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    Clinical Trial Results:
    A double-blind, randomized, placebo-controlled, Phase I/II Study evaluating the safety, immunogenicity and clinical activity of neoadjuvant treatment with WT1-A10 + AS15 Antigen-Specific Cancer Immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II or III breast cancer.

    Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
    Summary
    EudraCT number
    2010-019909-42
    Trial protocol
    BE   DE   GB   DK  
    Global end of trial date
    14 Nov 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    05 Mar 2016
    First version publication date
    05 Mar 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    113172
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01220128
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.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
    04 May 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    14 Nov 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Nov 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The study was conducted in 2 consecutive segments with specific objectives: Phase I Segment -Objectives concerning cohorts A, B, C and D: To evaluate the safety and immunogenicity of WT1 ASCI administration in combination with standard treatment. Phase II Segment -To further assess the safety, immunogenicity and the clinical activity of WT1 ASCI in combination with standard treatment per group and in the overall population (i.e., including the patients enrolled during the Phase I segment of the study).
    Protection of trial subjects
    The vaccine/placebo recipients were to be observed closely for at least 30 minutes with appropriate medical treatment readily available in case of a rare anaphylactic reaction following the administration of vaccine(s)/product(s). For patients in Cohort B and C, the study product administration had to be done at least 60 minutes prior to administration of chemotherapy. The patient was observed closely for at least 30 minutes following the administration of the study product with appropriate medical treatment readily available in case of a rare anaphylactic reaction.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    11 Apr 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    Belgium: 9
    Country: Number of subjects enrolled
    France: 5
    Country: Number of subjects enrolled
    Germany: 34
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    Russian Federation: 5
    Country: Number of subjects enrolled
    United States: 3
    Worldwide total number of subjects
    60
    EEA total number of subjects
    52
    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)
    37
    From 65 to 84 years
    23
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

    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, Assessor
    Blinding implementation details
    Double-blind, randomized, placebo-controlled study including 2 segments, a Phase I segment and a Phase II segment. The Phase I segment was a randomized (2:1), double-blinded, placebo-controlled study for cohorts A, B and C and an open label, single treatment schedule study for Cohort D. The Phase II segment was a randomized (2:1), double-blinded, placebo-controlled study for cohorts A, B, C, and E.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort A-WT1 Group
    Arm description
    This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of WT1 ASCI according to the treatment schedule.
    Arm type
    Experimental

    Investigational medicinal product name
    WT1-A10 + AS15
    Investigational medicinal product code
    WT1-A10 + AS15
    Other name
    WT1 ASCI
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 6 or 8 injections at 3 weeks apart, injected intramuscularly in the deltoid or lateral region of the thigh and any aromatase inhibitor, administered intravenously in Cohort A Groups daily for either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).

    Investigational medicinal product name
    Aromatase inhibitor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    This treatment consisted of any aromatase inhibitor (e.g. letrozole or exemestane), administered intravenously in Cohort A Groups daily for either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).

    Arm title
    Cohort A-Placebo Group
    Arm description
    This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 6 or 8 doses at 3 weeks apart of sucrose/mannitol-based formulation reconstituted with an oil-in-water emulsion, injected intramuscularly in the deltoid or lateral region of the thigh and any aromatase inhibitor, administered intravenously in Cohort A Groups daily for either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).

    Investigational medicinal product name
    5-Fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Epirubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Aromatase inhibitor
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    This treatment consisted of any aromatase inhibitor (e.g. letrozole or exemestane), administered intravenously in Cohort A Groups daily for either 18 (if 6 doses of WT1 ASCI/placebo) or 24 weeks (if 8 doses of WT1 ASCI/placebo).

    Arm title
    Cohort B-WT1 Group
    Arm description
    This group included breast cancer patients who received WT1 ASCI and intravenous chemotherapy.
    Arm type
    Experimental

    Investigational medicinal product name
    WT1-A10 + AS15
    Investigational medicinal product code
    WT1-A10 + AS15
    Other name
    WT1 ASCI
    Pharmaceutical forms
    Powder for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 6 or 8 injections at 3 weeks apart, injected intramuscularly in the deltoid or lateral region of the thigh and 6 intravenous cycle-treatment chemotherapy regimens consisting of 6 3-weekly cycles of anthracycline/taxane-based therapy or 8 intravenous cycle-treatment regimens consisting of 4 3-weekly cycles of anthracycline-based therapy followed by 4 3-weekly or 12-weekly taxane administrations without trastuzumab.

    Investigational medicinal product name
    5-Fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Epirubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Arm title
    Cohort B-Placebo Group
    Arm description
    This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection
    Routes of administration
    Intraventricular use
    Dosage and administration details
    Subjects received 6 or 8 doses at 3 weeks apart of sucrose/mannitol-based formulation reconstituted with an oil-in-water emulsion, injected intramuscularly in the deltoid or lateral region of the thigh and 6 intravenous cycle-treatment chemotherapy regimens consisting of 6 3-weekly cycles of anthracycline/taxane-based therapy, or 8 intravenous cycle-treatment regimens consisting of 4 3-weekly cycles of anthracycline-based therapy followed by 4 3-weekly or 12-weekly taxane administrations without trastuzumab.

