Immunogenicity, Safety & Reactogenicity of GSK Vaccine Tritanrix™-HepB/Hib2.5 Compared to GSK Vaccine Tritanrix™-HepB/Hiberix™

Study Overview
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Brief Summary
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In order to reduce the amount of thiomersal in its vaccines, GSK Biologicals has developed a DTPw-HBV vaccine with low thiomersal content (Tritanrix™- HepB low thio). This vaccine is to be used in combination with a Hib low dose vaccine containing 2.5µg of PRP antigen (Hib 2.5). The purpose of this study is to generate clinical data with Tritanrix™-HepB low thio vaccine when extemporaneously mixed with Hib 2.5 vaccine. The control group will receive Tritanrix™-HepB/Hiberix™. Subjects received primary vaccination in study 208108/091 (double blind). Of these subjects 50% were randomised to participate in the PRP challenge study (208108/092) (open), and all subjects will be invited to participate in a booster study DTPWHBV=HIB2.5-093 (101477).

Official Title
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A Phase II, Double-blind, Randomized Study to Compare the Immunogenicity, Safety and Reactogenicity of GlaxoSmithKline (GSK) Biologicals' Tritanrix™-HepB/Hib2.5 to GSK Biologicals' Tritanrix™-HepB/Hiberix™ When Administered as a Three-dose Primary Vaccination Course to Healthy Infants at 6, 10 and 14 Weeks of Age. A Dose of Unconjugated Hib Vaccine (Plain PRP Booster) Will be Administered at the Age of 10 Months to 50% of the Subjects

Conditions
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Haemophilus Influenzae Type b

Intervention / Treatment
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* Biological: Tritanrix™-HepB low thio /
* Biological: Hib 2.5
* Biological: Tritanrix™-HepB
* Biological: Hiberix™
* Biological: Unconjugated Hib vaccine (plain PRP)


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. A male or female between, and including, 6 and 8 weeks 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. Born after a gestation period of 36 to 42 weeks. Born to a mother proven seronegative for HBsAg. Exclusion Criteria: Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days before each dose of vaccine, with the exception of oral polio vaccine (OPV). Bacille Calmette-Guérin (BCG) vaccine received after the first 2 weeks of life. Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs since birth. Previous vaccination against diphtheria, tetanus, pertussis, hepatitis B and/or Hib. History of, or intercurrent, diphtheria, tetanus, pertussis, hepatitis B and/or Hib disease. 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. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or history. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Other conditions which in the opinion of the investigator may potentially interfere with interpretation of study outcomes.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 8 Weeks

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br> | Biological: Tritanrix™-HepB low thio /<br>* One dose as intramuscular injection at 6, 10 and 14 weeks of age.<br>Biological: Hib 2.5<br>* One dose as intramuscular injection at 6, 10 and 14 weeks of age.<br>Biological: Unconjugated Hib vaccine (plain PRP)<br>* One dose as intramuscular injection at 10 months of age<br>|
| Active Comparator: Group B<br> | Biological: Tritanrix™-HepB<br>* One dose as intramuscular injection at 6, 10 and 14 weeks of age.<br>Biological: Hiberix™<br>* One dose as intramuscular injection at 6, 10 and 14 weeks of age.<br>Biological: Unconjugated Hib vaccine (plain PRP)<br>* One dose as intramuscular injection at 10 months of age<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| anti-PRP antibody concentration above a protocol defined cut-off value. |  | One month after the third dose of the primary vaccination course. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| anti-HBs antibody concentration |  | One month after the third dose of the primary vaccination course | 
| anti-PRP antibody concentration |  | One month after the third dose of the primary vaccination course | 
| anti-tetanus antibody concentration |  | One month after the third dose of the primary vaccination course | 
| anti-diphtheria antibody concentration |  | One month after the third dose of the primary vaccination course | 
| anti-Bordetella pertussis (BPT) antibody concentration |  | One month after the third dose of the primary vaccination course | 
| Vaccine response to Bordetella pertussis antigen. |  | One month after the third dose of the primary vaccination course | 
| Seropositivity/seroprotection rates and GMCs for antibodies against all vaccine antigens |  | Before the first dose of the primary vaccination course | 
| anti-PRP antibody concentration |  | Before and one month after the plain PRP challenge dose. | 
| Occurrence of solicited symptoms |  | During the 4-day follow-up period after each dose | 
| Occurrence of unsolicited symptoms |  | During the 31-day follow-up period after each dose | 
| Occurrence of serious adverse events |  | Over the full course of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pertussis, Tetanus, Hiberix™, Hepatitis B, DTPw-HBV vaccine, Tritanrix™-HepB, Haemophilus influenzae type b, Diphtheria, Hib vaccine