Concomitant Administration of a New Hexavalent Vaccine With a Meningococcal Serogroup C Conjugate Vaccine in Healthy Infants During Primary Series Immunisation Followed by Booster Vaccination

A Phase III Open-label Randomised Study to Evaluate the Immunogenicity and Safety of the Concomitant Administration of a New Hexavalent DTaP-IPV-HepB-PRP-T Combined Vaccine (Hexavalent Vaccine) Given at 2, 3, and 4 Months of Age With a Meningococcal Serogroup C Conjugate (MenC) Vaccine Given at 2 and 4 Months of Age

Primary Series Primary objectives

• To demonstrate that the concomitant administration of the hexavalent vaccine with a meningococcal serogroup C conjugate vaccine is non inferior to the administration of the hexavalent vaccine without a MenC vaccine concomitantly in term of seroprotection rate for hepatitis B one month after the third dose of the hexavalent vaccine
• To demonstrate that the concomitant administration of a MenC vaccine with the hexavalent vaccine induces an acceptable response for MenC in term of seroprotection rate (SPR) one month after the second dose of MenC

Booster Primary objectives

- To describe the immunogenicity of a booster dose of the hexavalent vaccine and of a meningococcal group ACWY conjugate (MenACWY) vaccine either co-administered at 12 months of age or given separately.

Study Overview

• Status: Completed
• Conditions: Virus Diseases; Bacterial Infections; Neisseria Meningitidis
• Intervention / Treatment: Biological: Hexavalent vaccine; Biological: NeisVac-C; Biological: Prevenar 13; Biological: RotaTeq; Biological: Nimenrix; Biological: M-M-RVAXPRO

Detailed Description

Primary Series Secondary objectives

• To describe the antibody response to all the hexavalent vaccine antigens one month after the third dose of the hexavalent vaccine when given concomitantly or not to MenC
• To describe the antibody response to MenC vaccine when a MenC vaccine is given concomitantly with the hexavalent vaccine, one month after the first and the second dose of MenC vaccine
• To describe the safety profile of the hexavalent vaccine after each and any injection when given concomitantly or not with a MenC vaccine

Booster Secondary objectives

• To describe the antibody (Ab) persistence at 12 months of age for the hexavalent valences following a 3-dose primary vaccination at 2, 3 and 4 months of age (prior to administration of a booster dose)
• To describe the safety of a booster dose of the hexavalent vaccine and of a meningococcal group ACWY conjugate (MenACWY) vaccine either co-administered at 12 months of age or given separately.

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 3

Contacts and Locations

Study Locations

• Finland
  • Espoo, Finland
    • Sanofi Pasteur MSD Investigational Site 003
  • Helsinki, Finland
    • Sanofi Pasteur MSD Investigational Site 001
  • Helsinki, Finland
    • Sanofi Pasteur MSD Investigational Site 002
  • Jarvenpaa, Finland
    • Sanofi Pasteur MSD Investigational Site 011
  • Kokkola, Finland
    • Sanofi Pasteur MSD Investigational Site 010
  • Oulu, Finland
    • Sanofi Pasteur MSD Investigational Site 004
  • Pori, Finland
    • Sanofi Pasteur MSD Investigational Site 005
  • Seinajoki, Finland
    • Sanofi Pasteur MSD Investigational Site 009
  • Tampere, Finland
    • Sanofi Pasteur MSD Investigational Site 006
  • Turku, Finland
    • Sanofi Pasteur MSD Investigational Site 007
  • Vantaa, Finland
    • Sanofi Pasteur MSD Investigational Site 008

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy infant 46 to 74 days of age (both inclusive)
• Born at full term of pregnancy (≥37 weeks) and/or with a birth weight≥2.5 kg
• Subject's parent(s) or legal representative able to comply with the study procedures

Exclusion Criteria:

