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Study of Menactra® in Healthy Subjects at 9 Months and Concomitantly With Pentacel® at 15 to 18 Months of Age

Sponsor
Sanofi Pasteur, a Sanofi Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01659996
Collaborator
(none)
1,394
Enrollment
58
Locations
3
Arms
38
Duration (Months)
24
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the study is to further characterize the safety and immunogenicity of Menactra® in the population <2 years of age when administered alone and when the second dose is administered concomitantly with the 4th dose of Pentacel®, a licensed pediatric vaccine.

Primary Objectives:

  • To evaluate and compare the antibody responses to meningococcal serogroups A, C, Y, and W-135 induced by 2 injections of Menactra® in subjects aged 9 months at the first vaccination visit and 15 to 18 months at the second vaccination visit.

  • To evaluate and compare the antibody responses to Pertussis (pertussis toxoid [PT], filamentous haemagglutinin [FHA] and pertactin [PRN]) antigens induced by a dose of Pentacel® when administered concomitantly with Menactra® to those elicited by a dose of Pentacel® administered alone.

  • To evaluate and compare the antibody responses to polyribosylribitol phosphate (PRP), tetanus and diphtheria antigens induced by a dose of Pentacel® when administered concomitantly with Menactra® to those elicited by a dose of Pentacel® alone.

Observational Objectives:

  • To describe the safety profile (immediate unsolicited AEs within 30 minutes of each trial vaccination, solicited reactions within 7 days of each vaccination, unsolicited AEs within 30 days of each vaccination, and serious adverse events [SAEs] throughout the course of the trial from Day 0 up to Day 30 after the last trial vaccination[s]) in all trial groups

  • To describe the antibody responses to meningococcal serogroups A, C, Y, and W-135, measured by SBA HC, 30 days after the second Menactra® administration

  • To describe the antibody responses to Pentacel® (PT, FHA, PRN, FIM, diphtheria, tetanus, polio, PRP) measured by enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), or functional assays.

Condition or Disease Intervention/Treatment Phase
  • Biological: Meningococcal polysaccharide diphtheria toxoid conjugate
  • Biological: Meningococcal polysaccharide diphtheria toxoid conjugate + Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed
  • Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate
 Phase 4

Detailed Description

Participants will be vaccinated according to their randomized groups at age 9 months and at age 15 to 18 months. They will undergo immunogenicity assessment and safety monitoring post-vaccination.

Study Design

Study Type:
Interventional
Actual Enrollment :
1394 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
An Immunogenicity and Safety Evaluation of Menactra® (Meningococcal [Groups A, C, Y and W-135] Polysaccharide Diphtheria Toxoid Conjugate Vaccine) When Administered to Healthy Subjects at 9 Months and Concomitantly With Pentacel® at 15 to 18 Months of Age.
Study Start Date :
Jul 1, 2012
Actual Primary Completion Date :
Nov 1, 2014
Actual Study Completion Date :
Sep 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Menactra Vaccine Group

Participants will receive Meningococcal polysaccharide diphtheria toxoid conjugate (Menactra®) at 9 months of age and Menactra® at 15 to 18 months of age.

Biological: Meningococcal polysaccharide diphtheria toxoid conjugate
0.5 mL, Intramuscular
Other Names:
  • Menactra®

    		•
    Experimental: Menactra and Pentacel Vaccine Group

    Participants will receive Meningococcal polysaccharide diphtheria toxoid conjugate (Menactra®) at 9 months of age and Menactra® + Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed (Pentacel®) concomitantly at 15 to 18 months of age.

    Biological: Meningococcal polysaccharide diphtheria toxoid conjugate + Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed
    0.5 mL, Intramuscular
    Other Names:
  • Menactra®
  • Pentacel®

    		•
    Active Comparator: Pentacel Vaccine Group

    Participants will receive only Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Pentacel®) at 15 to 18 months of age.

    Biological: Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate
    0.5 mL, Intramuscular
    Other Names:
  • Pentacel®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Study Participants Achieving Menactra Response for Meningococcal Serogroups A, C, Y, and W-135 Following the Second Menactra Vaccination [Day 30 post second Menactra vaccination]

      Titers of antibodies to serogroups A, C, Y, and W-135 were measured by serum bactericidal assay using human complement (hSBA or SBA-HC). Menactra vaccine response defined as subjects with an hSBA titer <1:8 at baseline achieving an hSBA titer ≥1:8, and subjects with an hSBA titer ≥1:8 at baseline achieving a ≥ 4-fold increase in hSBA titer.

    2. Geometric Mean Concentrations of Pertussis Vaccine Antibodies Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine [Day 30 post-vaccination 2]

      Pertussis antibodies, anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), Pertactin (PRN) antibodies were measured by enzyme-linked immunosorbent assay (ELISA).

    3. Percentage of Participants With Pertussis Vaccine Responses Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine [Day 30 post-vaccination 2]

      Pertussis antibodies, anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), and Pertactin (PRN) antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Pertussis response was defined as: ≥4 × baseline concentration, if the anti-pertussis antibody concentration at baseline is <4 × lower limit of quantification (LLOQ), Or ≥2 × baseline concentration, if the anti-pertussis antibody concentration at baseline is ≥4 × LLOQ

    4. Percentage of Participants With Antibody Responses to Diphtheria, Tetanus and Polyribosylribitol Phosphate Antigens Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine [Day 30 post-vaccination 2]

      Anti-Tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA), anti-polyribosylribitol phosphate (PRP) antibodies were measured using a Farr-type radioimmunoassay, and anti-diphtheria antibodies were measured by a toxin neutralization test. The vaccine responses were defined as: Anti-PRP antibody concentrations ≥1.0 μg/mL; Anti-tetanus antibody concentrations ≥1.0 IU/mL and Anti-diphtheria antibody concentrations ≥1.0 IU/mL, respectively, 30 days after vaccination with Pentacel® in participants in Groups 2 and 3.

