Safety and Immunogenicity of 2 or 3 Doses of MenACWY Conjugate Vaccine in Healthy Infants and the Effects of a Booster Dose of MenACWY Administered in the Second Year of Life

A Phase 3b, Randomized, Open-Label, Multi-Center Study to Evaluate the Safety and Immunogenicity of 2 or 3 Doses of MenACWY Conjugate Vaccine in Healthy Infants and the Effects of a Booster Dose of MenACWY Administered in the Second Year of Life.

The purpose of this study was to assess immunogenicity of a 3-dose versus 4-dose infant vaccination schedule including kinetics of immune response in the early phases of the series.

Study Overview

• Status: Completed
• Conditions: Meningococcal Disease; Meningococcal Meningitis
• Intervention / Treatment: Biological: MenACWY-CRM; Biological: MenACWY-CRM; Biological: Routine Vaccines

• Study Type: Interventional
• Enrollment (Actual): 751
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Sudbury, Ontario, Canada
    • Toronto, Ontario, Canada
  • Quebec
    • Pierrefonds, Quebec, Canada
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Arkansas
    • Fayetteville, Arkansas, United States
    • Jonesboro, Arkansas, United States
    • Little Rock, Arkansas, United States
  • California
    • Fountain Valley, California, United States
    • Huntington Beach, California, United States
    • Madera, California, United States
  • Idaho
    • Nampa, Idaho, United States
  • Kansas
    • Topeka, Kansas, United States, 66604
      • Cotton ONeil Clinical Research
    • Topeka, Kansas, United States, 66614
      • Cotton ONeil Clinical Research
  • Kentucky
    • Bardstown, Kentucky, United States
    • Louisville, Kentucky, United States
      • Bluegrass Clinical Research (Bardstown Road)
    • Louisville, Kentucky, United States
      • Bluegrass Clinical Research (Brownsboro Park Blvd)
    • Springfield, Kentucky, United States
  • Louisiana
    • Haughton, Louisiana, United States
    • Shreveport, Louisiana, United States
  • Michigan
    • Niles, Michigan, United States
  • Nebraska
    • Lincoln, Nebraska, United States
    • Omaha, Nebraska, United States
      • Children's Physicians Dundee
    • Omaha, Nebraska, United States
      • Creighton Univ
  • New York
    • Binghamton, New York, United States
    • Johnson City, New York, United States
    • Syracuse, New York, United States
  • Ohio
    • Dayton, Ohio, United States
    • Huber Heights, Ohio, United States
    • Kettering, Ohio, United States
  • Oklahoma
    • Tulsa, Oklahoma, United States
  • Tennessee
    • Kingsport, Tennessee, United States
    • Lebanon, Tennessee, United States
  • Texas
    • San Antonio, Texas, United States
    • Tomball, Texas, United States
  • Utah
    • Layton, Utah, United States
    • Saint George, Utah, United States
    • Salt Lake City, Utah, United States
  • Virginia
    • Richmond, Virginia, United States
  • Washington
    • Spokane, Washington, United States, 99202
      • Rockwood Clinic P S
    • Spokane, Washington, United States, 99218
      • Rockwood Clinic P S

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants of both genders who are in generally good health will be eligible for this study. For infants to be enrolled, the parents/legal representatives need to provide written informed consent and to be available for all study visits.

Exclusion Criteria:

• Serious, acute, or chronic illnesses are reasons for exclusion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MenACWY3; Subjects received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.	Biological: MenACWY-CRM; This group received a 3-dose primary series at 2, 4, and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.; Biological: MenACWY-CRM; This group received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.; Biological: Routine Vaccines; Each 0.5 mL dose of the pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein) is formulated to contain approximately 2.2 μg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides.
Experimental: MenACWY4; All the subjects received a 3-dose primary series at 2, 4 and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.	Biological: MenACWY-CRM; This group received a 3-dose primary series at 2, 4, and 6 months of age and a toddler dose at 12 months of age. Approximately half of the subjects had serum collected at Month 3, and the remainder had serum collected at Month 4.; Biological: MenACWY-CRM; This group received a 2-dose primary series at 2 and 4 months of age and a toddler dose at 12 months of age.; Biological: Routine Vaccines; Each 0.5 mL dose of the pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein) is formulated to contain approximately 2.2 μg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides.
Placebo Comparator: Routine Vaccines; Subjects received routine vaccines only, including PCV-13, at 2, 4 and 6 months of age and a toddler dose at 12 months of age.	Biological: Routine Vaccines; Each 0.5 mL dose of the pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein) is formulated to contain approximately 2.2 μg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Serum Bactericidal Activity Using Human Complement (hSBA) ≥ 1:8 Against N. Meningitidis Serogroups A, C, W and Y Following a 4-dose Schedule of Men ACWY Vaccination.	The immune response was assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y following 4 doses of Men ACWY vaccine given to infants at 2, 4, 6 and 12 months of age.	13 months of age
Percentage of Subjects With hSBA ≥ 1:8 Against N. Meningitidis Serogroups A, C, W and Y Following 4-Dose and 3-Dose Schedule of Men ACWY Vaccination.	The immune response was assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y following 4 doses of Men ACWY vaccine given to infants at 2, 4,6 and 12 months of age and 3 doses of Men ACWY given to infants at 2, 4 and 12 months of age.	13 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With hSBA ≥1:8 Against N. Meningitidis Serogroups A, C, W and Y at Baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age.	Antibody levels were assessed in terms of percentage of subjects with hSBA ≥ 1:8 against N. meningitidis serogroups A, C, W and Y at baseline (2 months of age) and at 3, 4, 5 and 7 months of age.	Baseline (2 months of age), 3 months, 4 months , 5 months and 7 months of age
Geometric Mean hSBA Titers Against N Meningitis Serogroups A, C, W and Y at Baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age.	Antibody levels were assessed in terms of geometric mean titers (GMTs) against N. meningitidis serogroups A, C, W and Y at baseline (2 Months of Age) and at 3, 4, 5, and 7 Months of Age.	Baseline(2 months of age), 3 months, 4 months , 5 months and 7 months of age.
Percentage of Subjects With hSBA ≥1:8 Following 2 and 3 Infant Doses of MenACWY.	Percentage of subjects with hSBA ≥1:8 against N meningitis serogroups A, C, W and Y was assessed following 2 and 3 infant doses of MenACWY as measured prior to the toddler dose at 12 months of age.	12 months of age.
Geometric Mean hSBA Titers Following 2 and 3 Infant Doses of MenACWY.	The immune response was assessed in terms of GMTs against N. meningitidis serogroups A, C, W and Y following 2 and 3 infant doses of MenACWY as measured prior to the toddler dose at 12 months of age.	12 months of age
GMTs at 13 Months of Age After Completion of 3- and 4-Dose Series of MenACWY.	Immune response was assessed in terms of GMTs against N meningitis serogroups A, C, W and Y at 1 month after completion of a 3- and 4- dose series of MenACWY.	13 months of age
Percentage of Subjects With 4-fold Increase in hSBA Titers Against N Meningitis Serogroups A, C, W and Y Between 12 and 13 Months of Age.	The immune response was assessed in terms of percentage of subjects with 4-fold increase in hSBA titers between post and pre toddler dose against N meningitis serogroups A, C, W and Y, 1 month after completing a 3- or 4-dose series of MenACWY.	13 months of age
Effect of Concomitant Administration of 2 or 3 Doses of MenACWY on Immune Response to PCV-13 Antigens at 7 Months of Age.	Percentage of subjects with IgG concentration ≥ 0.35 μg/mL against pneumococcal conjugate vaccine (PCV-13) antigens at 7 Months of age following concomitant administration of 2 or 3 doses of MenACWY with PCV-13.	7 months of age.
Effect of Concomitant Administration of 3 or 4 Doses of MenACWY on Immune Response to PCV-13 Antigens at 13 Months of Age.	Geometric mean concentrations (GMCs) of antibodies against PCV-13 vaccine antigens at 13 months of age following concomitant administration of a 3- or 4-dose series of MenACWY with PCV-13.	13 months of age.
Percentage Of Subjects Reporting at Least One Severe Systemic Solicited Adverse Event.	Safety was assessed as the percentages of subjects who reported severe solicited systemic adverse events within 30 minutes through day 7 of MenACWY administration with concomitant vaccines vs. concomitant vaccines alone.	Within 7 days
Number Of Subjects Reporting Solicited Local or Systemic Adverse Events.	Safety was assessed as the number of subjects who reported solicited local or systemic adverse events between 6 hours and day 7 after administration of MenACWY with concomitant vaccines vs. concomitant vaccines alone.	Day 1 through Day 7
Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination.		13 months of age

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Publications and helpful links

General Publications

• Block SL, Shepard J, Garfield H, Xie F, Han L, Dull PM, Smolenov I. Immunogenicity and Safety of a 3- and 4-dose Vaccination Series of a Meningococcal ACWY Conjugate Vaccine in Infants: Results of a Phase 3b, Randomized, Open-label Trial. Pediatr Infect Dis J. 2016 Feb;35(2):e48-59. doi: 10.1097/INF.0000000000000965.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: September 27, 2010
• First Submitted That Met QC Criteria: October 4, 2010
• First Posted (Estimate): October 5, 2010

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Meningitis; Infants; Persistence; Conjugate Vaccine; Meningococcal; ACWY
• 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
• Other Study ID Numbers: V59_36