Evaluation of Meningococcal Immune Response Among Children Who Previously Received MenACWY Conjugate Vaccine

A Phase IIIb, Open-Label, Controlled, Multi-Center Study to Evaluate the Persistence Of Antibody Responses Among Children Who Previously Received Novartis MenACWY Conjugate Vaccine

The primary objective was to evaluate the persistence of bactericidal antibodies in children 40 and 60 months of age previously enrolled in the V59P14 (NCT00474526) study who received Novartis MenACWY Conjugate Vaccine. The study also enrolled age-matched subjects who have never received any meningococcal vaccine (naïve subjects) to serve as a control group. In addition, the response of a booster dose at 60 months was evaluated.

Study Overview

• Status: Completed
• Conditions: Meningococcal Meningitis
• Intervention / Treatment: Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine

• Study Type: Interventional
• Enrollment (Actual): 433
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Alabama Clinical Therapeutics 806 St. Vincent's Drive, Suite 615
  • California
    • Downey, California, United States, 90241
      • Premier Health Research 9317 Firestone Blvd.
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland 3505 Broadway, 6th Floor, Room 624
    • Paramount, California, United States, 90723
      • Center for Clinical Trials, LLC 16415 S. Colorado Ave., Suite 308
    • Paramount, California, United States, 90723
      • Center for Clinical Trials, LLC 16660 Paramount Blvd., Suite 301
    • Pleasanton, California, United States, 94588
      • Kaiser Permanente Pleasanton 7601 Stoneridge Drive, Second Floor
    • San Francisco, California, United States, 94115
      • Kaiser Permanente San Francisco 2200 O'Farrell St., Sixth Floor
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Santa Clara 710 Lawrence Expressway, Pediatric Clinic Department
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital 2300 Children's Plaza, Box 155
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatric/Adult Research 201 South Fifth Street, Suite 102
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • 28 Annapolis Pediatrics, 200 Forbes Street, Suite 200
  • Ohio
    • Cleveland, Ohio, United States, 44121
      • Senders Pediatrics 2054 South Green Road
  • Pennsylvania
    • East Norriton, Pennsylvania, United States, 19402
      • Pediatric Medical Associates 160 West Germantown Pike Suite D2
    • Erie, Pennsylvania, United States, 16505
      • Children's Health Care 2501 West 12th Street
    • Harleysville, Pennsylvania, United States, 19438
      • Pennridge Pediatric Associates 270 Main Street
    • Hermitage, Pennsylvania, United States, 16148
      • Kid's Way Pediatrics 3068 Innovation Way
    • Rydal, Pennsylvania, United States, 19046
      • Pediatric Medical Associates 1077 Rydal Road Suite 300
    • Sellersville, Pennsylvania, United States, 18960
      • Pennridge Pediatric Associates 711 Lawn Avenue
    • Upper Saint Clair, Pennsylvania, United States, 15241
      • PEAK Research 2859 Washington Rd., Ste. 412B

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children eligible to be enrolled in the study are those whose parents provide written informed consent, and are in generally good health based on the clinical judgment of the investigators.
• Group 1 and 2 (Follow up) subjects must be 40 +/- 3 months of age at the time of enrollment and participated in the original V59P14 study (NCT00474526).
• Group 3 and 4 (Naïve) subjects must be healthy, meningococcal vaccine-naïve children ages 40 +/- 3 months (Group 3) or 60 +/-3 months (Group 4) at the time of enrollment, respectively.

Exclusion Criteria:

• Serious, acute, or chronic illnesses are reasons for exclusion.
• Subjects who have received any vaccine (excluding influenza vaccines) 28 days preceding enrollment visit. Influenza vaccines (including FluMist®) are excluded for the 14 days prior to the enrollment visit.
• Subjects who have received any meningococcal vaccine since birth (Groups 3 & 4 -naive) or last study dose in V59P14 (NCT00474526) trial (Groups 1 & 2 - follow on).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACWY - 4; Subjects who had previously received 4 doses of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine in the parent study during their first year of life are administered one booster dose of the same vaccine at 60 months of age.	Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine
Experimental: ACWY - 2; Subjects who had previously received 1 or 2 doses of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine in the parent study during their second year of life, are administered one booster dose of the same vaccine at 60 months of age.	Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine
Other: Naïve - 40; Control subjects, age-matched with the intervention groups subjects (40 months of age), to receive 1 optional dose of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine.	Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine
Active Comparator: Naïve - 60; Control subjects, age-matched with the intervention groups subjects (60 months of age), are administered one dose of Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine.	Biological: Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Subjects With Human Serum Bactericidal Assay (hSBA) Titers ≥ 1:8 Directed Against N. Meningitidis Serogroups A, C, W-135, and Y	The persistence of the antibody response in subjects of 40 months of age, previously vaccinated with MenACWY-CRM in the parent study, and baseline antibody levels in age-matched naive subjects, is measured by the percentage of subjects with human Serum Bactericidal Assay (hSBA) titers ≥ 1:8 directed against N. meningitidis serogroups A, C, W-135, and Y.	Visit 9 (continuation from the parent study), 40-month visit.
Percentages of Subjects With Human Serum Bactericidal Assay (hSBA) Titers ≥ 1:8 Directed Against N. Meningitidis Serogroups A, C, W-135, and Y	The persistence of the antibody response in subjects of 60 months of age previously vaccinated with MenACWY-CRM in the parent study, and baseline antibody levels in age-matched naive subjects, is measured by the percentages of subjects with human Serum Bactericidal Assay (hSBA) titers ≥ 1:8 directed against N. meningitidis serogroups A, C, W-135, and Y.	Visit 10, 60 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Subjects With hSBA Titers ≥ 1:4 Against N Meningitidis Serogroups A, C, W-135, and Y in Subjects of 40 Months of Age	The persistence of the antibody response in subjects of 40 months of age previously vaccinated with MenACWY-CRM in the parent study, and baseline antibody levels in age-matched naive subjects, is measured by the percentage of subjects with human Serum Bactericidal Assay (hSBA) titers ≥ 1:4 directed against N. meningitidis serogroups A, C, W-135, and Y.	Visit 9, 40 months of age.
Percentages of Subjects With hSBA Titers ≥ 1:4 Against N Meningitidis Serogroups A, C, W-135, and Y Subjects of 60 Months of Age	The persistence of the antibody response in subjects of 60 months of age previously vaccinated with MenACWY-CRM in the parent study, and baseline antibody levels in age-matched naive subjects, is measured by the percentage of subjects with human Serum Bactericidal Assay (hSBA) titers ≥ 1:4 directed against N. meningitidis serogroups A, C, W-135, and Y.	Visit 10, 60 months of age.
hSBA Geometric Mean Titers (GMTs) Directed Against N. Meningitidis Serogroups A, C, W-135, and Y in Subjects of 40 Months of Age	The persistence of the antibody response in children of 40 months of age previously vaccinated with MenACWY-CRM in study V59P14 (NCT00474526), and baseline antibody levels in age-matched naive subjects, is measured by the hSBA GMTs directed against N meningitidis serogroups A, C, W-135, and Y.	Visit 9 (continuation from the parent study), 40-months of age.
hSBA GMTs Directed Against N Meningitidis Serogroups A, C, W-135, and Y in Subjects of 60 Months of Age	The persistence of the antibody response in children of 60 months of age previously vaccinated with MenACWY-CRM in study V59P14 (NCT00474526), and baseline antibody levels in age-matched naive subjects is measured by the hSBA GMTs directed against N meningitidis serogroups A, C, W-135, and Y.	Visit 10, 60 months of age.
Percentages of Subjects With hSBA Titers ≥ 1:8, and ≥ 1:4 Directed Against N. Meningitidis Serogroups A, C, W-135, and Y, at 1 Month Post-vaccination	The antibody response to one booster dose of MenACWY-CRM in children of 60 months of age who had previously received at least one dose of MenACWY-CRM in the parent study compared to the antibody response to one dose of MenACWY-CRM in meningococcal vaccine-naïve subjects, is measured by the percentage of subjects with hSBA titers ≥ 1:8 and ≥1:4 directed against N. meningitidis serogroups A, C, W-135, and Y, at 1 month post-vaccination.	Visit 11, 1 month after vaccination.
Percentage of Subjects With Seroresponse at 1 Month Post-vaccination	The antibody response to one booster dose of MenACWY-CRM in children of 60 months of age who had previously received at least one dose of MenACWY-CRM in the parent study, compared to the antibody response to one dose of MenACWY-CRM in meningococcal vaccine-naïve subjects, is measured by the percentage of subjects with seroresponse at 1 month post-vaccination. Seroresponse is defined as hSBA ≥ 1:8 for subjects with pre-vaccination hSBA titer ≤1:4, and as at least a four-fold rise in hSBA for subjects with pre-vaccination hSBA titer ≥ 1:4.	Visit 11, 1 month after vaccination.
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) and Other Indicators of Reactogenicity	Number of subjects reporting solicited local and systemic Adverse Events (AEs) and other indicators of reactogenicity after receiving study vaccination. Note: solicited AEs were not recorded for naive subjects at 40 months of age, but only SAEs and medically attended AEs.	From day 1 to 7 after vaccination.
Number of Subjects Reporting Unsolicited AEs and SAEs	Number of subjects reporting unsolicited AEs, serious adverse events (SAEs) and medically attended AEs after receiving study vaccination.	Day 1 to 7 after vaccination for any unsolicited AEs, day 1 to study termination for SAEs and medically attended AEs (for the naive-40 group), day 8 to study termination for SAEs and medically attended AEs (for the other groups).

Collaborators and Investigators

• Sponsor: Novartis Vaccines
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Klein NP, Block SL, Essink B, Barbi S, Smolenov I, Keshavan P. Antibody persistence and booster response following MenACWY-CRM vaccination in children as assessed by two different assay methods. Vaccine. 2019 Jul 26;37(32):4460-4467. doi: 10.1016/j.vaccine.2019.06.076. Epub 2019 Jul 3.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: June 16, 2010
• First Submitted That Met QC Criteria: June 21, 2010
• First Posted (Estimate): June 22, 2010

Study Record Updates

• Last Update Posted (Actual): August 14, 2017
• Last Update Submitted That Met QC Criteria: July 12, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Children; Meningitis; Persistence; Conjugate Vaccine; Meningococcal; ACWY; Booster dose
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Meningococcal Infections; Neisseriaceae Infections; Meningitis, Meningococcal; Meningitis
• Other Study ID Numbers: V59P14E1