    Other Outcome Measures

    1. Geometric Mean Titers of Individual Meningococcal Antibodies in Serum Bactericidal Assay With Human Complement (SBA-HC) Analysis Following Vaccination With Menactra Vaccine [Day 0 (pre-vaccination) and Day 30 post-vaccination 2]

      Geometric mean titers (GMTs) of antibodies to serogroups A, C, Y, and W-135 were measured by serum bactericidal assay with human complement (SBA HC) before any vaccination and post-vaccination 2

    2. Geometric Mean Titers of Individual Antibodies to Filamentous Hemagglutinin, Pertactin, Diphtheria, Tetanus and Polio Antigens Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine [Day 0 (pre-vaccination) and Day 30 post-vaccination 2]

      Filamentous hemagglutinin (FHA), Fimbriae types 2 and 3 (FIM), Pertactin (PRN) and anti-Tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA); anti-Diphtheria antibodies were measured by a toxin neutralization test.

    3. Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With Menactra Only, or Pentacel Only or Menactra Concomitantly With Pentacel Vaccine [Day 0 to Day 7 after any vaccination]

      Solicited injection-site reactions: Tenderness, Erythema, and Swelling. Solicited Systemic Reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 solicited reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - ≥ 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses ≥ 3 feeds / meals or refuses most feeds / meals; and Irritability - Inconsolable.

    4. Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination at 9 Months of Age With Menactra Vaccine. [Day 0 to Day 7 after 9-month vaccination]

      Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited Systemic Reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 solicited reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - ≥ 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses ≥ 3 feeds / meals or refuses most feeds/meals; and Irritability - Inconsolable.

    5. Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With Menactra Only, or Pentacel Only, or Menactra Concomitantly With Pentacel Vaccine [Day 0 to Day 7 after the 15 to 18 month vaccination]

      Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited systemic reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - ≥ 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses ≥ 3 feeds/meals or refuses most feeds/meals; and Irritability - Inconsolable.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    9 Months to 18 Months
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Aged 9 months (249 to 305 days) for Groups 1 and 2, or 15 to 18 months (420 to 570 days) for Group 3 on the day of the first trial visit

    • Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative

    • Received 3 doses of any DTaP-containing vaccines

    • Received 3 doses of a Hib-containing vaccine, or 2 doses if the subject received PRP-OMP (PedvaxHIB® or Comvax®[HepB-Hib])

    • Received at least 3 doses of a CRM197-based pneumococcal conjugate vaccine (Pneumococcal conjugate vaccine [PCV] or 13-Valent pneumococcal conjugate vaccine [PCV13])

    • Subject and parent/ legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures.

    Exclusion Criteria:

    • Participation in the 4 weeks preceding the first trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure

    • Receipt of any vaccine in the 4 weeks preceding each trial vaccination or planned receipt of any vaccine in the 4 weeks following each trial vaccination, except for influenza vaccination, which may be received at least 2 weeks before or after the trial vaccination(s)

    • Vaccination against meningococcal disease with either the trial vaccine or another vaccine, or receipt of the 4th dose of any DTaP-containing vaccines, receipt of the 4th dose of a Hib-containing vaccine, or receipt of the 3rd dose of PRP-OMP (PedvaxHIB® or Comvax® [Hep B-Hib]) prior to enrollment or during the conduction of the trial, except for Group 1 subjects, who may receive Hib vaccine at 12 months

    • Receipt of immune globulins, blood or blood-derived products in the past 3 months

    • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). Topical steroids are not included in this exclusion criterion

    • History of invasive meningococcal infection, confirmed either clinically, serologically, or microbiologically

    • Personal history of Guillain-Barré Syndrome

    • History of encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis containing vaccine that is not attributable to another identifiable cause

    • Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to one of the vaccines used in the trial or to a vaccine containing any of the same substances

    • Known thrombocytopenia, as reported by the parent/ legally acceptable representative, contraindicating intramuscular vaccination

    • Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination

    • In an emergency setting or hospitalized involuntarily

    • Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion

    • Moderate or severe acute illness/ infection (according to investigator judgment) or febrile illness (temperature ≥ 100.4°F [≥ 38.0°C]) on the day of vaccination. A prospective subject should not be included in the trial until the condition has resolved or the febrile event has subsided

    • Receipt of oral or injectable antibiotic therapy within 72 hours prior to any trial blood draw (topical antibiotics, drops, or ointments are not included in this criterion)

    • Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed trial.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States 35235
    2 Pinson Alabama United States 35126
    3 Tucson Arizona United States 85741
    4 Fayetteville Arkansas United States 72703
    5 Jonesboro Arkansas United States 72401
    6 Little Rock Arkansas United States 72205
    7 Chino California United States 91710
    8 Downey California United States 90241
    9 La Puente California United States 91744
    10 Lakewood California United States 90711
    11 Paramount California United States 90723
    12 Norwich Connecticut United States 06360
    13 Marietta Georgia United States 30062
    14 Woodstock Georgia United States 30189
    15 Dekalb Illinois United States 60115
    16 Indianapolis Indiana United States 46256
    17 Bossier City Louisiana United States 71111
    18 Woburn Massachusetts United States 01801
    19 Worcester Massachusetts United States 01655
    20 Bridgeton Missouri United States 63044
    21 Kansas City Missouri United States 64114
    22 Elkhorn Nebraska United States 68022
    23 Lincoln Nebraska United States 68504
    24 Lincoln Nebraska United States 68516
    25 Omaha Nebraska United States 68198
    26 Clyde North Carolina United States 28721
    27 Fargo North Dakota United States 58103
    28 Cincinnati Ohio United States 45245
    29 Fairfield Ohio United States 45014
    30 Huber Heights Ohio United States 45424
    31 Kettering Ohio United States 45420
    32 Tulsa Oklahoma United States 74127
    33 Erie Pennsylvania United States 16505
    34 Harleysville Pennsylvania United States 19438
    35 Hermitage Pennsylvania United States 16148
    36 Scranton Pennsylvania United States 18510
    37 Sellersville Pennsylvania United States 18960
    38 Jackson Tennessee United States 38305
    39 Kingsport Tennessee United States 37660
    40 Austin Texas United States 78705
    41 Dallas Texas United States 75230
    42 Fort Worth Texas United States 76107
    43 Houston Texas United States 77055
    44 Hurst Texas United States 76054
    45 San Antonio Texas United States 78229
    46 Layton Utah United States 84041
    47 Layton Utah United States 84047
    48 Murray Utah United States 84107
    49 Orem Utah United States 84057
    50 Payson Utah United States 84651
    51 Roy Utah United States 84067
    52 Spanish Fork Utah United States 84660
    53 Syracuse Utah United States 84075
    54 Midlothian Virginia United States 23113
    55 Spokane Washington United States 99202
    56 Spokane Washington United States 99218
    57 Ponce Puerto Rico 00731
    58 San Juan Puerto Rico 00918

