Clinical trial NCT00427908: Study in Children to Evaluate Non-Inferiority and Persistence up to 5 Years of GSK Bio Meningococcal Vaccine 134612
Official title: Evaluate Non-Inferiority and Persistence of the Immune Response of GSK Biologicals' Meningococcal Vaccine 134612 Versus Meningitec™ or Mencevax™ ACWY in Healthy Subjects (1-10 Years of Age)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Meningococcal
Keywords: Meningococcal serogroups A, C, W-135 and/or Y diseases
Conjugate vaccine
Immunogenicity
Meningococcal vaccine
Persistence
Non-inferiority
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-01-29
Enrollment: 613
Sex: ALL
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study has 2 phases, a vaccination phase and a long-term follow-up phase. In the vaccination phase of this study, the new meningococcal vaccine 134612 will be evaluated in children using Mencevax™ ACWY (in children above 2 years) or Meningitec™ (in children below 2 years) as controls. In the long-term follow-up phase of the study, the long-term protection offered by the vaccines will be assessed up to 5 years after vaccination.

Subjects will be randomized in the primary vaccination phase of the study; no new subjects will be enrolled during the long-term follow-up phase of the study.

Detailed description: Subjects will be enrolled in 3 age strata. Subjects including and above two years of age will receive either GSK Biologicals meningococcal vaccine 134612 or Mencevax™ ACWY, subjects below two years of age will receive either GSK Biologicals meningococcal vaccine 134612 or Meningitec™. All subjects will have 7 blood samples taken: prior and one month after vaccination and one, two, three, four and five years after vaccination.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, September 2007.

Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that their parent or guardian can and will comply with the requirements of the protocol.
* A male or female between, and including, 1 through 10 years 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.

Exclusion Criteria:

For the primary phase:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine, or planned use during the study period.
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose.
* Planned administration/ administration of a vaccine not foreseen by the study protocol within one month of the dose of vaccine(s).
* Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C, W, and/or Y (for subjects below 6 years) or within the last five previous years (for subjects 6 years old or above).
* Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroup A, C, W, and/or Y.
* Previous vaccination with tetanus toxoid containing vaccine within the last 28 days.
* History of meningococcal disease due to serogroup A, C, W, or Y.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) 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 any neurologic disorders or seizures.
* Acute disease at the time of enrolment.
* Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

For the long term persistence phase:

* History of meningococcal serogroup A, C, W, and/or Y disease.
* Administration of a meningococcal polysaccharide or a meningococcal polysaccharide conjugate vaccine not planned in the protocol.

