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    Clinical Trial Results:
    A multicentre, multinational, parallel group, observer-blind, randomised, placebo-controlled study on the Group B Streptococcus vaccine (GBS-NN/NN2), investigating the immunogenicity and safety of four vaccination regimens in pregnant woman, assessing IgG specific to AlpN proteins in cord blood and maternal blood, and the safety profile in mother and infant up to 6 months post-delivery

    Summary
    EudraCT number
    		 2021-003214-40
    Trial protocol
    		 DK  
    Global end of trial date
    18 Oct 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Dec 2024
    First version publication date
    06 Dec 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MVX0004
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MinervaX ApS
    Sponsor organisation address
    Nordre Fasanvej 215, Frederiksberg, Denmark, 2000
    Public contact
    Clinical Trials Information, MinervaX Aps, +45 39 17 82 82, lio@minervax.com
    Scientific contact
    Clinical Trials Information, MinervaX Aps, +45 39 17 82 82, lio@minervax.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Jun 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    26 Apr 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Oct 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the concentrations of IgG specific to the AlpN proteins (RibN, Alp1N, Alp2N and AlpCN) in cord blood from babies, born to women who received the GBS-NN/NN2 vaccine or placebo, according to four vaccination regimens during pregnancy, between the GBS-NN/NN2 and placebo groups: • Group 1: 2 doses GBS-NN/NN2 at 26 & 30 weeks GA • Group 2: 2 doses GBS-NN/NN2 at 22 & 26 weeks GA • Group 3: 2 doses GBS-NN/NN2 at 22 & 30 weeks GA • Group 4: 1 dose GBS-NN/NN2 at 26 weeks GA • Group 5: Placebo at 22, 26, and 30 weeks GA
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Dec 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Denmark: 59
    Country: Number of subjects enrolled
    United Kingdom: 15
    Country: Number of subjects enrolled
    South Africa: 195
    Worldwide total number of subjects
    269
    EEA total number of subjects
    59
    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)
    269
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The first participant first visit took place on 17 February 2022 and the last participant last visit took place on 18 October 2023.

    Pre-assignment
    Screening details
    		 A total of 400 maternal participants signed the ICF and were enrolled in the study, of whom 272 were eligible and randomised to one of the 5 study groups (3 participants were randomised in error). Enrolment was stopped with 269 randomised participants who received at least one dose of the study vaccine or placebo.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group 1: 4 week dose interval; 2 doses
    Arm description
    		 Participants received one injection of placebo at 22 (±1) weeks GA (gestational age), one injection of GBS-NN/NN2 at 26 (±1) weeks GA and one injection of GBS- NN/NN2 at 30 (±1) weeks GA
    Arm type
    		 Experimental

    Investigational medicinal product name
    GBS-NN/NN2 Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL GBS-NN/NN2 containing 50 μg of GBS-NN and 50 μg of GBS-NN2 and 0.5 mg of aluminium, given by intramuscular injection

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL normal saline given by intramuscular injection

    Arm title
    		 Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses
    Arm description
    		 Participants received one injection of GBS-NN/NN2 at 22 (±1) weeks GA, one injection of GBS-NN/NN2 at 26 (±1) weeks GA and one injection of placebo at 30 (±1) weeks GA
    Arm type
    		 Experimental

    Investigational medicinal product name
    GBS-NN/NN2 Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL GBS-NN/NN2 containing 50 μg of GBS-NN and 50 μg of GBS-NN2 and 0.5 mg of aluminium, given by intramuscular injection

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL normal saline given by intramuscular injection

    Arm title
    		 Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses
    Arm description
    		 Participants received one injection of GBS-NN/NN2 at 22 (±1) weeks GA, one injection of placebo at 26 (±1) weeks GA and one injection of GBS- NN/NN2 at 30 (±1) weeks GA
    Arm type
    		 Experimental

    Investigational medicinal product name
    GBS-NN/NN2 Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL GBS-NN/NN2 containing 50 μg of GBS-NN and 50 μg of GBS-NN2 and 0.5 mg of aluminium, given by intramuscular injection

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL normal saline given by intramuscular injection

    Arm title
    		 Group 4: Single Dose
    Arm description
    		 Participants received one injection of placebo at 22 (±1) weeks GA, one injection of GBS-NN/NN2 at 26 (±1) weeks GA, and one injection of placebo at 30 (±1) weeks GA.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GBS-NN/NN2 Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL GBS-NN/NN2 containing 50 μg of GBS-NN and 50 μg of GBS-NN2 and 0.5 mg of aluminium, given by intramuscular injection

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL normal saline given by intramuscular injection

