Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   44353   clinical trials with a EudraCT protocol, of which   7380   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Prospective, Randomized, Double-Blind, Placebo-controlled, Multicenter, Phase III Study Assessing Efficacy and Safety of the IMUNOR® Therapy Versus Placebo in Patients with Recurrent Vulvovaginitis Episodes

    Summary
    EudraCT number
    		 2015-001472-22
    Trial protocol
    		 SK   CZ  
    Global end of trial date
    08 Apr 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    18 Jul 2025
    First version publication date
    18 Jul 2025
    Other versions
    Summary report(s)
    		 Synopsis

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IMUNOR-201501
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ImunomedicA, a.s.
    Sponsor organisation address
    Chuderov 118, Ústí nad Labem, Czechia, 400 11
    Public contact
    Ing. Zdeňka Svobodová, ImunomedicA, a.s., 00420 777872 067, imunomedica@iol.cz
    Scientific contact
    Ing. Zdeňka Svobodová, ImunomedicA, a.s., 00420 777872 067, imunomedica@iol.cz
    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
    01 Jul 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Apr 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Apr 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To confirm efficacy of IMUNOR® based on reduction of the number of documented mycotic and bacterial vulvovaginitis episodes during 12 months observation, compared to patients receiving placebo.
    Protection of trial subjects
    The study was conducted in accordance with the approved version of the Study Protocol, the ICH Guideline for Good Clinical Practice (ICH-GCP E6(R2)), the Declaration of Helsinki, the General Data Protection Regulation (Regulation (EU) 2016/679), as well as applicable national and international legislation and Standard Operating Procedures (SOPs) related to the conduct of clinical trials. Prior planning or performing of any study-related procedure, a written informed consent had to be obtained from patient.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Feb 2016
    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
    Slovakia: 27
    Country: Number of subjects enrolled
    Czechia: 110
    Worldwide total number of subjects
    137
    EEA total number of subjects
    137
    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)
    137
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 At Visit 1 (Screening, Day -21 to -7), written ICF had to be obtained prior performing of any Study related procedure. Patients considered eligible based on past medical history and clinical examination and those willing to provide written ICF, had to undergo further assessment of their eligibility based on defined inclusion and exclusion criteria.

    Period 1
    Period 1 title
    Treatment period 1
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Blinding of the IMP was done centrally by the sponsor.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 IMUNOR group
    Arm description
    		 Administration of IMUNOR® - active treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    IMUNOR®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral lyophilisate
    Routes of administration
    Oral use
    Dosage and administration details
    IMUNOR® was administered as 1 dose/week, orally for a total period of 3 months within treatment period 1. Prior each administration, re-constitution of the IMP was performed. The content of a vial had to be dissolved under gently shaking in approximately 3 mL of drinking water (up to the vial neck). Upon complete dissolution of the lyophilizate, the solution could be administered.

    Arm title
    		 Placebo group
    Arm description
    		 Administration of placebo.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral lyophilisate
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was administered as 1 dose/week, orally for a total period of 3 months within treatment period 1. Prior each administration, re-constitution of the IMP was performed. The content of a vial had to be dissolved under gently shaking in approximately 3 mL of drinking water (up to the vial neck). Upon complete dissolution of the lyophilizate, the solution could be administered.

    Number of subjects in period 1
    		IMUNOR group Placebo group
    Started
    91
    46
    Completed
    90
    46
    Not completed
    1
    0
         Randomized by mistake, no IMP dose used
    1
    -
    Period 2
    Period 2 title
    Observation period 1
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Blinding of the IMP was done centrally by the sponsor.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 IMUNOR group - SOC
    Arm description
    		 Standard of care without intervention.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Placebo group - SOC
    Arm description
    		 Standard of care without intervention.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2
    		IMUNOR group - SOC Placebo group - SOC
    Started
    90
    46
    Completed
    85
    45
    Not completed
    5
    1
         Consent withdrawn by subject
    3
    -
         Adverse event, non-fatal
    1
    -
         Need of systemic antifungal medication
    -
    1
         Used prohibited medication - systemic corticoid
    1
    -
    Period 3
    Period 3 title
    Treatment period 2
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Blinding of the IMP was done centrally by the sponsor.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 IMUNOR group
    Arm description
    		 Administration of IMUNOR® - active treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    IMUNOR®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral lyophilisate
    Routes of administration
    Oral use
    Dosage and administration details
    IMUNOR® was administered as 1 dose/week, orally for a total period of 3 months within treatment period 2. Prior each administration, re-constitution of the IMP was performed. The content of a vial had to be dissolved under gently shaking in approximately 3 mL of drinking water (up to the vial neck). Upon complete dissolution of the lyophilizate, the solution could be administered.

    Arm title
    		 Placebo group
    Arm description
    		 Administration of placebo.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral lyophilisate
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was administered as 1 dose/week, orally for a total period of 3 months within treatment period 2. Prior each administration, re-constitution of the IMP was performed. The content of a vial had to be dissolved under gently shaking in approximately 3 mL of drinking water (up to the vial neck). Upon complete dissolution of the lyophilizate, the solution could be administered.

    Number of subjects in period 3
    		IMUNOR group Placebo group
    Started
    85
    45
    Completed
    83
    42
    Not completed
    2
    3
         Consent withdrawn by subject
    -
    1
         Pregnancy
    -
    1
         Need of systemic antifungal medication
    1
    -
         Used prohibited medication - Fluco Sandoz
    1
    -
         Protocol deviation
    -
    1
    Period 4
    Period 4 title
    Observation period 2
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor
    Blinding implementation details
    Blinding of the IMP was done centrally by the sponsor.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 IMUNOR group - SOC
    Arm description
    		 Standard of care without intervention.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Placebo group - SOC
    Arm description
    		 Standard of care without intervention.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 4
    		IMUNOR group - SOC Placebo group - SOC
    Started
    83
    42
    Completed
    78
    42
    Not completed
    5
    0
         Consent withdrawn by subject
    2
    -
         Withdrawal due to need of systemic antifungal th
    1
    -
         Oncological disease unrelated to study drug
    1
    -
         Lost to follow-up
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    IMUNOR group
    Reporting group description
    		 Administration of IMUNOR® - active treatment.

    Reporting group title
    Placebo group
    Reporting group description
    		 Administration of placebo.

    Reporting group values
    		 IMUNOR group Placebo group Total
    Number of subjects
    		 91 46 137
    Age categorical
    Age at randomization
    Units: Subjects
        Adults (18-50 years)
    		 91 46 137
    Age continuous
    Age at randomization
    Units: years
        arithmetic mean (standard deviation)
    		 34.7 ( 8.25 ) 33.5 ( 8.33 ) -
    Gender categorical
    Female
    Units: Subjects
        Female
    		 91 46 137
    Race
    White (Caucasian)
    Units: Subjects
        White (Caucasian)
    		 91 46 137
    Prevailing etiology
    Bacterial, Mycotic, Not specified
    Units: Subjects
        Bacterial
    		 11 1 12
        Mycotic
    		 51 26 77
        Not specified
    		 29 19 48
    Height
    Height [cm]
    Units: centimetre
        arithmetic mean (standard deviation)
    		 168.1 ( 5.49 ) 168.6 ( 6.73 ) -
    Weight
    Weight [kg]
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    		 65.0 ( 12.60 ) 61.5 ( 8.92 ) -
    BMI
    BMI [kg/m2]
    Units: kilogram(s)/square metre
        arithmetic mean (standard deviation)
    		 22.98 ( 4.128 ) 21.60 ( 2.815 ) -
    Subject analysis sets

    Subject analysis set title
    Full Analysis Set - IMUNOR
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    IMUNOR group: All patients of the safety set and have at least one measurement after baseline.

    Subject analysis set title
    Full Analysis Set - Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo group: All patients of the safety set and have at least one measurement after baseline.

    Subject analysis set title
    Per-Protocol Set - IMUNOR
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    IMUNOR group: All patients of the Full Analysis Set without any relevant protocol violations (major protocol deviations) and complete data for the primary efficacy variable.

    Subject analysis set title
    Per-Protocol Set - Placebo
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Placebo group: All patients of the Full Analysis Set without any relevant protocol violations (major protocol deviations) and complete data for the primary efficacy variable.

    Subject analysis sets values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects
    90
    46
    52
    21
    Age categorical
    Age at randomization
    Units: Subjects
        Adults (18-50 years)
    90
    46
    52
    21
    Age continuous
    Age at randomization
    Units: years
        arithmetic mean (standard deviation)
    34.7 ( 8.25 )
    33.5 ( 8.33 )
    33.6 ( 8.39 )
    31.5 ( 7.54 )
    Gender categorical
    Female
    Units: Subjects
        Female
    90
    46
    52
    21
    Race
    White (Caucasian)
    Units: Subjects
        White (Caucasian)
    90
    46
    52
    21
    Prevailing etiology
    Bacterial, Mycotic, Not specified
    Units: Subjects
        Bacterial
    11
    1
    7
    1
        Mycotic
    51
    26
    42
    18
        Not specified
    28
    19
    3
    2
    Height
    Height [cm]
    Units: centimetre
        arithmetic mean (standard deviation)
    168.1 ( 5.49 )
    168.6 ( 6.73 )
    168.5 ( 5.29 )
    167.0 ( 6.67 )
    Weight
    Weight [kg]
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    65.0 ( 12.60 )
    61.5 ( 8.92 )
    64.1 ( 11.86 )
    61.1 ( 9.87 )
    BMI
    BMI [kg/m2]
    Units: kilogram(s)/square metre
        arithmetic mean (standard deviation)
    22.98 ( 4.128 )
    21.60 ( 2.815 )
    22.56 ( 3.986 )
    21.85 ( 3.069 )

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    IMUNOR group
    Reporting group description
    		 Administration of IMUNOR® - active treatment.

    Reporting group title
    Placebo group
    Reporting group description
    		 Administration of placebo.
    Reporting group title
    IMUNOR group - SOC
    Reporting group description
    		 Standard of care without intervention.

    Reporting group title
    Placebo group - SOC
    Reporting group description
    		 Standard of care without intervention.
    Reporting group title
    IMUNOR group
    Reporting group description
    		 Administration of IMUNOR® - active treatment.

    Reporting group title
    Placebo group
    Reporting group description
    		 Administration of placebo.
    Reporting group title
    IMUNOR group - SOC
    Reporting group description
    		 Standard of care without intervention.

    Reporting group title
    Placebo group - SOC
    Reporting group description
    		 Standard of care without intervention.

    Subject analysis set title
    Full Analysis Set - IMUNOR
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    IMUNOR group: All patients of the safety set and have at least one measurement after baseline.

    Subject analysis set title
    Full Analysis Set - Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo group: All patients of the safety set and have at least one measurement after baseline.

    Subject analysis set title
    Per-Protocol Set - IMUNOR
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    IMUNOR group: All patients of the Full Analysis Set without any relevant protocol violations (major protocol deviations) and complete data for the primary efficacy variable.

    Subject analysis set title
    Per-Protocol Set - Placebo
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Placebo group: All patients of the Full Analysis Set without any relevant protocol violations (major protocol deviations) and complete data for the primary efficacy variable.

    Primary: Primary endpoint - number of vulvovaginitis episodes during 12 months

    		 Close Top of page
    End point title
    		 Primary endpoint - number of vulvovaginitis episodes during 12 months
    End point description
    Number of vulvovaginitis episodes, irrespective of their etiology, during the complete study duration (12-month period) were compared between the IMUNOR® group and the placebo group.
    End point type
    Primary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    90
    46
    52
    21
    Units: number
        0 episodes
    45
    13
    27
    4
        1 episode
    25
    15
    12
    5
        2 episodes
    13
    7
    9
    6
        3 episodes
    3
    4
    2
    3
        4 episodes
    3
    7
    1
    3
        6 episodes
    1
    0
    1
    0
    Attachments
    		 Primary endpoint - statistical results
    Statistical analysis title
    		 Statistical analysis - Primary endpoint - PPS
    Statistical analysis description
    The primary endpoint was tested on the PPS. Only vulvovaginitis episodes that started after randomization, and before / during EOS, were considered for this analysis. The following null hypothesis was tested against the alternative hypothesis: • Null hypothesis H0: The number of episodes during the study duration is equal to or higher under IMUNOR® than that for placebo. • Alternative hypothesis H1: The number of episodes during the study duration is smaller under IMUNOR® than that for placeb
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.0069 [2]
    Method
    		 Regression, Linear
    Parameter type
    		 Ratio of mean counts
    Point estimate
    0.489
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.291
         upper limit
    		 0.822
    Notes
    [1] - To test the hypothesis, a generalized linear model with negative binomial distribution with natural logarithm link function was used. The use of negative binomial regression is suitable for cases where the dependent variable is the count and accounts for cases where overdispersion is present. Generalized linear model with number of vulvovaginitis episodes as dependent variable and treatment group as independent class variable was fitted in SAS.
    [2] - P-value obtained for parameter estimate for the IMUNOR® group was used as the hypothesis test for difference between treatments.
    Statistical analysis title
    		 Statistical analysis - Primary endpoint - FAS
    Statistical analysis description
    The same analysis as for the PPS was performed on the FAS as sensitivity analysis. The following null hypothesis was tested against the alternative hypothesis: • Null hypothesis H0: The number of episodes during the study duration is equal to or higher under IMUNOR® than that for placebo. • Alternative hypothesis H1: The number of episodes during the study duration is smaller under IMUNOR® than that for placebo.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.0067 [4]
    Method
    		 Regression, Linear
    Parameter type
    		 Ratio of mean counts
    Point estimate
    0.578
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.389
         upper limit
    		 0.859
    Notes
    [3] - To test the hypothesis, a generalized linear model with negative binomial distribution with natural logarithm link function was used. The use of negative binomial regression is suitable for cases where the dependent variable is the count and accounts for cases where overdispersion is present. Generalized linear model with number of vulvovaginitis episodes as dependent variable and treatment group as independent class variable was fitted in SAS.
    [4] - P-value obtained for parameter estimate for the IMUNOR® group was used as the hypothesis test for difference between treatments.

    Secondary: Secondary endpoint 1 - number of vulvovaginitis episodes during 6 months

    		 Close Top of page
    End point title
    		 Secondary endpoint 1 - number of vulvovaginitis episodes during 6 months
    End point description
    Efficacy of IMUNOR® based on reduction of the number of mycotic or bacterial vulvovaginitis episodes during 6 months of treatment as compared to placebo.
    End point type
    Secondary
    End point timeframe
    initial 6-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    62
    27
    49
    19
    Units: number
        0 episodes
    32
    6
    27
    4
        1 episode
    16
    8
    11
    5
        2 episodes
    10
    7
    8
    6
        3 episodes
    1
    2
    1
    2
        4 episodes
    2
    4
    1
    2
        6 episodes
    1
    0
    1
    0
    Attachments
    		 Secondary endpoint 1 - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 1 - PPS
    Statistical analysis description
    The same methodology as for the primary endpoint was used.
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.019 [6]
    Method
    		 Regression, Linear
    Parameter type
    		 Ratio of mean counts
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.28
         upper limit
    		 0.892
    Notes
    [5] - To test the hypothesis, a generalized linear model with negative binomial distribution with natural logarithm link function was used. The use of negative binomial regression is suitable for cases where the dependent variable is the count and accounts for cases where overdispersion is present. Generalized linear model with number of vulvovaginitis episodes as dependent variable and treatment group as independent class variable was fitted in SAS.
    [6] - P-value obtained for parameter estimate for the IMUNOR® group was used as the hypothesis test for difference between treatments.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 1 - FAS
    Statistical analysis description
    The same methodology as for the primary endpoint was used.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 = 0.009 [8]
    Method
    		 Regression, Linear
    Parameter type
    		 Ratio of mean counts
    Point estimate
    0.525
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.323
         upper limit
    		 0.851
    Notes
    [7] - To test the hypothesis, a generalized linear model with negative binomial distribution with natural logarithm link function was used. The use of negative binomial regression is suitable for cases where the dependent variable is the count and accounts for cases where overdispersion is present. Generalized linear model with number of vulvovaginitis episodes as dependent variable and treatment group as independent class variable was fitted in SAS.
    [8] - P-value obtained for parameter estimate for the IMUNOR® group was used as the hypothesis test for difference between treatments.

