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    Clinical Trial Results:
    A phase 3 open-label study to evaluate the immunogenicity and safety of a mixed (HEXA/PENTA/HEXA) primary series schedule that includes V419 (PR5I) at 2 and 6 months of age and Pediacel at 4 months of age.

    Summary
    EudraCT number
    2012-004221-25
    Trial protocol
    ES  
    Global end of trial date
    19 Mar 2014

    Results information
    Results version number
    v2(current)
    This version publication date
    01 Jun 2019
    First version publication date
    27 May 2015
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    V419-010
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01839188
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Merck Protocol Number: V419-010, MCMVaccBV Protocol ID: PRI02C
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Mar 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Mar 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the immune response and the safety of a primary series schedule that includes V419 (PR5I) at 2 and 6 months of age and Pediacel at 4 months of age. Primary objectives of this study were 1) to demonstrate that the mixed schedule induces acceptable responses for Hepatitis B (HB) one month after completion of the mixed schedule; and 2) to demonstrate that the mixed schedule induces acceptable responses for Haemophilus influenza type b (Hib) one month after completion of the mixed schedule. Secondary objectives of this study were: 1) to describe the antibody response to all PR5I antigens one month after completion of the mixed schedule; 2) to describe the antibody response to meningococcal serogroup C (MCC) conjugate vaccine one month after the second dose of MenC vaccine; and 3) to describe the safety profile after each dose of study vaccines administered.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research. The following additional measures defined for this individual study were in place for the protection of trial subjects: Subjects in the study received the study vaccines (PR5I and Pediacel®) in line with the recommended infant immunisation schedule in Spain, and the immunisation schedule was consistent with other paediatric vaccines routinely given at the same age. NeisVac-C®, Prevenar 13®, and RotaTeq® were administered in accordance with their respective Summary of Product Characteristics. Subjects with allergy to any of the vaccine components or history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines (including concomitants) were not vaccinated. Vaccines were administered by qualified study personnel. After each vaccination, subjects were kept under observation for 30 minutes to ensure their safety. Adequate treatment provisions, including epinephrine, were available for immediate use, should an anaphylactic or anaphylactoid reaction occur.
    Background therapy
    Infants were previously vaccinated with only 1 dose of monovalent Hepatitis B vaccine, within the 3 days after birth, outside of the study context.
    Evidence for comparator
    -
    Actual start date of recruitment
    01 May 2013
    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
    Spain: 385
    Worldwide total number of subjects
    385
    EEA total number of subjects
    385
    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)
    385
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study enrolled N=385 infant participants previously vaccinated with only 1 dose of monovalent Hepatitis B vaccine, within 3 days after birth, outside of study context.

    Pre-assignment
    Screening details
    Participants progressed through the study as a single group, with all participants receiving the same mixed-schedule vaccination series. Vaccination (V1) was administered on Study Day 0 (2 months of age), with V2 (4 months of age) and V3 (6 months of age) administered at Study Months 2 and 4, respectively.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Arm description
    [Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by intramuscular (IM) injection + oral RotaTeq®, given at 2 months of age. [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age. [Vaccination 3]: Single dose of PR5I (V419) by IM injection + oral RotaTeq®, given at 6 months of age.
    Arm type
    Experimental

    Investigational medicinal product name
    PR5I
    Investigational medicinal product code
    Other name
    V419; Vaxelis®; DTaP-HBIPV-Hib
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hexavalent PR5I vaccine (DTaPHB-IPV-Hib = Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed [DTaP], Hepatitis B [HB; Recombinant DNA], Inactivated Poliovirus [IPV], and Haemophilus influenzae type b [Hib] conjugate vaccine [adsorbed]) at 0.5 mL for IM injection (left upper thigh) at 2 and 6 months of age.

    Investigational medicinal product name
    Pediacel®
    Investigational medicinal product code
    Other name
    DTaP-IPV-Hib
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Pentavalent Pediacel® vaccine (DTaPIPV-Hib = Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed [DTaP], Inactivated Poliovirus [IPV], and Haemophilus influenzae type b [Hib] conjugate vaccine [adsorbed]) at 0.5 mL for IM injection (left upper thigh) at 4 months of age.