    Arm title
    		 Group 5: Placebo
    Arm description
    		 Participants received one injection of placebo at 22, 26 and 30 weeks (±1) GA
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL normal saline given by intramuscular injection

    Number of subjects in period 1
    		Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Started
    61
    59
    59
    60
    30
    Completed
    59
    54
    56
    52
    29
    Not completed
    2
    5
    3
    8
    1
         Consent withdrawn by subject
    2
    3
    2
    4
    -
         Adverse event, non-fatal
    -
    -
    -
    1
    -
         Baby loss
    -
    1
    -
    -
    -
         Lost to follow-up
    -
    1
    -
    3
    -
         Relocated to another province
    -
    -
    1
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group 1: 4 week dose interval; 2 doses
    Reporting group description
    		 Participants received one injection of placebo at 22 (±1) weeks GA (gestational age), one injection of GBS-NN/NN2 at 26 (±1) weeks GA and one injection of GBS- NN/NN2 at 30 (±1) weeks GA

    Reporting group title
    Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses
    Reporting group description
    		 Participants received one injection of GBS-NN/NN2 at 22 (±1) weeks GA, one injection of GBS-NN/NN2 at 26 (±1) weeks GA and one injection of placebo at 30 (±1) weeks GA

    Reporting group title
    Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses
    Reporting group description
    		 Participants received one injection of GBS-NN/NN2 at 22 (±1) weeks GA, one injection of placebo at 26 (±1) weeks GA and one injection of GBS- NN/NN2 at 30 (±1) weeks GA

    Reporting group title
    Group 4: Single Dose
    Reporting group description
    		 Participants received one injection of placebo at 22 (±1) weeks GA, one injection of GBS-NN/NN2 at 26 (±1) weeks GA, and one injection of placebo at 30 (±1) weeks GA.

    Reporting group title
    Group 5: Placebo
    Reporting group description
    		 Participants received one injection of placebo at 22, 26 and 30 weeks (±1) GA

    Reporting group values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo Total
    Number of subjects
    		 61 59 59 60 30 269
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0
        Adults (18-64 years)
    		 61 59 59 60 30 269
        From 65-84 years
    		 0 0 0 0 0 0
        85 years and over
    		 0 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 28.9 ( 5.26 ) 27.5 ( 4.81 ) 27.8 ( 5.34 ) 27.3 ( 5.37 ) 28.3 ( 6.65 ) -
    Gender categorical
    Units: Subjects
        Female
    		 61 59 59 60 30 269
        Male
    		 0 0 0 0 0 0
    Region of Enrollment
    Units: Subjects
        Denmark
    		 13 14 12 13 7 59
        United Kingdom
    		 4 3 4 3 1 15
        South Africe
    		 44 42 43 44 22 195
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 2 0 1 0 1 4
        Not Hispanic or Latino
    		 59 59 58 60 29 265
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 161.7 ( 7.84 ) 162.2 ( 8.00 ) 163.3 ( 7.58 ) 160.5 ( 6.88 ) 160.5 ( 6.92 ) -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 71.1 ( 14.00 ) 73 ( 12.11 ) 73.6 ( 14.52 ) 70.6 ( 14.59 ) 74.2 ( 13.38 ) -
    BMI
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 27.2 ( 5.28 ) 27.9 ( 5.32 ) 27.6 ( 5.35 ) 27.5 ( 5.57 ) 28.8 ( 5.38 ) -

    End points

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    End points reporting groups
    Reporting group title
    Group 1: 4 week dose interval; 2 doses
    Reporting group description
    		 Participants received one injection of placebo at 22 (±1) weeks GA (gestational age), one injection of GBS-NN/NN2 at 26 (±1) weeks GA and one injection of GBS- NN/NN2 at 30 (±1) weeks GA

    Reporting group title
    Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses
    Reporting group description
    		 Participants received one injection of GBS-NN/NN2 at 22 (±1) weeks GA, one injection of GBS-NN/NN2 at 26 (±1) weeks GA and one injection of placebo at 30 (±1) weeks GA

    Reporting group title
    Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses
    Reporting group description
    		 Participants received one injection of GBS-NN/NN2 at 22 (±1) weeks GA, one injection of placebo at 26 (±1) weeks GA and one injection of GBS- NN/NN2 at 30 (±1) weeks GA

    Reporting group title
    Group 4: Single Dose
    Reporting group description
    		 Participants received one injection of placebo at 22 (±1) weeks GA, one injection of GBS-NN/NN2 at 26 (±1) weeks GA, and one injection of placebo at 30 (±1) weeks GA.