    Sponsors and Collaborators

    • Sanofi Pasteur, a Sanofi Company

    Investigators

    • Study Director: Medical Director, Sanofi Pasteur Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Sanofi Pasteur, a Sanofi Company
    ClinicalTrials.gov Identifier:
    NCT01659996
    Other Study ID Numbers:
    • MTA55
    • U1111-1120-1368
    First Posted:
    Aug 8, 2012
    Last Update Posted:
    Dec 15, 2015
    Last Verified:
    Nov 1, 2015
    Keywords provided by Sanofi Pasteur, a Sanofi Company
    Meningitis
    Meningococcal Infection
    Diphtheria
    Pertussis
    Menactra®
    Pentacel®
    Additional relevant MeSH terms:
    Whooping Cough
    Diphtheria
    Meningococcal Infections
    Meningitis

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled from 24 July 2012 to 14 June 2013 in 62 clinical centers in the United States.
    Pre-assignment Detail A total of 1394 participants were enrolled for the study, data on 1288 participants who met all the inclusion and none of the exclusion criteria and who completed the vaccination schedule are presented in this report.
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description All participants received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months All participants received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months. Study participants received only Pentacel vaccine at 15 to 18 months of age
    Period Title: Overall Study
    STARTED 421 395 472
    COMPLETED 413 388 461
    NOT COMPLETED 8 7 11

    Baseline Characteristics

    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group Total
    Arm/Group Description Study participants received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months Study participants received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months Study participants received only Pentacel vaccine at 15 to 18 months of age Total of all reporting groups
    Overall Participants 421 395 472 1288
    Age (Count of Participants)
    <=18 years
    421
    100%
    395
    100%
    472
    100%
    1288
    100%
    Between 18 and 65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (Days) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Days]
    284.5
    (10.8)
    284.6
    (10.6)
    483.9
    (30.3)
    353.6
    (96.8)
    Sex: Female, Male (Count of Participants)
    Female
    219
    52%
    171
    43.3%
    232
    49.2%
    622
    48.3%
    Male
    202
    48%
    224
    56.7%
    240
    50.8%
    666
    51.7%
    Region of Enrollment (Number) [Number]
    United States
    421
    100%
    395
    100%
    472
    100%
    1288
    100%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Study Participants Achieving Menactra Response for Meningococcal Serogroups A, C, Y, and W-135 Following the Second Menactra Vaccination
    Description Titers of antibodies to serogroups A, C, Y, and W-135 were measured by serum bactericidal assay using human complement (hSBA or SBA-HC). Menactra vaccine response defined as subjects with an hSBA titer <1:8 at baseline achieving an hSBA titer ≥1:8, and subjects with an hSBA titer ≥1:8 at baseline achieving a ≥ 4-fold increase in hSBA titer.
    Time Frame Day 30 post second Menactra vaccination

