Study of a New Formulation of DTPa-HBV-IPV/Hib Vaccine Administered as a Booster Dose to 18-23 Months Old Children

Study Overview
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Brief Summary
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The new formulation administered as a 4th consecutive dose will be compared to the current formulation of the vaccine in this partially double blind study. The study will be double-blind with respect to the two DTPa-HBV-IPV/Hib groups. The study will be open with respect to the DTPa-HBV-IPV group.

Official Title
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Immunogenicity and Reactogenicity Study of a New Formulation of GSK Biologicals' DTPa-HBV-IPV/Hib Vaccine Administered as a Booster Dose to 18-23 Months Old Children

Conditions
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Poliomyelitis, Acellular Pertussis, Tetanus, Diphtheria, Hepatitis B

Intervention / Treatment
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* Biological: Infanrix™ penta
* Biological: Infanrix™ hexa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study. Subjects must have completed full three-dose primary vaccination course with DTPa-HBV-IPV/Hib or DTPa-HBV-IPV in the primary study DTPa-HBV-IPV-109 (study NCT00320463). A male or female between, and including 18 and 23 months of age at the time of the booster vaccination. Written informed consent obtained from the parent or guardian of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the booster dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the booster dose. Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the booster dose. Participation in another clinical study, between the primary study NCT00320463 and the present booster study, or at any time during the study, in which the subject has been or will be exposed to an investigational or a non-investigational product. Previous booster vaccination against diphtheria, tetanus, pertussis, poliomyelitis and hepatitis B since the conclusion visit of study NCT00320463. Previous booster vaccination against Haemophilus influenzae diseases in the DTPa-HBV-IPV/Hib groups, since the conclusion visit of study NCT00320463. History of exposure to diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and/or Haemophilus influenzae disease since the conclusion visit of study NCT00320463. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on physical examination. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products within the three months preceding the booster dose or planned administration during the study period. Any of the following adverse events having occurred after previous administration of DTP vaccine: Hypersensitivity reaction due to the vaccine. Encephalopathy defined as an acute, severe central nervous system disorder of unknown etiology occurring within 7 days following previous vaccination and generally consisting of major alterations in consciousness, unresponsiveness, generalized or focal seizures that persist more than a few hours, with failure to recover within 24 hours. Any of the following adverse events having occurred after previous administration of DTP vaccine: Temperature of >= 40.0 °C (axillary temperature), within 48 hours of vaccination. Collapse or shock-like state within 48 hours of vaccination. Persistent, inconsolable crying lasting >= 3 hours, occurring within 48 hours of vaccination. Convulsions with or without fever, occurring within 3 days of vaccination

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 23 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infanrix hexa Preservative-Free Formulation Group<br>Subjects received a booster dose of the preservative-free formulation of Infanrix™ hexa | Biological: Infanrix™ hexa<br>* Subjects received a booster dose<br>|
| Active Comparator: Infanrix hexa Preservative-Containing Formulation Group<br>Subjects received a booster dose of the preservative-containing formulation of Infanrix™ hexa | Biological: Infanrix™ hexa<br>* Subjects received a booster dose<br>|
| Active Comparator: Infanrix penta Preservative-Free Formulation Group<br>Subjects received a booster dose of the preservative-free formulation of Infanrix™ penta. | Biological: Infanrix™ penta<br>* Subjects received a booster dose<br>* Other names: Pediarix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-hepatitis B (HB) Antibody Concentrations Above the Cut-off One Month After the Booster Dose | Anti-HB antibodies cut-off value assessed was ≥ 10 milli-international units per milliliter (mIU/mL) | One month after the booster dose | 
| Number of Subjects With Anti-polyribosyl-ribitol-phosphate (PRP) Antibodies Concentrations Above the Cut-off One Month After the Booster Dose | Anti-PRP antibodies cut-off value assessed was ≥ 0.15 microgram per milliliter (µg/mL) | One month after the booster dose | 
| Number of Subjects With Anti-diphtheria and Anti-tetanus Antibodies Concentration Above the Cut-off One Month After the Booster Dose | Anti-diphtheria and anti-tetanus antibodies cut-off value assessed was ≥ 0.1 international units per milliliter (IU/mL) | One month after the booster dose | 
| Number of Subjects With Anti-poliovirus Antibodies Concentration Above the Cut-off One Month After the Booster Dose | Anti-poliovirus antibodies cut-off value assessed was ≥ 8 effective dose 50 (ED50) | One month after the booster dose | 
| Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibodies Concentration One Month After the Booster Dose | Concentration of anti-PT, ant-FHA and anti-PRN antibodies given as geometric mean concentration (GMC) in Enzyme-Linked Immuno Sorbent Assay (ELISA) unit per millilitre (EL.U/mL) | One month after the booster dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-hepatitis B (HB) Antibody Concentrations Above the Cut-off Before and One Month After the Booster Dose | Anti-HB antibodies cut-off value assessed were ≥ 10 mIU/mL and ≥ 100 mIU/mL Number of subjects with cut-off ≥ 10 mIU/mL one month after the booster dose was already presented in the primary outcomes | Before (Pre) and one month after (Post) the booster dose | 
| Anti-HB Antibodies Concentration | Concentration of anti-HB antibodies given as GMC in mIU/mL | Before (Pre) and one month after (Post) the booster dose | 
| Number of Subjects With Anti-PRP Antibodies Concentrations Above the Cut-off Before and One Month After the Booster Dose | Anti-PRP antibodies cut-off value assessed were ≥ 0.15 µg/mL and ≥ 1.0 µg/mL Number of subjects with cut-off ≥ 0.15 µg/mL one month after the booster dose was already presented in the primary outcomes | Before (Pre) and one month after (Post) the booster dose | 
| Anti-PRP Antibodies Concentration | Concentration of anti-PRP antibodies given as GMC in µg/mL | Before (Pre) and one month after (Post) the booster dose | 
| Number of Subjects With Anti-diphtheria and Anti-tetanus Antibodies Concentration Above the Cut-off Before the Booster Dose | Anti-diphtheria and anti-tetanus antibodies cut-off value assessed was ≥ 0.1 IU/mL | Before the booster dose administration (at baseline) | 
| Anti-diphtheria and Anti-tetanus Antibodies Concentration | Concentration of anti-diphtheria and anti-tetanus antibodies given as GMC in IU/mL | Before (Pre) and one month after (Post) the booster dose | 
| Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibodies Concentration Above the Cut-off Before and One Month After the Booster Dose | Anti-PT, anti-FHA and anti-PRN antibodies cut-off value assessed were ≥ 5 EL.U/mL | Before (Pre) and one month after (Post) the booster dose | 
| Anti-PT, Anti-FHA, and Anti-PRN Antibodies Concentration Before the Booster Dose | Concentration of anti-PT, anti-FHA and anti-PRN antibodies given as GMC in EL.U/mL | Before the booster dose administration (at baseline) | 
| Number of Subjects With Anti-poliovirus Antibodies Concentration Above the Cut-off Before the Booster Dose | Anti-poliovirus antibodies cut-off value assessed was ≥ 8 ED50 | Before the booster dose | 
| Anti-poliovirus Antibodies Titer | Concentration of anti-poliovirus antibodies given as geometric mean titers (GMT) | Before (Pre) and one month after (Post) the booster dose | 
| Number of Subjects Reporting Solicited Symptoms | Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include drowsiness, fever, irritability, and loss of appetite | Within the 4-day (Day 0-3) post-vaccination period | 
| Number of Subjects Reporting Unsolicited Adverse Events (AE) | 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. | Within the 31-day (Day 0-30) post-vaccination period | 
| Number of Subjects Reporting Serious Adverse Events (SAE) | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above | Up to one month after the booster dose administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infanrix hexa, combined vaccine