• Participation in another clinical study investigating a vaccine, drug, medical device, or medical procedure
• Receipt of any vaccine in the 4 weeks preceding each study vaccination
• Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b, meningococcal, pneumococcal, rotavirus infection
• Know or suspected congenital, hereditary or acquired immunodeficiency
• History of seizures or encephalopathy
• Known thrombocytopenia
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular injection
• Chronic illness that could interfere with trial conduct or completion
• Known or suspected hypersensitivity to any of the study vaccines' active substance or excipients or history of a life-threatening reaction to a vaccine(s) containing the same substances as the study vaccines
• Contraindication to any of the study vaccines
• Known personal or maternal history of hepatitis B or hepatitis C seropositivity
• History of diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilus influenzae type b or meningococcal serogroup C infection
• Receipt of immune globulin, blood or blood-derived products, immunosuppressive drugs, systemic corticosteroid since birth
• Identified as a natural or adopted child of the investigator or employee with direct involvement in the current study.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 2	Biological: Hexavalent vaccine; 0.5 mL intramuscular injection at 2, 3 and 4 months of age (primary series) 0.5 mL intramuscular injection at 12 or 13 months of age (booster); Other Names: Diphtheria, tetanus, pertussis, hepatitis B,; poliomyelitis and Haemophilus influenzae type b conjugate vaccine (adsorbed).; Biological: Prevenar 13; 0.5 mL intramuscular injection at 2 and 4 months of age (primary series) 0.5 mL intramuscular injection at 13 months of age (booster); Other Names: Pneumococcal conjugate vaccine (13-valent, adsorbed); Biological: RotaTeq; 2 mL oral administration at 2, 3 and 4 months; Other Names: Human-bovine rotavirus reassortants (live) vaccine; Biological: Nimenrix; 0.5 mL intramuscular injection at 12 months; Other Names: Meningococcal group A, C, W-135 and Y conjugate vaccine; Biological: M-M-RVAXPRO; 0.5 mL intramuscular or subcutaneous injection at 13 months of age; Other Names: Measles, mumps and rubella vaccine (live)
Experimental: Group 1	Biological: Hexavalent vaccine; 0.5 mL intramuscular injection at 2, 3 and 4 months of age (primary series) 0.5 mL intramuscular injection at 12 or 13 months of age (booster); Other Names: Diphtheria, tetanus, pertussis, hepatitis B,; poliomyelitis and Haemophilus influenzae type b conjugate vaccine (adsorbed).; Biological: NeisVac-C; 0.5 mL intramuscular injection at 2 and 4 months of age; Other Names: Meningococcal group C polysaccharide conjugate vaccine adsorbed; Biological: Prevenar 13; 0.5 mL intramuscular injection at 2 and 4 months of age (primary series) 0.5 mL intramuscular injection at 13 months of age (booster); Other Names: Pneumococcal conjugate vaccine (13-valent, adsorbed); Biological: RotaTeq; 2 mL oral administration at 2, 3 and 4 months; Other Names: Human-bovine rotavirus reassortants (live) vaccine; Biological: Nimenrix; 0.5 mL intramuscular injection at 12 months; Other Names: Meningococcal group A, C, W-135 and Y conjugate vaccine; Biological: M-M-RVAXPRO; 0.5 mL intramuscular or subcutaneous injection at 13 months of age; Other Names: Measles, mumps and rubella vaccine (live)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with an anti-hepatitis B concentration ≥10 IU/mL	Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine)
Proportion of subjects with an anti-MenC titre ≥1:8 dil	Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine)

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with an anti-polyribosylribitol phosphate concentration ≥0.15 µg/mL	Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster) and Month 13 (One month post-booster)
Proportion of subjects with an anti-diphtheria concentration ≥0.01 IU/mL	Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster)
Proportion of subjects with an anti-tetanus concentration ≥0.01 IU/mL	Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster)
Proportion of subjects with an anti-inactivated poliovirus 1, 2, 3 titre ≥1:8 dil	Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster) and Month 13 (One month post-booster)
Proportion of subjects with pertussis vaccine response	Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine)
Proportion of subjects with an anti-MenC titre ≥1:8 dil	Month 3 (One month after dose 1 of MenC vaccine)
Solicited injection-site and systemic reactions	Day 1 to Day 7 following vaccination
Unsolicited adverse events	Day 1 to Day 30 following vaccination
Serious adverse events	From signature of the informed consent to the last visit of the subject, an expected average of 11 months
Proportion of subjects with an anti-polyribosylribitol phosphate concentration ≥1 µg/mL	Month 12 (Pre-booster) and Month 13 (One month post-booster)
Proportion of subjects with an anti-diphtheria concentration ≥0.1 IU/mL	Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster) and Month 13 (One month post-booster)
Proportion of subjects with an anti-tetanus concentration ≥0.1 IU/mL	Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster) and Month 13 (One month post-booster)
Proportion of subjects with an anti-MenA, anti-MenC, anti-MenW-135, anti-MenY titre ≥1:8 dil	Month 13 (One month after MenAWCY vaccine)
Proportion of subjects with an anti-hepatitis B concentration ≥10 IU/mL	Month 12 (Pre-booster) and Month 13 (One month post-booster)
Proportion of subjects with pertussis booster response	Month 13 (One month post-booster)

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Vesikari T, Borrow R, Da Costa X, Thomas S, Eymin C, Boisnard F, Lockhart S. Concomitant administration of a fully liquid ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal ACWY conjugate vaccine in toddlers. Vaccine. 2018 Dec 18;36(52):8019-8027. doi: 10.1016/j.vaccine.2018.10.100. Epub 2018 Nov 22.
• Vesikari T, Borrow R, Da Costa X, Richard P, Eymin C, Boisnard F, Lockhart S. Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants. Vaccine. 2017 Jan 11;35(3):452-458. doi: 10.1016/j.vaccine.2016.11.053. Epub 2016 Dec 9.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: April 19, 2013
• First Submitted That Met QC Criteria: April 19, 2013
• First Posted (Estimate): April 24, 2013

Study Record Updates

• Last Update Posted (Actual): September 11, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Virus Diseases; Bacterial Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: HXM01C; 2012-005547-24 (EudraCT Number)