    Outcome Measure Data

    Analysis Population Description
    Antibody titers to the meningococcal serogroups were assessed in the Per-protocol population of the participants in Menactra Vaccine Group and Menactra + Pentacel Vaccine Group.
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description Study participants that received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months. Study participants that received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months. Study participants that received only Pentacel vaccine at 15 to 18 months of age
    Measure Participants 352 333 0
    Serogroup A (N=346, 329, 0)
    96.24
    22.9%
    96.35
    24.4%
    Serogroup C (N=352, 333, 0)
    98.86
    23.5%
    97.60
    24.7%
    Serogroup Y (N=351, 333, 0)
    98.86
    23.5%
    96.40
    24.4%
    Serogroup W-135 (N=351, 330, 0)
    98.86
    23.5%
    97.58
    24.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Menactra Vaccine Group, Menactra + Pentacel Vaccine Group
    Comments Meningococcal serogroup A: The null hypothesis (H0: pm - ppm > δ) was tested against the alternative hypothesis (H1: pm - ppm ≤ δ), where pm and ppm were the proportions of subjects in Group 1 and in Group 2, respectively, who achieved a Menactra vaccine response for meningococcal serogroups A, C, Y and W-135, with δ = 0.10.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments If the upper limit of the two-sided 95% confidence interval (CI) of the difference between the two proportions was < δ for serogroup A and assuming the difference between the two proportions was normally distributed, the inferiority assumption was to be rejected.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference between 2 percentages
    Estimated Value -0.110
    Confidence Interval (2-Sided) 95%
    -3.11 to 2.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Menactra Vaccine Group, Menactra + Pentacel Vaccine Group
    Comments Meningococcal serogroup C: The null hypothesis (H0: pm - ppm > δ) was tested against the alternative hypothesis (H1: pm - ppm ≤ δ), where pm and ppm were the proportions of subjects in Group 1 and in Group 2, respectively, who achieved a Menactra vaccine response for meningococcal serogroups A, C, Y and W-135, with δ = 0.10.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments If the upper limit of the two-sided 95% CI of the difference between the two proportions was < δ for serogroup C and assuming the difference between the two proportions was normally distributed, the inferiority assumption was to be rejected.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference between 2 percentages
    Estimated Value 1.27
    Confidence Interval (2-Sided) 95%
    -0.84 to 3.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Menactra Vaccine Group, Menactra + Pentacel Vaccine Group
    Comments Meningococcal serogroup Y: The null hypothesis (H0: pm - ppm > δ) was tested against the alternative hypothesis (H1: pm - ppm ≤ δ), where pm and ppm were the proportions of subjects in Group 1 and in Group 2, respectively, who achieved a Menactra vaccine response for meningococcal serogroups A, C, Y and W-135, with δ = 0.10.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments If the upper limit of the two-sided 95% CI of the difference between the two proportions was < δ for serogroup Y and assuming the difference between the two proportions was normally distributed, the inferiority assumption was to be rejected.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference between 2 percentages
    Estimated Value 2.46
    Confidence Interval (2-Sided) 95%
    0.14 to 5.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Menactra Vaccine Group, Menactra + Pentacel Vaccine Group
    Comments Meningococcal serogroup W-135: The null hypothesis (H0: pm - ppm > δ) was tested against the alternative hypothesis (H1: pm - ppm ≤ δ), where pm and ppm were the proportions of subjects in Group 1 and in Group 2, respectively, who achieved a Menactra vaccine response for meningococcal serogroups A, C, Y and W-135, with δ = 0.10.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments If the upper limit of the two-sided 95% CI of the difference between the two proportions was < δ for serogroup W-135 and assuming the difference between the two proportions was normally distributed, the inferiority assumption was to be rejected.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference between 2 percentages
    Estimated Value 1.28
    Confidence Interval (2-Sided) 95%
    -0.84 to 3.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Other Pre-specified Outcome
    Title Geometric Mean Titers of Individual Meningococcal Antibodies in Serum Bactericidal Assay With Human Complement (SBA-HC) Analysis Following Vaccination With Menactra Vaccine
    Description Geometric mean titers (GMTs) of antibodies to serogroups A, C, Y, and W-135 were measured by serum bactericidal assay with human complement (SBA HC) before any vaccination and post-vaccination 2
    Time Frame Day 0 (pre-vaccination) and Day 30 post-vaccination 2

    Outcome Measure Data

    Analysis Population Description
    Geometric mean titers of individual antibodies were assessed in the Per-protocol population in the Menactra Vaccine Group and Menactra + Pentacel Vaccine Group participants.
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description Study participants that received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months Study participants that received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months. Study participants that received only Pentacel vaccine at 15 to 18 months of age
    Measure Participants 356 336 0
    Serogroup A (Pre-vaccination; N=352, 332, 0)
    3.4
    4.3
    Serogroup A (Post-vaccination; N=350, 332, 0)
    104.8
    104.5
    Serogroup C (Pre-vaccination; N=352, 332, 0)
    2.2
    2.1
    Serogroup C (Post-vaccination; N=350, 332, 0)
    157.9
    129.1
    Serogroup Y (Pre-vaccination; N=352, 332, 0)
    2.1
    2.1
    Serogroup Y (Post-vaccination; N=350, 332, 0)
    77.8
    62.2
    Serogroup W-135 (Pre-vaccination; N=352, 332, 0)
    2.1
    2.1
    Serogroup W-135 (Post-vaccination; N=350, 332, 0)
    90.3
    81.1
    3. Other Pre-specified Outcome
    Title Geometric Mean Titers of Individual Antibodies to Filamentous Hemagglutinin, Pertactin, Diphtheria, Tetanus and Polio Antigens Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine
    Description Filamentous hemagglutinin (FHA), Fimbriae types 2 and 3 (FIM), Pertactin (PRN) and anti-Tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA); anti-Diphtheria antibodies were measured by a toxin neutralization test.
    Time Frame Day 0 (pre-vaccination) and Day 30 post-vaccination 2

    Outcome Measure Data

    Analysis Population Description
    Geometric mean titers of individual vaccine antibodies were assessed in the Per-protocol population of the Menactra + Pentacel Vaccine Group and the Pentacel Vaccine Group participants.
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description Study participants that received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months Study participants that received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months. Study participants that received only Pentacel vaccine at 15 to 18 months of age
    Measure Participants 0 336 418
    Anti-FIM (pre-vaccination; N=0, 335, 418)
    17.6
    23.2
    Anti-FIM (post-vaccination; N=0, 332, 417)
    220.8
    265.5
    Anti-PRN (pre-vaccination; N=0, 334, 418)
    10.3
    11.1
    Anti-PRN (post-vaccination; N=0, 331, 417)
    120.9
    133.9
    Anti-Diphtheria (pre-vaccination; N=0, 328, 418)
    0.3
    0.2
    Anti-Diphtheria (post-vaccination; N=0, 324, 416)
    3.3
    4.2
    Anti-Tetanus (pre-vaccination; N=0, 329, 414)
    0.2
    0.2
    Anti-Tetanus (post-vaccination; N=0, 326, 415)
    3.7
    3.9
    Anti-Polio 1 (pre-vaccination; N=0, 326, 415)
    83.1
    76.9
    Anti-Polio 1 (post-vaccination; N=0, 323, 414)
    2140
    1887
    Anti-Polio 2 (pre-vaccination; N=0, 328, 417)
    157.0
    182.8
    Anti-Polio 2 (post-vaccination; N=0, 324, 414)
    3172
    3071
    Anti-Polio 3 (pre-vaccination; N=0, 327, 417)
    107.1
    130.2
    Anti-Polio 3 (post-vaccination; N=0, 323, 415)
    4629
    3765
    4. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With Menactra Only, or Pentacel Only or Menactra Concomitantly With Pentacel Vaccine
    Description Solicited injection-site reactions: Tenderness, Erythema, and Swelling. Solicited Systemic Reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 solicited reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - ≥ 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses ≥ 3 feeds / meals or refuses most feeds / meals; and Irritability - Inconsolable.
    Time Frame Day 0 to Day 7 after any vaccination

    Outcome Measure Data

    Analysis Population Description
    Solicited reactions were assessed in all subjects who received at least one dose of study vaccine, according to the vaccine actually received (Safety Analysis Population).
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description Study participants that received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months. Study participants that received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months. Study participants that received only Pentacel vaccine at 15 to 18 months of age.
    Measure Participants 421 395 472
    Any injection-site Tenderness (N = 420, 393, 463)
    52.1
    12.4%
    61.6
    15.6%
    51.4
    10.9%
    Grade 3 inj.-siteTenderness (N = 420, 393, 463)
    1.0
    0.2%
    4.3
    1.1%
    1.9
    0.4%
    Any injection-site Erythema (N = 420, 393, 463)
    25.2
    6%
    38.7
    9.8%
    31.1
    6.6%
    Grade 3 inj.-site Erythema (N = 420, 393, 463)
    0.2
    0%
    0.8
    0.2%
    1.1
    0.2%
    Any injection-site Swelling (N = 420, 393, 463)
    15.0
    3.6%
    23.2
    5.9%
    21.4
    4.5%
    Grade 3 inj.-site Swelling (N = 420, 393, 463)
    0.0
    0%
    0.3
    0.1%
    0.6
    0.1%
    Any Fever (N = 421, 394, 463)
    16.9
    4%
    21.6
    5.5%
    12.3
    2.6%
    Grade 3 Fever (N = 421, 394, 463)
    1.4
    0.3%
    2.8
    0.7%
    0.9
    0.2%
    Any Vomiting (N = 420, 393, 463)
    22.6
    5.4%
    17.3
    4.4%
    9.9
    2.1%
    Grade 3 Vomiting (N = 420, 393, 463)
    0.5
    0.1%
    0.3
    0.1%
    0.6
    0.1%
    Any Crying abnormal (N = 420, 393, 463)
    52.9
    12.6%
    52.2
    13.2%
    39.1
    8.3%
    Grade 3 Crying abnormal (N = 420, 393, 463)
    4.0
    1%
    5.1
    1.3%
    2.2
    0.5%
    Any Drowsiness (N = 420, 393, 463)
    49.8
    11.8%
    52.4
    13.3%
    30.0
    6.4%
    Grade 3 Drowsiness (N = 421, 394, 463)
    3.1
    0.7%
    2.0
    0.5%
    1.7
    0.4%
    Appetite lost (N = 420, 393, 463)
    43.3
    10.3%
    47.8
    12.1%
    35.2
    7.5%
    Grade 3 Appetite lost (N = 420, 393, 463)
    2.1
    0.5%
    3.3
    0.8%
    1.3
    0.3%
    Any Irritability (N = 420, 393, 463)
    70.5
    16.7%
    72.3
    18.3%
    58.5
    12.4%
    Grade 3 Irritability (N = 420, 393, 463)
    6.4
    1.5%
    6.9
    1.7%
    2.4
    0.5%
    5. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination at 9 Months of Age With Menactra Vaccine.
    Description Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited Systemic Reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 solicited reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - ≥ 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses ≥ 3 feeds / meals or refuses most feeds/meals; and Irritability - Inconsolable.
    Time Frame Day 0 to Day 7 after 9-month vaccination

    Outcome Measure Data

    Analysis Population Description
    Solicited reactions were assessed in subjects who received at least one dose of study vaccine at 9 month of age, according to the vaccine actually received (Safety Analysis Population).
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description Study participants that received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months. Study participants that received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months. Study participants that received only Pentacel vaccine at 15 to 18 months of age.
    Measure Participants 421 395 0
    Any injection-site Tenderness (N = 419, 387, 0)
    32.2
    7.6%
    34.1
    8.6%
    Grade 3 injection-site Tenderness (N=419, 387, 0)
    0.2
    0%
    0.8
    0.2%
    Any injection-site Erythema (N = 419, 387, 0)
    16.9
    4%
    24.3
    6.2%
    Grade 3 injection-site Erythema (N = 419, 387, 0)
    0.0
    0%
    0.0
    0%
    Any injection-site Swelling (N = 419, 385, 0)
    10.0
    2.4%
    9.4
    2.4%
    Grade 3 injection-site Swelling (N = 419, 385, 0)
    0.0
    0%
    0.0
    0%
    Any Fever (N = 421, 389, 0)
    10.5
    2.5%
    10.3
    2.6%
    Grade 3 Fever (N = 421, 389, 0)
    0.7
    0.2%
    1.5
    0.4%
    Any Vomiting (N = 419, 387, 0)
    15.5
    3.7%
    12.9
    3.3%
    Grade 3 Vomiting (N = 419, 387, 0)
    0.5
    0.1%
    0.0
    0%
    Any Crying abnormal (N = 419, 387, 0)
    38.9
    9.2%
    37.5
    9.5%
    Grade 3 Crying abnormal (N = 419, 387, 0)
    3.3
    0.8%
    2.8
    0.7%
    Any Drowsiness (N = 419, 387, 0)
    37.2
    8.8%
    37.0
    9.4%
    Grade 3 Drowsiness (N = 419, 387, 0)
    2.1
    0.5%
    0.8
    0.2%
    Appetite lost (N = 419, 387, 0)
    25.3
    6%
    28.7
    7.3%
    Grade 3 Appetite lost (N = 419, 387, 0)
    1.4
    0.3%
    1.8
    0.5%
    Any Irritability (N = 419, 387, 0)
    56.1
    13.3%
    54.8
    13.9%
    Grade 3 Irritability (N = 419, 387, 0)
    4.8
    1.1%
    3.1
    0.8%
    6. Primary Outcome
    Title Geometric Mean Concentrations of Pertussis Vaccine Antibodies Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine
    Description Pertussis antibodies, anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), Pertactin (PRN) antibodies were measured by enzyme-linked immunosorbent assay (ELISA).
    Time Frame Day 30 post-vaccination 2

