Immune Response Post Pry Vaccination of 2 Formulations of DTPw-HBV Vaccine Given With Rotavirus Vaccine to Infants

Study Overview
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Brief Summary
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To compare the two formulations of GSK Biologicals' DTPw-HBV vaccine to concomitant administration of CSL's DTPw vaccine and GSK Biologicals' HBV with respect to the antibody response to the diphtheria antigen after a three-dose primary vaccination course.

Detailed Description
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Randomized study with five groups to receive one of the following vaccination regimens: One of the two formulations of GSK Biologicals' DTPw-HBV + GSK Biologicals' HRV One of the two formulations of GSK Biologicals' DTPw-HBV + Placebo CSL's DTPw + GSK Biologicals' HBV

Official Title
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A Phase III, Partially Blind, Randomized Study to Evaluate the Immunogenicity, Safety and Reactogenicity of GlaxoSmithKline (GSK) Biologicals' Tritanrix™-HepB and GSK Biologicals Kft's DTPw-HBV Vaccines as Compared to Concomitant Administration of Commonwealth Serum Laboratory's (CSL's) DTPw (Triple Antigen™) and GSK Biologicals' HBV (Engerix™-B), When Co-administered With GSK Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine, to Healthy Infants at 3, 4½ and 6 Months of Age, After a Birth Dose of Hepatitis B Vaccine.

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: Tritanrix™-HepB
* Biological: Rotarix™
* Biological: Zilbrix™
* Biological: Triple Antigen™
* Biological: Engerix™-B
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects who the investigator believes that their parent/guardian can and will comply with the requirements of the protocol. Administration of one dose of hepatitis B vaccine at birth. A male or female between, and including, 11 and 17 weeks of age at the time of the first DTPw vaccination. Free of obvious health problems 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 the first dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs since birth. Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days before the first vaccine dose or planned administration during the study period with the exception of oral polio vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing is required) Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 3 Weeks
Maximum Age: 4 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tritanrix™-HepB+Rotarix™ Group<br>Subjects received 3 doses of Tritanrix™-HepB vaccine at 3, 4.5 and 6 months of age, intramuscularly into the right anterolateral thigh concomitantly with 2 oral doses of Rotarix™ vaccine at 3 and 4.5 months of age. | Biological: Tritanrix™-HepB<br>* GSK Biologicals' combined diphtheria-tetanus-whole cell Bordetella pertussis -hepatitis B vaccine.<br>* Other names: DTPw-HBV;Biological: Rotarix™<br>* GSK Biologicals' live attenuated human rotavirus vaccine<br>* Other names: HRV vaccine;|
| Experimental: Tritanrix™-HepB+Placebo Group<br>Subjects received 3 doses of Tritanrix™-HepB vaccine at 3, 4.5 and 6 months of age, intramuscularly into the right anterolateral thigh concomitantly with 2 oral doses of Placebo for Rotarix™ vaccine at 3 and 4.5 months of age. | Biological: Tritanrix™-HepB<br>* GSK Biologicals' combined diphtheria-tetanus-whole cell Bordetella pertussis -hepatitis B vaccine.<br>* Other names: DTPw-HBV;Drug: Placebo<br>* Placebo for the Rotarix™ vaccine<br>|
| Active Comparator: Zilbrix™+Rotarix™ Group<br>Subjects received 3 doses of Zilbrix™ vaccine at 3, 4.5 and 6 months of age, intramuscularly into the right anterolateral thigh concomitantly with 2 oral doses of Rotarix™ vaccine at 3 and 4.5 months of age. | Biological: Rotarix™<br>* GSK Biologicals' live attenuated human rotavirus vaccine<br>* Other names: HRV vaccine;Biological: Zilbrix™<br>* GSK Biologicals Kft's combined diphtheria-tetanus whole-cell B. pertussis-hepatitis B vaccine<br>* Other names: DTPw-HBV Kft;|
| Active Comparator: Zilbrix™+Placebo Group<br>Subjects received 3 doses of Zilbrix™ vaccine at 3, 4.5 and 6 months of age, intramuscularly into the right anterolateral thigh concomitantly with 2 oral doses of Placebo for Rotarix™ vaccine at 3 and 4.5 months of age. | Biological: Zilbrix™<br>* GSK Biologicals Kft's combined diphtheria-tetanus whole-cell B. pertussis-hepatitis B vaccine<br>* Other names: DTPw-HBV Kft;Drug: Placebo<br>* Placebo for the Rotarix™ vaccine<br>|
| Active Comparator: Triple Antigen™+Engerix™-B Group<br>Subjects received 3 separate doses of Triple Antigen™ and Engerix™-B vaccines at 3, 4.5 and 6 months of age, intramuscularly into the left and right anterolateral thighs, respectively. | Biological: Triple Antigen™<br>* Commonwealth Serum Laboratory's (CSL's) combined diphtheria-tetanus-whole cell B. pertussis vaccine.<br>* Other names: DTPwcsl vaccine;Biological: Engerix™-B<br>* GSK Biologicals' hepatitis B vaccine<br>* Other names: HBV vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection Status for Anti-diphteria (Anti-DT) Antibodies | Seroprotection status (SP) defined vaccinated subjects with antibody concentrations greater than or equal to (≥) 0.1 international units per millitre (IU/mL) as assessed by the Enzyme-linked Immunosorbent Assay (ELISA) or ≥ 0.016 IU/mL by neautralization assay on Vero cells in subjects seronegative for ELISA. | At one month post dose 3 [PIII(M4)] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects for Anti-DT Antibodies as Assessed by ELISA | A seroprotected subject is a vaccinated subject with concentrations ≥ 0.1 IU/mL. | At one month post dose 3 [PIII(M4)] | 
| Number of Seroprotected Subjects for Anti-Hepatitis B (Anti-HBs) Antibodies | A seroprotected subject was defined as a vaccinated subject with antibody concentrations ≥ 10 milli-international units per millilitre (mIU/mL). | At one most post dose 3 [PIII(M4)] | 
| Number of Seropositive Subjects With Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations ≥ the Established Cut-off Values | A seropositive subject was defined as a subject with Anti-BPT antibody concentrations ≥ 15 ELISA units per millilitre (EL.U/mL), as assessed by the Enzyme-Linked Immunosorbent Assay (ELISA). | At one month post dose 3 [PIII(M4)] | 
| Number of Subjects With Vaccine Response to BPT Antigen | Vaccine response (VR) was defined as the appearance of antibodies in subjects seronegative at pre-vaccination and antibody concentrations ≥ the cut-off values post-vaccination in subjects who were seropositive at pre-vaccination. | At one month post dose 3 [PIII(M4)] | 
| Number of Seropositive Subjects With Anti-rotavirus (Anti-RV) Antibodies Above the Cut-off Values | A seropositive subject was defined as a subject with anti-RV antibody concentrations ≥ 20 units per millilitre (U/mL). | At 2.5 months after dose 2 of Rotarix [PIII(M4)] | 
| Number of Seroprotected Subjects for Anti-Tetanus (Anti-T) Antigen | A seroprotected subject was defined as a vaccinated subject with anti-T antibody concentrations ≥ the cut-off value of 0.1 international units per millilitre (IU/mL). | At one month post dose 3 [PIII(M4)] | 
| Number of Seroprotected Subjects for Anti-Poliovirus Types 1, 2, 3 (Anti-Polio 1, 2, 3) | A seroprotected subject was defined as a vaccinated subject with anti-Polio type 1,2 ,3 antibody titers ≥ 8 | At one month post dose 3 [PIII(M4)] | 
| Concentrations of Anti-HBs Antibodies | Concentrations of anti-HB, antibodies, expressed as Geometric Mean Concentrations (GMCs), were measured in mIU/mL. | At one month post dose 3 [PIII(M4)] | 
| Concentrations of Anti-DT Antibodies | Concentrations of anti-DT antibodies, expressed as Geometric Mean Concentrations (GMCs), were measured in IU/mL. | At one month post dose 3 [PIII(M4)] | 
| Concentrations of Anti-T Antibodies | Concentrations, expressed as Geometric Mean Concentrations (GMCs), were measured in international units per millillitre (IU/mL). | At one month post dose 3 [PIII(M4)] | 
| Concentrations of Anti-BPT Antibodies | Concentrations, expressed as Geometric Mean Concentrations (GMCs), were measured in EL.U/mL. | At one month post dose 3 [PIII(M4)] | 
| Concentrations of Anti-RV Antibodies | Concentrations, expressed as Geometric Mean Concentrations (GMCs), were measured in U/mL. | At 2.5 months post dose 2 of Rotarix [PIII(M4)] | 
| Anti-Polio Type 1, 2, 3 Antibody Titers | Anti-Polio type 1, 2 and 3 antibody titers were expressed as Geometric Mean Titers (GMTs). | At one month post dose 3 [PIII(M4)] | 
| Number of Subjects With Solicited Local Symptoms | Solicited local symptoms were pain, redness and swelling. Any = occurence of symptom regardless of intensity grade. Grade 3 pain = Significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater than 30 millimeters (mm). | During the 8-Day (Days 0-7) follow-up period | 
| Number of Subjects With Any Solicited General Symptoms | Assessed solicited general symptoms were diarrhea, drowsiness, fever [defined as rectal temperature equal to or above 38.0 degrees Celsius (°C)], irritability, loss of appetite [loss of appet.] and vomiting. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. Grade 3 loss of appetite = symptoms that prevents eating. Grade 3 diarrhea = ≥ 6 looser than normal stools per (/) day. Grade 3 vomiting = ≥ 3 episodes of vomiting/day. | During the 8-day period (Days 0-7) post-vaccination | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | Number of subjects with any unsolicited adverse events (AEs) An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | During the 31-day (Days 0-30) follow-up period | 
| Number of Subjects With Serious Adverse Events (SAEs) | 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. | From Month 0 to Month 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diphtheria, Pertussis, Prophylaxis, Hepatitis B diseases, Tetanus