Clinical trial NCT00718666: The Long-term Antibody Persistence of GSK Biologicals' Meningococcal Vaccine GSK134612 in Healthy Toddlers
Official title: Long Term Antibody Persistence Study of GSK Biologicals' Meningococcal Vaccine GSK 134612 Administered as 1 or 2 Doses to Healthy Toddlers at 9-12 Months of Age and as a Booster Dose at 5 Years Post-primary Vaccination
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Meningococcal
Keywords: Safety
Vaccines, conjugate
Immunogenicity
Meningococcal vaccine
Booster vaccination
Primary vaccination
Neisseria meningitides
Toddlers
Humans
Meningococcal disease
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-07-21
Enrollment: 387
Sex: ALL
Minimum age (years): 2
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: In this study, the concentration of antibody to the vaccine one year, three and five years after vaccination in subjects who were vaccinated with GSK Biologicals' meningococcal vaccine GSK134612 in a previous study (whose objectives \& outcome measures are presented in a separate protocol posting with NCT number =00471081) will be evaluated. The safety and immune response of a booster dose of vaccine GSK134612 administered at 5 years post-primary vaccination will also be evaluated. In addition, the immune response to a dose of vaccine GSK134612 administered to age-matched controls not previously given a meningococcal vaccine will be evaluated.

This protocol posting has been updated further to protocol amendment 2, dated 28 october 2010. The sections impacted are summary, study design, outcome measures, intervention, and eligibility criteria.

Detailed description: GSK Biologicals has developed a meningococcal conjugate vaccine (GSK134612). This candidate vaccine has been shown to be well tolerated and immunogenic in toddlers.

The purpose of this study is to evaluate the antibody persistence at approximately 1 year, 3 years and 5 years post-administration of one dose or two doses of GlaxoSmithKline (GSK) Biologicals' meningococcal vaccine GSK134612 when given to healthy toddlers 9-12 months of age. To evaluate, the safety and immunogenicity of a booster dose of GSK134612 administered to all eligible subjects at 5 years after the primary vaccination. To evaluate the safety and immunogenicity in a new group of subjects aged 5-6 years (naive control group) who will receive a single dose of vaccine GSK134612.

Eligibility criteria: Inclusion Criteria:

All subjects must satisfy the following criteria for the persistence phase of the study entry:

* A male or female toddler who was vaccinated 1, 3 or 5 years ago with the last dose of MenACWY-TT in study with NCT number=00471081.
* Written informed consent obtained from parents/guardian of the subject.
* Healthy subjects as established by medical history before entering into the study.
* Having completed the active phase of the vaccination study with NCT number=00471081 (i.e., not withdrawn, had received all planned doses of study vaccines, provided a post-vaccination blood sample after the final dose).

All subjects must meet the following criteria prior to receiving the booster vaccination:

* Written informed consent obtained from parents/guardian of the subject.
* Subjects who can and will comply with the requirements of the protocol.
* Subjects who provide a blood sample 5 years after last vaccination in study with NCT number=00471081.

All subjects must satisfy the following criteria prior to enrollment in the naïve control group:

* Subjects who the investigator believes can and will comply with the requirements of the protocol.
* A male or female between, and including, 5-6 years of age at the time of the vaccination.
* Written informed consent obtained from parents/guardian of the subject.
* Healthy subjects as established by medical history and history-directed physical examination before entering into the study.

Exclusion Criteria:

Exclusion criteria for persistence study entry

* Use of any investigational or non-registered product (drug or vaccine) within 30 days of each persistence timepoint.
* Vaccination with meningococcal polysaccharide or conjugate vaccine of serogroup A, B, C, W-135, and/or Y outside of study with NCT number=00471081.
* History of any meningococcal disease due to serogroup A, B, C, W-135, or Y.
* Any confirmed or suspected immunosuppressive or immunodeficiency condition based on medical history and physical examination (no laboratory testing is required).
* Administration of immunoglobulins and/or any blood products within the three months preceding each persistence timepoint.
* Concurrently participating in another clinical study within 30 days of each persistence timepoint, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* Bleeding disorders, such as thrombocytopenia, or subjects on anti-coagulant therapy.
* Subjects withdrew consent to be contacted for follow-up studies.