    Reporting group title
    Group 5: Placebo
    Reporting group description
    		 Participants received one injection of placebo at 22, 26 and 30 weeks (±1) GA

    Primary: Concentrations of Immunoglobulin (Ig) G Antibodies Specific to the AlpN Proteins in μg/mL in Cord Blood From Each Baby

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    End point title
    		 Concentrations of Immunoglobulin (Ig) G Antibodies Specific to the AlpN Proteins in μg/mL in Cord Blood From Each Baby
    End point description
    Concentrations of IgG antibodies specific to the AlpN proteins in μg/mL in cord blood from each baby at birth
    End point type
    Primary
    End point timeframe
    Delivery
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    59 [1]
    57 [2]
    56 [3]
    55 [4]
    28
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Alp1N
    11.13 ( 239.4 )
    5.51 ( 169.7 )
    7.35 ( 238.2 )
    2.58 ( 730.1 )
    0.08 ( 89.1 )
        Alp2N
    6.97 ( 326.5 )
    5.30 ( 282.3 )
    5.08 ( 377.4 )
    2.58 ( 740.2 )
    0.05 ( 126.2 )
        AlpCN
    9.08 ( 236.9 )
    6.85 ( 311.7 )
    6.70 ( 369.2 )
    2.68 ( 691.3 )
    0.08 ( 156.6 )
        RibN
    3.55 ( 224 )
    1.97 ( 418.7 )
    3.42 ( 258.3 )
    1.15 ( 601.0 )
    0.06 ( 125.5 )
    Attachments
    		 Untitled (Filename: Primary endpoint statistical analysis.docx)
    Notes
    [1] - Alp1N = 57, Alp2N = 52, AlpCN = 52, RibN = 54
    [2] - Alp1N = 54, Alp2N = 50, AlpCN = 56, RibN = 53
    [3] - Alp1N = 52, Alp2N = 50, AlpCN = 53, RibN = 54
    [4] - Alp1N = 52, Alp2N = 53, AlpCN = 53, RibN = 54
    Statistical analysis title
    		 Analysis of primary immunogenicity endpoint
    Statistical analysis description
    Group 1 was selected as the perceived standard and reference group, whereas Groups 2 and 3 each represent useful practical alternatives that are expected to perform on a comparable level. Group 4 represents a sub-optimal but still useful vaccination schedule that would be likely to occur in real life. Antibody concentrations for the 4 AlpN proteins were described through seroprotection levels (concentrations above 0.1, 0.2, 0.5, 1, 2, 4, and 8 µg/mL) and geometric mean concentrations (GMCs).
    Comparison groups
    Group 1: 4 week dose interval; 2 doses v Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses v Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses v Group 4: Single Dose v Group 5: Placebo
    Number of subjects included in analysis
    255
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    P-value
    		 > 0.001 [6]
    Method
    		 Please see comment
    Parameter type
    		 Geometric mean
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.5
         upper limit
    		 97.5
    Notes
    [5] - The non-inferiority hypotheses tests had margins of 15 percentage point difference on the absolute scale for the seroprotection and a ratio of 2/3 for the GMC. Non-inferiority tests were performed using a one-sided 5% significance level. Confidence intervals of the point estimates were reported using a two-sided 95% confidence level.
    [6] - Method: Hypothesis tests for geometric mean ratios were based on one-sided t-tests on the log-transformed concentration ratios. The difference in seroprotection was tested using the Newcombe-Wilson method *See attached table for p-value overview

    Secondary: Injection Site Reactions in the Mother

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    End point title
    		 Injection Site Reactions in the Mother
    End point description
    Number of participants with solicited injection site reactions following vaccination
    End point type
    Secondary
    End point timeframe
    7 days following each injection
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    61
    59
    59
    60
    30
    Units: participant
        Redness : 0 - 2.4 cm
    7
    5
    9
    5
    5
        Redness : 2.5 - 5.0 cm
    2
    1
    2
    0
    0
        Redness : 5.1 - 10.0 cm
    0
    1
    0
    0
    0
        Redness : >10 cm
    0
    0
    0
    0
    0
        Swelling : Palpable "firmness" only
    14
    10
    9
    6
    1
        Swelling : 0 - 2.4 cm
    5
    2
    2
    2
    0
        Swelling : 2.5 - 5.0 cm
    0
    2
    0
    0
    0
        Swelling : 5.1 - 10.0 cm
    0
    0
    0
    0
    0
        Tenderness: Mild
    14
    17
    18
    16
    3
        Tenderness: Moderate
    15
    12
    13
    10
    1
        Tenderness: Severe
    0
    0
    1
    0
    0
        Itching
    23
    20
    15
    14
    4
        Pain: Mild
    35
    35
    34
    24
    3
        Pain: Moderate
    3
    3
    2
    0
    0
        Pain: Severe
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Adverse Events Following the Vaccinations in the Mother