    Secondary: Secondary endpoint 2 - number of vulvovaginitis episodes during 12 months - prevailing bacterial etiology

    		 Close Top of page
    End point title
    		 Secondary endpoint 2 - number of vulvovaginitis episodes during 12 months - prevailing bacterial etiology
    End point description
    Efficacy of IMUNOR® based on reduction of the number of vulvovaginitis episodes during 12 months observation, as compared to placebo, in patients with prevailing bacterial etiology.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    11
    1
    7
    1
    Units: number
        0 episodes
    7
    1
    4
    1
        1 episode
    1
    0
    1
    0
        2 episodes
    2
    0
    1
    0
        3 episodes
    1
    0
    1
    0
    Attachments
    		 Secondary endpoint 2 - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 2 - PPS
    Statistical analysis description
    The same methodology as for the primary endpoint was used. The analysis was performed on subset of patients with confirmed prevailing bacterial etiology of vulvovaginitis episodes (documented prior randomization). Vulvovaginitis episodes that started after randomization and before / during EOS were considered.
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0 [10]
    Method
    		 Regression, Linear
    Confidence interval
    Notes
    [9] - To test the hypothesis, a generalized linear model with negative binomial distribution with natural logarithm link function was used. The use of negative binomial regression is suitable for cases where the dependent variable is the count and accounts for cases where overdispersion is present. Generalized linear model with number of vulvovaginitis episodes as dependent variable and treatment group as independent class variable was fitted in SAS.
    [10] - The comparison between treatments was not performed due to low number of patients in the placebo group. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 2 - FAS
    Statistical analysis description
    The same methodology as for the primary endpoint was used. The analysis was performed on subset of patients with confirmed prevailing bacterial etiology of vulvovaginitis episodes (documented prior randomization). Vulvovaginitis episodes that started after randomization and before / during EOS were considered.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    12
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 = 0 [12]
    Method
    		 Regression, Linear
    Confidence interval
    Notes
    [11] - To test the hypothesis, a generalized linear model with negative binomial distribution with natural logarithm link function was used. The use of negative binomial regression is suitable for cases where the dependent variable is the count and accounts for cases where overdispersion is present. Generalized linear model with number of vulvovaginitis episodes as dependent variable and treatment group as independent class variable was fitted in SAS.
    [12] - The comparison between treatments was not performed due to low number of patients in the placebo group. P-value was not calculated.

    Secondary: Secondary endpoint 3 - number of vulvovaginitis episodes during 12 months - prevailing mycotic etiology

    		 Close Top of page
    End point title
    		 Secondary endpoint 3 - number of vulvovaginitis episodes during 12 months - prevailing mycotic etiology
    End point description
    Efficacy of IMUNOR® based on reduction of the number of vulvovaginitis episodes during 12 months observation, as compared to placebo, in patients with prevailing mycotic etiology.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    51
    26
    42
    18
    Units: number
        0 episodes
    25
    5
    23
    3
        1 episode
    15
    8
    10
    5
        2 episodes
    8
    7
    7
    6
        3 episodes
    0
    2
    0
    2
        4 episodes
    2
    4
    1
    2
        6 episodes
    1
    0
    1
    0
    Attachments
    		 Secondary endpoint 3 - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 3 - PPS
    Statistical analysis description
    For analysis of this endpoint the same methodology as for the primary endpoint was used. The analysis was performed on subset of patients with confirmed prevailing mycotic etiology of vulvovaginitis episodes (documented prior randomization). Vulvovaginitis episodes that started after randomization and before / during EOS were considered.
    Comparison groups
    Per-Protocol Set - Placebo v Per-Protocol Set - IMUNOR
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.0106 [14]
    Method
    		 Regression, Linear
    Parameter type
    		 Ratio of mean counts
    Point estimate
    0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.263
         upper limit
    		 0.839
    Notes
    [13] - To test the hypothesis, a generalized linear model with negative binomial distribution with natural logarithm link function was used. The use of negative binomial regression is suitable for cases where the dependent variable is the count and accounts for cases where overdispersion is present. Generalized linear model with number of vulvovaginitis episodes as dependent variable and treatment group as independent class variable was fitted in SAS.
    [14] - P-value obtained for parameter estimate for the IMUNOR® group was used as the hypothesis test for difference between treatments.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 3 - FAS
    Statistical analysis description
    For analysis of this endpoint the same methodology as for the primary endpoint was used. The analysis was performed on subset of patients with confirmed prevailing mycotic etiology of vulvovaginitis episodes (documented prior randomization). Vulvovaginitis episodes that started after randomization and before / during EOS were considered.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    77
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    P-value
    		 = 0.0086 [16]
    Method
    		 Regression, Linear
    Parameter type
    		 Ratio of mean counts
    Point estimate
    0.521
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.321
         upper limit
    		 0.847
    Notes
    [15] - To test the hypothesis, a generalized linear model with negative binomial distribution with natural logarithm link function was used. The use of negative binomial regression is suitable for cases where the dependent variable is the count and accounts for cases where overdispersion is present. Generalized linear model with number of vulvovaginitis episodes as dependent variable and treatment group as independent class variable was fitted in SAS.
    [16] - P-value obtained for parameter estimate for the IMUNOR® group was used as the hypothesis test for difference between treatments.

    Secondary: Secondary endpoint 4 - mean duration of vulvovaginitis episodes

    		 Close Top of page
    End point title
    		 Secondary endpoint 4 - mean duration of vulvovaginitis episodes
    End point description
    Comparison of the mean duration of vulvovaginitis episodes.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    90
    46
    52
    21
    Units: number
        Number of vulvovaginitis episodes with known durat
    34
    27
    20
    13
    Attachments
    		 Secondary endpoint 4 - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 4 - PPS
    Statistical analysis description
    For all vulvovaginitis episodes, their duration was reported in the study database as part of AE data. If the duration was unavailable after DB lock for any reason, the sponsor provided the available information on duration via a note-to-file (when retrievable).
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    P-value
    		 = 0.0951 [18]
    Method
    		 Regression, Linear
    Parameter type
    		 Ratio of mean durations
    Point estimate
    1.701
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.898
         upper limit
    		 3.221
    Notes
    [17] - The duration of VV episode was expected to be lognormally distributed, therefore logarithmically transformed values of duration were used for the analysis. The difference in mean duration of VV episodes was analysed using a mixed effects model accounting for repeated VV episodes in the same patient using patient as random effect. SAS procedure proc mixed was used for the model. Least square estimates were back transformed by exponentiation and presented as mean duration for each treatment group.
    [18] - Corresponding p-value for difference in least square means was presented. The presented results should be interpreted with caution due to the limited availability of data on episode duration.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 4 - FAS
    Statistical analysis description
    For all vulvovaginitis episodes, their duration was reported in the study database as part of AE data. If the duration was unavailable after DB lock for any reason, the sponsor provided the available information on duration via a note-to-file (when retrievable).
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    P-value
    		 = 0.0447 [20]
    Method
    		 Regression, Linear
    Parameter type
    		 Ratio of mean durations
    Point estimate
    1.593
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.012
         upper limit
    		 2.507
    Notes
    [19] - The duration of VV episode was expected to be lognormally distributed, therefore logarithmically transformed values of duration were used for the analysis. The difference in mean duration of VV episodes was analysed using a mixed effects model accounting for repeated VV episodes in the same patient using patient as random effect. SAS procedure proc mixed was used for the model. Least square estimates were back transformed by exponentiation and presented as mean duration for each treatment group.
    [20] - Corresponding p-value for difference in least square means was presented. The presented results should be interpreted with caution due to the limited availability of data on episode duration.

    Secondary: Secondary endpoint 5 - proportion of patients withdrawn from the study due to the need of use of oral antifungal medication

    		 Close Top of page
    End point title
    		 Secondary endpoint 5 - proportion of patients withdrawn from the study due to the need of use of oral antifungal medication
    End point description
    Comparison of proportion of patients withdrawn from the study due to the need of use of oral antifungal medication.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    90
    46
    52
    21
    Units: percent
    number (not applicable)
        Number of patients withdrawn due to need of th
    2
    1
    0
    1
        Percentage of patients withdrawn due to need of th
    2.2
    2.2
    0
    4.8
    Attachments
    		 Secondary endpoint 5 - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 5 - PPS
    Statistical analysis description
    For each treatment group, the number of patients withdrawn due to the need of use of oral antifungal medication, along with percentage out of total number of patients in the treatment group, was reported. Comparison between treatments was not performed due to low number of patients.
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 other [21]
    P-value
    		 = 0 [22]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [21] - Descriptive Summary
    [22] - Descriptive Summary. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 5 - FAS
    Statistical analysis description
    For each treatment group, the number of patients withdrawn due to the need of use of oral antifungal medication, along with percentage out of total number of patients in the treatment group, was reported. Comparison between treatments was not performed due to low number of patients.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 other [23]
    P-value
    		 = 0 [24]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [23] - Descriptive Summary
    [24] - Descriptive Summary. P-value was not calculated.

    Secondary: Secondary endpoint 6 - use of local symptomatic and/or topical antifungal/antibacterial treatment

    		 Close Top of page
    End point title
    		 Secondary endpoint 6 - use of local symptomatic and/or topical antifungal/antibacterial treatment
    End point description
    Comparison of the use of local symptomatic and/or topical antifungal/antibacterial treatment.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    90
    46
    52
    21
    Units: number
        G01AC05 / Dequalinium
    8
    5
    6
    3
        D01AC20 / Imidazoles/triazoles in combination with
    7
    4
    5
    2
        G01AF12 / Fenticonazole
    5
    2
    4
    1
        G01AF20 / Combinations of imidazole derivatives
    7
    5
    3
    2
        G01AX05 / Nifuratel
    4
    0
    4
    0
        G01AX / Other antiinfectives and antiseptics
    6
    4
    2
    1
        D03AX / Other cicatrizants
    8
    5
    2
    0
        G01AA10 / Clindamycin
    2
    1
    1
    1
        G01AF15 / Butoconazole
    5
    3
    2
    0
        G02CC03 / Benzydamine
    3
    1
    2
    0
        J01FA10 / Azithromycin
    1
    1
    1
    1
        J01XE01 / Nitrofurantoin
    2
    0
    2
    0
        D07AC13 / Mometasone
    1
    0
    1
    0
        D07CA01 / Hydrocortisone and antibiotics
    5
    4
    1
    0
        G01AX12 / Ciclopirox
    0
    1
    0
    1
        G04BD04 / Oxybutynin
    1
    0
    1
    0
        J01AA02 / Doxycycline
    1
    0
    1
    0
        J01CA04 / Amoxicillin
    0
    1
    0
    1
        J01FF01 / Clindamycin
    1
    0
    1
    0
        J01MA06 / Norfloxacin
    1
    0
    1
    0
        J01XX01 / Fosfomycin
    1
    0
    1
    0
        J02AC01 / Fluconazole
    2
    2
    1
    0
        P01AB01 / Metronidazole
    0
    2
    0
    1
        V07AB / Solvents and diluting agents
    1
    0
    1
    0
        M01AB05 / Diclofenac
    1
    0
    0
    0
        J01CR04 / Sultamicillin
    1
    0
    0
    0
        J01XX / Other antibacterials
    0
    1
    0
    0
        D08AD / Boric acid products
    1
    0
    0
    0
        J01MA01 / Ofloxacin
    1
    0
    0
    0
        G01AA51 / Nystatin, combinations
    17
    12
    10
    7
        G01AA01 / Nystatin
    1
    0
    0
    0
        D01AA01 / Nystatin
    3
    2
    1
    1
        G01AA02 / Natamycin
    2
    1
    2
    1
        D01AA02 / Natamycin
    1
    1
    1
    1
        G01AF02 / Clotrimazole
    25
    20
    17
    12
        D01AC01 / Clotrimazole
    7
    6
    3
    4
        G01AF05 / Econazole
    3
    3
    2
    2
        D01AC03 / Econazole
    0
    1
    0
    0
    Attachments
    		 Secondary endpoint 6 - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 6 - PPS
    Statistical analysis description
    Descriptive Summary
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 other [25]
    P-value
    		 = 0 [26]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [25] - Descriptive Summary
    [26] - Descriptive Summary. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 6 - FAS
    Statistical analysis description
    Descriptive Summary
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 other [27]
    P-value
    		 = 0 [28]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [27] - Descriptive Summary
    [28] - Descriptive Summary. P-value was not calculated.

    Secondary: Secondary endpoint 7a - QoL - EQ-5D dimensions - by visit

    		 Close Top of page
    End point title
    		 Secondary endpoint 7a - QoL - EQ-5D dimensions - by visit
    End point description
    Summary of EQ-5D dimensions by scheduled visit and treatment group.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    90
    46
    52
    21
    Units: number of subjects
        Mobility - EOS - I have no problems
    79
    43
    47
    18
        Mobility - EOS - I have slight problems
    5
    1
    3
    1
        Mobility - EOS - I have moderate problems
    0
    1
    0
    1
        Mobility - EOS - Missing
    6
    1
    2
    1
        Self-care - EOS - I have no problems
    84
    44
    50
    19
        Self-care - EOS - I have slight problems
    0
    1
    0
    1
        Self-care - EOS - Missing
    6
    1
    2
    1
        Usual activities - EOS - I have no problems
    79
    40
    47
    17
        Usual activities - EOS - I have slight problems
    4
    5
    3
    3
        Usual activities - EOS - I have moderate problems
    1
    0
    0
    0
        Usual activities - EOS - Missing
    6
    1
    2
    1
        Pain/discomfort - EOS - I have no pain/discomfort
    62
    34
    39
    17
        Pain/discomfort - EOS - I have slight pain/discom
    18
    10
    8
    3
        Pain/discomfort - EOS - I have moderate pain/disco
    3
    1
    3
    0
        Pain/discomfort - EOS - I have severe pain or disc
    1
    0
    0
    0
        Pain/discomfort - EOS - Missing
    6
    1
    2
    1
        Anxiety/depression - EOS - I am not A/D
    70
    39
    43
    17
        Anxiety/depression - EOS - I am slightly A/D
    11
    3
    6
    0
        Anxiety/depression - EOS - I am moderately A/D
    0
    3
    0
    3
        Anxiety/depression - EOS - I am severely A/D
    3
    0
    1
    0
        Anxiety/depression - EOS - Missing
    6
    1
    2
    1
    Attachments
    		 Secondary endpoint 7a - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7a - PPS
    Statistical analysis description
    The results of the EQ-5D-5L questionnaire were presented descriptively and stratified by the scheduled visit and treatment group. Individual items were presented by category.
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 other [29]
    P-value
    		 = 0 [30]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [29] - Descriptive Summary
    [30] - Descriptive Summary. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7a - FAS
    Statistical analysis description
    The results of the EQ-5D-5L questionnaire were presented descriptively and stratified by the scheduled visit and treatment group. Individual items were presented by category.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 other [31]
    P-value
    		 = 0 [32]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [31] - Descriptive Summary
    [32] - Descriptive Summary. P-value was not calculated.