    Investigational medicinal product name
    5-Fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Epirubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Arm title
    Cohort C-WT1 Group
    Arm description
    This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin AUC, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
    Arm type
    Experimental

    Investigational medicinal product name
    WT1-A10 + AS15
    Investigational medicinal product code
    WT1-A10 + AS15
    Other name
    WT1 ASCI
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 6 or 8 injections at 3 weeks apart, injected intramuscularly in the deltoid or lateral region of the thigh and 6 intravenous cycle-treatment chemotherapy regimens consisting of 6 3-weekly cycles of anthracycline/taxane-based therapy, or 8 intravenous cycle-treatment regimens consisting of 4 3-weekly cycles of anthracycline-based therapy followed by 4 3-weekly or 12-weekly taxane administrations with trastuzumab.

    Investigational medicinal product name
    5-Fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Epirubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Trastuzumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohort C Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Carboplatin AUC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohort C Groups in 6 doses at 3 weeks apart, on the same day as WT1 ASCI/placebo administration (Day 1 of each cycle).

    Arm title
    Cohort C-Placebo Group
    Arm description
    This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin AUC, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 6 or 8 doses at 3 weeks apart of sucrose/mannitol-based formulation reconstituted with an oil-in-water emulsion, injected intramuscularly in the deltoid or lateral region of the thigh and 6 intravenous cycle-treatment chemotherapy regimens consisting of 6 3-weekly cycles of anthracycline/taxane-based therapy, or 8 intravenous cycle-treatment regimens consisting of 4 3-weekly cycles of anthracycline-based therapy followed by 4 3-weekly or 12-weekly taxane administrations with trastuzumab.

    Investigational medicinal product name
    5-Fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Epirubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Carboplatin AUC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohort C Groups in 6 doses at 3 weeks apart, on the same day as WT1 ASCI/placebo administration (Day 1 of each cycle).

    Investigational medicinal product name
    Trastuzumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohort C Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohort B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Arm title
    Cohort D-WT1-D14 Group
    Arm description
    This group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received WT1 ASCI, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.
    Arm type
    Experimental

    Investigational medicinal product name
    WT1-A10 + AS15
    Investigational medicinal product code
    WT1-A10 + AS15
    Other name
    WT1 ASCI
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 6 or 8 injections at 3 weeks apart, injected intramuscularly in the deltoid or lateral region of the thigh and 6 intravenous cycle-treatment chemotherapy regimens consisting of 6, 3-weekly cycles of anthracycline/taxane-based therapy, or 8 intravenous cycle-treatment regimens consisting of 4 3-weekly cycles of anthracycline-based therapy followed by 4 three-weekly taxane administrations without trastuzumab.

    Investigational medicinal product name
    5-Fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses at 3 weeks apart, and for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses in Cohort C Groups and 6 doses 3 weeks apart in Cohorts A Placebo, B and D Groups, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 or 6 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 6 doses 3 weeks apart (Cohort C patients with this schedule did not receive this treatment), while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Epirubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: for the 6 WT1 ASCI-dose schedule 3 doses 3 weeks apart, while for the 8 WT1 ASCI-dose schedule 4 doses at 3 weeks apart. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously in Cohorts A Placebo, B, C and D/E Groups: only in the 8 WT1 ASCI-dose schedule patients received 4 at 3 weeks apart or 12 weekly doses. For Cohorts A Placebo, B and C Groups, the administration was on the same day as the administration of WT1 ASCI/placebo (Day 1 of each cycle). For Cohort D/E Groups, the administration was on Day 14 of each cycle.

    Number of subjects in period 1
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Started
    15
    7
    9
    6
    11
    4
    8
    Completed
    11
    6
    6
    6
    11
    4
    3
    Not completed
    4
    1
    3
    0
    0
    0
    5
         Progressive disease
    -
    -
    2
    -
    -
    -
    -
         Sponsor study termination
    -
    1
    -
    -
    -
    -
    1
         Adverse event, serious fatal
    2
    -
    -
    -
    -
    -
    1
         Adverse event, non-fatal
    1
    -
    -
    -
    -
    -
    3
         Unspecified
    -
    -
    1
    -
    -
    -
    -
         Consent withdrawn by subject
    1
    -
    -
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort A-WT1 Group
    Reporting group description
    This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of WT1 ASCI according to the treatment schedule.

    Reporting group title
    Cohort A-Placebo Group
    Reporting group description
    This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

    Reporting group title
    Cohort B-WT1 Group
    Reporting group description
    This group included breast cancer patients who received WT1 ASCI and intravenous chemotherapy.

    Reporting group title
    Cohort B-Placebo Group
    Reporting group description
    This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

    Reporting group title
    Cohort C-WT1 Group
    Reporting group description
    This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin AUC, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

    Reporting group title
    Cohort C-Placebo Group
    Reporting group description
    This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin AUC, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

    Reporting group title
    Cohort D-WT1-D14 Group
    Reporting group description
    This group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received WT1 ASCI, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

    Reporting group values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group Total
    Number of subjects
    15 7 9 6 11 4 8 60
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    69.3 ± 10.4 70.9 ± 7.1 49.3 ± 15.6 60.7 ± 9.8 52.9 ± 10.6 53.3 ± 6.2 49.6 ± 8.7 -
    Gender categorical
    Units: Subjects
        Female
    15 7 9 6 11 4 8 60
        Male
    0 0 0 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Cohort A-WT1 Group
    Reporting group description
    This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of WT1 ASCI according to the treatment schedule.

    Reporting group title
    Cohort A-Placebo Group
    Reporting group description
    This group included postmenopausal patients with hormone receptor-positive breast cancer who received aromatase inhibitor (AI) as neoadjuvant therapy, concurrently with administration of placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

    Reporting group title
    Cohort B-WT1 Group
    Reporting group description
    This group included breast cancer patients who received WT1 ASCI and intravenous chemotherapy.

    Reporting group title
    Cohort B-Placebo Group
    Reporting group description
    This group included breast cancer patients who received placebo, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

    Reporting group title
    Cohort C-WT1 Group
    Reporting group description
    This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin AUC, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

    Reporting group title
    Cohort C-Placebo Group
    Reporting group description
    This group included patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who received neoadjuvant trastuzumab (Herceptin) therapy, concurrently with administration of placebo, 5-Fluorouracil, Carboplatin AUC, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

    Reporting group title
    Cohort D-WT1-D14 Group
    Reporting group description
    This group included patients with hormone receptor-positive and HER2 non-overexpressing breast cancer, who received WT1 ASCI, 5-Fluorouracil, Cyclophosphamide, Docetaxel, Doxorubicin, Epirubicin and Paclitaxel according to the treatment schedule.

    Primary: Number of subjects with severe toxicities

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    End point title
    Number of subjects with severe toxicities [1] [2]
    End point description
    End point type
    Primary
    End point timeframe
    During the whole study period
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort B-WT1 Group Cohort C-WT1 Group
    Number of subjects analysed
    9
    11
    Units: Subjects
        Any severe toxicity
    1
    1
    No statistical analyses for this end point

    Primary: Number of patients with an anti-WT1 humoral response

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    End point title
    Number of patients with an anti-WT1 humoral response [3]
    End point description
    At post-WT1 ASCI/placebo Dose 4 (Week 13)
    End point type
    Primary
    End point timeframe
    For initially seronegative patients: post-administration antibody concentration ≥ 9 EU/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration. The main analysis for the Phase
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    10
    4
    8
    6
    11
    3
    3
    Units: Subjects
        Anti-WT1 response
    10
    0
    0
    0
    6
    0
    2
    No statistical analyses for this end point

    Primary: Number of patients with adverse events (AEs)

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    End point title
    Number of patients with adverse events (AEs) [4]
    End point description
    An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.
    End point type
    Primary
    End point timeframe
    During the 31-day (Days 0-30) following vaccination
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Any AE(s)
    15
    5
    9
    6
    11
    4
    7
    No statistical analyses for this end point

    Primary: Number of subjects with serious adverse events SAE(s)

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    End point title
    Number of subjects with serious adverse events SAE(s) [5]
    End point description
    A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, causes disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient. In this study, an event which was part of the natural course of the disease under study (i.e., disease progression/recurrence) was captured in the study/as an efficacy measure. Therefore it was not reported as an SAE. Progression/recurrence of the tumor was recorded in the clinical assessments in the electronic case report form (eCRF). Death due to progressive disease was recorded on a specific form in the eCRF but not as an SAE.
    End point type
    Primary
    End point timeframe
    During the entire study period
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Any SAE(s)
    3
    0
    4
    2
    5
    1
    5
    No statistical analyses for this end point

    Primary: Number of subjects with alanine aminotransferase increased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with alanine aminotransferase increased abnormality, by CTCAE maximum grade [6]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    12
    5
    8
    4
    6
    2
    1
        Grade 1
    2
    1
    1
    2
    5
    2
    2
        Grade 2
    0
    0
    0
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    1
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with alkaline phosphatase increased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with alkaline phosphatase increased abnormality, by CTCAE maximum grade [7]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    10
    5
    8
    6
    7
    3
    1
        Grade 1
    5
    1
    1
    0
    4
    1
    2
        Grade 2
    0
    0
    0
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with anemia, by CTCAE maximum grade

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    End point title
    Number of subjects with anemia, by CTCAE maximum grade [8]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [8] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    12
    7
    1
    0
    0
    0
    2
        Grade 1
    2
    0
    7
    4
    7
    3
    2
        Grade 2
    1
    0
    0
    0
    4
    1
    0
        Grade 3
    0
    0
    1
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    0
    0
    0
    0
    0
    4
    No statistical analyses for this end point

    Primary: Number of subjects with aspartate aminotransferase increased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with aspartate aminotransferase increased abnormality, by CTCAE maximum grade [9]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [9] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    12
    4
    8
    6
    7
    1
    2
        Grade 1
    3
    2
    1
    0
    4
    3
    1
        Grade 2
    1
    0
    0
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with blood bilirubin increased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with blood bilirubin increased abnormality, by CTCAE maximum grade [10]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [10] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    15
    5
    9
    6
    11
    2
    3
        Grade 1
    0
    1
    0
    0
    0
    0
    0
        Grade 2
    0
    0
    0
    0
    0
    1
    0
        Grade 3
    0
    0
    0
    0
    0
    1
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with creatine increased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with creatine increased abnormality, by CTCAE maximum grade [11]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [11] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    11
    4
    8
    5
    10
    3
    3
        Grade 1
    4
    2
    1
    1
    1
    1
    0
        Grade 2
    0
    0
    0
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    4
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with hemoglobin increased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with hemoglobin increased abnormality, by CTCAE maximum grade [12]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [12] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    15
    6
    9
    6
    11
    4
    4
        Grade 1
    0
    1
    0
    0
    0
    0
    0
        Grade 2
    0
    0
    0
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    0
    0
    0
    0
    0
    4
    No statistical analyses for this end point

    Primary: Number of subjects with hypercalcemia abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with hypercalcemia abnormality, by CTCAE maximum grade [13]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [13] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    14
    3
    8
    6
    11
    4
    3
        Grade 1
    1
    3
    1
    0
    0
    0
    0
        Grade 2
    0
    0
    0
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    3
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with hyperkalemia abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with hyperkalemia abnormality, by CTCAE maximum grade [14]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [14] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    15
    5
    7
    6
    10
    4
    3
        Grade 1
    0
    1
    1
    0
    1
    0
    0
        Grade 2
    0
    0
    1
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with hypernatremia abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with hypernatremia abnormality, by CTCAE maximum grade [15]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [15] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    14
    4
    9
    6
    10
    4
    3
        Grade 1
    1
    2
    0
    0
    0
    0
    0
        Grade 2
    0
    0
    0
    0
    1
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with hypoalbuminemia abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with hypoalbuminemia abnormality, by CTCAE maximum grade [16]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [16] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    13
    6
    9
    5
    9
    3
    3
        Grade 1
    1
    0
    0
    1
    2
    1
    0
        Grade 2
    1
    0
    0
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with hypocalcemia abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with hypocalcemia abnormality, by CTCAE maximum grade [17]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [17] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    12
    6
    5
    4
    10
    3
    3
        Grade 1
    3
    0
    3
    1
    1
    1
    0
        Grade 2
    0
    0
    1
    1
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with hypokalemia abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with hypokalemia abnormality, by CTCAE maximum grade [18]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [18] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    15
    6
    9
    6
    10
    4
    3
        Grade 1
    0
    0
    0
    0
    1
    0
    0
        Grade 2
    0
    0
    1
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with hyponatremia abnormality, by CTCAE maximum grade

    Close Top of page
    End point title
    Number of subjects with hyponatremia abnormality, by CTCAE maximum grade [19]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and post 30 days post last vaccination
    Notes
    [19] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    15
    6
    5
    6
    11
    4
    3
        Grade 1
    0
    0
    4
    0
    0
    0
    0
        Grade 2
    0
    0
    0
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    1
    0
    0
    0
    0
    5
    No statistical analyses for this end point

    Primary: Number of subjects with lymphocyte count decreased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with lymphocyte count decreased abnormality, by CTCAE maximum grade [20]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [20] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    9
    4
    0
    0
    2
    1
    1
        Grade 1
    5
    2
    3
    2
    3
    1
    1
        Grade 2
    1
    1
    5
    2
    5
    1
    2
        Grade 3
    0
    0
    1
    2
    1
    1
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    0
    0
    0
    0
    0
    4
    No statistical analyses for this end point

    Primary: Number of subjects with lymphocyte count increased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with lymphocyte count increased abnormality, by CTCAE maximum grade [21]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [21] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    15
    7
    9
    6
    11
    4
    4
        Grade 1
    0
    0
    0
    0
    0
    0
    0
        Grade 2
    0
    0
    0
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    0
    0
    0
    0
    0
    4
    No statistical analyses for this end point

    Primary: Number of subjects with neutrophil count decreased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with neutrophil count decreased abnormality, by CTCAE maximum grade [22]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [22] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    12
    6
    7
    5
    10
    3
    0
        Grade 1
    3
    0
    1
    1
    1
    0
    0
        Grade 2
    0
    1
    1
    0
    0
    0
    1
        Grade 3
    0
    0
    0
    0
    0
    1
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    3
        Grade Unknown
    0
    0
    0
    0
    0
    0
    4
    No statistical analyses for this end point

    Primary: Number of subjects with platelet count decreased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with platelet count decreased abnormality, by CTCAE maximum grade [23]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [23] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    14
    6
    8
    5
    5
    2
    2
        Grade 1
    1
    1
    1
    1
    5
    2
    2
        Grade 2
    0
    0
    0
    0
    1
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    0
    0
    0
    0
    0
    4
    No statistical analyses for this end point

