A Study to Evaluate the Safety, Immunogenicity and Efficacy of GlaxoSmithKline (GSK) Biologicals' Candidate Malaria Vaccine RTS,S/AS02A, When Administered to Children Aged 1 to 4 Years Living in a Malaria-endemic Region of Mozambique.

A Study to Evaluate the Safety, Immunogenicity and Efficacy of GlaxoSmithKline Biologicals' Candidate Malaria Vaccine RTS,S/AS02A, Administered Intramuscularly According to a 0, 1 and 2 Month Vaccination Schedule in Toddlers and Children Aged 1 to 4 Years in a Malaria-endemic Region of Mozambique.

Malaria is an important cause of death and serious illness among Mozambican children. Although the risk of malaria can be reduced by drugs and by impregnated bed nets, it would be helpful if children could be protected against malaria by a vaccine.

GSK Biologicals is developing in partnership with Malaria Vaccine Initiative at PATH a candidate malaria vaccine RTS,S/AS02 for the routine immunization of infants and children living in malaria endemic areas. The vaccine would offer protection against malaria disease due to the parasite Plasmodium falciparum and also would provide protection against infection with hepatitis B virus. Previous studies have shown the candidate malaria vaccine RTS,S/AS02 to be safe when administered in adults and children aged 1-11 years. However, to assess if this vaccine could provide protection against malaria in children, this study has been undertaken.

In this study, the participating children will either receive either 3 doses of the new malaria vaccine or the control vaccine which has been selected because of its benefit to the children in preventing important childhood diseases. The control vaccines include the following:

• If the child is of 24 months or older, he/she may receive 3 doses of a vaccine, called Engerix-B™, which protects against hepatitis B.
• If the child is less than 24 months, he/she may receive: two doses of a vaccine called Prevnar® and one dose of a vaccine called Hiberix™. Prevnar® prevents pneumonia and meningitis caused by some Streptococcus pneumoniae bacteria. Hiberix™ prevents severe infections such as pneumonia and meningitis caused by Haemophilus influenzae type b bacteria (Hib). All children will be monitored for the development of malaria disease over an 18-month period extending from the third vaccination. All participants will also be monitored for vaccine safety from first vaccination to study close.

Inclusion Criteria:

• Healthy male and female children, 1 to 4 years of age at the time of first vaccination (up to but not including 5th birthday).
• Written/thumbprinted and witnessed informed consent obtained from the parents or legal guardians.

Exclusion Criteria:

• Major congenital defects or serious chronic illness.
• History of allergic reactions to vaccination or to any component of the Hiberix™, Prevnar® or Engerix-B™ vaccines.
• Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune modifying drugs within six months prior to the first vaccine dose .
• Previous vaccination with an experimental vaccine or with hepatitis B vaccine in children equal to or more than 18 months of age.
• Simultaneous participation in any other clinical trial.
• 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.
• Planned administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of vaccine. An exception, is the receipt of an EPI or licensed vaccine.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.