Immunogenicity, Safety and 1 Year Persistence of Antibodies After Either One or Two Doses of Meningococcal ACWY Conjugate Vaccine in Healthy Children 2 Through 10 Years of Age.

A Phase 3b, Randomized, Observer-Blind, Placebo-Controlled Multi-Center Study Comparing Immunogenicity, Safety and 1 Year Persistence of Antibodies After Either One or Two Doses of Novartis Meningococcal ACWY Conjugate Vaccine, Administered to Healthy Children 2 to 10 Years of Age.

This study was designed to conduct a comparative trial to further evaluate the safety, immunogenicity and antibody persistence of two doses of Novartis MenACWY conjugate vaccine, given 2 months apart, versus one dose of Novartis MenACWY conjugate vaccine in children 2 through 10 years of age.

Study Overview

• Status: Completed
• Conditions: Meningococcal Disease; Infections, Meningococcal
• Intervention / Treatment: Biological: MenACWY-CRM

• Study Type: Interventional
• Enrollment (Actual): 715
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • GSK Investigational Site
  • California
    • Sacramento, California, United States, 95822
      • GSK Investigational Site
  • Florida
    • Lake Mary, Florida, United States, 32746
      • GSK Investigational Site
  • Georgia
    • Marietta, Georgia, United States, 30062
      • GSK Investigational Site
    • Woodstock, Georgia, United States, 30189
      • GSK Investigational Site
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
      • GSK Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40291
      • GSK Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • GSK Investigational Site
  • Michigan
    • Niles, Michigan, United States, 49120
      • GSK Investigational Site
    • Stevensville, Michigan, United States, 49127
      • GSK Investigational Site
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • GSK Investigational Site
    • Fremont, Nebraska, United States, 68025
      • GSK Investigational Site
    • Omaha, Nebraska, United States, 68134
      • GSK Investigational Site
  • New York
    • Johnson City, New York, United States, 13790
      • GSK Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44121
      • GSK Investigational Site
    • Cleveland, Ohio, United States, 44122
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78705
      • GSK Investigational Site
    • Fort Worth, Texas, United States, 76135
      • GSK Investigational Site
  • Utah
    • West Jordan, Utah, United States, 84088
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 10 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy children, 2 to 10 years of age who have up to date routine childhood vaccination, according to U.S. ACIP recommendations

Exclusion Criteria:

1. Unwilling or unable to give written informed assent or consent to participate in the study.
2. Perceived to be unreliable or unavailable for the duration of the study period.
3. Previous confirmed or suspected disease caused by N. meningitidis.
4. Previously immunized with a meningococcal vaccine (licensed or investigational).
5. Receipt of any investigational or non-registered product within 30 days prior to enrolment or who expect to receive an investigational drug or vaccine prior to the completion of the study.

6. Receipt or plan to receive any vaccines within 30 days before and after administration of each dose of the study vaccine.

   (certain exceptions influenza vaccines apply)

7. Significant acute infection within the 7 days prior to enrolment or body temperature of 38°C or greater within 3 days prior to enrolment.
8. Previous serious acute, chronic or progressive disease, epilepsy or any progressive neurological disease or history of Guillain-Barre syndrome.
9. History of any anaphylaxis, serious vaccine reactions, or allergy to any vaccine components