    Outcome Measure Data

    Analysis Population Description
    Geometric Mean Concentrations (GMC) of Pertussis vaccine antibodies were assessed in the Per-protocol population of participants in Menactra + Pentacel Vaccine Group and Pentacel Vaccine Group.
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description Study participants that received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months Study participants that received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months. Study participants that received only Pentacel vaccine at 15 to 18 months of age
    Measure Participants 0 332 417
    Anti-Pertussis Toxoid (PT; N=0, 332, 417)
    73.5
    69.7
    Anti-Filamentous hemagglutinin FHA; N=0, 331, 417)
    113.7
    110.1
    Anti-Pertactin (PRN; N=0, 331, 417)
    120.9
    133.9
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Menactra + Pentacel Vaccine Group, Pentacel Vaccine Group
    Comments Pertussis toxoid (PT): The null hypothesis (H0: GMCp / GMCpm > 1.5) was tested against the alternative hypothesis (H1: GMCp / GMCpm ≤ 1.5), where GMCp and GMCpm were the GMCs of antibodies against the pertussis antigen (PT) in Group 3 and in Group 2, respectively
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Assuming that the antibodies concentration was log normally distributed, if the upper limit of the two-sided 95% CI of the ratio of the two GMCs is ≤ 1.5 for each antigen, the inferiority assumption was to be rejected.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.949
    Confidence Interval (2-Sided) 95%
    0.852 to 1.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Menactra + Pentacel Vaccine Group, Pentacel Vaccine Group
    Comments Filamentous hemagglutinin (FHA): The null hypothesis (H0: GMCp / GMCpm > 1.5) was tested against the alternative hypothesis (H1: GMCp / GMCpm ≤ 1.5), where GMCp and GMCpm were the GMCs of antibodies against the pertussis antigen (FHA) in Group 3 and in Group 2, respectively
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Assuming that the antibodies concentration was log normally distributed, if the upper limit of the two-sided 95% CI of the ratio of the two GMCs is ≤ 1.5 for each antigen, the inferiority assumption was to be rejected.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.968
    Confidence Interval (2-Sided) 95%
    0.866 to 1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Menactra + Pentacel Vaccine Group, Pentacel Vaccine Group
    Comments Pertactin (PRN): The null hypothesis (H0: GMCp / GMCpm > 1.5) was tested against the alternative hypothesis (H1: GMCp / GMCpm ≤ 1.5), where GMCp and GMCpm were the GMCs of antibodies against the pertussis antigen (PRN) in Group 3 and in Group 2, respectively
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments Assuming that the antibodies concentration was log normally distributed, if the upper limit of the two-sided 95% CI of the ratio of the two GMCs is ≤ 1.5 for each antigen, the inferiority assumption was to be rejected.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.11
    Confidence Interval (2-Sided) 95%
    0.937 to 1.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Primary Outcome
    Title Percentage of Participants With Pertussis Vaccine Responses Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine
    Description Pertussis antibodies, anti-Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), and Pertactin (PRN) antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Pertussis response was defined as: ≥4 × baseline concentration, if the anti-pertussis antibody concentration at baseline is <4 × lower limit of quantification (LLOQ), Or ≥2 × baseline concentration, if the anti-pertussis antibody concentration at baseline is ≥4 × LLOQ
    Time Frame Day 30 post-vaccination 2

    Outcome Measure Data

    Analysis Population Description
    Antibody responses to Pertussis vaccine antigens were assessed in the Per-protocol population of the Menactra + Pentacel Vaccine Group and Pentacel Vaccine Group participants.
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description Study participants that received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months Study participants that received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months. Study participants that received only Pentacel vaccine at 15 to 18 months of age
    Measure Participants 0 330 417
    Anti-Pertussis Toxoid (PT; N=0, 330, 417)
    90.91
    21.6%
    89.69
    22.7%
    Anti-Filamentous hemagglutinin (FHA; N=0,329, 417)
    93.62
    22.2%
    94.48
    23.9%
    Anti-Pertactin (PRN; N=0, 329, 417)
    93.62
    22.2%
    93.53
    23.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Menactra + Pentacel Vaccine Group, Pentacel Vaccine Group
    Comments Pertussis toxoid (PT) antigen: The null hypothesis (H0: pp - ppm > δ) was tested against the alternative hypothesis (H1: pp - ppm ≤ δ), where pp and ppm were the proportions of subjects in Group 3 and Group 2, respectively, who achieved a pertussis vaccine response in antibodies against the pertussis antigen (PT), with δ = 0.10.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments If the upper limit of the two-sided 95% CI of the difference between the two proportions was < δ for each antibody and assuming the difference between the two proportions was normally distributed, the inferiority assumption was to be rejected.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference between 2 percentages
    Estimated Value -1.22
    Confidence Interval (2-Sided) 95%
    -5.44 to 3.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Menactra + Pentacel Vaccine Group, Pentacel Vaccine Group
    Comments Filamentous hemagglutinin (FHA) antigen: The null hypothesis (H0: pp - ppm > δ) was tested against the alternative hypothesis (H1: pp - ppm ≤ δ), where pp and ppm were the proportions of subjects in Group 3 and Group 2, respectively, who achieved a pertussis vaccine response in antibodies against the pertussis antigen (FHA), with δ = 0.10.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments If the upper limit of the two-sided 95% CI of the difference between the two proportions was < δ for each antibody and assuming the difference between the two proportions was normally distributed, the inferiority assumption was to be rejected.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference between 2 percentages
    Estimated Value 0.867
    Confidence Interval (2-Sided) 95%
    -2.54 to 4.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Menactra + Pentacel Vaccine Group, Pentacel Vaccine Group
    Comments Pertactin (PRN) antigen: The null hypothesis (H0: pp - ppm > δ) was tested against the alternative hypothesis (H1: pp - ppm ≤ δ), where pp and ppm were the proportions of subjects in Group 3 and Group 2, respectively, who achieved a pertussis vaccine response in antibodies against the pertussis antigen (PRN), with δ = 0.10.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments If the upper limit of the two-sided 95% CI of the difference between the two proportions was < δ for each antibody and assuming the difference between the two proportions was normally distributed, the inferiority assumption was to be rejected.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference between 2 percentages
    Estimated Value -0.092
    Confidence Interval (2-Sided) 95%
    -3.62 to 3.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Other Pre-specified Outcome
    Title Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With Menactra Only, or Pentacel Only, or Menactra Concomitantly With Pentacel Vaccine
    Description Solicited injection site reactions: Tenderness, Erythema, and Swelling. Solicited systemic reactions: Fever (Temperature), Vomiting, Abnormal crying, Drowsiness, Loss of appetite, and Irritability. Grade 3 reactions defined as: Tenderness - cries when injected limb is moved, or the movement of the injected limb is reduced; Erythema and Swelling - ≥ 50 mm; Fever > 39.5°C or > 103.1 °F; Vomiting - ≥ 6 episodes per 24 hours or requiring parenteral hydration; Abnormal crying > 3 hours; Drowsiness - Sleeping most of the time or difficult to wake up; Loss of appetite - Refuses ≥ 3 feeds/meals or refuses most feeds/meals; and Irritability - Inconsolable.
    Time Frame Day 0 to Day 7 after the 15 to 18 month vaccination

