Co-Administration of Meningococcal Vaccine GSK134612 With Infanrix Hexa™ Versus Individual Administration of Each Vaccine

Phase 3

Completed

Conditions: Infections, Meningococcal

Interventions: Biological: Meningococcal vaccine GSK134612
Biological: Meningitec™
Biological: Infanrix™ hexa

Registration Number: NCT00508261

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study is to demonstrate, in 12-23 months old subjects, the non-inferiority of meningococcal vaccine GSK134612 co-administered with Infanrix hexa™, compared to each vaccine administered individually and to licensed meningococcal vaccine Meningitec™.

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

Detailed Description: Multicentre study with 4 parallel groups. One group will receive GSK134612 co-administered with Infanrix hexa™, two groups will receive sequential administration of GSK134612 and Infanrix hexa™ and the final group will receive Meningitec™.

For subjects in Groups B and C, three blood samples will be taken: prior to first vaccination and 1 month after each vaccination.

For subjects in Groups A and D, two blood samples will be taken: prior to and 1 month after vaccination.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 793

Inclusion Criteria

Subjects who 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 23 months of age at the time of the first 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.
Documented three-dose primary vaccination with DTPa, hepatitis B, inactivated polio and Haemophilus influenzae type b conjugate vaccines, completed at least 180 days before administration of the first study vaccination.

Exclusion Criteria

Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines 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) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
Planned administration/ administration of any vaccine not foreseen by the study protocol, including measles, mumps, rubella, varicella and pneumococcal vaccines, within 30 days before the first dose of vaccine(s) and 30 days after the last dose of vaccine(s).
Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C, W and/or Y.
Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroup A, C, W and/or Y.
Previous booster vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis or Haemophilus influenzae type b.
History of meningococcal disease.
Any confirmed or suspected immunosuppressive or immunodeficient condition (congenital or secondary), including human immunodeficiency virus (HIV) infection, based on medical history and physical examination.
History of reactions or allergic disease likely to be exacerbated by any component of the vaccine(s).
Major congenital defects or serious chronic illness.
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.

Additional criteria for subjects receiving Infanrix hexa™

Hypersensitivity reaction due to previous vaccination with Infanrix hexa™.
Encephalopathy defined as an acute, severe central nervous system disorder occurring within 7 days following vaccination and generally consisting of major alterations in consciousness, unresponsiveness, generalised or focal seizures that persist more than a few hours, with failure to recover within 24 hours.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group B	Infanrix™ hexa	Meningococcal vaccine GSK134612 followed one month later by Infanrix hexa™
Group A	Infanrix™ hexa	Meningococcal vaccine GSK134612 co-administered with Infanrix hexa™
Group A	Meningococcal vaccine GSK134612	Meningococcal vaccine GSK134612 co-administered with Infanrix hexa™
Group B	Meningococcal vaccine GSK134612	Meningococcal vaccine GSK134612 followed one month later by Infanrix hexa™
Group C	Meningococcal vaccine GSK134612	Infanrix hexa™ followed one month later by Meningococcal vaccine GSK134612
Group C	Infanrix™ hexa	Infanrix hexa™ followed one month later by Meningococcal vaccine GSK134612
Group D	Meningitec™	Meningitec™ vaccination