    Primary: Number of subjects with white blood cell decreased abnormality, by CTCAE maximum grade

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    End point title
    Number of subjects with white blood cell decreased abnormality, by CTCAE maximum grade [24]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [24] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Grade 0
    13
    7
    6
    3
    7
    2
    0
        Grade 1
    2
    0
    2
    2
    4
    1
    1
        Grade 2
    0
    0
    1
    1
    0
    1
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    3
        Grade 4
    0
    0
    0
    0
    0
    0
    0
        Grade Unknown
    0
    0
    0
    0
    0
    0
    4
    No statistical analyses for this end point

    Primary: Number of patients with adverse events (AEs), by CTCAE maximum grade reported

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    End point title
    Number of patients with adverse events (AEs), by CTCAE maximum grade reported [25]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [25] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Any AE(s) Grade 1
    6
    1
    0
    0
    0
    0
    0
        Any AE(s) Grade 2
    6
    4
    6
    0
    4
    3
    2
        Any AE(s) Grade 3
    3
    0
    0
    5
    3
    0
    1
        Any AE(s) Grade 4
    0
    0
    2
    1
    4
    1
    4
        Any AE(s) Grade 5
    0
    0
    1
    0
    0
    0
    0
        Any AE(s)
    15
    5
    9
    6
    11
    4
    7
    No statistical analyses for this end point

    Primary: Number of subjects with serious adverse events (SAEs), by CTCAE maximum grade reported

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    End point title
    Number of subjects with serious adverse events (SAEs), by CTCAE maximum grade reported [26]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [26] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Any SAE(s) Grade 1
    0
    0
    0
    0
    0
    0
    0
        Any SAE(s) Grade 2
    1
    0
    1
    0
    0
    0
    0
        Any SAE(s) Grade 3
    2
    0
    0
    1
    1
    0
    1
        Any SAE(s) Grade 4
    0
    0
    2
    1
    4
    1
    4
        Any SAE(s) Grade 5
    0
    0
    1
    0
    0
    0
    0
        Any SAE(s)
    3
    0
    4
    2
    5
    1
    5
    No statistical analyses for this end point

    Primary: Number of subjects with adverse events (AEs) assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported

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    End point title
    Number of subjects with adverse events (AEs) assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported [27]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [27] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Any related AE(s) Grade 1
    7
    2
    0
    0
    5
    0
    2
        Any related AE(s) Grade 2
    4
    0
    3
    0
    1
    1
    4
        Any related AE(s) Grade 3
    1
    0
    0
    0
    1
    0
    0
        Any related AE(s) Grade 4
    0
    0
    0
    0
    0
    0
    0
        Any related AE(s) Grade 5
    0
    0
    0
    0
    0
    0
    0
        Any related AE(s)
    12
    2
    3
    0
    7
    1
    6
    No statistical analyses for this end point

    Primary: Number of subjects with serious adverse events (SAEs), assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported

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    End point title
    Number of subjects with serious adverse events (SAEs), assessed by the investigators as causally related to WT1 ASCI treatment, by CTCAE maximum grade reported [28]
    End point description
    End point type
    Primary
    End point timeframe
    During the treatment period and up to 30 days post last vaccination
    Notes
    [28] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    15
    7
    9
    6
    11
    4
    8
    Units: Subjects
        Any related SAE(s) Grade 1
    0
    0
    0
    0
    0
    0
    0
        Any related SAE(s) Grade 2
    1
    0
    0
    0
    0
    0
    0
        Any related SAE(s) Grade 3
    0
    0
    0
    0
    1
    0
    0
        Any related SAE(s) Grade 4
    0
    0
    0
    0
    0
    0
    0
        Any related SAE(s) Grade 5
    0
    0
    0
    0
    0
    0
    0
        Any related SAE(s)
    1
    0
    0
    0
    1
    0
    0
    No statistical analyses for this end point

    Primary: Number of subjects with breast cancer pathological response

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    End point title
    Number of subjects with breast cancer pathological response [29]
    End point description
    The pathological response in lymph nodes was evaluated by presence or absence of tumor cells by histopathological examination. Partial responses mark the disappearance of tumor cells, with only small clusters or dispersed cells remaining (more than 90% loss) while complete response indicate no identifiable malignant cells. However, ductal carcinoma in situ may be present.
    End point type
    Primary
    End point timeframe
    During Phase II of the study period
    Notes
    [29] - 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Number of subjects analysed
    13
    6
    9
    6
    11
    4
    4
    Units: Subjects
        Partial respose
    4
    3
    5
    3
    3
    1
    3
        Complete response
    0
    0
    0
    2
    6
    3
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs were reported during the 31-day period (Days 0-30). SAEs during the entire study period.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Cohort A-WT1 Group
    Reporting group description
    This group included Cohort A postmenopausal patients with hormone receptor-positive breast cancer who were to receive aromatase inhibitor (AI) as neoadjuvant therapy concurrently with administration of 6 or 8 doses of WT1 ASCI starting on Day 0. AI treatment was to be administered daily for duration of either 18 (if 6 doses of WT1 ASCI) or 24 weeks (if 8 doses of WT1 ASCI).

    Reporting group title
    Cohort A-Placebo Group
    Reporting group description
    This group included Cohort A postmenopausal patients with hormone receptor-positive breast cancer who were to receive aromatase inhibitor (AI) as neoadjuvant therapy concurrently with administration of 6 or 8 doses of placebo starting on Day 0. AI treatment was to be administered daily for duration of either 18 (if 6 doses of placebo) or 24 weeks (if 8 doses of placebo).

    Reporting group title
    Cohort B-WT1 Group
    Reporting group description
    This group included Cohort B breast cancer patients who were to receive Cohort B neoadjuvant chemotherapy concurrently with administration of 6 or 8 doses of WT1 ASCI starting on study Day 0. Cohort B neoadjuvant chemotherapy was planned to consist either 1) if 6 doses of WT1 ASCI: 6 cycle-treatment chemotherapy regimens consisting of 6 3-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI: 8 cycle-treatment regimens consisting of 4 3-weekly cycles of anthracycline-based therapy followed by 4 3-weekly or 12-weekly taxane administrations without trastuzumab. Note that some departing from the planned for Cohort B neoadjuvant chemotherapy to be administered, which was assessed by the investigators as not impacting results for the group.

    Reporting group title
    Cohort B-Placebo Group
    Reporting group description
    This group included Cohort B breast cancer patients who were to receive Cohort B neoadjuvant chemotherapy concurrently with administration of 6 or 8 doses of placebo starting on study Day 0. Cohort B neoadjuvant chemotherapy was planned to consist either 1) if 6 doses of placebo: 6 cycle-treatment chemotherapy regimens consisting of 6 3-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of placebo: 8 cycle-treatment regimens consisting of 4 3-weekly cycles of anthracycline-based therapy followed by 4 3-weekly or 12-weekly taxane administrations without trastuzumab. Note that some departing from the planned for Cohort B neoadjuvant chemotherapy to be administered, which was assessed by the investigators as not impacting results for the group.

    Reporting group title
    Cohort C-WT1 Group
    Reporting group description
    This group included Cohort C patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who were to receive Cohorts C/D neoadjuvant chemotherapy, that is, trastuzumab (Herceptin) therapy combined with chemotherapy, concurrently with administration of WT1 ASCI starting on study Day 0. Cohorts C/D neoadjuvant chemotherapy was planned to consist either 1) if 6 doses of WT1 ASCI: 6 cycle-treatment chemotherapy regimens consisting of 6 3-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI: 8 cycle-treatment regimens consisting of 4 3-weekly cycles of anthracycline-based therapy followed by 4 3-weekly or 12-weekly taxane administrations with trastuzumab. Note that some departing from the planned for Cohorts C/D neoadjuvant chemotherapy to be administered, which was assessed by the investigators as not impacting results for the group.

    Reporting group title
    Cohort C-Placebo Group
    Reporting group description
    This group included Cohort C patients with Human Epidermal Growth Factor Receptor 2 (HER2)-overexpressing breast cancer who were to receive Cohorts C/D neoadjuvant chemotherapy, that is, trastuzumab (Herceptin) therapy combined with chemotherapy, concurrently with administration of placebo starting on study Day 0. Cohorts C/D neoadjuvant chemotherapy was planned to consist either 1) if 6 doses of placebo: 6 cycle-treatment chemotherapy regimens consisting of 6 3-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of placebo: 8 cycle-treatment regimens consisting of 4 3-weekly cycles of anthracycline-based therapy followed by 4 3-weekly or 12-weekly taxane administrations with trastuzumab. Note that some departing from the planned for Cohorts C/D neoadjuvant chemotherapy to be administered, which was assessed by the investigators as not impacting results for the group.

    Reporting group title
    Cohort D-WT1-D14 Group
    Reporting group description
    This group included Cohort D patients with hormone receptor-positive and HER2 non-overexpressing breast cancer who were to receive Cohorts C/D neoadjuvant chemotherapy and to be administered WT1 ASCI on Day 14 of each 3-weekly cycle of chemotherapy. Cohorts C/D neoadjuvant chemotherapy in was planned to consist either 1) if 6 doses of WT1 ASCI: 6 cycle-treatment chemotherapy regimens consisting of 6, 3-weekly cycles of anthracycline/taxane-based therapy, or 2) if 8 doses of WT1 ASCI: 8 cycle-treatment regimens consisting of 4 3-weekly cycles of anthracycline-based therapy followed by 4 three-weekly taxane administrations without trastuzumab. Note that some departing from the planned for Cohorts C/D neoadjuvant chemotherapy to be administered, which was assessed by the investigators as not impacting results for the group.

    Serious adverse events
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 15 (20.00%)
    0 / 7 (0.00%)
    4 / 9 (44.44%)
    2 / 6 (33.33%)
    5 / 11 (45.45%)
    1 / 4 (25.00%)
    5 / 8 (62.50%)
         number of deaths (all causes)
    0
    0
    1
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Renal cancer
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    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
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    4 / 11 (36.36%)
    0 / 4 (0.00%)
    3 / 8 (37.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 4
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
    1 / 4 (25.00%)
    2 / 8 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vestibular disorder
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    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
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    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
    Nausea
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    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
    Vomiting
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    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
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    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
    Polymyalgia rheumatica
         subjects affected / exposed
    1 / 15 (6.67%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    1 / 4 (25.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cohort A-WT1 Group Cohort A-Placebo Group Cohort B-WT1 Group Cohort B-Placebo Group Cohort C-WT1 Group Cohort C-Placebo Group Cohort D-WT1-D14 Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 15 (100.00%)
    5 / 7 (71.43%)
    9 / 9 (100.00%)
    6 / 6 (100.00%)
    11 / 11 (100.00%)
    4 / 4 (100.00%)
    7 / 8 (87.50%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    2
    Flushing
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 15 (20.00%)
    0 / 7 (0.00%)
    8 / 9 (88.89%)
    4 / 6 (66.67%)
    7 / 11 (63.64%)
    4 / 4 (100.00%)
    2 / 8 (25.00%)
         occurrences all number
    3
    0
    8
    4
    7
    4
    2
    Injection site pain
         subjects affected / exposed
    4 / 15 (26.67%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    4 / 11 (36.36%)
    0 / 4 (0.00%)
    4 / 8 (50.00%)
         occurrences all number
    4
    0
    0
    0
    4
    0
    4
    Injection site erythema
         subjects affected / exposed
    5 / 15 (33.33%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    3 / 11 (27.27%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    5
    0
    0
    0
    3
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    3 / 9 (33.33%)
    0 / 6 (0.00%)
    3 / 11 (27.27%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    3
    0
    3
    2
    0
    Injection site reaction
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    0
    Injection site swelling
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    2
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    3 / 9 (33.33%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    0
    Chills
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    Injection site discomfort
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    2 / 6 (33.33%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    2
    0
    0
    Investigations
    Weight decreased
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    2 / 6 (33.33%)
    4 / 11 (36.36%)
    0 / 4 (0.00%)
    3 / 8 (37.50%)
         occurrences all number
    0
    0
    0
    2
    4
    0
    3
    Anaemia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    2 / 6 (33.33%)
    4 / 11 (36.36%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    4
    0
    0
    Leukopenia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    3 / 6 (50.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    0
    0
    0
    3
    0
    0
    2
    Febrile neutropenia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    Thrombocytopenia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    3 / 9 (33.33%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    3
    0
    2
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 15 (33.33%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    3 / 11 (27.27%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    5
    0
    0
    0
    3
    0
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    5 / 11 (45.45%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    0
    5
    2
    0
    Dysgeusia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    3 / 6 (50.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    0
    0
    2
    3
    0
    0
    2
    Paraesthesia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    0
    2
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 7 (0.00%)
    6 / 9 (66.67%)
    0 / 6 (0.00%)
    8 / 11 (72.73%)
    2 / 4 (50.00%)
    3 / 8 (37.50%)
         occurrences all number
    2
    0
    6
    0
    8
    2
    3
    Diarrhoea
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    3 / 9 (33.33%)
    0 / 6 (0.00%)
    3 / 11 (27.27%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    0
    0
    3
    0
    3
    0
    2
    Stomatitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    2 / 6 (33.33%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    0
    0
    2
    2
    2
    0
    2
    Constipation
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    4 / 11 (36.36%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    0
    4
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    3 / 9 (33.33%)
    2 / 6 (33.33%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    3
    2
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    4 / 9 (44.44%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    0
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    2 / 6 (33.33%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    9 / 9 (100.00%)
    5 / 6 (83.33%)
    8 / 11 (72.73%)
    3 / 4 (75.00%)
    3 / 8 (37.50%)
         occurrences all number
    0
    0
    9
    5
    8
    3
    3
    Dry skin
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 15 (20.00%)
    2 / 7 (28.57%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    3 / 11 (27.27%)
    2 / 4 (50.00%)
    0 / 8 (0.00%)
         occurrences all number
    3
    2
    2
    0
    3
    2
    0
    Myalgia
         subjects affected / exposed
    4 / 15 (26.67%)
    0 / 7 (0.00%)
    4 / 9 (44.44%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    4
    0
    4
    0
    2
    0
    2
    Bone pain
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 7 (0.00%)
    3 / 9 (33.33%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    3
    0
    2
    0
    0
    Back pain
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    2 / 6 (33.33%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    2
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    3 / 11 (27.27%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 15 (13.33%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Gingivitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    2 / 6 (33.33%)
    0 / 11 (0.00%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    0 / 15 (0.00%)
    0 / 7 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
    0 / 4 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Jan 2011
    1. Change in placebo from a lyophilized sucrose formulation reconstituted with a 1/500 dilution of SB62 oil-in-water emulsion to a lyophilized sucrose/mannitol formulation reconstituted with the same dilution of the SB62 oil-in-water emulsion. This change was implemented due to differences in cake height of the lyophilized sucrose formulation compared to lyophilized WT1-A10 and CpG 7909, which would compromise the double blinding of the study. 2. Extension of active follow-up of patients from one to three years. This was requested by the Agence Française de Sécurité Sanitaire des Produits the Santé. 3. In the safety Section (Section 9.1.3), the list of autoimmune diseases to be reported has been replaced by a list of potential immune-mediated diseases (pIMDs). pIMDs include autoimmune diseases and other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Moreover, it is specified that all pIMDs will be recorded in the eCRF and reported to GSK Biologicals within 24 hours using the Serious Adverse Event (SAE) screen, regardless of whether the pIMDs are AEs or SAEs. This ensures expedited reporting of all pIMDs. In addition, SAEs related to study treatment are introduced as a separate category of adverse events, to be recorded from receipt of the first study product until the end of follow –up. Contact information for an emergency unblinding request has also been updated. 4. In the sections describing the molecular and immunological read-outs and the translational research, the distinction between the use of fresh tumor samples or Formalin-Fixed, Paraffin Embedded (FFPE) samples for specific tests has been removed. This allows the use of any of these two types of samples in case updated technologies would be employed for specific analyses. Moreover, it is specified that if appropriate, plasma derived from Peripheral Blood Mononuclear Cell (PBMC) purification may be used as backup material for serum in some tests.
    26 Aug 2011
    • In case of cardiac assessment during treatment, it has been specified that for patients on 18-week regimens, this assessment should be done between Visit 3 and Visit 4, such that results are available at Visit 4. • Instructions for the processing of tissue samples collected from the resected tumor or tumor bed have been adapted. • Based on feedback from investigators during the investigators’ meeting the following additional changes were done: • The extension of a cohort into the Phase II part of the study depends on the outcome of an intermediate assessment of the immunogenicity of the investigational treatment. The serum sample to be used for this evaluation has been changed from a Post-dose 3 sample to a Post-dose 4 sample to ascertain that sufficient time is allowed for an immune response to develop. • The strict timings for screening tests/examinations are made less stringent. All assessments required for screening, except pregnancy testing can be performed within four weeks prior to randomization of the patient. • Exclusion criterion no 13 (Section 4.4) has been rephrased to make clear that only patients receiving therapeutic anticoagulation are excluded from the study. • In the context of postponement of study treatment in an individual patient, the parameters for blood/bone marrow disorders have been adapted for Cohort B and C, such as to avoid frequent postponement of study treatment administration due to side effects of standard treatment. • The tumor imaging at Visit 4 as well as the post-treatment systemic imaging during the presurgery period have been changed from being mandatory to being optional (according to the investigator’s discretion). The description of tumor imaging has been clarified.
    08 Apr 2013
    • The analysis of the immunogenicity results of the cohort B (unblinded data) evaluating the concurrent administration of the WT1-A10 + AS15 ASCI on day 1 of each cycle of neoadjuvant chemotherapy and during the corticosteroids treatment showed that the above criteria was not fulfilled. Therefore enrolment into the Phase II segment of cohort B has been stopped. But preliminary data has suggested the induction of an anti-WT1 humoral response by the WT1-A10 + AS01B ASCI in absence of concurrent administration of chemotherapy and corticosteroids in two other clinical studies in acute myeloid leukemia. So, the administration of the WT1-A10 + AS15 ASCI will also be evaluated on day 14 of each cycle of neoadjuvant chemotherapy in a new cohort of patients, in order to gain a better understanding of the role of the chemotherapy and corticosteroids on the immune response induced by the WT1-A10 + AS15 ASCI. • The patients in this new cohort, the cohort D, will receive the WT1-A10 + AS15 ASCI at day 14 (D14) of each cycle of the standard neoadjuvant chemotherapy in an open label, non-randomised design. In the absence of a safety signal and if the WT1-A10 + AS15 ASCI induces an adequate immune response according the same rules defined per protocol (see section 3.1.3.1), an additional group of patients with the same eligibility criteria may be recruited in a double blind, randomised phase II segment of the study (Cohort E). These patients will be randomised to receive either WT1-A10 + AS15 ASCI or placebo on D14 of each cycle of neoadjuvant chemotherapy. The patient population eligible for cohorts D and E is presenting a hormone receptor-positive and HER2 non-overexpressing breast cancer. • Also, the assessment of the anti-CpG7909 humoral response and the anti-WT1 T-cell immune response was moved to translational research section as these assessments are not part of the endpoints of the study and will have no direct impact on the study design, i.e. decision making process.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    18 Jul 2014
    The study was terminated, based on scientific and medical relevance, due to negative Phase III studies which assessed another study product from same technology platform.
    -

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The Phase II segment was not completed with only 3 patients enrolled in Cohort A. Consequently, analysis for DFS and OS outcomes was cancelled and the collected clinical activity results are to be considered with caution and uninterpretable.
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