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    End point title
    		 Adverse Events Following the Vaccinations in the Mother
    End point description
    Number of participants with solicited and other adverse events following the vaccinations
    End point type
    Secondary
    End point timeframe
    To Day 84
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    61
    59
    59
    60
    30
    Units: Participants
        Number
    56
    54
    57
    56
    26
    No statistical analyses for this end point

    Secondary: Clinically Significant Abnormal Laboratory Tests in the Mother

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    End point title
    		 Clinically Significant Abnormal Laboratory Tests in the Mother
    End point description
    Number of participants with clinically significant abnormal laboratory tests in the mother
    End point type
    Secondary
    End point timeframe
    To Day 84
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    61
    59
    59
    60
    30
    Units: Participants
        Number
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Clinically Significant Changes in Vital Signs in the Mother

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    End point title
    		 Clinically Significant Changes in Vital Signs in the Mother
    End point description
    Number of participants with clinically significant changes in vital signs (heart rate, blood pressure, oral temperature) in the mother
    End point type
    Secondary
    End point timeframe
    To Day 84
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    61
    59
    59
    60
    30
    Units: Participants
        Number
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Clinically Significant Changes in Physical Examination in the Mother

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    End point title
    		 Clinically Significant Changes in Physical Examination in the Mother
    End point description
    Number of participants with clinically significant changes in physical examination in the mother
    End point type
    Secondary
    End point timeframe
    To Day 84
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    61
    59
    59
    60
    30
    Units: Participants
        Number
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Gestational Age

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    End point title
    		 Gestational Age
    End point description
    Gestational age at birth
    End point type
    Secondary
    End point timeframe
    Delivery
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    61
    59
    59
    60
    30
    Units: Age (months)
    arithmetic mean (standard deviation)
        Age
    38.7 ( 2.88 )
    38.9 ( 2.39 )
    38.9 ( 2.30 )
    38.8 ( 2.37 )
    39.4 ( 1.45 )
    No statistical analyses for this end point

    Secondary: Weight of the Baby

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    End point title
    		 Weight of the Baby
    End point description
    Weight of the baby
    End point type
    Secondary
    End point timeframe
    Delivery
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    61
    59
    59
    60
    30
    Units: Grams
    arithmetic mean (standard deviation)
        Weight of the Baby
    3165.4 ( 585.45 )
    3086.5 ( 679.5 )
    3230.1 ( 638.71 )
    2955.3 ( 598.35 )
    3272.4 ( 629.2 )
    No statistical analyses for this end point

    Secondary: Length of the Baby

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    End point title
    		 Length of the Baby
    End point description
    Length of the baby
    End point type
    Secondary
    End point timeframe
    Delivery
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    61
    59
    59
    60
    30
    Units: centimeters
    arithmetic mean (standard deviation)
        Length of the baby
    50.3 ( 3.59 )
    49.9 ( 2.96 )
    49.3 ( 4.88 )
    48.9 ( 4.42 )
    49.7 ( 4.45 )
    No statistical analyses for this end point

    Secondary: Head Circumference of the Baby

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    End point title
    		 Head Circumference of the Baby
    End point description
    Head Circumference of the Baby
    End point type
    Secondary
    End point timeframe
    Delivery
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    61
    59
    59
    60
    30
    Units: centimetre
    arithmetic mean (standard deviation)
        Head Circumference of the Baby
    34.4 ( 1.83 )
    34.3 ( 1.68 )
    33.8 ( 2.49 )
    34.0 ( 2.19 )
    34.8 ( 1.6 )
    No statistical analyses for this end point

    Secondary: Apgar Score in the Baby

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    End point title
    		 Apgar Score in the Baby
    End point description
    Apgar score in the baby (Appearance; Pulse; Grimace response; Activity; Respiration). Range 0 to 10 where high scores are good and low scores are bad.
    End point type
    Secondary
    End point timeframe
    1, 5 and 10 minutes
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    61
    59
    59
    60
    30
    Units: Score on a scale
    arithmetic mean (standard deviation)
        APGAR score at 1 minute
    8.8 ( 1.39 )
    9.0 ( 0.91 )
    8.8 ( 1.00 )
    8.9 ( 1.38 )
    8.8 ( 1.22 )
        APGAR score at 5 minutes
    9.7 ( 1.34 )
    9.8 ( 0.54 )
    9.8 ( 0.60 )
    9.9 ( 0.32 )
    9.8 ( 0.62 )
        APGAR score at 10 minutes
    9.9 ( 0.29 )
    9.9 ( 0.28 )
    9.9 ( 0.33 )
    9.9 ( 0.29 )
    10.0 ( 0.00 )
    No statistical analyses for this end point