    Investigational medicinal product name
    RotaTeq®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution in single-dose container
    Routes of administration
    Intramuscular use, Oral use
    Dosage and administration details
    Human-bovine rotavirus reassortants (live) vaccine 2 mL oral administration at 2, 4 and 6 months of age. RotaTeq® administered prior to any other vaccine administration to avoid having the infant participants spit up the RotaTeq® when crying.

    Investigational medicinal product name
    NeisVac-C®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Meningococcal group C (MCC) polysaccharide conjugate vaccine (adsorbed) at 0.5 mL for IM injection (right upper thigh) at 2 and 4 months of age.

    Investigational medicinal product name
    Prevenar 13®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Pneumococcal polysaccharide conjugate vaccine [PCV; 13-valent, adsorbed]) at 0.5 mL for IM injection (right upper thigh) at 2 and 4 months of age.

    Number of subjects in period 1
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Started
    385
    Treated
    385
    Completed
    384
    Not completed
    1
         Consent withdrawn by subject
             1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Reporting group description
    [Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by intramuscular (IM) injection + oral RotaTeq®, given at 2 months of age. [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age. [Vaccination 3]: Single dose of PR5I (V419) by IM injection + oral RotaTeq®, given at 6 months of age.

    Reporting group values
    PR5I (V1); Pediacel® (V2); PR5I (V3) Total
    Number of subjects
    385 385
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    385 385
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    0 0
        From 65-84 years
    0 0
        85 years and over
    0 0
    Age Continuous
    Units: Days
        arithmetic mean (standard deviation)
    60.72 ± 7.75 -
    Sex: Female, Male
    Units: Subjects
        Female
    199 199
        Male
    186 186
    Body Weight
    Units: kg
        arithmetic mean (standard deviation)
    5.14 ± 0.59 -
    Subject analysis sets

    Subject analysis set title
    PR5I (V1)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    [Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 2 months of age.

    Subject analysis set title
    Pediacel® (V2)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age.

    Subject analysis set title
    PR5I (V3)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    [Vaccination 3]: Single dose of PR5I (V419) by IM injection + oral RotaTeq®, given at 6 months of age.

    Subject analysis set title
    PR5I (V1)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    [Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 2 months of age.

    Subject analysis set title
    Pediacel® (V2)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age.

    Subject analysis set title
    PR5I (V3)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    [Vaccination 3]: Single dose of PR5I (V419) by IM injection + oral RotaTeq®, given at 6 months of age.

    Subject analysis set title
    PR5I (V1); Pediacel® (V2)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    [Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by intramuscular (IM) injection + oral RotaTeq®, given at 2 months of age. [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age.

    Subject analysis sets values
    PR5I (V1) Pediacel® (V2) PR5I (V3) PR5I (V1) Pediacel® (V2) PR5I (V3) PR5I (V1); Pediacel® (V2)
    Number of subjects
    384
    383
    383
    385
    385
    384
    385
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: Days
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    Sex: Female, Male
    Units: Subjects
        Female
        Male
    Body Weight
    Units: kg
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    ±
    ±
    ±
    ±

    End points

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    End points reporting groups
    Reporting group title
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Reporting group description
    [Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by intramuscular (IM) injection + oral RotaTeq®, given at 2 months of age. [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age. [Vaccination 3]: Single dose of PR5I (V419) by IM injection + oral RotaTeq®, given at 6 months of age.

    Subject analysis set title
    PR5I (V1)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    [Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 2 months of age.

    Subject analysis set title
    Pediacel® (V2)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age.

    Subject analysis set title
    PR5I (V3)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    [Vaccination 3]: Single dose of PR5I (V419) by IM injection + oral RotaTeq®, given at 6 months of age.

    Subject analysis set title
    PR5I (V1)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    [Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 2 months of age.

    Subject analysis set title
    Pediacel® (V2)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age.

    Subject analysis set title
    PR5I (V3)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    [Vaccination 3]: Single dose of PR5I (V419) by IM injection + oral RotaTeq®, given at 6 months of age.

    Subject analysis set title
    PR5I (V1); Pediacel® (V2)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    [Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by intramuscular (IM) injection + oral RotaTeq®, given at 2 months of age. [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age.

    Primary: Percentage of Participants with an Anti-Hepatitis B Surface Antigen (HBsAg) Antibody Titer ≥ 10 mIU/mL

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    End point title
    Percentage of Participants with an Anti-Hepatitis B Surface Antigen (HBsAg) Antibody Titer ≥ 10 mIU/mL [1]
    End point description
    The percentage of participants with an anti-HBsAg antibody titer ≥ 10 mill-International Units/mL (mIU/mL) was assessed. Participant serum samples were collected for analysis with an enhanced chemiluminescence assay to determine the concentration of antibodies to HBsAg. Analysis Population: all participants receiving ≥ 1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Primary
    End point timeframe
    Month 5 (one month after receiving Vaccination 3)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This is a single arm study, subjects were all enrolled in the same treatment group. The success of the study required that the primary objective was achieved for both Hepatitis B and PRP. For Hepatitis B, the immune response to PR5I vaccine was considered as acceptable if the lower bound of the 2-sided 95% CI of the % of subjects with anti-HBs titre ≥10 mIU/mL one month after the third dose of the mixed schedule was greater than 90%.
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    369
    Units: Percentage of Participants
        number (confidence interval 95%)
    98.9 (97.2 to 99.7)
    No statistical analyses for this end point

    Primary: Percentage of Participants with an Anti-Polyribosylribitol Phosphate (PRP) Antibody Titer ≥ 0.15 µg/mL

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    End point title
    Percentage of Participants with an Anti-Polyribosylribitol Phosphate (PRP) Antibody Titer ≥ 0.15 µg/mL [2]
    End point description
    The percentage of participants with an anti-Polyribosylribitol Phosphate (PRP) antibody titer ≥ 0.15 µg/mL was assessed. Participant serum samples were collected for analysis by radioimmunoassay to determine the concentration of antibodies to PRP, a Haemophilus influenzae type b (Hib) capsular polysaccharide. Analysis Population: all participants receiving ≥ 1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Primary
    End point timeframe
    Month 5 (one month after receiving Vaccination 3)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This is a single arm study, subjects were all enrolled in the same treatment group. The success of the study required that the primary objective was achieved for both Hepatitis B and PRP. For Hib (PRP), the immune response to PR5I vaccine was considered as acceptable if the lower bound of the 2-sided 95% CI of the % of subjects with anti-PRP titre ≥0.15 μg/mL one month after the third dose of the mixed schedule was greater than 80%.
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    365
    Units: Percentage of Participants
        number (confidence interval 95%)
    100.0 (99.0 to 100.0)
    No statistical analyses for this end point

    Secondary: Geometric Mean Concentration of Antibodies to Hepatitis B Surface Antigen (HBsAg)

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    End point title
    Geometric Mean Concentration of Antibodies to Hepatitis B Surface Antigen (HBsAg)
    End point description
    Participant serum samples were collected for analysis with an enhanced chemiluminescence assay to determine the geometric mean concentration of antibodies to Hepatitis B Surface Antigen (HBsAg). The unit of measure is milli International Units/mL (mIU/mL). Analysis Population: all participants receiving ≥1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Secondary
    End point timeframe
    Month 5 (one month after receiving Vaccination 3)
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    369
    Units: mIU/mL
        geometric mean (confidence interval 95%)
    1054.97 (911.49 to 1221.03)
    No statistical analyses for this end point

    Secondary: Geometric Mean Concentration of Antibodies to Polyribosylribitol Phosphate (PRP) Antigen

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    End point title
    Geometric Mean Concentration of Antibodies to Polyribosylribitol Phosphate (PRP) Antigen
    End point description
    Participant serum samples were collected for analysis by radioimmunoassay (RIA) to determine the geometric mean concentration of antibodies to polyribosylribitol phosphate (PRP), a Haemophilus influenzae type b (Hib) capsular polysaccharide. Analysis Population: all participants receiving ≥1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Secondary
    End point timeframe
    Month 5 (one month after receiving Vaccination 3)
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    365
    Units: μg/mL
        geometric mean (confidence interval 95%)
    8.00 (7.17 to 8.93)
    No statistical analyses for this end point

    Secondary: Geometric Mean Concentration of Antibodies to Diphtheria Toxin

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    End point title
    Geometric Mean Concentration of Antibodies to Diphtheria Toxin
    End point description
    Participant serum samples were collected for analysis with a Micrometabolic Inhibition Test (MIT) to determine the geometric mean concentration of neutralizing antibodies to diphtheria toxin. The unit of measure is International Units/mL (IU/mL). Analysis Population: all participants receiving ≥1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Secondary
    End point timeframe
    Month 5 (one month after receiving Vaccination 3)
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    359
    Units: IU/mL
        geometric mean (confidence interval 95%)
    0.47 (0.42 to 0.52)
    No statistical analyses for this end point

    Secondary: Geometric Mean Concentration of Antibodies to Tetanus Toxin

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    End point title
    Geometric Mean Concentration of Antibodies to Tetanus Toxin
    End point description
    Participant serum samples were collected for analysis by Enzyme-linked Immunosorbent Assay (ELISA) to determine the geometric mean concentration of antibodies to tetanus toxin. The unit of measure is International Units/mL (IU/mL). Analysis Population: all participants receiving ≥1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Secondary
    End point timeframe
    Month 5 (one month after receiving Vaccination 3)
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    350
    Units: IU/mL
        geometric mean (confidence interval 95%)
    2.44 (2.31 to 2.59)
    No statistical analyses for this end point

    Secondary: Geometric Mean Concentrations of Antibodies to Pertussis Antigens

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    End point title
    Geometric Mean Concentrations of Antibodies to Pertussis Antigens
    End point description
    Participant serum samples were collected for analysis by ELISA to determine the geometric mean concentration of antibodies (Abs) to the following Pertussis antigens: pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and fimbriae types (FIM) 2&3. The unit of measure is ELISA Units/mL (EU/mL). Analysis Population: all participants receiving ≥1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Secondary
    End point timeframe
    Month 5 (one month after receiving Vaccination 3)
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    349
    Units: EU/mL
    geometric mean (confidence interval 95%)
        Anti-PT Abs
    107.46 (101.55 to 113.71)
        Anti-FHA Abs
    67.09 (62.38 to 72.15)
        Anti-PRN Abs
    56.46 (51.60 to 61.78)
        Anti-FIM 2&3 Abs
    360.99 (332.58 to 391.82)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers for Antibodies to Inactivated Poliovirus 1-3 (IPV1-3)

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    End point title
    Geometric Mean Titers for Antibodies to Inactivated Poliovirus 1-3 (IPV1-3)
    End point description
    Participant serum samples were collected for analysis with a Micrometabolic Inhibition Test (MIT) to determine the geometric mean titer of neutralizing antibodies (Abs) to Inactivated Poliovirus 1, 2, & 3 (IPV1, IPV2, & IPV3). The unit of measure is titer, expressed as the reciprocal dilution of the highest dilution that neutralizes 50% of the challenge virus. Analysis Population: all participants receiving ≥1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Secondary
    End point timeframe
    Month 5 (one month after receiving Vaccination 3)
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    356
    Units: Titer
    geometric mean (confidence interval 95%)
        Anti-IPV1 Abs
    663.97 (588.10 to 749.62)
        Anti-IPV2 Abs
    1198.93 (1051.90 to 1366.51)
        Anti-IPV3 Abs
    764.64 (664.70 to 879.61)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Responding to Polyribosylribitol Phosphate (PRP) Antigen, Diptheria Toxin (D), Tetanus Toxin (T), and Inactivated Poliovirus 1, 2, & 3 (IPV1, IPV2, & IPV3)

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    End point title
    Percentage of Participants Responding to Polyribosylribitol Phosphate (PRP) Antigen, Diptheria Toxin (D), Tetanus Toxin (T), and Inactivated Poliovirus 1, 2, & 3 (IPV1, IPV2, & IPV3)
    End point description
    Participants were considered as responding if the observed concentration or titer for antibodies (Abs) to specific antigens exceeded the following thresholds: 1) For anti-PRP Abs (Hib capsular polysaccharide) – Response defined as a concentration ≥1 µg/mL (measured by RIA); 2) For anti-D Abs – Response defined at 2 concentrations: ≥0.01 IU/mL and ≥0.10 IU/mL (measured by MIT); 3) For anti-T Abs – Response defined at 2 concentrations: ≥0.01 IU/mL and ≥0.10 IU/mL (measured by ELISA); 4) For anti-IPV1, anti-IPV2, and anti-IPV3 Abs – Response defined as a titer ≥ 8 (measured by MIT). The percentage of participants considered as responding to the individual antigen (per the response threshold[s]) were assessed. Analysis Population: All participants receiving ≥1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Secondary
    End point timeframe
    Month 5 (one month after receiving Vaccination 3)
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    370
    Units: Percentage of Participants
    number (confidence interval 95%)
        Anti-PRP Ab ≥ 1 μg/mL
    95.3 (92.6 to 97.3)
        Anti-Diptheria Ab ≥0.01 IU/mL
    100.0 (99.0 to 100.0)
        Anti-Diptheria Ab ≥0.10 IU/mL
    92.2 (88.9 to 94.8)
        Anti-Tetanus ≥0.01 IU/mL
    100.0 (99.0 to 100.0)
        Anti-Tetanus Ab ≥0.10 IU/mL
    100.0 (99.0 to 100.0)
        Anti-IPV1 Ab Titer ≥8
    100.0 (99.0 to 100.0)
        Anti-IPV2 Ab Titer ≥8
    100.0 (99.0 to 100.0)
        Anti-IPV3 Ab Titer ≥8
    100.0 (99.0 to 100.0)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titer of Anti-Meningococcal Group C Polysaccharide Conjugate (MCC) Antibodies

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    End point title
    Geometric Mean Titer of Anti-Meningococcal Group C Polysaccharide Conjugate (MCC) Antibodies
    End point description
    Participant serum samples were collected to determine the geometric mean titer of anti-MCC antibodies, measured by the Serum Bactericidal Antibody assay using rabbit complement (rSBA). The unit of measure is titer, expressed as the reciprocal of the final serum dilution giving ≥50% killing of the challenge bacterial strain. Analysis Population: all participants receiving ≥1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Secondary
    End point timeframe
    Month 3 (one month after receiving Vaccination 2)
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    375
    Units: Titer
        geometric mean (confidence interval 95%)
    739.63 (659.94 to 828.96)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an Anti-Meningococcal Group C Polysaccharide Conjugate (MCC) Antibody Titer ≥ 8

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    End point title
    Percentage of Participants with an Anti-Meningococcal Group C Polysaccharide Conjugate (MCC) Antibody Titer ≥ 8
    End point description
    The percentage of participants with an anti-MCC antibody titer ≥ 8 was assessed. Participant serum samples were collected and analyzed for anti-MCC antibodies with the Serum Bactericidal Antibody assay using rabbit complement (rSBA). Analysis Population: all participants receiving ≥ 1 dose of study vaccination without protocol deviation, having post-vaccination immunogenicity data available for the evaluation of the respective analysis endpoint.
    End point type
    Secondary
    End point timeframe
    Month 3 (one month after receiving Vaccination 2)
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    375
    Units: Percentage of Participants
        number (confidence interval 95%)
    99.2 (97.7 to 99.8)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Body Temperature ≥ 38°C after Each Vaccination

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    End point title
    Percentage of Participants with a Body Temperature ≥ 38°C after Each Vaccination
    End point description
    The percentage of participants with a body temperature ≥ 38.0°C from Day 1 to Day 5 after each vaccination was assessed. Per protocol, the participant’s parent(s)/legal representative recorded daily body temperature measurements each evening by the axillary route (N=3 collected via rectal route; N=1 collected via oral route) and recorded these observations on the Vaccine Report Card (VRC). Temperatures were based on actual temperatures recorded with no adjustments for the route of assessment. Analysis Population: all participants receiving ≥ 1 dose of any vaccination with corresponding safety follow-up data, having available body temperature data.
    End point type
    Secondary
    End point timeframe
    Up to Day 5 following each vaccination
    End point values
    PR5I (V1) Pediacel® (V2) PR5I (V3)
    Number of subjects analysed
    384
    383
    383
    Units: Percentage of Participants
        number (not applicable)
    4.9
    6.3
    4.7
    No statistical analyses for this end point

    Secondary: Number of Participants Experiencing a Solicited Injection Site Reaction (ISR) Related to the PR5I/Pediacel® Vaccination

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    End point title
    Number of Participants Experiencing a Solicited Injection Site Reaction (ISR) Related to the PR5I/Pediacel® Vaccination
    End point description
    The number of participants experiencing solicited ISRs related to the PRI5 or Pediacel® vaccination was assessed. Solicited ISRs (erythema, pain and swelling) occurring at the PR5I or Pediacel® injection site were always considered related to the PR5I or Pediacel® vaccine, respectively. All AEs/ISRs were recorded on the VRC by the participant’s parent(s)/legal representative. Data are presented for the number of participants experiencing solicited ISRs up to Day 5 after each vaccination and after any vaccination. Analysis Population: All participants receiving ≥1 dose of PR5I/Pediacel® vaccination with corresponding safety follow-up data after each vaccination (for V1, V2, and V3 arms) and after any vaccination (for overall V1; V2; V3 arm) with PR5I/Pediacel®.
    End point type
    Secondary
    End point timeframe
    Up to Day 5 following each vaccination
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3) PR5I (V1) Pediacel® (V2) PR5I (V3)
    Number of subjects analysed
    385
    385
    385
    384
    Units: Participants
        Injection-site erythema
    136
    81
    65
    69
        Injection-site pain
    200
    152
    97
    93
        Injection-site swelling
    121
    68
    52
    65
    No statistical analyses for this end point

    Secondary: Number of Participants Experiencing a Solicited Injection Site Reaction (ISR) Related to the NeisVac-C® (MCC) Vaccination

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    End point title
    Number of Participants Experiencing a Solicited Injection Site Reaction (ISR) Related to the NeisVac-C® (MCC) Vaccination
    End point description
    The number of participants experiencing solicited ISRs related to the NeisVac-C® (MCC) vaccination was assessed. Solicited ISRs (erythema, pain and swelling) occurring at the NeisVac-C® (MCC) injection site were always considered related to the NeisVac-C® (MCC) vaccine. All AEs/ISRs were recorded on the VRC by the participant’s parent(s)/legal representative. Data are presented for the number of participants experiencing solicited ISRs up to Day 5 after each NeisVac-C® vaccination and after any NeisVac-C® vaccination. Analysis Population: all participants receiving ≥1 dose of NeisVac-C® vaccination with corresponding safety follow-up data after each vaccination (for V1 and V2 arms) and after any vaccination (for V1; V2 arm) with NeisVac-C®.
    End point type
    Secondary
    End point timeframe
    Up to Day 5 following each vaccination
    End point values
    PR5I (V1) Pediacel® (V2) PR5I (V1); Pediacel® (V2)
    Number of subjects analysed
    385
    385
    385
    Units: Participants
        Injection-site erythema
    41
    59
    85
        Injection-site pain
    113
    89
    151
        Injection-site swelling
    34
    42
    66
    No statistical analyses for this end point

    Secondary: Number of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) Related to the PR5I/Pediacel® Vaccination

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    End point title
    Number of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) Related to the PR5I/Pediacel® Vaccination
    End point description
    The number of participants experiencing unsolicited ISRs related to the PRI5 or Pediacel® vaccination was assessed. Unsolicited ISRs occurring at the PR5I or Pediacel® injection site were always considered related to the PR5I or Pediacel® vaccine, respectively. All AEs/ISRs were recorded on the VRC by the participant’s parent(s)/legal representative. Data are presented for the number of participants experiencing unsolicited ISRs up to Day 15 after each vaccination and after any vaccination. Analysis Population: all participants receiving ≥1 dose of PR5I/Pediacel® vaccination with corresponding safety follow-up data after each vaccination (for V1, V2, and V3 arms) and after any vaccination (for overall V1; V2; V3 arm) with PR5I/Pediacel®.
    End point type
    Secondary
    End point timeframe
    Up to Day 15 following each vaccination
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3) PR5I (V1) Pediacel® (V2) PR5I (V3)
    Number of subjects analysed
    385
    385
    385
    384
    Units: Participants
        Injection-site bruising
    1
    1
    0
    0
        Injection-site discomfort
    1
    0
    1
    0
        Injection-site haematoma
    3
    1
    1
    1
        Injection-site haemorrhage
    1
    0
    1
    0
        Injection-site induration
    16
    5
    4
    8
        Injection-site warmth
    1
    1
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) Related to the NeisVac-C® (MCC) Vaccination

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    End point title
    Number of Participants Experiencing an Unsolicited Injection Site Reaction (ISR) Related to the NeisVac-C® (MCC) Vaccination
    End point description
    The number of participants experiencing unsolicited ISRs related to the NeisVac-C® (MCC) vaccination was assessed. Unsolicited ISRs occurring at the NeisVac-C® (MCC) injection site were always considered related to the NeisVac-C® (MCC) vaccine. All AEs/ISRs were recorded on the VRC by the participant’s parent(s)/legal representative. Data are presented for the number of participants experiencing unsolicited ISRs up to Day 15 after each NeisVac-C® vaccination and after any NeisVac-C® vaccination. Analysis Population: all participants receiving ≥1 dose of NeisVac-C® vaccination with corresponding safety follow-up data after each vaccination (for V1 and V2 arms) and after any vaccination (for V1; V2 arm) with NeisVac-C®.
    End point type
    Secondary
    End point timeframe
    Up to Day 15 following each vaccination
    End point values
    PR5I (V1) Pediacel® (V2) PR5I (V1); Pediacel® (V2)
    Number of subjects analysed
    385
    385
    385
    Units: Participants
        Injection-site discolouration
    1
    0
    1
        Injection-site haematoma
    0
    2
    2
        Injection-site induration
    2
    2
    4
    No statistical analyses for this end point

    Secondary: Number of Participants Experiencing a Solicited Systemic Adverse Event (AE)

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    End point title
    Number of Participants Experiencing a Solicited Systemic Adverse Event (AE)
    End point description
    The number of participants experiencing solicited systemic AEs (crying, decreased appetite, irritability, somnolence, pyrexia, and vomiting) was assessed. Each day from Day 1 to Day 5 following each vaccination, the participant’s parent(s)/legal representative recorded all solicited AEs on the VRC. Data are presented for the number of participants experiencing solicited AEs up to Day 5 after each vaccination and after any vaccination. Analysis Population: all participants receiving ≥1 dose of any vaccination with corresponding safety follow-up data after each vaccination (for V1, V2, and V3 arms) and after any vaccination (for overall V1; V2; V3 arm).
    End point type
    Secondary
    End point timeframe
    Up to Day 5 following each vaccination
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3) PR5I (V1) Pediacel® (V2) PR5I (V3)
    Number of subjects analysed
    385
    385
    385
    384
    Units: Participants
        Crying
    255
    188
    131
    102
        Decreased appetite
    195
    141
    88
    76
        Irritability
    268
    196
    154
    119
        Pyrexia
    52
    19
    24
    18
        Somnolence
    229
    184
    126
    84
        Vomiting
    88
    56
    35
    27
    No statistical analyses for this end point

    Secondary: Number of Participants Experiencing an Unsolicited Systemic Adverse Event (AE)

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    End point title
    Number of Participants Experiencing an Unsolicited Systemic Adverse Event (AE)
    End point description
    The number of participants experiencing unsolicited systemic AEs was assessed. Data are presented for the number of participants experiencing unsolicited AEs up to Day 15 after each vaccination and after any vaccination. Analysis Population: all participants receiving ≥1 dose of any vaccination with corresponding safety follow-up data after each vaccination (for V1, V2, and V3 arms) and after any vaccination (for overall V1; V2; V3 arm).
    End point type
    Secondary
    End point timeframe
    Up to Day 15 following each vaccination
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3) PR5I (V1) Pediacel® (V2) PR5I (V3)
    Number of subjects analysed
    385
    385
    385
    384
    Units: Participants
    163
    58
    53
    89
    No statistical analyses for this end point

    Secondary: Number of Participants Experiencing a Serious Adverse Event (SAE)

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    End point title
    Number of Participants Experiencing a Serious Adverse Event (SAE)
    End point description
    An SAE is an adverse event (AE) that: results in death; is life threatening; results in persistent or significant disability or incapacity; results in or prolongs a hospitalization; is a congenital anomaly or birth defect; is a cancer; or may jeopardize the participant, potentially require medical or surgical intervention. Analysis Population: all participants receiving ≥1 dose of study vaccination.
    End point type
    Secondary
    End point timeframe
    Up to ~6 months (at any time during the study)
    End point values
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Number of subjects analysed
    385
    Units: Participants
    12
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to ~6 months (Serious adverse events and deaths were collected for the duration of the study. Solicited ISRs / AEs were collected up to 5 days following each vaccination; unsolicited ISRs / AEs were collected up to 15 days following each vaccination.)
    Adverse event reporting additional description
    Analysis population includes all participants receiving ≥1 dose of study vaccination.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Reporting group description
    [Vaccination 1]: Single doses of PR5I (V419) + NeisVac-C® + Prevenar 13® by intramuscular (IM) injection + oral RotaTeq®, given at 2 months of age. [Vaccination 2]: Single doses of Pediacel® + NeisVac-C® + Prevenar 13® by IM injection + oral RotaTeq®, given at 4 months of age. [Vaccination 3]: Single dose of PR5I (V419) by IM injection + oral RotaTeq®, given at 6 months of age.

    Serious adverse events
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 385 (3.12%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    1 / 385 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 385 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    1 / 385 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Choking
         subjects affected / exposed
    1 / 385 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Bronchiolitis
         subjects affected / exposed
    5 / 385 (1.30%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    1 / 385 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 385 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 385 (0.26%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    PR5I (V1); Pediacel® (V2); PR5I (V3)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    360 / 385 (93.51%)
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    229 / 385 (59.48%)
         occurrences all number
    414
    General disorders and administration site conditions
    Crying
         subjects affected / exposed
    255 / 385 (66.23%)
         occurrences all number
    452
    Injection site erythema
         subjects affected / exposed
    152 / 385 (39.48%)
         occurrences all number
    316
    Injection site induration
         subjects affected / exposed
    19 / 385 (4.94%)
         occurrences all number
    21
    Injection site pain
         subjects affected / exposed
    208 / 385 (54.03%)
         occurrences all number
    544
    Injection site swelling
         subjects affected / exposed
    130 / 385 (33.77%)
         occurrences all number
    261
    Pyrexia
         subjects affected / exposed
    56 / 385 (14.55%)
         occurrences all number
    69
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    268 / 385 (69.61%)
         occurrences all number
    499
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    11 / 385 (2.86%)
         occurrences all number
    12
    Vomiting
         subjects affected / exposed
    93 / 385 (24.16%)
         occurrences all number
    136
    Diarrhoea
         subjects affected / exposed
    15 / 385 (3.90%)
         occurrences all number
    17
    Skin and subcutaneous tissue disorders
    Dermatitis diaper
         subjects affected / exposed
    9 / 385 (2.34%)
         occurrences all number
    12
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    196 / 385 (50.91%)
         occurrences all number
    319
    Infections and infestations
    Bronchiolitis
         subjects affected / exposed
    16 / 385 (4.16%)
         occurrences all number
    16
    Conjunctivitis
         subjects affected / exposed
    11 / 385 (2.86%)
         occurrences all number
    11
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 385 (2.08%)
         occurrences all number
    9
    Nasopharyngitis
         subjects affected / exposed
    21 / 385 (5.45%)
         occurrences all number
    23
    Respiratory tract infection
         subjects affected / exposed
    12 / 385 (3.12%)
         occurrences all number
    13

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    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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