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.

• ClinicalTrials.gov Identifier: NCT01682876
• Recruitment Status: Completed
• First Posted: September 11, 2012
• Results First Posted: October 6, 2014
• Last Update Posted: June 14, 2019
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Meningococcal Disease; Infections, Meningococcal	Biological: MenACWY-CRM	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 715 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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.
• Actual Study Start Date: October 7, 2012
• Actual Primary Completion Date: July 2, 2013
• Actual Study Completion Date: May 30, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: One Month After Last Vaccination ( day 86) ]
   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.
2. 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 [ Time Frame: One Month After Last Vaccination (day 86) ]
   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.

Secondary Outcome Measures :

1. 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 [ Time Frame: One Month After Last Vaccination (day 86) ]
   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.
2. 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 [ Time Frame: One Month After Last Vaccination (day 86) ]
   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.
3. 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 [ Time Frame: One year after one vaccination or two vaccinations (day 422). ]
   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.
4. 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 [ Time Frame: One year after one vaccination or two vaccinations (day 422). ]
   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.
5. Number of 2 to 5 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination [ Time Frame: From Days 1-7 after each 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
6. Numbers of 6 to 10 Years-Old Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination [ Time Frame: From Days 1-7 after each 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
7. Number of Subjects Who Reported Selected AEs After Any Vaccination [ Time Frame: Day 1 to Day 86 ]
   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
8. Number of Subjects Who Reported Selected AEs After Any Vaccination [ Time Frame: Day 1 to Day 422 ]
   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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

GSK Investigational Site

Birmingham, Alabama, United States, 35205

United States, California

GSK Investigational Site

Sacramento, California, United States, 95822

United States, Florida

GSK Investigational Site

Lake Mary, Florida, United States, 32746

United States, Georgia

GSK Investigational Site

Marietta, Georgia, United States, 30062

GSK Investigational Site

Woodstock, Georgia, United States, 30189

United States, Iowa

GSK Investigational Site

Council Bluffs, Iowa, United States, 51503

United States, Kentucky

GSK Investigational Site

Louisville, Kentucky, United States, 40291

United States, Louisiana

GSK Investigational Site

Metairie, Louisiana, United States, 70006

United States, Michigan

GSK Investigational Site

Niles, Michigan, United States, 49120

GSK Investigational Site

Stevensville, Michigan, United States, 49127

United States, Nebraska

GSK Investigational Site

Bellevue, Nebraska, United States, 68005

GSK Investigational Site

Fremont, Nebraska, United States, 68025

GSK Investigational Site

Omaha, Nebraska, United States, 68134

United States, New York

GSK Investigational Site

Johnson City, New York, United States, 13790

United States, Ohio

GSK Investigational Site

Cleveland, Ohio, United States, 44121

GSK Investigational Site

Cleveland, Ohio, United States, 44122

United States, Texas

GSK Investigational Site

Austin, Texas, United States, 78705

GSK Investigational Site

Fort Worth, Texas, United States, 76135

United States, Utah

GSK Investigational Site

West Jordan, Utah, United States, 84088

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01682876
• Other Study ID Numbers: 205238; V59_57 ( Other Identifier: Novartis Vaccines ); 2011-004421-27 ( EudraCT Number )
• First Posted: September 11, 2012
• Results First Posted: October 6, 2014
• Last Update Posted: June 14, 2019
• Last Verified: June 2019

Keywords provided by GlaxoSmithKline:

Prevention of meningococcal disease, children, vaccine

Additional relevant MeSH terms:

Meningococcal Infections; Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections