Clinical trial NCT01839175: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neisseria Meningitidis
Bacterial Infections
Virus Diseases
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2013-04-24
Enrollment: 350
Sex: ALL
Minimum age (years): 46
Maximum age (years): 76
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of subjects with an anti-hepatitis B concentration ≥10 IU/mL
timeFrame: Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine)
measure: Proportion of subjects with an anti-MenC titre ≥1:8 dil
timeFrame: Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine)
Secondary outcomes:
measure: Proportion of subjects with an anti-polyribosylribitol phosphate concentration ≥0.15 µg/mL
timeFrame: 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)
measure: Proportion of subjects with an anti-diphtheria concentration ≥0.01 IU/mL
timeFrame: Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster)
measure: Proportion of subjects with an anti-tetanus concentration ≥0.01 IU/mL
timeFrame: Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine), Month 12 (Pre-booster)
measure: Proportion of subjects with an anti-inactivated poliovirus 1, 2, 3 titre ≥1:8 dil
timeFrame: 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)
measure: Proportion of subjects with pertussis vaccine response
timeFrame: Month 5 (One month after dose 3 of the hexavalent vaccine and dose 2 of MenC vaccine)
measure: Proportion of subjects with an anti-MenC titre ≥1:8 dil
timeFrame: Month 3 (One month after dose 1 of MenC vaccine)
measure: Solicited injection-site and systemic reactions
timeFrame: Day 1 to Day 7 following vaccination
measure: Unsolicited adverse events
timeFrame: Day 1 to Day 30 following vaccination
measure: Serious adverse events
timeFrame: From signature of the informed consent to the last visit of the subject, an expected average of 11 months
measure: Proportion of subjects with an anti-polyribosylribitol phosphate concentration ≥1 µg/mL
timeFrame: Month 12 (Pre-booster) and Month 13 (One month post-booster)
measure: Proportion of subjects with an anti-diphtheria concentration ≥0.1 IU/mL
timeFrame: 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)
measure: Proportion of subjects with an anti-tetanus concentration ≥0.1 IU/mL
timeFrame: 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)
measure: Proportion of subjects with an anti-MenA, anti-MenC, anti-MenW-135, anti-MenY titre ≥1:8 dil
timeFrame: Month 13 (One month after MenAWCY vaccine)
measure: Proportion of subjects with an anti-hepatitis B concentration ≥10 IU/mL
timeFrame: Month 12 (Pre-booster) and Month 13 (One month post-booster)
measure: Proportion of subjects with pertussis booster response
timeFrame: Month 13 (One month post-booster)
Other outcomes:
Locations:
city: Espoo
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 003
city: Helsinki
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 001
city: Helsinki
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 002
city: Jarvenpaa
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 011
city: Kokkola
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 010
city: Oulu
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 004
city: Pori
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 005
city: Seinajoki
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 009
city: Tampere
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 006
city: Turku
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 007
city: Vantaa
country: Finland
facility: Sanofi Pasteur MSD Investigational Site 008
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.