Exclusion criteria for primary (naive control)/booster vaccination at year 5 study entry (to be checked at Year 5)

* Child in care.
* Subjects who were enrolled in the Kaiser Healthcare system in study with NCT number=00471081, but are no longer enrolled.
* Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the primary (naive control)/booster vaccination, 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 primary (naive control)/booster vaccination. (For corticosteroids, this will mean prednisone, or equivalent, \>= 0.5 mg/kg/day. Inhaled and topical steroids are allowed).
* Vaccination with meningococcal polysaccharide or conjugate vaccine outside of study with NCT number=00471081.
* History of any meningococcal disease.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history (no laboratory testing is required).
* Administration of immunoglobulins and/or any blood products within the three months preceding the primary (naive control)/booster vaccination or planned administration during the study period.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* Bleeding disorders, such as thrombocytopenia, or subjects on anti-coagulant therapy.
* Subjects withdrew consent to be contacted for follow-up studies.
* Hypersensitivity to latex.
* Previous administration or planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting from 30 days of the study vaccination (primary vaccination for the naïve control group and booster vaccination for subjects primed in Study with NCT number = 00471081) and ending 30 days after with the exception of any licensed inactivated influenza vaccine (live attenuated influenza vaccine is not allowed).
* Previous administration or planned administration of tetanus or any tetanus containing vaccine during the period starting from 30 days of the study vaccination and ending 30 days after.
* A family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated.
* 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 neurological disorders or seizures.
* Acute disease at the time of vaccination. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., temperature by any method \< 99.5°F (37.5°C).

