( 105.55 )
    609.8 ( 949.70 )
    18.3 ( 87.50 )
    66.5 ( 172.62 )
    5.0 ( 0.00 )
    5.0 ( 0.00 )
    Statistical analysis title
    		 ANOVA to compare PRNT titers
    Statistical analysis description
    An ANOVA with the fixed factors treatment group (CV1, CV2, A, B, C, D, M1, M2) will be used to compare PRNT functional antibody geometric mean titers (GMT) per visit.
    Comparison groups
    Treatment Group A v Treatment Group B v Treatment Group C v Treatment Group D v Treatment Group M1 v Treatment Group M2 v Control Group CV1, A/C v Control Group CV2, B/D
    Number of subjects included in analysis
    247
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 ≤ 0.05
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (final values)
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -
    Variability estimate
    Standard deviation

    Secondary: Shedding (Saliva)

    		 Close Top of page
    End point title
    		 Shedding (Saliva) [2]
    End point description
    Shedding of live recombinant virus until day 196 (in a subset of subjects at one site)
    End point type
    Secondary
    End point timeframe
    Shedding of live recombinant virus on day 0, 7, 10, 14, 28 and day 196 after the first injection
    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: No statistic calculations were planned or performed - not one case of sheeding was observed. Shedding analysis relies on PCR methods amplifying measles sequences. As M1 and M2 groups receive a measles vaccination and the study vaccination (modified measles virus), a potential positive result would not be indicative of the reason and therefore these groups were not tested for shedding.
    End point values
    		 Treatment Group A Treatment Group B Treatment Group C Treatment Group D Control Group CV1, A/C Control Group CV2, B/D
    Number of subjects analysed
    7
    3
    8
    4
    4
    2
    Units: Subjects shedding measles virus
        Day 0
    0
    0
    0
    0
    0
    0
        Day 7
    0
    0
    0
    0
    0
    0
        Day 10
    0
    0
    0
    0
    0
    0
        Day 14
    0
    0
    0
    0
    0
    0
        Day 28
    0
    0
    0
    0
    0
    0
        Day 196
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Solicited Adverse Events (Safety population)

    		 Close Top of page
    End point title
    		 Solicited Adverse Events (Safety population)
    End point description
    Number of observed AEs per treatment group.
    End point type
    Secondary
    End point timeframe
    Throughout the study participation
    End point values
    		 Treatment Group A Treatment Group B Treatment Group C Treatment Group D Treatment Group M1 Treatment Group M2 Control Group CV1, A/C Control Group CV2, B/D
    Number of subjects analysed
    51
    47
    47
    50
    18
    16
    18
    16
    Units: Observations
        Numer of observations
    35
    32
    37
    41
    13
    10
    14
    10
    Statistical analysis title
    		 Fisher exact test to compare AE rates
    Comparison groups
    Treatment Group A v Treatment Group B v Treatment Group C v Treatment Group D v Treatment Group M1 v Treatment Group M2 v Control Group CV1, A/C v Control Group CV2, B/D
    Number of subjects included in analysis
    263
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [3]
    P-value
    		 ≤ 0.05
    Method
    		 Fisher exact
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [3] - Pairwise comparison of treatment groups.

    Secondary: Treatment Emergent Adverse Events

    		 Close Top of page
    End point title
    		 Treatment Emergent Adverse Events
    End point description
    Observations of unsolicited treatment emergent adverse events (TEAEs).
    End point type
    Secondary
    End point timeframe
    Throughout the study.
    End point values
    		 Treatment Group A Treatment Group B Treatment Group C Treatment Group D Treatment Group M1 Treatment Group M2 Control Group CV1, A/C Control Group CV2, B/D
    Number of subjects analysed
    51
    47
    47
    50
    18
    16
    18
    16
    Units: Observations
        TEAEs
    29
    27
    22
    18
    11
    9
    10
    7
        Serious TEAEs
    1
    2
    0
    1
    0
    0
    1
    1
        Severe TEAEs
    1
    2
    0
    2
    1
    1
    1
    0
        Related TEAEs
    8
    11
    4
    10
    4
    5
    2
    1
        Medically Attended TEAEs
    12
    15
    9
    8
    4
    3
    3
    1
        TEAEs where an action was taken
    0
    1
    0
    1
    0
    0
    0
    1
        TEAEs of special interest
    2
    2
    0
    1
    2
    0
    0
    0
    Statistical analysis title
    		 Fisher exact test to compare AE rates
    Statistical analysis description
    Pairwise comparison of TEAEs between treatment groups.
    Comparison groups
    Treatment Group A v Treatment Group B v Treatment Group C v Treatment Group D v Treatment Group M1 v Treatment Group M2 v Control Group CV1, A/C v Control Group CV2, B/D
    Number of subjects included in analysis
    263
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 ≤ 0.05
    Method
    		 Fisher exact
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -

    Secondary: Induction of a Chikungunya virus specific T cell response (subset of subjects)

