Clinical trial NCT00326118: Study in Toddlers to Demonstrate Non-inferiority of GSK Biologicals' Hib-MenC & to Evaluate Persistence up to 5 Years.
Official title: Study to Demonstrate Non-inferiority of GSK Biologicals' Hib-MenC With Priorix™, Versus MenC-CRM197 Vaccine With Hiberix™ & Priorix™ in Toddlers Primed With Hib But Not MenC & to Evaluate Persistence up to 5 Years After Vaccination.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Haemophilus Influenzae Type b
Neisseria Meningitidis
Keywords: Meningococcal serogroup C diseases
H.influenzae type b diseases
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-05-16
Enrollment: 433
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the primary phase of the study is to demonstrate the non-inferiority of a single dose of GSK Biologicals' Haemophilus influenzae type b and meningococcal C (Hib-MenC) conjugate vaccine when given in the second year of life to subjects primed in infancy with a Hib vaccine, but not with a meningococcal serogroup C vaccine, versus commercially available Hib and MenC vaccines.

In the extension phase, at Years 1, 2, 3, 4 \& 5, one blood sample is taken at each year to follow the antibody persistence up to 5 years after vaccination. No additional vaccine is administered during the extension phase. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed description: This multicenter study is open and has 2 treatment groups with Hiberix™ + a commercially available MenC vaccine as active controls. Priorix™ is given concomitantly in both groups. In the primary phase, two blood samples are taken from all subjects for immunogenicity analyses: before and one month after vaccination. In the extension phase, at Year 1, 2, 3, 4 \& 5, one blood sample is taken at each year to follow the antibody persistence up to 5 years after vaccination. No additional vaccine is administered during the extension phase.

Eligibility criteria: Inclusion Criteria:

Primary phase:

* Subjects whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
* A male or female between, and including, 12 and 18 months of age at the time of vaccination.
* Written informed consent obtained from the parent or guardian of the subject.
* Free of obvious health problems as established by medical history and clinical examination before entering into the study.
* Previously completed routine childhood vaccinations to the best of his/her parents'/guardians knowledge.
* Having completed primary vaccination with two doses of Haemophilus influenzae type b outer membrane protein (Hib-OMP) containing vaccine OR three doses of diphtheria, tetanus, acellular pertussis and Haemophilus influenzae type b (DTPa/Hib) containing vaccine at least 6 months before the study start.

Long-term persistence phase:

- Having participated in the vaccination study 106445

Exclusion Criteria:

For the primary vaccination phase:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Chronic administration (defined as more than 14 days) or planned administration of immuno-suppressants or other immune-modifying drugs within six months prior to vaccination.
* Planned administration/administration of a vaccine not foreseen by the protocol during the period starting from 30 days before vaccination and ending 30 days after vaccination.
* Administration of a meningococcal vaccine not foreseen by the study protocol during the period starting at birth and ending at first dose.
* Previous administration of a booster dose of Hib vaccine.
* Previous vaccination against measles, mumps, rubella.
* History of H. influenzae type b, meningococcal serogroup C and/or confirmed measles, mumps or rubella diseases.
* Known exposure to measles, mumps or rubella within 30 days prior to the start of the study.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus infection.
* A family history of congenital or hereditary immunodeficiency.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
* Major congenital defects or serious chronic illness.
* History of neurological disorders or more than one episode of febrile convulsion.
* Acute disease at the time of enrolment.
* Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

Additional exclusion criteria for the long-term persistence phase: to be checked each year.

* Previous administration of a booster dose of Hib, meningococcal serogroup C vaccines.
* History of H. influenzae type b, meningococcal serogroup C diseases.

Primary outcomes:
measure: Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Greater Than or Equal to 0.15 Micrograms Per Milliliter (µg/mL)
timeFrame: 1 month after vaccination
measure: Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Greater Than or Equal to 1:8 Titer
timeFrame: 1 month after vaccination
Secondary outcomes:
measure: Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Above the Cut-off Values
timeFrame: Prior to, 1 month, 1 year, 2 years, 3 years and 4 years after vaccination
measure: Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers Above the Cut-off Values
timeFrame: 5 years after vaccination
measure: Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers
timeFrame: Prior to, 1 month, 1 year, 2 years, 3 years and 4 years after vaccination.
measure: Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titers
timeFrame: 5 years after vaccination
measure: Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Above Cut-off Values
timeFrame: Prior to, 1 month, 1 year, 2 years, 3 years and 4 years after vaccination
measure: Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentration Above Cut-off Values
timeFrame: 5 years after vaccination
measure: Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations
timeFrame: Prior to, 1 month , 1 year, 2 years, 3 years and 4 years after vaccination
measure: Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations
timeFrame: 5 years after vaccination
measure: Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Above the Cut-off Values
timeFrame: Prior to, 1 month, 1 year, 2 years and 3 years after vaccination
measure: Anti-polysaccharide C (Anti-PSC) Antibody Concentrations
timeFrame: Prior to, 1 month, 1 year, 2 years and 3 years after vaccination
measure: Number of Subjects Reporting Solicited Local and General Symptoms
timeFrame: Within 4 days (Day 0 -Day 3) after vaccination
measure: Number of Subjects Reporting Unsolicited Symptoms
timeFrame: Within 31 days (Day 0 - Day 30) after vaccination
measure: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: Throughout the entire study period (up to year 5)
Other outcomes:
Locations:
city: Garran
country: Australia
facility: GSK Investigational Site
state: Australian Capital Territory
city: Randwick
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Westmead
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Herston
country: Australia
facility: GSK Investigational Site
state: Queensland
city: North Adelaide
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Carlton
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Perth
country: Australia
facility: GSK Investigational Site
state: Western Australia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Booy R, Richmond P, Nolan T, McVernon J, Marshall H, Nissen M, Reynolds G, Ziegler JB, Heron L, Lambert S, Caubet M, Mesaros N, Boutriau D. Immediate and longer term immunogenicity of a single dose of the combined haemophilus influenzae type B-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in primed toddlers 12 to 18 months of age. Pediatr Infect Dis J. 2011 Apr;30(4):340-2. doi: 10.1097/INF.0b013e31820013d2.
citation: Booy R, Richmond P, Nolan T, McVernon J, Marshall H, Nissen M, Reynolds G, Ziegler JB, Stoney T, Heron L, Lambert S, Mesaros N, Peddiraju K, Miller JM. Three-year antibody persistence and safety after a single dose of combined haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in Hib-primed toddlers. Pediatr Infect Dis J. 2013 Feb;32(2):169-74. doi: 10.1097/INF.0b013e3182787bff.
citation: Booy R et al. Immunogenicity and safety of the Hib-MenC-TT conjugate vaccine in Hib-primed toddlers: 3 year follow-up. Abstract presented at the 7th World Congress for World Society for Pediatric Infectious Diseases (WSPID). Melbourne, Australia, 16-19 November 2011.
citation: Booy R et al. Immunogenicity and safety of the Hib-MenC-TT conjugate vaccine in Hib-primed toddlers: 4 year follow-up. Abstract presented at the Communicable Diseases Network Australia - Communicable Diseases Control Conference 2013, Canberra, Australia, 19-20 March 2013.
citation: Booy R et al. Prolonged immunogenicity and safety of the HibMenC-TT conjugate vaccine in Hib-Primed toddlers. Abstract presented at the PHAA Communicable Disease Conference. Canberra, Australia, 4-6 April 2011.