Primary outcomes:
measure: Number of Subjects With Serum Bactericidal Assay (Using Human Complement) (hSBA) Titers ≥ the Cut-off
timeFrame: At Year 1 (12 months post primary vaccination)
measure: Number of Subjects With Serum Bactericidal Assay (Using Human Complement) (hSBA) Titers ≥ the Cut-off
timeFrame: At Year 3 (36 months post primnary vaccination)
measure: Number of Subjects With Serum Bactericidal Assay (Using Human Complement) (hSBA) Titers ≥ the Cut-off Values
timeFrame: At Year 5 (60 months post primary vaccination)
Secondary outcomes:
measure: Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Titers ≥ the Cut-off Values
timeFrame: At Year 1 (12 months post vaccination)
measure: Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Titers ≥ the Cut-off Values
timeFrame: At Year 3 (36 months post primary vaccination)
measure: Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Titers ≥ the Cut-off Values
timeFrame: At Year 5 (60 months post primary vaccination)
measure: hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Antibody Titers
timeFrame: At Year 1 (12 months post primary vaccination)
measure: hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Antibody Titers
timeFrame: At Year 3 (36 months post primary vaccination)
measure: hSBA-MenA, hSBA-MenC, hSBA-MenW-135, and hSBA-MenY Antibody Titers
timeFrame: At Year 5 (60 months post primary vaccination)
measure: Number of Subjects With Titers ≥ the Cut-off for Meningococcal Polysaccharides A , C, W-135 and Y Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay
timeFrame: At Year 1 (12 months post primary vaccination)
measure: Number of Subjects With Titers ≥ the Cut-off, for MenA , MenC, MenW-135 and MenY Serum Bactericidal Antibodies, Using Baby Rabbit Complement
timeFrame: At Year 3 (36 months post primary vaccination)
measure: Number of Subjects With Titers ≥ the Cut-off for Meningococcal Polysaccharides A , C, W-135 and Y Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay
timeFrame: At Year 3 (36 months post primary vaccination)
measure: Number of Subjects With Titers ≥ the Cut-off, for Meningococcal Polysaccharides A , C, W-135 and Y Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay
timeFrame: At Year 5 (60 months post-primary vacccination).
measure: Number of Subjects With Titers ≥ the Cut-off for Men-A , Men-C, Men-W-135 and Men-Y Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay
timeFrame: At Year 5 (60 months post-primary vacccination)
measure: rSBA Antibody Titers
timeFrame: At Year 1 (12 months post primary vaccination)
measure: rSBA Antibody Titers.
timeFrame: At Year 3 (36 months post-primary vaccination)
measure: rSBA Antibody Titers
timeFrame: At Year 3 (36 months following primary vaccination)
measure: rSBA Antibody Titers
timeFrame: At Year 5 (60 months post-primary vacccination)
measure: rSBA Antibody Titers.
timeFrame: At Year 5 (60 months following primary vaccination)
measure: Antibody to Polysacccharide N. Meningitidis Serogroup A, C, W-135 and Y (Anti-PSA, Anti-PSC, Anti-PSW-135 and Anti-PSY) Antibody Concentrations
timeFrame: At Year 1 (12 months post primary vaccination)
measure: Number of Subjects With Anti-PSA, Anti-PSC, Anti-PSW-135 and Anti-PSY ≥ the Cut-off Values
timeFrame: At Year 1 (12 months post primary vaccination)
measure: Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titers ≥ Cut-off Values
timeFrame: At Month 60 (pre-primary vaccination with Nimenrix vaccine)
measure: hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titers
timeFrame: At Month 60 (pre-vaccination with Nimenrix vaccine)
measure: Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers ≥ Cut-off Values
timeFrame: At Month 60 (pre-primary vaccination with Nimenrix vaccine)
measure: rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Antibody Titers
timeFrame: At Month 60 (pre-primary vaccination with Nimenrix vaccine)
measure: Number of Subjects With hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titers ≥ Cut-off Values
timeFrame: At Month 61, one month post-primary vaccination for Nimenrix Naive Group; one month post-booster for Nimenrix 1 and Nimenrix 2 Groups
measure: hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Titers
timeFrame: At Month 61, one month post-primary vaccination for Nimenrix Naive Group; one month post-booster for Nimenrix 1 and Nimenrix 2 Groups
measure: Number of Subjects With Vaccine Response for hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY Antibody Titers
timeFrame: At Month 61, one month post-primary vaccination for Nimenrix Naive Group; one month post-booster for Nimenrix 1 and Nimenrix 2 Groups
measure: Number of Subjects With rSBA-MenA, rSBA-MenC, rSBAMenW-135 and rSBA-MenY Titers ≥ the Cut-off Values
timeFrame: At Month 60 and 61 (just prior to and one month post-primary vaccination for Nimenrix Naive Group; one month post-booster vaccination for Nimenrix 1 and Nimenrix 2 Groups)
measure: rSBA Antibody Titers
timeFrame: At Month 60 and 61 (just prior to and one month post-primary vaccination for Nimenrix Naive Group; one month post-booster for Nimenrix 1 and Nimenrix 2 Groups)
measure: Number of Subjects With Vaccine Response With rSBA-MenA, rSBA-MenC, hSBA-MenW-135 and rSBA-MenY Antibody Titers
timeFrame: At Month 61 (one month post-primary vaccination for Nimenrix Naive Group; one month post-booster for Nimenrix 1 and Nimenrix 2 Groups)
measure: Number of Subjects Reporting Any and Grade 3 Solicited Local Symptom
timeFrame: During the 4-day (Days 0-3) post-primary vaccination for Nimenrix Naive Group and post-booster for Nimenrix 1 and Nimenrix 2 Groups
measure: Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptom
timeFrame: During the 4-day (Days 0-3) post-primary vaccination for Nimenrix Naive Group and post-booster for Nimenrix 1 and Nimenrix 2 Groups
measure: Number of Subjects Reporting Any Unsolicited Adverse Events (AEs)
timeFrame: During the 31-day (Days 0-30) post-primary vaccination for Nimenrix Naive Group and post-booster for Nimenrix 1 and Nimenrix 2 Groups
measure: Number of Subjects Reporting Any Serious Adverse Events (SAEs)
timeFrame: During the 181-day (Days 0-180) post primary vaccination for Nimenrix Naive Group and post booster for Nimenrix 1 and Nimenrix 2 Groups
measure: Number of Subjects Reporting Any New Onset of Chronic Illnesses (NOCIs)
timeFrame: During the 181-day (Days 0-180) post primary vaccination for Nimenrix Naive Group and post booster for Nimenrix 1 and Nimenrix 2 Groups
Other outcomes:
Locations:
city: Benton
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Antioch
country: United States
facility: GSK Investigational Site
state: California
city: Fremont
country: United States
facility: GSK Investigational Site
state: California
city: Hayward
country: United States
facility: GSK Investigational Site
state: California
city: Santa Rosa
country: United States
facility: GSK Investigational Site
state: California
city: Vacaville
country: United States
facility: GSK Investigational Site
state: California
city: Lakewood
country: United States
facility: GSK Investigational Site
state: Colorado
city: Littleton
country: United States
facility: GSK Investigational Site
state: Colorado
city: Littleton
country: United States
facility: GSK Investigational Site
state: Colorado
city: Westminster
country: United States
facility: GSK Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: GSK Investigational Site
state: Colorado
city: Canton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Amarillo
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Klein NP, Baine Y, Bianco V, Lestrate PR, Naz A, Blatter M, Friedland LR, Miller JM. One or two doses of quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine is immunogenic in 9- to 12-month-old children. Pediatr Infect Dis J. 2013 Jul;32(7):760-7. doi: 10.1097/INF.0b013e31828693c5.
citation: Klein NP, Baine Y, Kolhe D, Baccarini CI, Miller JM, Van der Wielen M. Five-year Antibody Persistence and Booster Response After 1 or 2 Doses of Meningococcal A, C, W and Y Tetanus Toxoid Conjugate Vaccine in Healthy Children. Pediatr Infect Dis J. 2016 Jun;35(6):662-72. doi: 10.1097/INF.0000000000001123.