    Outcome Measure Data

    Analysis Population Description
    Solicited reactions were assessed in all subjects who received at least one dose of 15 to 18 month study vaccine, according to the vaccine actually received (Safety Analysis Population).
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description Study participants that received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months. Study participants that received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months. Study participants that received only Pentacel vaccine at 15 to 18 months of age.
    Measure Participants 421 395 472
    Any injection-site Tenderness (N = 411, 382, 463)
    37.0
    8.8%
    54.7
    13.8%
    51.4
    10.9%
    Grade 3 inj.-site Tenderness (N = 411, 382, 463)
    0.7
    0.2%
    3.7
    0.9%
    1.9
    0.4%
    Any injection-site Erythema (N = 411, 382, 463)
    17.8
    4.2%
    30.1
    7.6%
    31.1
    6.6%
    Grade 3 injection-site Erythema (N=411, 382, 463)
    0.2
    0%
    0.8
    0.2%
    1.1
    0.2%
    Any injection-site Swelling (N = 411, 382, 463)
    9.2
    2.2%
    19.6
    5%
    21.4
    4.5%
    Grade 3 injection-site Swelling (N=411, 382, 463)
    0.0
    0%
    0.3
    0.1%
    0.6
    0.1%
    Any Fever (N = 412, 385, 463)
    8.5
    2%
    14.3
    3.6%
    12.3
    2.6%
    Grade 3 Fever (N = 412, 385, 463)
    0.7
    0.2%
    1.3
    0.3%
    0.9
    0.2%
    Any Vomiting (N = 411, 382, 463)
    10.0
    2.4%
    7.9
    2%
    9.9
    2.1%
    Grade 3 Vomiting (N = 411, 382, 463)
    0.0
    0%
    0.3
    0.1%
    0.6
    0.1%
    Any Crying abnormal (N = 411, 382, 463)
    33.8
    8%
    37.2
    9.4%
    39.1
    8.3%
    Grade 3 Crying abnormal (N = 411, 382, 463)
    1.0
    0.2%
    2.6
    0.7%
    2.2
    0.5%
    Any Drowsiness (N = 411, 382, 463)
    30.9
    7.3%
    40.6
    10.3%
    30.0
    6.4%
    Grade 3 Drowsiness (N = 411, 382, 463)
    1.0
    0.2%
    1.3
    0.3%
    1.7
    0.4%
    Appetite lost (N = 411, 382, 463)
    29.7
    7.1%
    34.0
    8.6%
    35.2
    7.5%
    Grade 3 Appetite lost (N = 411, 382, 463)
    0.7
    0.2%
    1.6
    0.4%
    1.3
    0.3%
    Any Irritability (N = 411, 382, 463)
    50.6
    12%
    57.9
    14.7%
    58.5
    12.4%
    Grade 3 Irritability (N = 411, 382, 463)
    2.7
    0.6%
    3.9
    1%
    2.4
    0.5%
    9. Primary Outcome
    Title Percentage of Participants With Antibody Responses to Diphtheria, Tetanus and Polyribosylribitol Phosphate Antigens Following Vaccination With Either Pentacel Only or Menactra Concomitantly With Pentacel Vaccine
    Description Anti-Tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA), anti-polyribosylribitol phosphate (PRP) antibodies were measured using a Farr-type radioimmunoassay, and anti-diphtheria antibodies were measured by a toxin neutralization test. The vaccine responses were defined as: Anti-PRP antibody concentrations ≥1.0 μg/mL; Anti-tetanus antibody concentrations ≥1.0 IU/mL and Anti-diphtheria antibody concentrations ≥1.0 IU/mL, respectively, 30 days after vaccination with Pentacel® in participants in Groups 2 and 3.
    Time Frame Day 30 post-vaccination 2

    Outcome Measure Data

    Analysis Population Description
    Antibody responses to Diphtheria, Tetanus, and Polyribosylribitol phosphate antigens were assessed in the Per-protocol population of the Menactra + Pentacel Vaccine Group and Pentacel Vaccine Group participants.
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description Study participants that received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months Study participants that received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months. Study participants that received only Pentacel vaccine at 15 to 18 months of age
    Measure Participants 0 336 418
    Anti-Diphtheria (N=0, 324, 416)
    99.69
    23.7%
    100.00
    25.3%
    Anti-Tetanus (N=0, 326, 415)
    100.00
    23.8%
    100.00
    25.3%
    Anti-Polyribosylribitol phosphate (N=0, 324, 416)
    97.53
    23.2%
    97.12
    24.6%

    Adverse Events

    Time Frame Adverse events data were collected from vaccination on Day 0 through Day 30 post-second (final) vaccination.
    Adverse Event Reporting Description
    Arm/Group Title Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Arm/Group Description Study participants received Menactra vaccine at 9 months of age and a second dose of Menactra vaccine at age 15 to 18 months Study participants received Menactra vaccine at 9 months of age and Menactra vaccine and Pentacel vaccine concomitantly at age 15 to 18 months Study participants received only Pentacel vaccine at 15 to 18 months of age
    All Cause Mortality
    Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/421 (3.1%) 11/395 (2.8%) 1/472 (0.2%)
    Cardiac disorders
    Aortic valve incompetence 1/421 (0.2%) 1 0/395 (0%) 0 0/472 (0%) 0
    Infections and infestations
    Bronchiolitis 1/421 (0.2%) 1 0/395 (0%) 0 0/472 (0%) 0
    Croup infectious 0/421 (0%) 0 2/395 (0.5%) 2 0/472 (0%) 0
    Gastroenteritis 1/421 (0.2%) 1 0/395 (0%) 0 0/472 (0%) 0
    Groin abscess 0/421 (0%) 0 2/395 (0.5%) 2 0/472 (0%) 0
    Neutropenic infection 0/421 (0%) 0 0/395 (0%) 0 1/472 (0.2%) 1
    Penile abscess 1/421 (0.2%) 1 0/395 (0%) 0 0/472 (0%) 0
    Pneumonia 0/421 (0%) 0 1/395 (0.3%) 1 0/472 (0%) 0
    Pneumonia bacterial 1/421 (0.2%) 1 0/395 (0%) 0 0/472 (0%) 0
    Respiratory syncytial virus bronchiolitis 1/421 (0.2%) 1 0/395 (0%) 0 0/472 (0%) 0
    Respiratory syncytial virus infection 1/421 (0.2%) 1 0/395 (0%) 0 0/472 (0%) 0
    Staphylococcal abscess 0/421 (0%) 0 1/395 (0.3%) 1 0/472 (0%) 0
    Subcutaneous abscess 0/421 (0%) 0 1/395 (0.3%) 1 0/472 (0%) 0
    Upper respiratory tract infection 1/421 (0.2%) 1 0/395 (0%) 0 0/472 (0%) 0
    Viral infection 1/421 (0.2%) 1 1/395 (0.3%) 1 0/472 (0%) 0
    Injury, poisoning and procedural complications
    Foreign body 1/421 (0.2%) 1 0/395 (0%) 0 0/472 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 0/421 (0%) 0 2/395 (0.5%) 2 0/472 (0%) 0
    Nervous system disorders
    Febrile convulsion 3/421 (0.7%) 4 1/395 (0.3%) 1 0/472 (0%) 0
    Other (Not Including Serious) Adverse Events
    Menactra Vaccine Group Menactra + Pentacel Vaccine Group Pentacel Vaccine Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 296/421 (70.3%) 318/395 (80.5%) 380/472 (80.5%)
    Gastrointestinal disorders
    Vomiting 95/420 (22.6%) 95 68/393 (17.3%) 68 46/472 (9.7%) 46
    Diarrhoea 30/421 (7.1%) 35 21/395 (5.3%) 22 26/472 (5.5%) 29
    Teething 31/421 (7.4%) 39 24/395 (6.1%) 33 42/472 (8.9%) 47
    General disorders
    Injection Site Tenderness 219/420 (52.1%) 219 242/393 (61.6%) 242 238/463 (51.4%) 238
    Injection Site Erythema 106/420 (25.2%) 106 152/393 (38.7%) 152 144/463 (31.1%) 144
    Fever 71/421 (16.9%) 71 85/394 (21.6%) 85 57/463 (12.3%) 57
    Pyrexia 42/421 (10%) 47 36/395 (9.1%) 40 25/472 (5.3%) 27
    Injection-site Swelling 63/420 (15%) 63 91/393 (23.2%) 91 99/463 (21.4%) 99
    Infections and infestations
    Otitis media 58/421 (13.8%) 69 50/395 (12.7%) 57 28/472 (5.9%) 29
    Upper respiratory tract infection 60/421 (14.3%) 64 52/395 (13.2%) 58 50/472 (10.6%) 51
    Metabolism and nutrition disorders
    Appetite lost 182/420 (43.3%) 182 188/393 (47.8%) 188 163/463 (35.2%) 163
    Nervous system disorders
    Drowsiness 209/420 (49.8%) 209 206/393 (52.4%) 206 139/463 (30%) 139
    Psychiatric disorders
    Crying abnormal 222/420 (52.9%) 222 205/393 (52.2%) 205 181/463 (39.1%) 181
    Irritability 296/420 (70.5%) 296 284/393 (72.3%) 284 271/463 (58.5%) 271
    Respiratory, thoracic and mediastinal disorders
    Cough 60/421 (14.3%) 66 44/395 (11.1%) 48 31/472 (6.6%) 31
    Rhinorrhoea 43/421 (10.2%) 48 47/395 (11.9%) 54 22/472 (4.7%) 22

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications

    Results Point of Contact

    Name/Title Medical Director
    Organization Sanofi Pasteur Inc.
    Phone
    Email RegistryContactUs@sanofipasteur.com
    Responsible Party:
    Sanofi Pasteur, a Sanofi Company
    ClinicalTrials.gov Identifier:
    NCT01659996
    Other Study ID Numbers:
    • MTA55
    • U1111-1120-1368
    First Posted:
    Aug 8, 2012
    Last Update Posted:
    Dec 15, 2015
    Last Verified:
    Nov 1, 2015