A Study to Evaluate the Efficacy, Immunogenicity and Safety in a Sporozoite Challenge Model of a Fractional Booster Dose of GSK Biologicals' Candidate Malaria Vaccine Administered to Previously Vaccinated Healthy Malaria-naïve Adults

Occurrence of P. falciparum parasitemia (defined by a positive blood slide) following sporozoite challenge. Post-challenge, parasitemia was determined by microscopy of Giemsa-stained thick blood films (smear). Microscopy was performed on thick smears using a validated standard operation procedure. P. falciparum infection was defined as asexual blood stage P. falciparum parasite density greater than (\>) 0 detected by blood slide reading. For the analysis of proportion affected (relative risk), all subjects included in the analysis were considered at risk of infection and no censoring or elimination was applied for subjects not completing the entire protocol-defined post-challenge follow-up (Day 50 - 28 days post challenge).

Time frame: During the sporozoite challenge dose follow-up period (from Day 22 up to Day 50)

Population: Analysis was performed on Per-Protocol Set which included all subjects fulfilling eligibility criteria, who received or not the Fx dose of study vaccine according to protocol, did not report any underlying medical condition influencing the efficacy response, underwent P. falciparum challenge and had available data concerning outcome measures.

Anti-CS antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in Enzyme-linked immunosorbent assay Unit per milliliter (EU/mL). The cut-off for the assay was equal to 1.9 EU/mL. GMC calculations are performed by taking the inverse logarithm of the mean of the log concentration transformations. Antibody concentrations below the cut-off of the assay will be given an arbitrary value of half the cut-off of the assay for the purpose of GMC calculation.

Time frame: At Day 1, prior to challenge (Day 22), 28 days post-challenge (Day 50) and at study end (Day 190)

Population: Analysis was performed on Per-Protocol Set which included all subjects fulfilling eligibility criteria, who received the Fx dose according to protocol, underwent P. falciparum challenge and had available immunogenicity data concerning outcome measures. Analysis was not performed on the Infectivity Control Group (no Fx dose being administered).

Anti-HBs IgG antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milli-International Unit per milliliter (mIU/mL). The cut-off for the assay was equal to 6.2 mIU/mL. GMC calculations are performed by taking the inverse logarithm of the mean of the log concentration transformations. Antibody concentrations below the cut-off of the assay will be given an arbitrary value of half the cut-off of the assay for the purpose of GMC calculation.

Time frame: At Day 1, prior to challenge (Day 22), 28 days post-challenge (Day 50) and at study end (Day 190)

Population: Analysis was performed on Per-Protocol Set which included all subjects fulfilling eligibility criteria, who received the Fx dose according to protocol, underwent P. falciparum challenge and had available immunogenicity data concerning outcome measures. Analysis was not performed on the Infectivity Control Group (no Fx dose being administered).

Biochemistry (Alanine Aminotransferase \[ALT\], Aspartate Aminotransferase \[AST\] and Creatinine) and hematological (Hemoglobin, Platelets, White Blood Cells \[WBC\] decrease and WBC increase) laboratory values were presented according to toxicity grading scales and tabulated by group. Grading scale adapted from FDA guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials (September 2007).

Time frame: At screening, Day(D)1, D8, D22 (day of first parasitemia) and D50 (28 days post-challenge) for the booster vaccination groups; and at screening, D22 (day of first parasitemia) and D50 (28 days post-challenge) for the infectivity control subjects

Population: Analysis was performed on Intent-To-Treat Set, which included all subjects who received at least one dose of study vaccine. All challenged infectivity controls were also included in this analysis.

AEs of specific interest are potential immune-mediated diseases (pIMDs) and meningitis. pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.

Time frame: From Day 1 up to study conclusion (Day 190)

Population: Analysis was performed on Intent-To-Treat Set, which included all subjects who received at least one dose of study vaccine. All challenged infectivity controls were also included in this analysis.

Solicited general AEs assessed are fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhea and/or abdominal pain), headache and fever. Any occurrence of symptom regardless of intensity grade and relationship to the vaccination. Fever was defined as temperature equal or greater than 37.5 °C (preferably oral route measure).

Time frame: Within 7 days after vaccination (day of vaccination and 6 subsequent days) in the booster vaccination groups

Population: Analysis was performed on Intent-To-Treat Set, which included all subjects from the P-Fx and NP-Fx groups who received the Fx dose of the study vaccine and with the symptoms sheet documented.

Solicited local AEs assessed are erythema, pain and swelling. Any occurrence of AE regardless of intensity grade are reported. Any Erythema or any Swelling symptom = any symptom recorded with a surface diameter greater than 0 millimeter.

Time frame: Within 7 days after vaccination (day of vaccination and 6 subsequent days) in the booster vaccination groups

Population: Analysis was performed on Intent-To-Treat Set, which included all subjects from the P-Fx and NP-Fx groups who received the Fx dose of the study vaccine and with the symptoms sheet documented.

An adverse event is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.

Time frame: Within 29 days after challenge (day of challenge and 28 subsequent days)

Population: Analysis was performed on Intent-To-Treat Set, which included all subjects who received at least one dose of study vaccine. All challenged infectivity controls were also included in this analysis.

An unsolicited adverse event is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited adverse event is any event 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.

Time frame: Up to 21 days after booster vaccination period (day of vaccination and 20 subsequent days), after booster vaccination

Population: Analysis was performed on Intent-To-Treat Set, which included all subjects from the P-Fx and NP-Fx groups who received the Fx dose of the study vaccine.

An SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.

Time frame: From Day 1 up to study conclusion (Day 190)

Population: Analysis was performed on Intent-To-Treat Set, which included all subjects who received at least one dose of study vaccine. All challenged infectivity controls were also included in this analysis.

For the analyses of time to onset of parasitemia (Kaplan-Meyer and log-rank), time at risk started on first day of challenge. Time at risk was censored on Day 50 (28 days post challenge), drop-out date, start date of anti-malarial treatment or date meeting an endpoint, whichever occured first. Time-at-risk was calculated as: censor date - date challenge + 1.

Time frame: During the sporozoite challenge period starting at Day 22 (after the vaccine dose administered at Day 1), up to Day 50

Population: Analysis was performed on Per-Protocol Set which included all subjects fulfilling eligibility criteria, who received or not the Fx dose of study vaccine according to protocol, did not report any underlying medical condition influencing the efficacy response, underwent P. falciparum challenge and had available data concerning outcome measures.