Primary outcomes:
measure: Number of Subjects With Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitides Serogroups A, C, W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) Antibodies Vaccine Response
timeFrame: One Month after vaccination
measure: Number of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE) vaccination
measure: Percentage of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE) to vaccination
measure: Number of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: One month after vaccination [PI(M1)]
measure: Percentage of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: One month after vaccination [PI(M1)]
Secondary outcomes:
measure: Number of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Values
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE) and one month post vaccination [PI(M1)]
measure: Number of Subjects With Anti-polysaccharide Meningococcal Serogroup A (Anti-PSA), Serogroup C (Anti-PSC), Serogroup W-135 (Anti-PSW-135) and Serogroup Y (Anti-PSY) Antibody Concentrations Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: Anti-PS Antibody Concentrations
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: Number of Subjects With Anti-PS Antibody Concentrations Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: Anti-PS Antibody Concentrations
timeFrame: Prior to (PRE) and one month post vaccination [PI(M1)]
measure: Number of Subjects With Anti-tetanus (Anti-TT) Antibody Concentrations Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: Anti-TT Antibody Concentrations
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: Number of Subjects With Anti-TT Antibody Concentrations
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: Anti-TT Antibody Concentrations
timeFrame: Prior to (PRE) and one month post vaccination [PI(M1)]
measure: Number of Subjects With Serum Bactericidal Assay Using Human Complement Against Neisseria Meningitides Serogroups A, C, W-135, Y (hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY) Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: hSBA Antibody Titers
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: Number of Subjects With hSBA Antibody Titers ≥ the Cut-off Value
timeFrame: Prior to (PRE) and one month after vaccination [PI(M1)]
measure: hSBA Antibody Titers
timeFrame: Prior to (PRE) and one month post vaccination [PI(M1)]
measure: Number of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)] and Persistence Year 1 [PI(M12)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)] and Persistence Year 1 [PI(M12)]
measure: Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)] and Persistence Year 1 [PI(M12)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)] and Persistence Year 1 [PI(M12)]
measure: Number of Subjects With Anti-PS Antibody Concentrations Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)] and Persistence Year 1 [PI(M12)]
measure: Anti-PS Antibody Concentrations
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)] and Persistence Year 1 [PI(M12)]
measure: Number of Subjects With Anti-PS Antibody Concentrations ≥ the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)] and Persistence Year 1 [PI(M12)]
measure: Anti-PS Antibody Concentrations
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)] and at Persistence Year 1 [PI(M12)]
measure: Number of Subjects With hSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)] and Persistence Year 1 [PI(M12)]
measure: hSBA Antibody Titers
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)] and Persistence Year 1 [PI(M12)]
measure: Number of Subjects With hSBA Antibody Titers ≥ to the Cut-off Value
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)] and Persistence Year 1 [PI(M12)]
measure: hSBA Antibody Titers
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)] and at Persistence Year 1 [PI(M12)]
measure: Number of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)] and Persistence Year 2 [PI(M24)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)] and Persistence Year 2 [PI(M24)]
measure: Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)] and Persistence Year 2 [PI(M24)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)] and Persistence Year 2 [PI(M24)]
measure: Anti-PS Antibody Concentrations
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)] and Persistence Year 2 [PI(M24)]
measure: Number of Subjects With Anti-PS Antibody Concentrations Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)] and Persistence Year 2 [PI(M24)]
measure: Number of Subjects With Anti-PS Antibody Concentrations ≥ the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)] and Persistence Year 2 [PI(M24)]
measure: Anti-PS Antibody Concentrations
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)] and Persistence Year 2 [PI(M24)]
measure: Number of Subjects With hSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)] and Persistence Year 2 [PI(M24)]
measure: hSBA Antibody Titers
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)] and Persistence Year 2 [PI(M24)]
measure: Number of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)] and Persistence Year 3 [PI(M36)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)] and Persistence Year 3 [PI(M36)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)] and at Persistence Year 3 [PI(M36)]
measure: Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)] and Persistence Year 3 [PI(M36)]
measure: Number of Subjects With hSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)] and Persistence Year 3 [PI(M36)]
measure: hSBA Antibody Titers
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)] and Persistence Year 3 [PI(M36)]
measure: Number of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)] and Persistence Year 4 [PI(M48)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)] and Persistence Year 4 [PI(M48)]
measure: Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)] and Persistence Year 4 [PI(M48)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)] and Persistence Year 4 [PI(M48)]
measure: rSBA Antibody Titers
timeFrame: At Persistence Year 4 [PI(M48)]
measure: Number of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: At Persistence Year 4 [PI(M48)]
measure: Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value
timeFrame: At Persistence Year 4 [PI(M48)]
measure: rSBA Antibody Titers (HPA Laboratory Assay)
timeFrame: At Persistence Year 4 [PI(M48)]
measure: Number of Subjects With hSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)]
measure: hSBA Antibody Titers
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)]
measure: Number of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)]
measure: Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)] and Persistence Year 4 [PI(M48)]
measure: Number of Subjects With rSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)] and Persistence Year 5 [PI(M60)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)] and Persistence Year 5 [PI(M60)]
measure: Number of Subjects With rSBA Antibody Titers ≥ the Cut-off Value
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)] and Persistence Year 5 [PI(M60)]
measure: rSBA Antibody Titers
timeFrame: Prior to (PRE), one month after vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)] and at Persistence Year 5 [PI(M60)]
measure: Number of Subjects With hSBA Antibody Titers Greater Than or Equal to the Cut-off Value
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)] and Persistence Year 5 [PI(M60)]
measure: hSBA Antibody Titers
timeFrame: Prior to (PRE), one month post vaccination [PI(M1)], at Persistence Year 1 [PI(M12)], Persistence Year 2 [PI(M24)], Persistence Year 3 [PI(M36)], Persistence Year 4 [PI(M48)] and Persistence Year 5 [PI(M60)]
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: During the 4-day (Day 0-3) follow-up period
measure: Number of Subjects With Solicited General Symptoms
timeFrame: During the 4-day (Day 0-3) follow-up period
measure: Number of Subjects With Rash
timeFrame: From administration of the vaccine dose until 6 months later
measure: Number of Subjects With New Onset of Chronic Illnesses (NOCIs)
timeFrame: From administration of the vaccine dose until 6 months later
measure: Number of Subjects With Adverse Events (AEs) Resulting in an Emergency Room (ER) Visit
timeFrame: From administration of the vaccine dose until 6 months later
measure: Number of Subjects With Unsolicited AEs
timeFrame: During the 31-day (Days 0-30) post-vaccination period
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Up to 6 Months after vaccination
measure: Number of Subjects With SAE(s)
timeFrame: From 6 Months after vaccination up to Year 1
measure: Number of Subjects With SAE(s)
timeFrame: From 6 Months after vaccination up to Year 2
measure: Number of Subjects With SAE(s)
timeFrame: From 6 Months following vaccination up to Year 3
measure: Number of Subjects With SAE(s)
timeFrame: From 6 Months following vaccination up to Year 4
measure: Number of Subjects With SAE(s)
timeFrame: From 6 Months following vaccination up to Year 5
Other outcomes:
Locations:
city: Espoo
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Jarvenpaa
country: Finland
facility: GSK Investigational Site
city: Lahti
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Pori
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Vantaa
country: Finland
facility: GSK Investigational Site
city: Vantaa
country: Finland
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Vesikari T, Forsten A, Boutriau D, Bianco V, Van der Wielen M, Miller JM. A randomized study to assess the immunogenicity, antibody persistence and safety of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in children aged 2-10 years. Hum Vaccin Immunother. 2012 Dec 1;8(12):1882-91. doi: 10.4161/hv.22165. Epub 2012 Oct 2.
citation: Vesikari T, Forsten A, Boutriau D, Bianco V, Van der Wielen M, Miller JM. Randomized trial to assess the immunogenicity, safety and antibody persistence up to three years after a single dose of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in toddlers. Hum Vaccin Immunother. 2012 Dec 1;8(12):1892-903. doi: 10.4161/hv.22166. Epub 2012 Oct 2.