    Secondary: Concentrations of IgG Antibodies Specific to the AlpN Proteins in μg/mL in Maternal Blood

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    End point title
    		 Concentrations of IgG Antibodies Specific to the AlpN Proteins in μg/mL in Maternal Blood
    End point description
    Concentrations of IgG Antibodies Specific to the AlpN Proteins in μg/mL in Maternal Blood
    End point type
    Secondary
    End point timeframe
    Delviery
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    58 [7]
    52 [8]
    54 [9]
    55 [10]
    27 [11]
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Alp1N
    40.57 ( 271 )
    15.81 ( 295.1 )
    32.91 ( 322.2 )
    12.38 ( 604.4 )
    1.03 ( 85.3 )
        Alp2N
    61.69 ( 384.9 )
    32.74 ( 275.1 )
    39.54 ( 239.9 )
    18.96 ( 491.4 )
    1.02 ( 95.9 )
        AlpCN
    48.11 ( 314.7 )
    25.17 ( 328.6 )
    27.53 ( 332.7 )
    16.38 ( 482.6 )
    1.10 ( 86.4 )
        RibN
    25.55 ( 323.2 )
    10.97 ( 305.5 )
    20.08 ( 473.4 )
    8.68 ( 614.4 )
    0.92 ( 74.4 )
    Notes
    [7] - Alp1N 56, Alp2N 56, AlpCN 58, RibN 56
    [8] - Alp1N 48, Alp2N 45, AlpCN 52, RibN 51
    [9] - Alp1N 54, Alp2N 49, AlpCN 54, RibN 52
    [10] - Alp1N 52, Alp2N 47, AlpCN 51, RibN 55
    [11] - Alp1N 27, Alp2N 28, AlpCN 27, RibN 23
    No statistical analyses for this end point

    Secondary: Concentrations of IgG Antibodies Specific to the AlpN Proteins in μg/mL in Blood From Each Baby

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    End point title
    		 Concentrations of IgG Antibodies Specific to the AlpN Proteins in μg/mL in Blood From Each Baby
    End point description
    1 month, 3 months
    End point type
    Secondary
    End point timeframe
    Concentrations of IgG Antibodies Specific to the AlpN Proteins in μg/mL in Blood From Each Baby
    End point values
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Number of subjects analysed
    58 [12]
    54 [13]
    52 [14]
    60 [15]
    30 [16]
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Alp1N: At 1 month of age
    5.60 ( 423.9 )
    3.23 ( 193.4 )
    6.43 ( 117.4 )
    1.42 ( 1441.5 )
    0.05 ( 316.9 )
        Alp1N: At 3 month of age
    1.84 ( 361.9 )
    1.39 ( 155.6 )
    2.00 ( 161.1 )
    0.58 ( 455.4 )
    0.03 ( 106.4 )
        Alp2N: At 1 month of age
    4.62 ( 348.2 )
    3.22 ( 274.4 )
    3.5585 ( 250.2 )
    1.42 ( 712.5 )
    0.05 ( 384.8 )
        Alp2N: At 3 month of age
    1.69 ( 268.7 )
    1.14 ( 251.3 )
    1.19 ( 244.8 )
    0.60 ( 505 )
    0.02 ( 111.8 )
        AlpCN: At 1 month of age
    5.27 ( 431.2 )
    3.94 ( 257.3 )
    4.1634 ( 398.7 )
    1.37 ( 1359.0 )
    0.07 ( 335.5 )
        AlpCN: At 3 month of age
    1.73 ( 354.3 )
    1.36 ( 301.0 )
    1.54 ( 217.4 )
    0.58 ( 431.9 )
    0.04 ( 116 )
        RibN: At 1 month of age
    2.48 ( 249.1 )
    1.37 ( 233 )
    2.20 ( 221.3 )
    0.64 ( 769.9 )
    0.05 ( 212 )
        RibN: At 3 month of age
    0.78 ( 282.2 )
    0.54 ( 223.2 )
    0.77 ( 230.4 )
    0.25 ( 354.7 )
    0.03 ( 85.7 )
    Notes
    [12] - 55, 58, 51, 50, 55, 58, 55, 58 respectively
    [13] - 54, 51, 51, 44, 53, 51, 54, 51 respectively
    [14] - 49, 52, 46, 46, 51, 52, 51, 52 respectively
    [15] - 51, 48, 49, 40, 51, 48, 51, 48 respecitvely
    [16] - 27, 28, 28, 28, 28, 28, 28, 28
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    TAES in the mother were assessed from the time of informed consent sign-off until Day 84 (Visit 7). From delivery (Visit 8) onwards, only Medically attended adverse events (MAAEs), Adverse events of special interest (AESIs) and SAEs were assessed.
    Adverse event reporting additional description
    Solicited local and systemic reactions were collected in electronic diaries up to 7 days following each administered vaccination. In addition, other AEs, i.e., unsolicited AEs, including MAAEs, SAEs, concomitant medication or vaccines were to be recorded in the electronic diary.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Group 1: 4 week dose interval; 2 doses
    Reporting group description
    		 Participants received one injection of placebo at 22 (±1) weeks GA (gestational age), one injection of GBS-NN/NN2 at 26 (±1) weeks GA and one injection of GBS- NN/NN2 at 30 (±1) weeks GA

    Reporting group title
    Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses
    Reporting group description
    		 Participants received one injection of GBS-NN/NN2 at 22 (±1) weeks GA, one injection of GBS-NN/NN2 at 26 (±1) weeks GA and one injection of placebo at 30 (±1) weeks GA

    Reporting group title
    Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses
    Reporting group description
    		 Participants received one injection of GBS-NN/NN2 at 22 (±1) weeks GA, one injection of placebo at 26 (±1) weeks GA and one injection of GBS- NN/NN2 at 30 (±1) weeks GA

    Reporting group title
    Group 4: Single Dose
    Reporting group description
    		 Participants received one injection of placebo at 22 (±1) weeks GA, one injection of GBS-NN/NN2 at 26 (±1) weeks GA, and one injection of placebo at 30 (±1) weeks GA.

    Reporting group title
    Group 5: Placebo
    Reporting group description
    		 Participants received one injection of placebo at 22, 26 and 30 weeks (±1) GA

    Serious adverse events
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    23 / 61 (37.70%)
    12 / 59 (20.34%)
    20 / 59 (33.90%)
    25 / 60 (41.67%)
    14 / 30 (46.67%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    2 / 59 (3.39%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Artificial rupture of membranes
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abortion threatened
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amniorrhoea
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cephalo-pelvic disproportion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Failed induction of labour
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    False labour
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    2 / 59 (3.39%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foetal growth restriction
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 59 (1.69%)
    1 / 59 (1.69%)
    4 / 60 (6.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foetal death
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 59 (1.69%)
    1 / 59 (1.69%)
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foetal distress syndrome
         subjects affected / exposed
    8 / 61 (13.11%)
    2 / 59 (3.39%)
    5 / 59 (8.47%)
    12 / 60 (20.00%)
    7 / 30 (23.33%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
    0 / 5
    0 / 12
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foetal hypokinesia
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 59 (3.39%)
    0 / 59 (0.00%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foetal macrosomia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foetal vascular malperfusion
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gestational hypertension
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 59 (1.69%)
    4 / 59 (6.78%)
    4 / 60 (6.67%)
    3 / 30 (10.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 4
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gestational diabetes
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HELLP syndrome
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage in pregnancy
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intrapartum haemorrhage
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large for dates baby
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meconium in amniotic fluid
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oligohydramnios
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Placenta praevia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Placental insufficiency
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postpartum haemorrhage
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 59 (3.39%)
    0 / 59 (0.00%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pre-eclampsia
         subjects affected / exposed
    3 / 61 (4.92%)
    3 / 59 (5.08%)
    2 / 59 (3.39%)
    4 / 60 (6.67%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 2
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Premature delivery
         subjects affected / exposed
    1 / 61 (1.64%)
    3 / 59 (5.08%)
    2 / 59 (3.39%)
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Premature labour
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 59 (3.39%)
    0 / 59 (0.00%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Premature rupture of membranes
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Premature separation of placenta
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prolonged labour
         subjects affected / exposed
    3 / 61 (4.92%)
    1 / 59 (1.69%)
    3 / 59 (5.08%)
    3 / 60 (5.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 3
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prolonged pregnancy
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prolonged rupture of membranes
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroplacental haematoma
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine hypotonus
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal discharge
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Foetal monitoring abnormal
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Perineal injury
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Bradycardia foetal
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastritis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Amniotic cavity infection
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 59 (1.69%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial vaginosis
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Beta haemolytic streptococcal infection
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometritis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia infection
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postpartum sepsis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 59 (1.69%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 59 (6.78%)
    5 / 59 (8.47%)
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 5