10. Impairment/alteration of immune function, either congenital or acquired or resulting from (for example):

    • receipt of immunosuppressive therapy,
    • receipt of immunostimulants,
    • receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives.
11. Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2 through 5 years (1 Vac) MenACWY-CRM 1; Subjects 2 through 5 years received one vaccination of MenACWY-CRM	Biological: MenACWY-CRM; The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm
Active Comparator: 2 through 5 years (2 Vac) MenACWY-CRM 2; Subjects 2 through 5 years received two vaccinations of MenACWY-CRM	Biological: MenACWY-CRM; The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm
Placebo Comparator: 6 through 10 years (1 Vac) MenACWY-CRM 3; Subjects 6 through 10 years received one vaccination of MenACWY-CRM	Biological: MenACWY-CRM; The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm
Active Comparator: 6 through 10 years (2 Vac) MenACWY-CRM 4; Subjects 6 through 10 years received two vaccinations of MenACWY-CRM	Biological: MenACWY-CRM; The investigational meningococcal (groups A, C, Y, and W-135 vaccine) oligosaccharide diphtheria CRM197 conjugate vaccine (MenACWY-CRM) was administered intramuscularly in the nondominant arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-inferiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination	Immunogenicity was measured as the percentage of subjects with overall seroresponse and associated 2-sided 97.5% Clopper-Pearson confidence interval (CI), directed against N. meningitidis serogroups A, C, W and Y, by serum bactericidal assay using human complement (hSBA) at 1 month after one vaccination or two vaccinations of MenACWY-CRM given two months apart. Seroresponse is defined as: a. postvaccination hSBA titer ≥1:8 for subjects with a prevaccination hSBA titer <1:4; b. for subjects with a prevaccination hSBA ≥1:4, an increase of at least four times of the prevaccination hSBA titer.	One Month After Last Vaccination ( day 86)
Superiority of Two Vaccinations Versus One Vaccination of MenACWY-CRM, by Age Cohort, as Measured by the Percentage of Subjects With hSBA Seroresponse Against N. Meningitidis Serogroups A, C, W and Y, at 1 Month After Last Vaccination	Immunogenicity was measured as the percentage of subjects with overall seroresponse and associated 2-sided 95% CI, directed against N. meningitidis serogroups A, C, W and Y, by hSBA at 1 month after one vaccination or two vaccinations of MenACWY-CRM. Seroresponse -postvaccination hSBA titer ≥1:8 for subjects with a prevaccination hSBA titer <1:4 and for subjects with a prevaccination hSBA ≥1:4, an increase of at least four times of the prevaccination hSBA titer.	One Month After Last Vaccination (day 86)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM	Immunogenicity was measured as the percentage of subjects who achieved hSBA titer ≥1:8 and associated 95% CI, at one month after one vaccination or two vaccinations of MenACWY-CRM.	One Month After Last Vaccination (day 86)
Geometric Mean Titers of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Month After One or Two Vaccination(s) of MenACWY-CRM	Immunogenicity was measured as hSBA geometric mean titers (GMTs) and 95% CI against N. meningitidis serogroups A, C, W and Y, one month after one vaccination or two vaccinations of MenACWY-CRM.	One Month After Last Vaccination (day 86)
Percentage of Subjects With hSBA Titer ≥1:8, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM	Immunogenicity was measured as the percentage of subjects with hSBA titer ≥1:8 and associated 95% CI at one year after one vaccination or two vaccinations of MenACWY-CRM.	One year after one vaccination or two vaccinations (day 422).
Geometric Mean Titers of Subjects, Directed Against N. Meningitidis Serogroups A, C, W and Y At One Year After One or Two Vaccination(s) of MenACWY-CRM	Immunogenicity was measured as hSBA GMTs and 95% CI against N. meningitidis serogroups A, C, W and Y at one year after one vaccination or two vaccinations of MenACWY-CRM.	One year after one vaccination or two vaccinations (day 422).
Number of 2 to 5 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination	Safety was assessed as the number of 2 to 5 years-old subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after one or two vaccination(s) of MenACWY-CRM	From Days 1-7 after each vaccination
Numbers of 6 to 10 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination	Safety was assessed as the number of 6 to 10 years-old subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after one or two vaccination(s) of MenACWY-CRM	From Days 1-7 after each vaccination
Number of Subjects Who Reported Selected AEs After Any Vaccination	Safety was assessed as the number subjects who reported Selected AEs from day 1 up to day 86 after one or two vaccination(s) of MenACWY-CRM	Day 1 to Day 86
Number of Subjects Who Reported Selected AEs After Any Vaccination	Safety was assessed as the number subjects who reported Selected AEs from day 1 up to day 422 after one or two vaccination(s) of MenACWY-CRM	Day 1 to Day 422

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Johnston W, Essink B, Kirstein J, Forleo-Neto E, Percell S, Han L, Keshavan P, Smolenov I. Comparative Assessment of a Single Dose and a 2-dose Vaccination Series of a Quadrivalent Meningococcal CRM-conjugate Vaccine (MenACWY-CRM) in Children 2-10 Years of Age. Pediatr Infect Dis J. 2016 Jan;35(1):e19-27. doi: 10.1097/INF.0000000000000931. Erratum In: Pediatr Infect Dis J. 2020 Jul;39(7):e162.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2012
• Primary Completion (Actual): July 2, 2013
• Study Completion (Actual): May 30, 2014

Study Registration Dates

• First Submitted: September 7, 2012
• First Submitted That Met QC Criteria: September 7, 2012
• First Posted (Estimate): September 11, 2012

Study Record Updates

• Last Update Posted (Actual): June 14, 2019
• Last Update Submitted That Met QC Criteria: June 13, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Prevention of meningococcal disease, children, vaccine
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningococcal Infections
• Other Study ID Numbers: 205238; V59_57 (Other Identifier: Novartis Vaccines); 2011-004421-27 (EudraCT Number)