Primary Outcome Measures

Name	Time	Method
Anti-PT, Anti-FHA and Anti-PRN Concentrations	1 month after the first vaccination (Month 1)	The analysis was based only on subjects receiving Infanrix-hexa vaccination. The results were calculated as geometric mean expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Number of Subjects With Anti-HBs Concentrations ≥ the Cut-off	1 month after vaccination with Nimenrix vaccine (Month 1)	The cut-off for the assay was greater than or equal to (≥) 10 milli-interantional units per milliliter (mIU/mL).
Number of Subjects With Anti-PRP Concentrations ≥ the Cut-off	1 month after vaccination with Nimenrix vaccine (Month 1)	The cut-off for the assay was ≥ 1μg/mL.
Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers ≥ the Cut-off.	1 month after vaccination with Nimenrix vaccine (Month 1)	The cut-off for the assay was greater than or equal to (≥) 1:8. The analysis was based only on subjects receiving Nimenrix vaccination at Day 0.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers ≥ the Cut-off Values	At month 0, month 1 and month 2	The cut-off values for the assay were ≥ 1:8 and ≥ 1:128
Numbers of Seroprotected Subjects for Anti-PRP ≥ the Cut-off	At month 0, month 1 and month 2	The cut-off for the assay was ≥ 1.0
Number of Seroprotected Subjects for Anti-HBs ≥ the Cut-offs	At month 0, month 1 and month 2	The cut-offs for the assay were ≥ 10 mIU/mL and ≥ 100 mIU/mL respectively .
Anti-HBs Antibody Concentrations	At month 0, month 1 and month 2	The results for the assay were tabulated as geometric mean expressed in milli-international units per milliliter (mIU/mL).
Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY Antibody Concentrations	At month 0, month 1 and month 2	The results for the assay were tabulated as geometric mean expressed in microgram per milliliter (μg/mL).
Number of Seroprotected Subjects for Anti-tetanus Toxoid (Anti-TT)	At month 0, month 1 and month 2	The cut-off for the assay was ≥ 0.1
Number of Subjects Seroprotected for Anti-polio Type 1, 2 & 3 ≥ the Cut-off	At month 0, month 1 and month 2	The cut-off for the assay was ≥ 1:8.
Anti-tetanus Toxoid (Anti-TT) Antibody Concentrations	At month 0, month 1 and month 2	The results for the assay were tabulated as geometric mean expressed in internationl units per milliliter (IU/mL).
Anti-diphtheria (Anti-D) Antibody Concentrations	At month 0, month 1 and month 2	The results for the assay were tabulated as geometric mean expressed in internationl units per milliliter (IU/mL).
Anti-polio Type 1, 2 & 3 Titers	At month 0, 1 and 2	The results for the assay were tabulated as geometric mean expressed in titers.
Anti-PRP Antibody Concentrations	At month 0, month 1 and month 2	The results for the assay were tabulated as geometric mean expressed in microgram per milliliter (μg/mL).
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Post-combined Diphtheria Vaccination	During the 4-day (Days 0-3) follow-up period after Infanrix-hexa vaccination	The analysis was based only on subjects receiving combined-diphtheria vaccination.
rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers	At month 0, month 1 and month 2	The results were tabulated as geometric mean expressed in titers.
Number of Subjects With a Vaccine Response to PT, FHA and PRN Antigens	1 month after vaccination (Month 1)	Vaccine response to these antigens is defined as appearance of antibodies in subjects who were seronegative (antibody concentration \< 5 EL.U/mL) at pre-vaccination or as at least a 2-fold increase in post-over pre-vaccination antibody concentrations in subjects seropositive at pre-vaccination. The analysis was based only on subjects receiving experimental vaccination.
Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations	At month 0, month 1 and month 2	The results were tabulated as geometric mean expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms Post-meningococcal Vaccination	During the 4-day (Days 0-3) follow-up period after Nimenrix or Meningitec vaccination	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as occurrence of any local symptom irrespective of intensity grade. Grade 3 Pain was defined as crying when limb was moved/ spontaneously painful.
Number of Subjects Reporting Any Rash	Day 0 - Month 7	Any was defined as occurrence of at least one symptom experienced.
Number of Subjects With Anti-polysaccharide A (Anti-PSA), Anti-PSC, Anti-PSW, and Anti-PSY ≥ the Cut-off	At month 0, month 1 and month 2	The cut-off for the assay were ≥ 0.3 microgram per milliliter (μg/mL) and ≥ 2.0 μg/mL, respectively.
Number of Subjects Seroprotected for Anti-diphtheria (Anti-D) ≥ the Cut-off	At month 0, month 1 and month 2	The cut-off for the assay was ≥ 0.1
Number of Subjects Reporting Any Conditions Prompting Emergency Room Visits (ER)	Day 0 - Month 7	Any was defined as occurrence of at least one symptom experienced.
Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) After the Second Dose	Occurring within Day 0-30 following vaccination	An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. "Any" was defined as an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. The analysis was based only on subjects receiving a second dose of vaccination.
Number of Subjects Reporting Any Solicited General Symptoms Following Each Dose	During the 4-day (Days 0-3) post-vaccination dose 1 (D1) and second dose (D2)	Solicited general symptoms assessed were drowsiness, fever, irritability and loss of appetite. Any was defined as occurrence of any general symptom irrespective of intensity grade and relationship. Subjects in the Nimenrix + Infanrix-hexa Group did not receive a second dose of vaccination.
Number of Subjects Reporting Any Unsolicited Adverse Events (AEs) After the First Dose	Occurring within Day 0-30 following vaccination	An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. "Any" was defined as an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.
Number of Subjects Reporting Any Serious Adverse Events (SAEs)	From dose 1 (Month 0) up to study end (Month 7)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/ incapacity.
Number of Subjects Reporting Any New Onset of Chronic Illnesses (NOCIs)	Day 0 - Month 7	Any was defined as occurrence of at least one symptom experienced.