Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Toddlers

Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Toddlers 12 to 23 Months of Age.

The purpose of the study was to evaluate the immunogenicity and describe the safety of a single dose of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine compared to the licensed Meningococcal polysaccharide groups A, C, W-135 and Y (Nimenrix®) Conjugate vaccine in toddlers 12 to 23 months of age in the European Union (EU). The toddlers were either meningococcal vaccine naïve or had received monovalent meningococcal C (MenC) vaccination during infancy to evaluate any potential impact of the meningococcal vaccine background on the immunogenicity and safety profile of the investigational product.

Primary Objectives:

• To demonstrate the non-inferiority of the antibody response to meningococcal serogroups A, C, Y, and W after a single dose of MenACYW Conjugate vaccine or Nimenrix® in toddlers who either were meningococcal vaccine naïve or had received monovalent MenC vaccination during infancy.
• To demonstrate the non-inferiority of the antibody response to meningococcal serogroups A, C, Y, and W after a single dose of MenACYW Conjugate vaccine or Nimenrix® in meningococcal vaccine naïve toddlers.

Secondary Objectives:

• To compare the antibody responses (geometric mean titers [GMTs]) to meningococcal serogroups A, C, Y, and W after a dose of MenACYW Conjugate vaccine or Nimenrix® as measured by serum bactericidal assay using human complement (hSBA) in toddlers who either were meningococcal vaccine naïve or had received monovalent MenC vaccination during infancy.
• To compare the antibody responses (GMTs) to meningococcal serogroups A, C, Y, and W after a dose of MenACYW Conjugate vaccine or Nimenrix® as measured by hSBA in meningococcal vaccine naïve toddlers.
• To compare the antibody responses (GMTs) to meningococcal serogroups A, C, Y, and W after a dose of MenACYW Conjugate vaccine or Nimenrix® as measured by hSBA in toddlers who received monovalent MenC vaccination during infancy.

Study Overview

• Status: Completed
• Conditions: Meningitis; Meningococcal Infections; Meningococcal Meningitis
• Intervention / Treatment: Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; Biological: Meningococcal polysaccharide groups A, C, W-135 and Y Conjugate vaccine

Detailed Description

Healthy toddlers were randomized depending on their meningococcal priming vaccination background (either meningococcal vaccine naïve or primed with MenC) and received a single dose of either MenACYW Conjugate vaccine or Nimenrix®. They were assessed for immunogenicity at baseline (pre-vaccination) and 30 to 44 days post-vaccination. Safety information were collected post-vaccination and throughout the entire study.

• Study Type: Interventional
• Enrollment (Actual): 918
• Phase: Phase 3

Contacts and Locations

Study Locations

• Finland
  • Espoo, Finland, 02230
    • Investigational Site 309
  • Helsinki, Finland, 00100
    • Investigational Site 301
  • Helsinki, Finland, 00930
    • Investigational Site 306
  • Järvenpää, Finland, 04400
    • Investigational Site 302
  • Kokkola, Finland, 67100
    • Investigational Site 304
  • Oulu, Finland, 90220
    • Investigational Site 307
  • Pori, Finland, 28100
    • Investigational Site 303
  • Seinäjoki, Finland, 60100
    • Investigational Site 305
  • Tampere, Finland, 33100
    • Investigational Site 308
  • Turku, Finland, 20520
    • Investigational Site 310
• Germany
  • Aschaffenburg, Germany, 63739
    • Investigator Site 412
  • Bramsche, Germany, 49565
    • Investigator Site 401
  • Bretten, Germany, 75015
    • Investigator Site 407
  • Bönnigheim, Germany, 74357
    • Investigator Site 411
  • Datteln, Germany, 45711
    • Investigator Site 413
  • Goch, Germany, 47574
    • Investigator Site 408
  • Hamburg, Germany, 22415
    • Investigator Site 406
  • Hamburg, Germany, 22415
    • Investigator Site 415
  • Ludwigsfelde, Germany, 14974
    • Investigator Site 404
  • Rosenheim, Germany, 83026
    • Investigator Site 409
  • Tauberbischofsheim, Germany, 97941
    • Investigator Site 402
  • Tauberbischofsheim, Germany, 97941
    • Investigator Site 403
• Hungary
  • Budapest, Hungary, H 1042
    • Investigational Site 102
  • Budapest, Hungary, H 1188
    • Investigational Site 101
  • Győr, Hungary, H 9024
    • Investigational Site 104
  • Miskolc, Hungary, H 3527
    • Investigational Site 105
  • Szeged, Hungary, H 6723
    • Investigational Site 103
  • Székesfehérvár, Hungary, H 8000
    • Investigational Site 106
• Spain
  • Barcelona, Spain, 08950
    • Investigator site 203
  • Galicia, Spain, 15706
    • Investigator site 204
  • Madrid, Spain, 28007
    • Investigator site 205
  • Madrid, Spain, 28046
    • Investigator site 202
  • Sevilla, Spain, 41014
    • Investigator site 201

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 12 to 23 months on the day of the first study visit.
• Participants had received all recommended standard-of-care non-meningococcal vaccinations according to his/her age as per local regulations.
• Informed consent form (ICF) had been signed and dated by the parent/legally acceptable representative.
• Participant and parent/legally acceptable representative were able to attend all scheduled visits and complied with all trial procedures.
• Covered by health insurance if required by local regulations.
• Participants had received any meningococcal vaccine in the second year of life (i.e., from 12 months of age).
• For Inclusion in Groups 1 and 2: Participants must not had received any vaccination against meningococcal disease with either a trial vaccine or a licensed meningococcal vaccine (i.e., polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, W, Y, B; or any monovalent or bivalent meningococcal vaccine).
• For Inclusion in Groups 3 and 4: Participants must had previously received at least 1 dose of licensed monovalent meningococcal C Conjugate (MenC) vaccine during infancy (i.e., before 12 months of age).

