Efficacy, Safety and Immunogenicity Study of GlaxoSmithKline(GSK) Biologicals' Candidate Malaria Vaccine 257049 in the Sporozoite Challenge Model in Healthy Malaria-naïve Adults

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01857869
• Collaborator: Walter Reed Army Institute of Research (WRAIR) (U.S. Fed), The PATH Malaria Vaccine Initiative (MVI) (Other)
• Enrollment: 64
• Location: 1
• Arms: 3
• Actual Duration (Months): 18.9
• Patients Per Site Per Month: 3.4

Study Details

Study Description

Brief Summary

This study is designed to evaluate safety, reactogenicity, immunogenicity, and efficacy of GSK Biological's malaria candidate vaccine 257049 administered as standard doses at 0 and 1 months and 1/5th standard dose at 7 months (delayed fractional dose group) and 257049 administered as three standard doses one month apart (0, 1, 2-month group) in healthy malaria-naïve volunteers aged 18-50 years in the sporozoite challenge model.

An additional, delayed sporozoite challenge will assess persistence of protection induced by the primary immune schedule and if an additional dose can provide protection in those unprotected by the initial vaccination series.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Biological: GSK257049 Dosage 1; Biological: GSK257049 Dosage 2; Procedure: Sporozoite-infected mosquitoes challenge	Phase 2

Detailed Description

This protocol posting has been amended to reflect changes in Amendment 1 of the Protocol (20 April 2014).

Rationale for Protocol Amendment 1:

• In order to assess whether protection is maintained over time, and assess boostability, the protocol has been amended to incorporate another sporozoite challenge, after a single boost of 1/5th standard dose of RTS,S/AS01B, or no boost.

Study design:

• Dependent upon enrolment date during the screening period, the study duration will be approximately 19 months for each vaccinated subject in the delayed fractional dose group, 14 months for each vaccinated subject in the 0, 1, 2-month group, 7 months for each infectivity control subject in the challenge phase and 6 months for each infectivity control subject in the rechallenge phase.

• Vaccination schedules:

• 0, 1, 7-month followed by sporozoite challenge 21 days (3 weeks) after the third vaccination, with subsequent boosting/no boosting at Booster Phase Study Day 0 followed by sporozoite rechallenge 3 weeks post boost/no boost.

• 0, 1, 2-month followed by sporozoite challenge 21 days (3 weeks) after the third vaccination, with subsequent boosting/no boosting at Booster Phase Study Day 0 followed by sporozoite rechallenge 3 weeks post boost/no boost.

• Safety and immunogenicity will be evaluated during the study up to 3 months after rechallenge (Booster Phase Study Day 105).

• Treatment allocation:

• Non-randomized for primary phase; subjects will be enrolled to different study groups in a consecutive manner, to ensure the day of sporozoite challenge (conducted over two days) is the same for all.

• For the booster and rechallenge phase, subjects unprotected during the first challenge will receive a 1/5th RTS,S/AS01B booster dose while subjects from each group who were protected in the first challenge will be randomized to receive a 1/5th RTS,S/AS01B booster dose or no booster dose.

