Efficacy of GSK Biologicals' Candidate Malaria Vaccine 257049 Against Malaria Disease in Infants and Children in Africa

Efficacy of GSK Biologicals' Candidate Malaria Vaccine (257049) Against Malaria Disease Caused by P. Falciparum Infection in Infants and Children in Africa

The purpose of this observer-blind study is to gather key efficacy, safety, and immunogenicity information on GSK's candidate malaria vaccine in infants and children.

The protocol posting document has been updated due to a protocol amendment dated 23 January 2012. An analysis time point has been added at Month 20. No changes have been made to the protocol endpoints or statistical methods but protocol endpoints will be analysed on data collected up to Month 20 once these data are available. The rationale is to have the full scope of protocol defined efficacy and safety endpoints related to a primary schedule without booster in both age categories followed up for 20 months earlier than at the initially planned study end time point (Visit 34 or Month 32 time point).

The protocol posting document was updated due to a protocol amendment dated 10 December 2010 to extend the study until December 2013 for all enrolled subjects (interval: Nov 2013-Jan 2014). Including the extension, the mean follow-up time for subjects from 5-17 months will be during 49 months post dose 1 (range: 41-55), while for subjects from 6-12 weeks, it will be during 41 months post dose 1 (range: 32-48). This study is double-blind during the first part and single-blind during the extension part. An analysis will be conducted at the end of the extension including an evaluation of safety and efficacy against clinical malaria, severe malaria and prevalent parasitemia.

The protocol posting document has been updated following the posting of results of the study (January 2015): The study remained double-blind until the end of the extension phase, and the analyses of Month 32 (initial end of study now becoming end of the first part of the study or primary study phase) and of the extension phase were conducted together.

Inclusion Criteria:

All subjects must satisfy the following criteria at study entry:

• A male or female child of:5-17 months (inclusive) of age at time of first vaccination,or between 6-12 weeks of age at time of first vaccination and NOT have already received a dose of vaccine against diphtheria, tetanus or pertussis or Hemophilus influenzae type B and must be > 28 days of age at screening.
• Signed informed consent or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child.
• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.

All subjects must satisfy the following criteria at the start of the extension phase:

• Subjects who were enrolled and who received at least one vaccine dose in the primary trial phase.
• Subjects who were present for Visit 35 on or before 30 September 2013.
• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) should be enrolled in the study.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:

• Acute disease at the time of enrollment.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality.
• Anemia associated with clinical signs or symptoms of decompensation or hemoglobin ≥ 5.0 g/dL.
• Major congenital defects.
• History of allergic reactions, significant IgE-mediated events or anaphylaxis to previous immunizations.
• Children with a past history of a neurological disorder or atypical febrile seizure.
• Children with malnutrition requiring hospital admission.
• Children currently meeting the criteria for HIV disease of Stage III or Stage IV severity as defined by the World Health Organization.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to a drug or vaccine that is not licensed for that indication with the exception of studies with the objective of improving the drug treatment or clinical management of severe malaria disease.
• Use of a drug or vaccine that is not approved for that indication other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Previous participation in any other malaria vaccine trial.
• Receipt of a vaccine within the preceding 7 days.
• Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.
• Any other findings that the investigator feels would result in data collected being incomplete or of poor quality