Exclusion Criteria:

• Participation in the 4 weeks preceding the 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 (28 days) preceding the trial vaccination or planned receipt of any vaccine prior to Visit 2 except for influenza vaccination, which may be received at least 2 weeks before or after study investigational vaccines. This exception included monovalent pandemic influenza vaccines and multivalent influenza vaccines.
• Receipt of immune globulins, blood or blood-derived products in the past 3 months.
• For Groups 1 and 2 only: Vaccination against meningococcal disease with either a trial vaccine or a licensed meningococcal vaccine (i.e., polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, W, Y, B; or any monovalent or bivalent meningococcal vaccine).
• For Groups 3 and 4 only: Vaccination against meningococcal disease with either a trial vaccine or a licensed meningococcal vaccine (i.e., polyvalent, polysaccharide, or Conjugate meningococcal vaccine containing serogroups A, C, W, Y, B; or any monovalent B meningococcal vaccine), except licensed monovalent meningococcal C Conjugate (MenC) vaccination received during infancy.
• 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).
• History of meningococcal infection, confirmed either clinically, serologically, or microbiologically.
• At high risk for meningococcal infection during the trial (specifically, but not limited to, participants with persistent complement deficiency, with anatomic or functional asplenia, or participants travelling to countries with high endemic or epidemic disease).
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances.
• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine.
• Personal history of Guillain-Barré Syndrome.
• Verbal report of thrombocytopenia, as reported by the parent/legally acceptable representative contraindicating intramuscular vaccination in the Investigator's opinion.
• Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion.
• 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) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw - Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1(Meningococcal Vaccine-Naive):MenACYW Conjugate Vaccine; Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular; Other Names: MenACYW Conjugate vaccine; Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 mL, Intramuscular; Other Names: MenACYW Conjugate vaccine
EXPERIMENTAL: Group 2 (Meningococcal Vaccine-Naive): Nimenrix®; Healthy, meningococcal vaccine naive toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.	Biological: Meningococcal polysaccharide groups A, C, W-135 and Y Conjugate vaccine; 0.5 mL, Intramuscular; Other Names: Nimenrix®
EXPERIMENTAL: Group 3 (MenC-Primed): MenACYW Conjugate Vaccine; Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of MenACYW Conjugate vaccine on Day 0.	Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular; Other Names: MenACYW Conjugate vaccine; Biological: Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 mL, Intramuscular; Other Names: MenACYW Conjugate vaccine
EXPERIMENTAL: Group 4 (MenC-Primed): Nimenrix®; Healthy, meningococcal C vaccine primed toddlers aged 12 to 23 months received a single dose of Nimenrix® vaccine on Day 0.	Biological: Meningococcal polysaccharide groups A, C, W-135 and Y Conjugate vaccine; 0.5 mL, Intramuscular; Other Names: Nimenrix®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Antibody Titers Greater Than or Equal to (>=) 1:8 Against Meningococcal Serogroups A, C, Y, and W in Toddlers Who Either Were Meningococcal Vaccine Naïve or Had Received Monovalent MenC Vaccination During Infancy	Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by serum bactericidal assay using human complement (hSBA). Data for this outcome measure were planned to be analyzed for the pooled population of MenACYW Conjugate vaccine and Nimenrix® reporting groups.	Day 30 (post-vaccination)
Percentage of Participants With Antibody Titers >=1:8 Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Meningococcal Vaccine Naïve Toddlers	Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.	Day 30 (post-vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Antibodies Against Meningococcal Serogroups A, C, Y, and W in Toddlers Who Either Were Meningococcal Vaccine Naïve or Had Received Monovalent MenC Vaccination During Infancy	Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.	Day 30 (post-vaccination)
Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Vaccine Naive Toddlers	Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.	Day 30 (post-vaccination)
Geometric Mean Titers of Antibodies Against Meningococcal Serogroups A, C, Y, and W Following Vaccination With MenACYW Conjugate Vaccine or Nimenrix® in Toddlers Who Had Received Monovalent MenC Vaccination During Infancy	Antibody titers against Meningococcal Serogroups A, C, Y, and W were measured by hSBA.	Day 30 (post-vaccination)

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 24, 2017
• Primary Completion (ACTUAL): October 26, 2017
• Study Completion (ACTUAL): October 26, 2017

Study Registration Dates

• First Submitted: November 3, 2016
• First Submitted That Met QC Criteria: November 3, 2016
• First Posted (ESTIMATE): November 4, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 5, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Meningitis; Meningococcal Meningitis; MenACYW Conjugate vaccine; Nimenrix®; Menjugate®
• 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; Neisseriaceae Infections; Meningitis, Meningococcal; Meningitis; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: MET51; U1111-1161-2935 (OTHER: WHO); 2016-000749-30 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes