Immunogenicity and Safety of GSK Biologicals' Infanrix/Hib in Children

Study Overview
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Brief Summary
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This protocol posting deals with objectives & outcome measures of the booster phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00412854). This Phase IIIB study will compare GSK Biologicals' DTPa/Hib vaccine to separately administered DTPa and Hib vaccines in Chinese children 18 to 24 months of age, in terms of safety and immunogenicity.

Official Title
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Immunogenicity and Reactogenicity Study of GlaxoSmithKline Biologicals' Infanrix™/Hib Vaccine Administered as a Booster Dose to 18-24 Months Old Children

Conditions
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Tetanus, Acellular Pertussis, Diphtheria

Intervention / Treatment
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* Biological: Infanrix™
* Biological: Hiberix™


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 should have completed the full three-dose primary vaccination course in study 104567. A male or female child between, and including, 18 and 24 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 (drug or vaccine) other than the study vaccine(s) within 30 days preceding 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 booster dose. Administration of a vaccine not foreseen by the study protocol within 30 days prior to vaccination, or planned administration during the study period, with the exception of measles or combined measles, mumps and rubella (MMR) vaccination. 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. Previous booster vaccination against diphtheria, tetanus, pertussis and/or Haemophilus influenzae type b diseases since the end of the primary study. History of diphtheria, tetanus, pertussis and/or Haemophilus influenzae type b diseases. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. A family history of congenital or hereditary immunodeficiency. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s). Major congenital defects or serious chronic illness. History of any progressive neurological disorders or seizures. Acute disease and/or fever at 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. Occurrence of any of the following adverse events (AEs) after previous administration of a diphtheria-tetanus-pertussis (DTP) vaccine: Hypersensitivity reaction due to any component of the vaccine. Encephalopathy. Fever ≥ 40.0 °C (axillary temperature) within 48 hours of vaccination. Collapse or shock-like state within 48 hours of vaccination. Persistent, inconsolable crying occurring within 48 hours of vaccination and lasting ≥ 3 hours. Seizures with or without fever occurring within 3 days of vaccination.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 24 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infanrix/Hib Single Injection Group<br>Subjects received 1 dose of Infanrix™ extemporaneously mixed with Hiberix™. | Biological: Infanrix™<br>* Intramuscular injection, one dose<br>Biological: Hiberix™<br>* Intramuscular injection, one dose<br>|
| Active Comparator: Infanrix + Hiberix Separate Injection Group<br>Subjects received two separate injections, one of Infanrix™ and one of Hiberix™. | Biological: Infanrix™<br>* Intramuscular injection, one dose<br>Biological: Hiberix™<br>* Intramuscular injection, one dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-polyribosyl-ribitol-phosphate (PRP) Antibody Concentrations | Geometric mean concentrations are given in microgram per milliliter (μg/mL). | One month after booster vaccination | 
| Anti-diphtheria Toxoid Antibody Concentrations | Geometric mean concentrations are given in international Unit per milliliter (IU/mL). | One month after booster vaccination | 
| Anti-tetanus Toxoid Antibody Concentrations | Geometric mean concentrations are given in IU/mL. | One month after booster vaccination | 
| Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibody Concentrations | Geometric mean concentrations are given in Enzyme-Linked Immuno Sorbent Assay (ELISA) unit per milliliter (EL.U/mL). | One month after booster vaccination | 
| The Number of Subjects Seroprotected for Anti-PRP, Anti-diphtheria and Anti-tetanus Antibodies and Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Assay cut-offs indicating seroprotection or seropositivity for the different antigens were the following: anti-PRP antibody concentrations ≥ 0.15 µg/mL, anti-diphtheria and anti-tetanus antibody concentrations ≥ 0.1 IU/mL, anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 20 EL.U/mL. | One month after booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-PRP Antibody Concentrations | Geometric mean concentrations are given in μg/mL. | Before booster vaccination | 
| Anti-diphtheria Toxoid Antibody Concentrations | Geometric mean concentrations are given in IU/mL. | Before booster vaccination | 
| Anti-tetanus Toxoid Antibody Concentrations | Geometric mean concentrations are given in IU/mL. | Before booster vaccination | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Geometric mean concentrations are given in EL.U/mL. | Before booster vaccination | 
| The Number of Subjects Seroprotected for Anti-PRP, Anti-diphtheria and Anti-tetanus Antibodies and Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies | Assay cut-offs indicating seroprotection or seropositivity for the different antigens were the following: anti-PRP antibody concentrations ≥ 0.15 µg/mL, anti-diphtheria and anti-tetanus antibody concentrations ≥ 0.1 IU/mL, anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 20 EL.U/mL. | Before booster vaccination | 
| Number of Subjects Reporting Solicited Local and General Symptoms | Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include drowsiness, fever, irritability, and loss of appetite. | During the 4-day follow-up period after booster vaccination | 
| 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. | During the 31-day follow-up period after booster vaccination | 
| 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 isability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | During the 31-day follow-up period after booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infanrix/Hib, Chinese children