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Group 1: 4 week dose interval; 2 doses Group 2: Early Intervention; 4 Week Dose Interval; 2 Doses Group 3: Early Intervention; 8 Week Dose Interval; 2 Doses Group 4: Single Dose Group 5: Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    56 / 61 (91.80%)
    54 / 59 (91.53%)
    57 / 59 (96.61%)
    56 / 60 (93.33%)
    26 / 30 (86.67%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 61 (3.28%)
    3 / 59 (5.08%)
    1 / 59 (1.69%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    2
    3
    2
    1
    0
    Blood pressure increased
         subjects affected / exposed
    3 / 61 (4.92%)
    2 / 59 (3.39%)
    4 / 59 (6.78%)
    1 / 60 (1.67%)
    2 / 30 (6.67%)
         occurrences all number
    3
    3
    4
    1
    2
    C-reactive protein increased
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 59 (3.39%)
    0 / 59 (0.00%)
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    0
    2
    0
    3
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 59 (0.00%)
    4 / 59 (6.78%)
    1 / 60 (1.67%)
    3 / 30 (10.00%)
         occurrences all number
    2
    0
    5
    2
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 61 (3.28%)
    3 / 59 (5.08%)
    0 / 59 (0.00%)
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    2
    3
    0
    2
    0
    Headache
         subjects affected / exposed
    8 / 61 (13.11%)
    7 / 59 (11.86%)
    5 / 59 (8.47%)
    4 / 60 (6.67%)
    4 / 30 (13.33%)
         occurrences all number
    8
    9
    5
    4
    8
    Pregnancy, puerperium and perinatal conditions
    Foetal hypokinesia
         subjects affected / exposed
    4 / 61 (6.56%)
    4 / 59 (6.78%)
    7 / 59 (11.86%)
    2 / 60 (3.33%)
    3 / 30 (10.00%)
         occurrences all number
    5
    6
    7
    4
    3
    Gestational hypertension
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 59 (3.39%)
    4 / 59 (6.78%)
    1 / 60 (1.67%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    4
    1
    2
    Prolonged pregnancy
         subjects affected / exposed
    1 / 61 (1.64%)
    3 / 59 (5.08%)
    1 / 59 (1.69%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    1
    3
    1
    0
    0
    Uterine contractions during pregnancy
         subjects affected / exposed
    4 / 61 (6.56%)
    1 / 59 (1.69%)
    1 / 59 (1.69%)
    3 / 60 (5.00%)
    1 / 30 (3.33%)
         occurrences all number
    4
    1
    2
    4
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 61 (4.92%)
    4 / 59 (6.78%)
    3 / 59 (5.08%)
    2 / 60 (3.33%)
    3 / 30 (10.00%)
         occurrences all number
    3
    4
    3
    2
    3
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 59 (6.78%)
    0 / 59 (0.00%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    1
    4
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    3 / 59 (5.08%)
    2 / 60 (3.33%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    3
    2
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    3 / 59 (5.08%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 61 (0.00%)
    0 / 59 (0.00%)
    4 / 59 (6.78%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    0
    0
    4
    1
    0
    Diarrhoea
         subjects affected / exposed
    6 / 61 (9.84%)
    2 / 59 (3.39%)
    2 / 59 (3.39%)
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    7
    2
    2
    2
    1
    Dyspepsia
         subjects affected / exposed
    2 / 61 (3.28%)
    4 / 59 (6.78%)
    6 / 59 (10.17%)
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    2
    5
    6
    3
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    2 / 59 (3.39%)
    2 / 60 (3.33%)
    3 / 30 (10.00%)
         occurrences all number
    1
    0
    2
    2
    3
    Nausea
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    1 / 59 (1.69%)
    1 / 60 (1.67%)
    2 / 30 (6.67%)
         occurrences all number
    1
    0
    1
    1
    2
    Vomiting
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 59 (1.69%)
    3 / 59 (5.08%)
    1 / 60 (1.67%)
    1 / 30 (3.33%)
         occurrences all number
    1
    1
    3
    1
    1
    Reproductive system and breast disorders
    Vaginal discharge
         subjects affected / exposed
    5 / 61 (8.20%)
    5 / 59 (8.47%)
    3 / 59 (5.08%)
    4 / 60 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    6
    5
    5
    4
    3
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 59 (0.00%)
    4 / 59 (6.78%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    4
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    3 / 61 (4.92%)
    1 / 59 (1.69%)
    4 / 59 (6.78%)
    0 / 60 (0.00%)
    1 / 30 (3.33%)
         occurrences all number
    3
    1
    5
    0
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 59 (1.69%)
    3 / 59 (5.08%)
    1 / 60 (1.67%)
    0 / 30 (0.00%)
         occurrences all number
    0
    1
    3
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 61 (3.28%)
    1 / 59 (1.69%)
    3 / 59 (5.08%)
    0 / 60 (0.00%)
    4 / 30 (13.33%)
         occurrences all number
    2
    1
    5
    0
    4
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 61 (1.64%)
    4 / 59 (6.78%)
    1 / 59 (1.69%)
    2 / 60 (3.33%)
    1 / 30 (3.33%)
         occurrences all number
    1
    5
    1
    3
    1
    Streptococcal urinary tract infection
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 59 (3.39%)
    3 / 59 (5.08%)
    0 / 60 (0.00%)
    0 / 30 (0.00%)
         occurrences all number
    0
    2
    3
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    9 / 61 (14.75%)
    5 / 59 (8.47%)
    9 / 59 (15.25%)
    6 / 60 (10.00%)
    5 / 30 (16.67%)
         occurrences all number
    10
    5
    9
    7
    6
    Urinary tract infection
         subjects affected / exposed
    15 / 61 (24.59%)
    13 / 59 (22.03%)
    8 / 59 (13.56%)
    14 / 60 (23.33%)
    7 / 30 (23.33%)
         occurrences all number
    17
    16
    9
    16
    8
    Vulvovaginal candidiasis
         subjects affected / exposed
    3 / 61 (4.92%)
    2 / 59 (3.39%)
    2 / 59 (3.39%)
    6 / 60 (10.00%)
    3 / 30 (10.00%)
         occurrences all number
    3
    3
    2
    6
    3

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Sep 2021
    MVX0004 Protocol Version 2.0 This protocol update was issued prior to study start to include a new investigational site in the UK (Site 4). In addition, the following main changes were made: • Addition of exclusion criterion #24 “The pregnancy was considered high risk by treating physicians” based on regulatory authority feedback. • Clarification of procedures for maintaining the blind during injections of vaccine/placebo, based on regulatory authority feedback. • Clarification that MAAEs, AESIs, SAEs and related concomitant medications were to be recorded for mothers and infants throughout the study until 6 months after delivery and that this would be checked 28 days post each vaccination, based on regulatory authority feedback. • Clarification that the investigational vaccine would be assembled either by the site pharmacy or by unblinded trained nursing staff. • Clarification of the randomisation procedure • Clarification of assessments of laboratory values indicating “liver injury”, including seriousness criteria. • Specification of the use of the FDA toxicity grading scale based on regulatory authority feedback. • Inclusion of safety monitoring by the DSMB based on regulatory authority feedback. • Clarification and change in wording of halting rules for the study based on regulatory authority feedback. • Specification of the “Estimand”.
    21 Nov 2021
    MVX0004 Protocol Version 3.0 This protocol update was issued prior to study start. The main changes were as follows based on regulatory authority feedback: • Ensure safety laboratory testing within 28 days pre-vaccination(s), and within 3-5 days post vaccination(s). • Update of the amount of blood taken from mothers up to 215 mL, due to implementation of the extra safety blood tests. • Clarification and change in wording of halting rules for the study based on regulatory authority feedback.
    08 Apr 2022
    This protocol update was issued after study start. The main changes were as follows: • Update of the time window for vital signs, urinalysis, immunogenicity blood sample and collection of breast milk (colostrum) sample from maternal participants from within 48 hours to within 72 hours of delivery to better comply with clinical practice. The samechange was made for the immunogenicity blood sample for infant participants. • Inclusion of South Africa as study country to ensure recruitment. • Revision of the GA for the vaccination schedule to clarify the intended dose regimens and avoid misinterpretations of the visit windows in the study schedule. • Update of the time window for participant inclusion to reflect the intended dose regimen as the first dose administered during GA 22 (22+0 – 22+6) ± 1 week. • Revision of the visit windows to allow increased flexibility in visit windows
    14 Apr 2023
    This protocol update was issued after study start to include an interim analysis of study data for the primary and key secondary endpoints available up to 72 hours after delivery (Visit 8). This analysis was added to inform decisions on the design of a long-term follow-up study as well as the vaccination regimens to be administered in Phase III studies. Interim analysis of these data would allow to advance the clinical development plan for the GBS-NN/NN2 vaccine and was expected to address the unmet medical need for GBS vaccination during pregnancy.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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