    Secondary: Secondary endpoint 7b - QoL - EQ-5D summary index and EQ-VAS - by visit

    		 Close Top of page
    End point title
    		 Secondary endpoint 7b - QoL - EQ-5D summary index and EQ-VAS - by visit
    End point description
    Summary of EQ-5D summary index and EQ-VAS by scheduled visit and treatment group.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    84
    45
    50
    20
    Units: value
    arithmetic mean (standard deviation)
        EQ-5D Summary Index - EOS
    0.953 ( 0.0986 )
    0.962 ( 0.0717 )
    0.963 ( 0.0739 )
    0.958 ( 0.0909 )
        EQ Overall Health (VAS) - EOS
    85.9 ( 15.76 )
    88.0 ( 12.65 )
    85.0 ( 16.19 )
    87.6 ( 16.31 )
    Attachments
    		 Secondary endpoint 7b - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7b - PPS
    Statistical analysis description
    The results of the EQ-5D-5L questionnaire were presented descriptively and stratified by the scheduled visit and treatment group. Overall score and VAS were presented as continuous variables.
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    		 other [33]
    P-value
    		 = 0 [34]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [33] - Descriptive Summary
    [34] - Descriptive Summary. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7b - FAS
    Statistical analysis description
    The results of the EQ-5D-5L questionnaire were presented descriptively and stratified by the scheduled visit and treatment group. Overall score and VAS were presented as continuous variables.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 other [35]
    P-value
    		 = 0 [36]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [35] - Descriptive Summary
    [36] - Descriptive Summary. P-value was not calculated.

    Secondary: Secondary endpoint 7c - QoL - study specific QoL questionnaire - by visit

    		 Close Top of page
    End point title
    		 Secondary endpoint 7c - QoL - study specific QoL questionnaire - by visit
    End point description
    Summary of study specific quality of life questionnaire by scheduled visit and treatment group.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    81
    44
    48
    20
    Units: value
    arithmetic mean (standard deviation)
        No. of days unable to work/study due to VV -EOS
    0.1 ( 0.37 )
    0.0 ( 0.15 )
    0.0 ( 0.20 )
    0.0 ( 0.00 )
        No. of days of partial work/study due to VV -EOS
    0.4 ( 1.28 )
    0.0 ( 0.21 )
    0.1 ( 0.55 )
    0.0 ( 0.00 )
        Quality of Life during actual episode/visit -EOS
    6.2 ( 2.29 )
    6.3 ( 2.38 )
    6.4 ( 1.94 )
    6.2 ( 2.30 )
    Attachments
    		 Secondary endpoint 7c - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7c - PPS
    Statistical analysis description
    Study specific QoL questions were summarized descriptively and stratified by scheduled visit and treatment group.
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    68
    Analysis specification
    Pre-specified
    Analysis type
    		 other [37]
    P-value
    		 = 0 [38]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [37] - Descriptive Summary
    [38] - Descriptive Summary. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7c - FAS
    Statistical analysis description
    Study specific QoL questions were summarized descriptively and stratified by scheduled visit and treatment group.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 other [39]
    P-value
    		 = 0 [40]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [39] - Descriptive Summary
    [40] - Descriptive Summary. P-value was not calculated.

    Secondary: Secondary endpoint 7d - QoL - EQ-5D dimensions - by episode order

    		 Close Top of page
    End point title
    		 Secondary endpoint 7d - QoL - EQ-5D dimensions - by episode order
    End point description
    Summary of EQ-5D dimensions by order of vulvovaginitis episode and treatment group.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    45
    33
    25
    17
    Units: number of subjects
        Mobility - E1 - I have no problems
    39
    20
    21
    9
        Mobility - E1 - I have slight problems
    3
    3
    2
    1
        Mobility - E1 - Missing
    3
    10
    2
    7
        Self-care - E1 - I have no problems
    42
    20
    23
    9
        Self-care - E1 - I have slight problems
    0
    3
    0
    1
        Self-care - E1 - Missing
    3
    10
    2
    7
        Usual activities - E1 - I have no problems
    38
    18
    21
    8
        Usual activities - E1 - I have slight problems
    3
    5
    2
    2
        Usual activities - E1 - I have moderate problems
    1
    0
    0
    0
        Usual activities - E1 - Missing
    3
    10
    2
    7
        Pain/discomfort - E1 - I have no pain/discomfort
    18
    12
    12
    6
        Pain/discomfort - E1 - I have slight pain/discom
    17
    7
    9
    2
        Pain/discomfort - E1 - I have moderate pain/disco
    7
    4
    2
    2
        Pain/discomfort - E1 - Missing
    3
    10
    2
    7
        Anxiety/depression - E1 - I am not A/D
    34
    14
    20
    7
        Anxiety/depression - E1 - I am slightly A/D
    7
    6
    2
    1
        Anxiety/depression - E1 - I am moderately A/D
    0
    3
    0
    2
        Anxiety/depression - E1 - I am severely A/D
    1
    0
    1
    0
        Anxiety/depression - E1 - Missing
    3
    10
    2
    7
    Attachments
    		 Secondary endpoint 7d - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7d - PPS
    Statistical analysis description
    The results of the EQ-5D-5L questionnaire were presented descriptively and stratified by vulvovaginitis episode order and treatment group. Individual items were presented by category.
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 other [41]
    P-value
    		 = 0 [42]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [41] - Descriptive Summary
    [42] - Descriptive Summary. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7d - FAS
    Statistical analysis description
    The results of the EQ-5D-5L questionnaire were presented descriptively and stratified by vulvovaginitis episode order and treatment group. Individual items were presented by category.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 other [43]
    P-value
    		 = 0 [44]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [43] - Descriptive Summary
    [44] - Descriptive Summary. P-value was not calculated.

    Secondary: Secondary endpoint 7e - QoL - EQ-5D summary index and EQ-VAS - by episode order

    		 Close Top of page
    End point title
    		 Secondary endpoint 7e - QoL - EQ-5D summary index and EQ-VAS - by episode order
    End point description
    Summary of EQ-5D summary index and EQ-VAS by order of vulvovaginitis episode and treatment group.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    42
    23
    23
    10
    Units: value
    arithmetic mean (standard deviation)
        EQ-5D Summary Index - E1
    0.932 ( 0.0700 )
    0.907 ( 0.1013 )
    0.939 ( 0.0733 )
    0.921 ( 0.1113 )
        EQ Overall Health (VAS) - E1
    69.5 ( 17.56 )
    63.9 ( 16.37 )
    69.3 ( 16.55 )
    66.0 ( 12.87 )
    Attachments
    		 Secondary endpoint 7e - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7e - PPS
    Statistical analysis description
    The results of the EQ-5D-5L questionnaire were presented descriptively and stratified by vulvovaginitis episode order and treatment group. Overall score and VAS were presented as continuous variables.
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 other [45]
    P-value
    		 = 0 [46]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [45] - Descriptive Summary
    [46] - Descriptive Summary. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7e - FAS
    Statistical analysis description
    The results of the EQ-5D-5L questionnaire were presented descriptively and stratified by vulvovaginitis episode order and treatment group. Overall score and VAS were presented as continuous variables.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    		 other [47]
    P-value
    		 = 0 [48]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [47] - Descriptive Summary
    [48] - Descriptive Summary. P-value was not calculated.

    Secondary: Secondary endpoint 7f - QoL - mean EQ-5D summary index and EQ-VAS

    		 Close Top of page
    End point title
    		 Secondary endpoint 7f - QoL - mean EQ-5D summary index and EQ-VAS
    End point description
    Mean EQ-5D summary index and EQ-VAS assessment during vulvovaginitis episodes between treatments.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    90
    46
    52
    21
    Units: value
    number (not applicable)
        Mean EQ-5D Summary Index
    0.92
    0.90
    0.95
    0.90
        Mean EQ Overall Health (VAS)
    68.75
    66.94
    69.68
    66.82
    Attachments
    		 Secondary endpoint 7f - statistical results
    Statistical analysis title
    		 Statistical analysis-Mean EQ-5D Summary Index -PPS
    Statistical analysis description
    Difference in mean EQ-5D summary index during vulvovaginitis episodes between treatments.
    Comparison groups
    Per-Protocol Set - Placebo v Per-Protocol Set - IMUNOR
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [49]
    P-value
    		 = 0.0724
    Method
    		 Regression, Linear
    Parameter type
    		 Difference in mean
    Point estimate
    0.051
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.005
         upper limit
    		 0.107
    Notes
    [49] - The presented results should be interpreted with caution due to the limited availability of data on episode duration.
    Statistical analysis title
    		 Statistical analysis-Mean EQ-5D Summary Index -FAS
    Statistical analysis description
    Difference in mean EQ-5D summary index during vulvovaginitis episodes between treatments.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [50]
    P-value
    		 = 0.2794
    Method
    		 Regression, Linear
    Parameter type
    		 Difference in mean
    Point estimate
    0.024
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.02
         upper limit
    		 0.069
    Notes
    [50] - The presented results should be interpreted with caution due to the limited availability of data on episode duration.
    Statistical analysis title
    		 Statistical analysis-Mean EQ-VAS -PPS
    Statistical analysis description
    Difference in mean EQ-VAS assessment during vulvovaginitis episodes between treatments.
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [51]
    P-value
    		 = 0.5295
    Method
    		 Regression, Linear
    Parameter type
    		 Difference in mean
    Point estimate
    2.861
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.298
         upper limit
    		 12.019
    Notes
    [51] - The presented results should be interpreted with caution due to the limited availability of data on episode duration.
    Statistical analysis title
    		 Statistical analysis-Mean EQ-VAS -FAS
    Statistical analysis description
    Difference in mean EQ-VAS assessment during vulvovaginitis episodes between treatments.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [52]
    P-value
    		 = 0.6248
    Method
    		 Regression, Linear
    Parameter type
    		 Difference in mean
    Point estimate
    1.811
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.579
         upper limit
    		 9.2
    Notes
    [52] - The presented results should be interpreted with caution due to the limited availability of data on episode duration.

    Secondary: Secondary endpoint 7g - QoL - study specific QoL questionnaire - by episode order

    		 Close Top of page
    End point title
    		 Secondary endpoint 7g - QoL - study specific QoL questionnaire - by episode order
    End point description
    Summary of study specific quality of life questionnaire by order of vulvovaginitis episode and treatment group.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    41
    20
    23
    9
    Units: value
    arithmetic mean (standard deviation)
        No. of days unable to work/study due to VV - E1
    0.0 ( 0.00 )
    0.4 ( 1.09 )
    0.0 ( 0.00 )
    0.0 ( 0.00 )
        No. of days of partial work/study due to VV - E1
    0.3 ( 1.28 )
    0.7 ( 1.59 )
    0.1 ( 0.42 )
    0.4 ( 1.33 )
        Quality of Life during actual episode/visit - E1
    5.4 ( 2.03 )
    4.4 ( 2.06 )
    5.0 ( 1.80 )
    4.3 ( 2.26 )
    Attachments
    		 Secondary endpoint 7g - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7g - PPS
    Statistical analysis description
    Study specific QoL questions were summarized descriptively and stratified by vulvovaginitis episode order and treatment group.
    Comparison groups
    Per-Protocol Set - IMUNOR v Per-Protocol Set - Placebo
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [53]
    P-value
    		 = 0 [54]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [53] - Descriptive Summary
    [54] - Descriptive Summary. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 7g - FAS
    Statistical analysis description
    Study specific QoL questions were summarized descriptively and stratified by vulvovaginitis episode order and treatment group.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 other [55]
    P-value
    		 = 0 [56]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [55] - Descriptive Summary
    [56] - Descriptive Summary. P-value was not calculated.

    Secondary: Secondary endpoint 8 - changes in vaginal biocenosis

    		 Close Top of page
    End point title
    		 Secondary endpoint 8 - changes in vaginal biocenosis
    End point description
    Summary of evaluation of changes in vaginal biocenosis by scheduled visit and treatment group.
    End point type
    Secondary
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    90
    46
    52
    21
    Units: number of subjects
        Visit 2 - Yes
    19
    6
    13
    2
        Visit 2 - No
    70
    39
    39
    18
        Visit 2 - Not done/available
    1
    1
    0
    1
        Visit 3 - Yes
    7
    2
    3
    1
        Visit 3 - No
    20
    11
    12
    6
        Visit 3 - Not done/available
    61
    33
    36
    14
        Visit 4 - Yes
    20
    11
    12
    4
        Visit 4 - No
    58
    31
    36
    15
        Visit 4 - Not done/available
    5
    1
    1
    0
        Visit 5 - Yes
    8
    3
    3
    0
        Visit 5 - No
    19
    11
    11
    4
        Visit 5 - Not done/available
    52
    28
    33
    15
        EOS - Yes
    22
    13
    16
    6
        EOS - No
    59
    32
    32
    14
        EOS - Not done/available
    9
    1
    4
    1
    Attachments
    		 Secondary endpoint 8 - statistical results
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 8 - PPS
    Statistical analysis description
    Vaginal biocenosis findings were reported as Presence or Absence of Candida species in cultivation result. Relative and absolute counts of individual responses “Yes”, “No” and “Not done/available” were summarized descriptively and stratified by scheduled visit and treatment group. The “Yes” category was reported overall as well as by specific Candida species.
    Comparison groups
    Per-Protocol Set - Placebo v Per-Protocol Set - IMUNOR
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 other [57]
    P-value
    		 = 0 [58]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [57] - Descriptive Summary. Data analysis was affected by the limited availability of cultivation results, e.g., due to non-performance of the examination during menstruation or in symptom-free patients with a negative objective finding.
    [58] - Descriptive Summary. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Secondary endpoint 8 - FAS
    Statistical analysis description
    Vaginal biocenosis findings were reported as Presence or Absence of Candida species in cultivation result. Relative and absolute counts of individual responses “Yes”, “No” and “Not done/available” were summarized descriptively and stratified by scheduled visit and treatment group. The “Yes” category was reported overall as well as by specific Candida species.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    136
    Analysis specification
    Pre-specified
    Analysis type
    		 other [59]
    P-value
    		 = 0 [60]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [59] - Descriptive Summary. Data analysis was affected by the limited availability of cultivation results, e.g., due to non-performance of the examination during menstruation or in symptom-free patients with a negative objective finding.
    [60] - Descriptive Summary. P-value was not calculated.

    Other pre-specified: Exploratory endpoint

    		 Close Top of page
    End point title
    		 Exploratory endpoint
    End point description
    Summary statistics, changes from baseline and frequencies of abnormal values of CD3+, CD4+, CD8+, CD16+/CD56+, CD19+, CD3+/HLA-DR3+ cell counts [109/], differential counts of CD3+, CD4+, CD8+, CD16+/CD56+, CD19+, CD3+/HLA-DR3+ cells [%], total IgG, total IgM, total IgA [g/L], anti-D-mannan IgM, anti-D-glucan IgG [U/mL], and phagocyte activity [%] stratified by scheduled visit and treatment group.
    End point type
    Other pre-specified
    End point timeframe
    12-month period
    End point values
    		 Full Analysis Set - IMUNOR Full Analysis Set - Placebo Per-Protocol Set - IMUNOR Per-Protocol Set - Placebo
    Number of subjects analysed
    78 [61]
    42 [62]
    46 [63]
    19 [64]
    Units: value
    arithmetic mean (standard deviation)
        Mean count of CD3+ cells [10^9/L] - Visit 5
    1.494 ( 0.5214 )
    1.668 ( 0.5214 )
    1.513 ( 0.4905 )
    1.850 ( 0.5322 )
        Mean diff. count of CD3+ cells [%] - Visit 5
    76.49 ( 5.970 )
    78.06 ( 5.840 )
    77.25 ( 5.601 )
    79.99 ( 3.235 )
        Mean count of CD4+ cells [10^9/L] - Visit 5
    0.940 ( 0.3466 )
    1.096 ( 0.3384 )
    0.951 ( 0.3095 )
    1.199 ( 0.3240 )
        Mean diff. count of CD4+ cells [%] - Visit 5
    48.16 ( 6.585 )
    51.44 ( 5.822 )
    48.86 ( 6.512 )
    52.16 ( 5.962 )
        Mean count of CD8+ cells [10^9/L] - Visit 5
    0.492 ( 0.2208 )
    0.513 ( 0.2168 )
    0.496 ( 0.2002 )
    0.577 ( 0.2437 )
        Mean diff. count of CD8+ cells [%] - Visit 5
    25.32 ( 6.574 )
    23.89 ( 6.234 )
    25.34 ( 5.413 )
    24.72 ( 5.781 )
        Mean count of CD16+/CD56+ cells [10^9/L] - Visit 5
    0.226 ( 0.1151 )
    0.219 ( 0.0974 )
    0.234 ( 0.1238 )
    0.204 ( 0.0820 )
        Mean diff. count of CD16+/CD56+ cells [%] -Visit 5
    11.98 ( 5.374 )
    10.44 ( 3.843 )
    11.90 ( 4.790 )
    8.86 ( 2.571 )
        Mean count of CD19+ cells [10^9/L] - Visit 5
    0.199 ( 0.1009 )
    0.221 ( 0.0957 )
    0.183 ( 0.0852 )
    0.227 ( 0.0902 )
        Mean diff. count of CD19+ cells [%] - Visit 5
    10.08 ( 3.393 )
    10.19 ( 3.375 )
    9.30 ( 3.063 )
    9.78 ( 3.273 )
        Mean count of CD3+/HLA-DR3+ cells [10^9/L]-Visit 5
    0.082 ( 0.0559 )
    0.086 ( 0.0701 )
    0.081 ( 0.0555 )
    0.101 ( 0.0687 )
        Mean diff. count of CD3+/HLA-DR3+cells [%]-Visit 5
    4.17 ( 2.605 )
    3.84 ( 2.537 )
    4.38 ( 2.739 )
    4.58 ( 2.573 )
        Mean level of total IgG [g/L] - Visit 5
    11.123 ( 2.1822 )
    10.769 ( 2.3199 )
    11.244 ( 2.2239 )
    10.741 ( 2.0338 )
        Mean level of total IgM [g/L] - Visit 5
    1.219 ( 0.4630 )
    1.480 ( 0.9116 )
    1.218 ( 0.4569 )
    1.402 ( 1.1996 )
        Mean level of total IgA [g/L] - Visit 5
    1.982 ( 0.8195 )
    2.215 ( 0.7795 )
    1.985 ( 0.5897 )
    2.125 ( 0.6267 )
        Mean level of anti-D-mannan IgM [U/mL] - Visit 5
    18.874 ( 16.4249 )
    20.926 ( 18.096 )
    17.268 ( 12.2924 )
    16.626 ( 14.7514 )
        Mean level of anti-D-mannan IgM [NTU] - Visit 5
    4.639 ( 2.3915 )
    6.453 ( 4.7492 )
    0 ( 0 )
    0 ( 0 )
        Mean level of anti-D-glucan IgG [U/mL] - Visit 5
    22.565 ( 23.4687 )
    19.809 ( 20.3833 )
    21.677 ( 21.2119 )
    23.000 ( 25.2827 )
        Mean level of anti-D-glucan IgG [NTU] - Visit 5
    27.630 ( 7.7873 )
    26.117 ( 7.6006 )
    0 ( 0 )
    0 ( 0 )
        Mean value of phagocyte activity [%] - Visit 5
    95.721 ( 7.3766 )
    95.892 ( 4.0825 )
    96.905 ( 3.1553 )
    95.721 ( 4.5385 )
    Attachments
    		 Exploratory endpoint - statistical results
    Notes
    [61] - Number of subjects with available values for each parameter is specified in the attached tables.
    [62] - Number of subjects with available values for each parameter is specified in the attached tables.
    [63] - Number of subjects with available values for each parameter is specified in the attached tables.
    [64] - Number of subjects with available values for each parameter is specified in the attached tables.
    Statistical analysis title
    		 Statistical analysis - Exploratory endpoint - PPS
    Statistical analysis description
    For all patients included in the sub-study, descriptive statistics were calculated for measured values at each scheduled timepoint and for changes from baseline. Additionally, geometric mean was also reported for measured values (not for change from baseline) as the variables of interest could have had log-normal distribution. Moreover, frequencies of normal and abnormal values were reported alongside descriptive statistics.
    Comparison groups
    Per-Protocol Set - Placebo v Per-Protocol Set - IMUNOR
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    		 other [65]
    P-value
    		 = 0 [66]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [65] - Descriptive Summary. For the assessment of anti-D-mannan IgM and anti-D-glucan IgG antibody levels, patients from study sites 004 and 005 were not included in the PPS due to different measurement units. The data were analysed within the FAS and separately for each unit.
    [66] - Descriptive Summary. P-value was not calculated.
    Statistical analysis title
    		 Statistical analysis - Exploratory endpoint - FAS
    Statistical analysis description
    For all patients included in the sub-study, descriptive statistics were calculated for measured values at each scheduled timepoint and for changes from baseline. Additionally, geometric mean was also reported for measured values (not for change from baseline) as the variables of interest could have had log-normal distribution. Moreover, frequencies of normal and abnormal values were reported alongside descriptive statistics.
    Comparison groups
    Full Analysis Set - IMUNOR v Full Analysis Set - Placebo
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 other [67]
    P-value
    		 = 0 [68]
    Method
    		 Descriptive Summary
    Confidence interval
    Notes
    [67] - Descriptive Summary. For the assessment of anti-D-mannan IgM and anti-D-glucan IgG antibody levels, patients from study sites 004 and 005 were not included in the PPS due to different measurement units. The data were analysed within the FAS and separately for each unit.
    [68] - Descriptive Summary. P-value was not calculated.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    12-month period per patient
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    IMUNOR group
    Reporting group description
    		 Administration of IMUNOR® as 1 dose/week, orally for a total of 3 months within treatment period 1 and treatment period 2. Each treatment period was followed by 3-month observation period. Total study duration was 12 months.

    Reporting group title
    Placebo group
    Reporting group description
    		 Administration of placebo as 1 dose/week, orally for a total of 3 months within treatment period 1 and treatment period 2. Each treatment period was followed by 3-month observation period. Total study duration was 12 months.

    Serious adverse events
    		 IMUNOR group Placebo group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 90 (4.44%)
    2 / 46 (4.35%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Joint injury
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Drug ineffective
    Additional description: Lack of efficacy of hormonal contraception. Pregnancy confirmed by urinal pregnancy tests and blood test (HCG = 537 IU/L) on 16-APR-2018. Pregnancy terminated upon subject’s request on 23-APR-2018.
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Acute psychosis
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Goiter
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Chondropathy
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 IMUNOR group Placebo group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    78 / 90 (86.67%)
    43 / 46 (93.48%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Essential hypertension
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Surgical and medical procedures
    Antibiotic therapy
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed
    1 / 90 (1.11%)
    1 / 46 (2.17%)
         occurrences all number
    1
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 90 (1.11%)
    1 / 46 (2.17%)
         occurrences all number
    1
    1
    Food allergy
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Hypersensitivity
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Milk allergy
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Bacterial vaginosis
         subjects affected / exposed
    19 / 90 (21.11%)
    15 / 46 (32.61%)
         occurrences all number
    30
    17
    Vulvovaginal discomfort
         subjects affected / exposed
    6 / 90 (6.67%)
    3 / 46 (6.52%)
         occurrences all number
    9
    4
    Vaginal haemorrhage
         subjects affected / exposed
    4 / 90 (4.44%)
    0 / 46 (0.00%)
         occurrences all number
    5
    0
    Cervical dysplasia
         subjects affected / exposed
    0 / 90 (0.00%)
    2 / 46 (4.35%)
         occurrences all number
    0
    2
    Vaginal discharge
         subjects affected / exposed
    2 / 90 (2.22%)
    0 / 46 (0.00%)
         occurrences all number
    2
    0
    Vulvovaginal pruritus
         subjects affected / exposed
    2 / 90 (2.22%)
    0 / 46 (0.00%)
         occurrences all number
    3
    0
    Amenorrhoea
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Breast disorder
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Dysmenorrhoea
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Dyspareunia
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Endometrial hyperplasia
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Ovarian cyst
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Pruritus genital
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Unexpected vaginal bleeding on hormonal IUD
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Uterine inflammation
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Uterine polyp
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 90 (1.11%)
    1 / 46 (2.17%)
         occurrences all number
    1
    1
    Affective disorder
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    1
    Investigations
    Weight decreased
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Limb injury
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Traumatic haematoma
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 90 (1.11%)
    1 / 46 (2.17%)
         occurrences all number
    3
    2
    Anaesthesia
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Migraine
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 90 (1.11%)
    1 / 46 (2.17%)
         occurrences all number
    1
    1
    Ear and labyrinth disorders
    Tinnitus auris
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 90 (0.00%)
    2 / 46 (4.35%)
         occurrences all number
    0
    2
    Anal fissure
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Duodenal ulcer
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    1
    Dermatitis atopic
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Urticaria
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    2
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 90 (1.11%)
    1 / 46 (2.17%)
         occurrences all number
    1
    1
    Cystitis noninfective
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Urethral syndrome
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Autoimmune thyroiditis
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 90 (2.22%)
    2 / 46 (4.35%)
         occurrences all number
    2
    2
    Tendon disorder
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    1
    Tenosynovitis
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Vulvovaginal mycotic infection
         subjects affected / exposed
    31 / 90 (34.44%)
    23 / 46 (50.00%)
         occurrences all number
    50
    42
    Vulvovaginitis
         subjects affected / exposed
    9 / 90 (10.00%)
    17 / 46 (36.96%)
         occurrences all number
    13
    18
    Bacterial vaginosis
         subjects affected / exposed
    17 / 90 (18.89%)
    6 / 46 (13.04%)
         occurrences all number
    29
    7
    Cystitis
         subjects affected / exposed
    13 / 90 (14.44%)
    9 / 46 (19.57%)
         occurrences all number
    20
    11
    Bacterial vulvovaginitis
         subjects affected / exposed
    13 / 90 (14.44%)
    6 / 46 (13.04%)
         occurrences all number
    15
    9
    Vulvitis
         subjects affected / exposed
    13 / 90 (14.44%)
    6 / 46 (13.04%)
         occurrences all number
    15
    7
    Vulvovaginal candidiasis
         subjects affected / exposed
    9 / 90 (10.00%)
    8 / 46 (17.39%)
         occurrences all number
    9
    8
    Lactobacillus infection
         subjects affected / exposed
    12 / 90 (13.33%)
    3 / 46 (6.52%)
         occurrences all number
    14
    5
    Bronchitis
         subjects affected / exposed
    7 / 90 (7.78%)
    1 / 46 (2.17%)
         occurrences all number
    8
    1
    Nasopharyngitis
         subjects affected / exposed
    6 / 90 (6.67%)
    2 / 46 (4.35%)
         occurrences all number
    7
    2
    Urinary tract infection
         subjects affected / exposed
    7 / 90 (7.78%)
    0 / 46 (0.00%)
         occurrences all number
    10
    0
    Tonsillitis
         subjects affected / exposed
    3 / 90 (3.33%)
    1 / 46 (2.17%)
         occurrences all number
    3
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 90 (1.11%)
    2 / 46 (4.35%)
         occurrences all number
    1
    2
    Genital herpes
         subjects affected / exposed
    1 / 90 (1.11%)
    1 / 46 (2.17%)
         occurrences all number
    3
    1
    Influenza
         subjects affected / exposed
    2 / 90 (2.22%)
    0 / 46 (0.00%)
         occurrences all number
    2
    0
    Laryngitis
         subjects affected / exposed
    2 / 90 (2.22%)
    0 / 46 (0.00%)
         occurrences all number
    2
    0
    Sinusitis
         subjects affected / exposed
    2 / 90 (2.22%)
    0 / 46 (0.00%)
         occurrences all number
    2
    0
    Viral infection
         subjects affected / exposed
    2 / 90 (2.22%)
    0 / 46 (0.00%)
         occurrences all number
    2
    0
    Bacteriuria
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    1
    Cervicitis
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    1
    Tracheitis
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Ureaplasma cervicitis
         subjects affected / exposed
    1 / 90 (1.11%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    Vaginal infection
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    2
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    0 / 90 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Dec 2015
    Substantial Amendment No. 01 (Consolidated Study Protocol, final version 1.0, dated 27 July 2015) Approvals: MEC CZ 16.9.2015 / RA CZ 24.8.2015 / MEC SK 5.12.2015 / RA SK 17.8.2015 Main changes: • Postponement of the recruitment period to September 2015 – February 2016 (including FPLV to September 2016 and LPLV to March 2017); • Change of the CRO and electronic data capture system; • Simplification of the randomization process; • Change in packaging of the IMP.
    13 Jan 2016
    Substantial Amendment No. 02 (Consolidated Study Protocol, final version 2.0, dated 09 November 2015) Approvals: MEC CZ 9.12.2015 / RA CZ 4.12.2015 / MEC SK 14.12.2015 / LEC SK 16.12.2015 / RA SK 13.1.2016 Main changes: • Postponement of the recruitment period to January – June 2016 (including FPLV to January 2016 and LPLV to July 2017); • Implementation of the pharmacoeconomic sub-study; • Merge of Visit 6 and the Premature study withdrawal visit; • Update of the information about the source of Reference Safety Information; • QPS Netherlands responsible for data management (instead of QPS Austria GmbH).
    01 Aug 2016
    Substantial Amendment No. 03 (Consolidated Study Protocol, final version 4.0, dated 11 May 2016) Approvals: MEC CZ 8.6.2016 / RA CZ 3.6.2016 / MEC SK 19.7.2016 / LEC SK 1.8.2016 / RA SK 28.6.2016 Main changes: • Prolongation of the recruitment period to March 2017 (including postponement of the LPLV to April 2018); • Central evaluation of the reported results of immunology tests; • Prolongation of the screening period (enabling treatment of vulvovaginitis episodes recorded during screening); • Specification of requirements for reporting clinically significant deviations of evaluated laboratory parameters.
    31 Mar 2017
    Substantial Amendment No. 04 (Consolidated Study Protocol, final version 5.0, dated 15 February 2017) Approvals: MEC CZ 8.3.2017 (corrected vote received on 28.4.2017) / RA CZ 20.3.2017 / MEC SK 14.3.2017 / LEC SK 31.3.2017 / RA SK 15.3.2017 Main changes: • Prolongation of the recruitment period to December 2017 (including postponement of the LPLV to January 2019); • Clarification of the exclusion criterion No. 11 (in accordance with the list of prohibited and permitted treatments); • Specification of the procedure in the case of non-compliance detected at Visit 5 / after the end of IMP administration.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    inclusion of inflammatory and non-inflammatory conditions for acute vaginitis (N 76.0); limited availability of data on episode duration and cultivation results; no comparison for prevailing bacterial etiology due to low no. of placebo patients
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Aug 11 22:19:55 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA