Vaccine Efficacy Against Rotavirus Diarrhea; Vaccine Given With Routine Childhood Vaccinations in Healthy African Infants

Multi-Center Study to Assess the Efficacy, Safety and Immunogenicity of 2 or 3 Doses of GSK Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine Given Concomitantly With Routine EPI Vaccinations in Healthy Infants

The primary objective of this study is to determine if the GSK Biologicals' human rotavirus (HRV) vaccine (pooled HRV groups) given concomitantly with routine expanded program on immunisation (EPI) vaccinations can prevent severe rotavirus gastroenteritis (≥11 on the 20-point Vesikari scoring system [Ruuska, 1990]) caused by the circulating wild-type RV strains during the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 5.

The primary objective will be reached if the lower limit of the 95% confidence interval (CI) on vaccine efficacy is >0%.

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

The study will have three groups: Rotarix 3-Dose Group, Rotarix 2-Dose Group and Placebo Group. Three-dose immunisation will be administered in healthy infants at approximately 6, 10, and 14 weeks of age. Routine EPI vaccinations will be administered concomitantly with the study vaccines. This study will also evaluate immunogenicity and safety relative to the placebo.

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 child between, and including, 5 and 10 weeks of age at the time of the first study vaccination.
• Written informed consent obtained from the parent or guardian of the subject who is of legal age
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• In South Africa, birth weight > 2000 grams or if weight unknown, gestation period > 36 weeks.

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.
• 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
• Planned administration of a vaccine not foreseen by the study protocol within 14 days before each dose of study vaccine(s) and ending 14 days after.
• Chronic administration (defined as more than 14 days) of immunosuppressants since birth.
• History of use of experimental rotavirus vaccine.
• Previous routine vaccination except Bacille Calmette-Guérin (BCG), hepatitis B virus (HBV) and oral poliovirus (OPV) vaccination at birth
• Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract, intussusception or other medical condition determined to be serious by the investigator.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination
• History of allergic disease or reaction likely to be exacerbated by any component of the vaccine.
• Acute disease at the time of enrolment.
• Gastroenteritis within 7 days preceding the first study vaccine administration
• Previous confirmed occurrence of rotavirus gastroenteritis (RV GE).
• A family history of congenital or hereditary immunodeficiency.
• Administration of immunoglobulins and/or blood products since birth or planned administration during the study period.
• History of any neurologic disorders or seizures.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.