    		 Close Top of page
    End point title
    		 Induction of a Chikungunya virus specific T cell response (subset of subjects)
    End point description
    Please note that for some timepoints testing has not been done. "Not done" cannot be entered but only numerical values. "9999" should serve as indicator of a test which was not performed.
    End point type
    Secondary
    End point timeframe
    Study Days 0, 28, 56, and 224
    End point values
    		 Treatment Group A Treatment Group B Treatment Group C Treatment Group D Treatment Group M1 Treatment Group M2 Control Group CV1, A/C Control Group CV2, B/D
    Number of subjects analysed
    15
    12
    14
    11
    5
    4
    5
    5
    Units: Subjects with CHIKV-specific T-cells
        Day 0
    0
    1
    0
    0
    0
    9999
    0
    0
        Day 28
    2
    9999
    1
    9999
    9999
    9999
    0
    9999
        Day 56
    6
    3
    7
    1
    3
    0
    0
    1
        Day 224
    5
    4
    3
    3
    0
    0
    0
    1
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Day 0 after the first vaccination up to day 224
    Adverse event reporting additional description
    Solicited and unsolicited local and systemic adverse events (AEs) were recorded throughout the study.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Treatment Group A
    Reporting group description
    		 Group A subjects received vaccinations with MVCHIK low dose on study day 0 and 28, placebo on day 196.

    Reporting group title
    Treatment Group B
    Reporting group description
    		 Group B subjects received vaccinations with placebo on study day 0. MV-CHIK low dose on day 28 and MV-CHIK boosting dose on day 196.

    Reporting group title
    Treatment Group C
    Reporting group description
    		 Group C subjects received vaccinations with MVCHIK high dose on study day 0 and 28, placebo on day 196.

    Reporting group title
    Treatment Group D
    Reporting group description
    		 Group D subjects received vaccinations with placebo on study day 0, MV-CHIK high dose on study day 28 and MV-CHIK boosting dose on day 196.

    Reporting group title
    Treatment Group M1
    Reporting group description
    		 Measles Booster Group M1 subjects received vaccinations with Priorix® on study day -28, MV-CHIK on day 0 and 28 and placebo on day 168 and 196.

    Reporting group title
    Treatment Group M2
    Reporting group description
    		 Measles Booster Group M2 subjects received vaccinations with Priorix® on study day -28, placebo on day 0 and 28 and MV-CHIK on day 168 and 196.

    Reporting group title
    Control Group CV1, A/C
    Reporting group description
    		 Control Group CV1, A/C subjects received vaccinations with Priorix® on study day 0 and 28, placebo on day 196.

    Reporting group title
    Control Group CV2, B/D
    Reporting group description
    		 Control Group CV2, B/D subjects received vaccinations with placebo on study day 0, Priorix® on day 28 and one boosting dose with Priorix® on day 196.

    Serious adverse events
    		 Treatment Group A Treatment Group B Treatment Group C Treatment Group D Treatment Group M1 Treatment Group M2 Control Group CV1, A/C Control Group CV2, B/D
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 51 (1.96%)
    2 / 47 (4.26%)
    0 / 47 (0.00%)
    1 / 50 (2.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    1 / 16 (6.25%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Laryngeal cancer
    Additional description: One subject of control group CV1 experienced laryngeal cancer 5 days after receiving placebo. The subject was hospitalized and biopsy and tracheotomy were performed. The event was assessed severe in intensity and considered not related.
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
    Additional description: One subject of group D experienced papillary thyroid cancer 4 months after receiving the first dose of MV-CHIK. The event was considered severe in intensity and not related to the study drug. Subject terminated early after Visit 3 due to this SAE.
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    1 / 50 (2.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ligament rupture
    Additional description: 1 subject of group B experienced ligament rupture left knee 3 months and 12 days after receiving the first dose of MV-CHIK. The subject was hospitalized and surgery was performed. The event was considered not related to the study drug.
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 47 (2.13%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion
    Additional description: 1 subject group B experienced suspected abortion 1 month and 10 days after receiving placebo. This was considered an important medical event and was judged to be mild and possibly related to the study treatment.
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 47 (2.13%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Umbilical hernia
    Additional description: 1 subject of group A experienced umbilical hernia 4 weeks after the second dose of MVCHIK. The subject was hospitalized and surgery was performed.The event was considered moderate in severity and not related to the study drug.
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
    Additional description: 1 subject of control group CV2 experienced type 2 diabetes mellitus reported the same month the subject received the first dose of control vaccine. The subject was hospitalized and a diagnostic test performed. The event was assessed not related.
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Treatment Group A Treatment Group B Treatment Group C Treatment Group D Treatment Group M1 Treatment Group M2 Control Group CV1, A/C Control Group CV2, B/D
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    42 / 51 (82.35%)
    39 / 47 (82.98%)
    39 / 47 (82.98%)
    42 / 50 (84.00%)
    15 / 18 (83.33%)
    14 / 16 (87.50%)
    14 / 18 (77.78%)
    12 / 16 (75.00%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 47 (2.13%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 47 (0.00%)
    1 / 47 (2.13%)
    3 / 50 (6.00%)
    1 / 18 (5.56%)
    1 / 16 (6.25%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    1
    3
    1
    1
    1
    0
    Fatigue
         subjects affected / exposed
    2 / 51 (3.92%)
    1 / 47 (2.13%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    2
    1
    0
    0
    1
    0
    0
    0
    Axillary pain
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 47 (2.13%)
    0 / 47 (0.00%)
    1 / 50 (2.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    2
    1
    0
    0
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 47 (2.13%)
    1 / 47 (2.13%)
    2 / 50 (4.00%)
    2 / 18 (11.11%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    2
    3
    2
    8
    4
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 47 (2.13%)
    4 / 47 (8.51%)
    1 / 50 (2.00%)
    2 / 18 (11.11%)
    1 / 16 (6.25%)
    1 / 18 (5.56%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    5
    1
    3
    1
    1
    1
    Cough
         subjects affected / exposed
    1 / 51 (1.96%)
    2 / 47 (4.26%)
    1 / 47 (2.13%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    1 / 16 (6.25%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    1
    2
    1
    0
    1
    1
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    1 / 47 (2.13%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    Sneezing
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Injury
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    1 / 47 (2.13%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    Skin abrasion
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    1 / 50 (2.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    Contusion
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    7 / 51 (13.73%)
    2 / 47 (4.26%)
    1 / 47 (2.13%)
    4 / 50 (8.00%)
    1 / 18 (5.56%)
    2 / 16 (12.50%)
    2 / 18 (11.11%)
    1 / 16 (6.25%)
         occurrences all number
    8
    2
    1
    9
    1
    2
    2
    1
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    1
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    1 / 47 (2.13%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    2 / 16 (12.50%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Eye pruritus
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    3 / 51 (5.88%)
    0 / 47 (0.00%)
    2 / 47 (4.26%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    3
    0
    2
    0
    0
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 47 (2.13%)
    0 / 47 (0.00%)
    1 / 50 (2.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    1
    1
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 47 (2.13%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    1
    1
    0
    Toothache
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    1 / 50 (2.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    1
    0
    Skin and subcutaneous tissue disorders
    Dermatitis contact
         subjects affected / exposed
    1 / 51 (1.96%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    1 / 50 (2.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 47 (2.13%)
    0 / 47 (0.00%)
    1 / 50 (2.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    1
    1
    0
    0
    0
    Erythema multiforme
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Renal and urinary disorders
    Hypertonic bladder
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 51 (3.92%)
    2 / 47 (4.26%)
    2 / 47 (4.26%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    2
    2
    3
    0
    0
    1
    0
    1
    Myalgia
         subjects affected / exposed
    2 / 51 (3.92%)
    2 / 47 (4.26%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    2
    2
    0
    0
    4
    0
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    0 / 51 (0.00%)
    1 / 47 (2.13%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    Bursitis
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    7 / 51 (13.73%)
    4 / 47 (8.51%)
    4 / 47 (8.51%)
    4 / 50 (8.00%)
    2 / 18 (11.11%)
    1 / 16 (6.25%)
    2 / 18 (11.11%)
    2 / 16 (12.50%)
         occurrences all number
    7
    4
    5
    5
    5
    1
    2
    3
    Rhinitis
         subjects affected / exposed
    2 / 51 (3.92%)
    0 / 47 (0.00%)
    3 / 47 (6.38%)
    2 / 50 (4.00%)
    2 / 18 (11.11%)
    2 / 16 (12.50%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    3
    2
    3
    2
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 51 (5.88%)
    3 / 47 (6.38%)
    1 / 47 (2.13%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    3
    4
    2
    0
    0
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 51 (1.96%)
    1 / 47 (2.13%)
    1 / 47 (2.13%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    0
    1
    0
    Gingivitis
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    Hordeolum
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Vaginal infection
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    0 / 18 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Metabolism and nutrition disorders
    Appetite disorder
         subjects affected / exposed
    0 / 51 (0.00%)
    0 / 47 (0.00%)
    0 / 47 (0.00%)
    0 / 50 (0.00%)
    1 / 18 (5.56%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 16 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Aug 2016
    Protocol Amendment 1 (substantial, dated 26-Apr-2016) incorporated in Protocol version 1.3 (26-Apr-2016) before the first study submission. The protocol was amended:  To precisely define the primary endpoint as immunogenicity on Day 56 for all treatment groups  To adapt the study design (by shifting study visits) to enable immunogenicity measurements on Day 56 for all treatment groups  To change the definition from three cohorts consisting of two different treatment regimens each, to a more reasonable definition of six treatment groups  To define the dates of study visits based on an interval of 28 days and to rename the study days as follows: Screening Visit on Study Day -35; Visit 0 on Study Day -28; Visit 1 on Study Day 0; Visit 2 on Study Day 28; Visit 3 on Study Day 56; Visit 4 on Study Day 168; Visit 5 on Study Day 196; Visit 6 on Study Day 224  To state the study objectives more precisely  To include a preliminary data analysis  To describe the role of the DSMB  To remove the safety assessment by telephone call, 12 months after the first vaccination  To clarify that the control-vaccine Priorix® can be exchanged by MMR-Vax-Pro® or equal measles vaccine In addition, to correct typos, include some formal changes and update the list of abbreviations

    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
    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-Thu May 15 02:45:45 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA