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    Clinical Trial Results:
    Prospective, open-label, multicentre clinical trial, phase I/IIa, to investigate the safety and tolerability of allogeneic B-cell concentrates CD3+-depleted, CD19+-enriched, cryopreserved (single administration after day 120 following allogeneic stem cell transplantation, donor-identical) in 4 groups with escalating doses for immune response enhancement, measured as response to a preponed single vaccination

    Summary
    EudraCT number
    		 2012-003033-42
    Trial protocol
    		 DE  
    Global end of trial date
    21 Mar 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Jun 2022
    First version publication date
    10 Jun 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    UKER-BLZ-PH1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Universitätsklinikum Erlangen
    Sponsor organisation address
    Ulmenweg 18, Erlangen, Germany, 91054
    Public contact
    Medizinische Klinik 5, Universitätsklinikum Erlangen, +49 91318543112, julia.winkler@uk-erlangen.de
    Scientific contact
    Medizinische Klinik 5, Universitätsklinikum Erlangen, +49 91318543112, julia.winkler@uk-erlangen.de
    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
    21 Mar 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Mar 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Mar 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the safety and tolerability of escalating doses of the study medication in patients after allogeneic stem cell transplantation (donor-identical)
    Protection of trial subjects
    Treatment with antihistamines 30min Prior to IMP Administration to avoid allergic reactions; cardiopulmonal Monitoring during the first 4 Hours following IMP Administration; inpatient Setting for at least 18 Hours following IMP Administration; sterility testing Prior to IMP Administration to avoid Transmission of infectious agents; only patients at low Risk for EBV reactivation and GvHD could be enrolled
    Background therapy
    		 Additional pilot vaccination with Pentavac (Diphterie, Tetanus, pertussis, Polio, HiB) and Prevenar 13 (Pneumokokken) at day 8 +/- 3 days after IMP Administration to determine the functionality of transfered B lymphocytes. Basic immunization following stem cell transplantation according EBMT scheme
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jul 2013
    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
    Germany: 28
    Worldwide total number of subjects
    28
    EEA total number of subjects
    28
    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)
    22
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 male or female subjects, 18 - 75 years, with Status post allogeneic SCT 120 - 160 days before IMP Administration; EBV-serostatus as follows: R-/D- or R+/D- or R+/D+; no EBV reactivation > 10.000 copies/ml, no acute GvHD grade III or IV, no chronic GvHD (middle/high Risk accord. to NIH staging), initial donor willing to participate in leukapheresis

    Period 1
    Period 1 title
    Screening
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dose group I
    Arm description
    		 0,5 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    0,5 x 1.000.000 B-lymphocytes per kg BW once

    Arm title
    		 Dose group II
    Arm description
    		 1 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    1 x 1.000.000 B-lymphocytes per kg BW once

    Arm title
    		 Dose group III
    Arm description
    		 2 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    2 x 1.000.000 B-lymphocytes per kg BW once

    Arm title
    		 Dose group IV
    Arm description
    		 4 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    4 x 1.000.000 B-lymphocytes per kg BW once

    Number of subjects in period 1
    		Dose group I Dose group II Dose group III Dose group IV
    Started
    6
    5
    10
    7
    Pre-treatment examination
    6
    5
    10
    7
    Completed
    3
    3
    6
    3
    Not completed
    3
    2
    4
    4
         Physician decision
    3
    -
    2
    1
         Consent withdrawn by subject
    -
    -
    -
    1
         Adverse event, non-fatal
    -
    -
    -
    1
         IMP unavailable
    -
    -
    2
    -
         donor unavailable
    -
    2
    -
    1
    Period 2
    Period 2 title
    Treatment
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dose group I
    Arm description
    		 0,5 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    0,5 x 1.000.000 B-lymphocytes per kg BW once

    Arm title
    		 Dose group II
    Arm description
    		 1 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    1 x 1.000.000 B-lymphocytes per kg BW once

    Arm title
    		 Dose group III
    Arm description
    		 2 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    2 x 1.000.000 B-lymphocytes per kg BW once

    Arm title
    		 Dose group IV
    Arm description
    		 4 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    4 x 1.000.000 B-lymphocytes per kg BW once

    Number of subjects in period 2
    		Dose group I Dose group II Dose group III Dose group IV
    Started
    3
    3
    6
    3
    Completed
    3
    3
    6
    3
    Period 3
    Period 3 title
    Post-treatment
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dose group I
    Arm description
    		 0,5 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    0,5 x 1.000.000 B-lymphocytes per kg BW once

    Arm title
    		 Dose group II
    Arm description
    		 1 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    1 x 1.000.000 B-lymphocytes per kg BW once

    Arm title
    		 Dose group III
    Arm description
    		 2 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    2 x 1.000.000 B-lymphocytes per kg BW once

    Arm title
    		 Dose group IV
    Arm description
    		 4 x 1.000.000 B-lymphocytes per kg BW
    Arm type
    		 Experimental

    Investigational medicinal product name
    Allogeneic B-cell concentrate CD3+-depleted, CD19+-enriched, cryopreserved
    Investigational medicinal product code
    EV substance code SUB112494
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    4 x 1.000.000 B-lymphocytes per kg BW once

    Number of subjects in period 3
    		Dose group I Dose group II Dose group III Dose group IV
    Started
    3
    3
    6
    3
    Completed
    3
    3
    6
    2
    Not completed
    0
    0
    0
    1
         Adverse event, serious fatal
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Screening
    Reporting group description
    		 -

    Reporting group values
    		 Screening Total
    Number of subjects
    		 28 28
    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 (full range (min-max))
    		 54 (18 to 79) -
    Gender categorical
    Units: Subjects
        Female
    		 8 8
        Male
    		 20 20
    Subject analysis sets

    Subject analysis set title
    SES
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    all subjects treated with the IMP at any dose level

    Subject analysis set title
    FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    all treated subjects with Primary and secondary Parameters available

    Subject analysis set title
    SES Dose level I / II
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    all subjects treated with IMP at a dose level of 0,5x10.000.000 cells/kg bw or 1x10.000.000 cells/kg bw

    Subject analysis set title
    SES Dose level III / IV
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    all subjects treated with IMP at a dose level of 2x10.000.000 cells/kg bw or 3-4x10.000.000 cells/kg bw

    Subject analysis sets values
    		 SES FAS SES Dose level I / II SES Dose level III / IV
    Number of subjects
    15
    14
    6
    9
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    52 (21 to 70)
    51 (21 to 70)
    Gender categorical
    Units: Subjects
        Female
    6
    6
        Male
    9
    8

    End points

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    End points reporting groups
    Reporting group title
    Dose group I
    Reporting group description
    		 0,5 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group II
    Reporting group description
    		 1 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group III
    Reporting group description
    		 2 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group IV
    Reporting group description
    		 4 x 1.000.000 B-lymphocytes per kg BW
    Reporting group title
    Dose group I
    Reporting group description
    		 0,5 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group II
    Reporting group description
    		 1 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group III
    Reporting group description
    		 2 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group IV
    Reporting group description
    		 4 x 1.000.000 B-lymphocytes per kg BW
    Reporting group title
    Dose group I
    Reporting group description
    		 0,5 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group II
    Reporting group description
    		 1 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group III
    Reporting group description
    		 2 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group IV
    Reporting group description
    		 4 x 1.000.000 B-lymphocytes per kg BW

    Subject analysis set title
    SES
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    all subjects treated with the IMP at any dose level

    Subject analysis set title
    FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    all treated subjects with Primary and secondary Parameters available

    Subject analysis set title
    SES Dose level I / II
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    all subjects treated with IMP at a dose level of 0,5x10.000.000 cells/kg bw or 1x10.000.000 cells/kg bw

    Subject analysis set title
    SES Dose level III / IV
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    all subjects treated with IMP at a dose level of 2x10.000.000 cells/kg bw or 3-4x10.000.000 cells/kg bw

    Primary: Number and severity of TEAEs

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    End point title
    		 Number and severity of TEAEs [1]
    End point description
    Severity: 3 TEAEs severity grade 3 (hypertriglyceridaemia, CRP increase, CMV colitis), others grade 1/2
    End point type
    Primary
    End point timeframe
    day 1 (IMP Administration) to EoS visit (day 120 - 127 after IMP Administration)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Safety Parameters were analysed for treated subjects (SES) in a descriptive manner only. No formal statistical hypothesis was tested.
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV SES
    Number of subjects analysed
    3
    3
    6
    3
    15
    Units: number of events
    39
    29
    35
    38
    141
    No statistical analyses for this end point

    Primary: Number and severity of ARs

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    End point title
    		 Number and severity of ARs [2]
    End point description
    End point type
    Primary
    End point timeframe
    day 1 (IMP Administration) to EoS visit (day 120 - 127 after IMP Administration)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Safety Parameters were analysed for treated subjects (SES) in a descriptive manner only. No formal statistical hypothesis was tested.
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV SES
    Number of subjects analysed
    3
    3
    6
    3
    15
    Units: number of events
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number and severity of TESAEs

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    End point title
    		 Number and severity of TESAEs [3]
    End point description
    Severity: 1 TESAE severity grade 5 (fatal, septic shock), 2 TESAEs severity grade 2 (moderate; fever, diarrhea)
    End point type
    Primary
    End point timeframe
    day 1 (IMP Administration) to EoS visit (day 120 - 127 after IMP Administration)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Safety Parameters were analysed for treated subjects (SES) in a descriptive manner only. No formal statistical hypothesis was tested.
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV SES
    Number of subjects analysed
    3
    3
    6
    3
    15
    Units: number of events
    1
    0
    0
    2
    3
    No statistical analyses for this end point

    Primary: Number and severity of SARs

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    End point title
    		 Number and severity of SARs [4]
    End point description
    End point type
    Primary
    End point timeframe
    day 1 (IMP Administration) to EoS visit (day 120 - 127 after IMP Administration)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Safety Parameters were analysed for treated subjects (SES) in a descriptive manner only. No formal statistical hypothesis was tested.
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV SES
    Number of subjects analysed
    3
    3
    6
    3
    15
    Units: number of events
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number and severity of AESIs

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    End point title
    		 Number and severity of AESIs [5]
    End point description
    The following Events were defined as AESI: De-novo acute GvHD or Deterioration of a pre-existing acute GvHD De-novo chronic GvHD or Deterioration of a pre-existing chronic GvHD Severe allergic reaction CTCAE grade 3 or higher EBV reactivation within <14d after IMP Administration requiring immediate treatment
    End point type
    Primary
    End point timeframe
    day 1 (IMP Administration) to EoS visit (day 120 - 127 after IMP Administration)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Safety Parameters were analysed for treated subjects (SES) in a descriptive manner only. No formal statistical hypothesis was tested.
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV SES
    Number of subjects analysed
    3
    3
    6
    3
    15
    Units: number of events
    1
    1
    1
    1
    4
    No statistical analyses for this end point

    Primary: Occurence of PTLD

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    End point title
    		 Occurence of PTLD [6]
    End point description
    End point type
    Primary
    End point timeframe
    day 1 (IMP Administration) to EoS visit (day 120 - 127 after IMP Administration)
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Safety Parameters were analysed for treated subjects (SES) in a descriptive manner only. No formal statistical hypothesis was tested.
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV SES
    Number of subjects analysed
    3
    3
    6
    3
    15
    Units: number of events
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Frequency of >50.000 EBV DNA copies/ml plasma

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    End point title
    		 Frequency of >50.000 EBV DNA copies/ml plasma [7]
    End point description
    End point type
    Primary
    End point timeframe
    day 1 (IMP Administration) to EoS visit (day 120 - 127 after IMP Administration)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Safety Parameters were analysed for treated subjects (SES) in a descriptive manner only. No formal statistical hypothesis was tested.
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV SES
    Number of subjects analysed
    3
    3
    6
    3
    15
    Units: number of events
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change in percentage of antibody-producing cells

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    End point title
    		 Change in percentage of antibody-producing cells
    End point description
    percentage v10 - percentage v1
    End point type
    Secondary
    End point timeframe
    visit 1 (screening) to v10 EoS visit (day 120 - 127 after IMP Administration)
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV
    Number of subjects analysed
    3
    3
    6
    2 [8]
    Units: percent
        arithmetic mean (standard deviation)
    -2.2 ( 0.5 )
    -0.7 ( 0.6 )
    -4.9 ( 0.4 )
    1.2 ( 1.9 )
    Notes
    [8] - 1 subject died due to septic shock on day 63 after IMP administration
    No statistical analyses for this end point

    Secondary: Change in number of B-lymphocytes

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    End point title
    		 Change in number of B-lymphocytes
    End point description
    value v10 - value v1
    End point type
    Secondary
    End point timeframe
    visit 1 (screening) to v10 EoS visit (day 120 - 127 after IMP Administration)
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV
    Number of subjects analysed
    3
    3
    6
    2 [9]
    Units: cells/microlitre
        arithmetic mean (standard deviation)
    324.3 ( 86.4 )
    421.3 ( 245 )
    383.3 ( 297.4 )
    188 ( 171.8 )
    Notes
    [9] - 1 subject died due to septic shock on day 63 after IMP administration
    No statistical analyses for this end point

    Secondary: Change in percentage of naive B-lymphocytes

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    End point title
    		 Change in percentage of naive B-lymphocytes
    End point description
    percentage v10 - percentage v1
    End point type
    Secondary
    End point timeframe
    visit 1 (screening) to v10 EoS visit (day 120 - 127 after IMP Administration)
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV
    Number of subjects analysed
    3
    3
    6
    2 [10]
    Units: percent
        arithmetic mean (standard deviation)
    -13 ( 4.3 )
    3.9 ( 22.7 )
    -1 ( 6.3 )
    -3.6 ( 9.9 )
    Notes
    [10] - 1 subject died due to septic shock on day 63 after IMP administration
    No statistical analyses for this end point

    Secondary: Change in percentage of memory B-lymphocytes

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    End point title
    		 Change in percentage of memory B-lymphocytes
    End point description
    percentage v10 - percentage v1
    End point type
    Secondary
    End point timeframe
    visit 1 (screening) to v10 EoS visit (day 120 - 127 after IMP Administration)
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV
    Number of subjects analysed
    3
    3
    6
    2
    Units: percent
        arithmetic mean (standard deviation)
    0 ( 1.5 )
    1.5 ( 2.5 )
    -1.5 ( 2.3 )
    0.6 ( 4.7 )
    No statistical analyses for this end point

    Secondary: Change in antigen-specific antibody-concentration: Tetanus titer

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    End point title
    		 Change in antigen-specific antibody-concentration: Tetanus titer
    End point description
    value v7 - value v5
    End point type
    Secondary
    End point timeframe
    Visit 5 (day 8 +/- 3 days after IMP administration) to visit 7 (day 39 +/- 3 days after IMP administration)
    End point values
    		 SES Dose level I / II SES Dose level III / IV
    Number of subjects analysed
    6
    9
    Units: IU/ml
        arithmetic mean (standard deviation)
    0.3137 ( 1.038 )
    1.9056 ( 2.394 )
    No statistical analyses for this end point

    Secondary: CMV-reactivation requiring specific treatment

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    End point title
    		 CMV-reactivation requiring specific treatment
    End point description
    End point type
    Secondary
    End point timeframe
    day 1 (IMP Administration) to EoS visit (day 120 - 127 after IMP Administration)
    End point values
    		 Dose group I Dose group II Dose group III Dose group IV FAS
    Number of subjects analysed
    3
    3
    6
    2
    14
    Units: number of subjects
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change in antigen-specific antibody-concentration: Diphteria titer

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    End point title
    		 Change in antigen-specific antibody-concentration: Diphteria titer
    End point description
    v7 - v5
    End point type
    Secondary
    End point timeframe
    Visit 5 (day 8 +/- 3 days after IMP administration) to visit 7 (day 39 +/- 3 days after IMP administration)
    End point values
    		 SES Dose level I / II SES Dose level III / IV
    Number of subjects analysed
    6
    9
    Units: IU/ml
        arithmetic mean (standard deviation)
    1.82867 ( 3.042 )
    1.6919 ( 2.254 )
    No statistical analyses for this end point

    Secondary: Change in antigen-specific antibody-concentration: Pertussis titer

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    End point title
    		 Change in antigen-specific antibody-concentration: Pertussis titer
    End point description
    value v7 - value v5
    End point type
    Secondary
    End point timeframe
    Visit 5 (day 8 +/- 3 days after IMP administration) to visit 7 (day 39 +/- 3 days after IMP administration)
    End point values
    		 SES Dose level I / II SES Dose level III / IV
    Number of subjects analysed
    6
    9
    Units: IU/ml
        arithmetic mean (standard deviation)
    29.75 ( 92.98 )
    26.91 ( 38.33 )
    No statistical analyses for this end point

    Secondary: Change in antigen-specific antibody-concentration: HiB titer

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    End point title
    		 Change in antigen-specific antibody-concentration: HiB titer
    End point description
    value v7 - value v5
    End point type
    Secondary
    End point timeframe
    Visit 5 (day 8 +/- 3 days after IMP administration) to visit 7 (day 39 +/- 3 days after IMP administration)
    End point values
    		 SES Dose level I / II SES Dose level III / IV
    Number of subjects analysed
    6
    9
    Units: IU/ml
        arithmetic mean (standard deviation)
    9.9867 ( 14.58 )
    3.0752 ( 3.352 )
    No statistical analyses for this end point

    Secondary: Change in antigen-specific antibody-concentration: Polio titer

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    End point title
    		 Change in antigen-specific antibody-concentration: Polio titer
    End point description
    value v7 - value v5
    End point type
    Secondary
    End point timeframe
    Visit 5 (day 8 +/- 3 days after IMP administration) to visit 7 (day 39 +/- 3 days after IMP administration)
    End point values
    		 SES Dose level I / II SES Dose level III / IV
    Number of subjects analysed
    6
    9
    Units: IU/ml
        arithmetic mean (standard deviation)
    2.64 ( 50.97 )
    -0.15 ( 8.276 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    day 1 (IMP Administration) to EoS visit (day 120 - 127 after IMP Administration)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Dose group I
    Reporting group description
    		 0,5 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group II
    Reporting group description
    		 1 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group III
    Reporting group description
    		 2 x 1.000.000 B-lymphocytes per kg BW

    Reporting group title
    Dose group IV
    Reporting group description
    		 4 x 1.000.000 B-lymphocytes per kg BW

    Serious adverse events
    		 Dose group I Dose group II Dose group III Dose group IV
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 3 (66.67%)
         number of deaths (all causes)
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    1
    General disorders and administration site conditions
    Pyrexia
    Additional description: Fever and CRP increase following 3rd vaccination with Prevenar/Pentavac; Outcome: resolved
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (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
    Cytomegalovirus colitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         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
    Septic shock
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         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 / 1
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Dose group I Dose group II Dose group III Dose group IV
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    6 / 6 (100.00%)
    3 / 3 (100.00%)
    Vascular disorders
    Hypotonia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypertensive crisis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypertonia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    3 / 3 (100.00%)
         occurrences all number
    0
    1
    0
    4
    General disorders and administration site conditions
    Mucosal inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Oedema peripheral
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    2 / 3 (66.67%)
         occurrences all number
    0
    1
    2
    2
    Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Fatigue
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Body temperature increased
         subjects affected / exposed
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Vaccination site pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Adverse drug reaction
    Additional description: coagulation disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Feeling hot
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    1
    Acute graft versus host disease
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Acute graft versus host disease in skin
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    2
    Chronic graft versus host disease
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 3 (100.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    7
    0
    1
    Chronic graft versus host disease in skin
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Graft versus host disease in liver
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Immunisation reaction
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    2
    1
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Investigations
    Cortisol decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Liver function test abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    1
    2
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Blood creatine increased
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Vaccination complication
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Skin abrasion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Scrotal haematoma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Mouth injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Ligament sprain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Spinal fracture
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cardiac disorders
    Extrasystoles
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Sinus bradycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nervous system disorders
    Tremor
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Vertigo positional
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Pancytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Hypergammaglobulinaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Eosinophilia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 3 (66.67%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Leukopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Leukocytosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Neutropenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    0
    1
    Eye disorders
    Periorbital oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Dry eye
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    0
    2
    Keratitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cataract
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    0
    0
    0
    3
    Oral lichen planus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Dry mouth
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    2
    0
    0
    3
    Trichoglossia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    0
    1
    Proctitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Abdominal distension
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Nausea
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    1
    0
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Alcoholic liver disease
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Hepatic steatosis
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Dermatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Erythema
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    1
    1
    Pruritus
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    1
    1
    4
    0
    Night sweats
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pigmentation disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Adrenal insufficiency
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    1
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Muscle spasms
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    0
    1
    Back pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Arthralgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Gouty arthritis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Osteoarthropathy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infections and infestations
    Campylobacter gastroenteritis
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Febrile infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Infection
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    0
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    2
    1
    0
    1
    Folliculitis
         subjects affected / exposed
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    3
    0
    0
    2
    Paronychia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    2
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cervicitis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Septic shock
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Candida infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
         occurrences all number
    2
    2
    1
    1
    Cytomegalovirus colitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    2
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    2 / 3 (66.67%)
         occurrences all number
    0
    1
    3
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    0
    2
    0
    3
    Folate deficiency
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    2 / 3 (66.67%)
         occurrences all number
    1
    1
    1
    2
    Vitamin B12 deficiency
         subjects affected / exposed
    2 / 3 (66.67%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    2 / 3 (66.67%)
         occurrences all number
    2
    0
    2
    2
    Vitamin D deficiency
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Sep 2013
    Changes due to deficiency letter
    28 Jul 2014
    NIMP: altern. vaccination allowed
    20 Jun 2016
    Dose Level IV changed from 4x10.000.000 cells/kg bw to 3-4x10.000.000 cells/kg bw (manufacturing issue)

    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
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    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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