This protocol posting has been amended to reflect changes in Amendment 2 of the Protocol (08 January 2015) Rationale for Protocol Amendment 2: In order to have sufficient blood samples for future assay development or testing, evaluation of Hepatitis B (HBs) cellular-mediated immunogenicity (CMI) was de-prioritised from a secondary outcome measure to a tertiary secondary outcome measure and will only be conducted if sufficient cells are available from the thawn cryotube(s) that will be used for circumsporozoite protein (CS) testing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candidate Malaria Vaccine 257049 in the Sporozoite Challenge Model in Healthy Malaria-naïve Adults
• Actual Study Start Date: May 20, 2013
• Actual Primary Completion Date: Mar 24, 2014
• Actual Study Completion Date: Dec 16, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK257049-0,1,7M Group Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by another dose of GSK257049 vaccine.	Biological: GSK257049 Dosage 1; RTS,S/AS01B administered as 0.5 mL dose at 0 and 1 months and 0.1 mL dose at 7 months for 0,1,7 M Group (delayed fractional dose group). In subjects unprotected in the first challenge, to receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge. In subjects protected in the first challenge, randomization to receive or not receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge.; Other Names: S/AS01B RTS
Experimental: GSK257049-0,1,2M Group Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months).	Biological: GSK257049 Dosage 2; RTS,S/AS01B administered as three doses of 0.5mL given one month apart (0, 1, 2 M group) in the challenge model. In subjects unprotected in the first challenge, to receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge. In subjects protected in the first challenge, randomization to receive or not receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge.; Other Names: RTS S/AS01B
Experimental: Infectivity Control Group Volunteers who did not receive any immunization but underwent sporozoite challenge	Procedure: Sporozoite-infected mosquitoes challenge; Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the volunteers. For each volunteer, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. The challenge is scheduled to occur approximately 21 days (3 weeks) after the last vaccination visit (Study Day 196). Volunteers who reconsent for the boost/rechallenge phase will be rechallenged with sporozoite-infected mosquitoes, scheduled to occur approximately 21 days (3 weeks) after the booster dose (Booster Phase Study Day 21).

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Challenge [28 days post-challenge (Study Day 245)]

   The definition of malaria for primary and secondary efficacy outcomes is the appearance of asexual blood stage P. falciparum parasites detected by blood slide at any time post challenge/rechallenge up to 28 days.

Secondary Outcome Measures

1. Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Challenge [Up to 28 days post-challenge (Study Day 245)]

   The time to onset was expressed in days. The definition of malaria infection for primary and secondary efficacy outcomes is the appearance of asexual blood stage P. falciparum parasites detected by blood slide at any time post challenge/rechallenge up to 28 days.

2. Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge [Up to 28 days post rechallenge (Booster Phase Day 49)]

   The definition of malaria infection for primary and secondary efficacy outcomes is the appearance of asexual blood stage P. falciparum parasites detected by blood slide at any time post challenge/rechallenge up to 28 days.

3. Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Rechallenge [Up to 28 days post rechallenge (Booster Phase Day 49)]

   The time to onset was expressed in days. The definition of malaria infection for primary and secondary efficacy outcomes is the appearance of asexual blood stage P. falciparum parasites detected by blood slide at any time post challenge/rechallenge up to 28 days.

4. Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations [7 days before vaccination (D-7), post-dose 1 at Day 28, post-dose 2 at Days 42, 56, 98, 196, at DoC Primary Phase (PP) (Day of CHMI = Day 217), at DoC PP (Day 217) + 7, 14, 28, 42, 56, 70, 84, 159 days (Days 224, 231, 245, 259, 273, 287, 301, 376).]

   Anti-CS antibody concentrations were determined by Enzyme Linked Immunosorbent Assay (ELISA) and expressed as EU/mL.

5. Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase [At Day 0 of rechallenge (pre-booster dose) and at DoC PP (Day 217 = Day of rechallenge)]

   Anti-CS antibody concentrations were determined by Enzyme Linked Immunosorbent Assay (ELISA) and expressed as EU/mL.

6. Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells [7 days before vaccination (D-7), post-dose 1 at Day 14, post-dose 2 at Day 42, at DoC PP (Day of CHMI = Day 217), at DoC PP (Day 217) + 7, 28, 84, 159 days (Days 224, 245, 301, 376).]

   Frequency of Cluster of Differentiation 4 (CD4) polypositives T-cells with at least 2 cytokines/activation markers between CD40-Ligand (CD40-L), interferon gamma (INF-g), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-a) was assessed for peripheral blood mononuclear cells (PBMC) with intracellular cytokine staining (ICS).

7. Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells [7 days before vaccination (D-7), post-dose 1 at Day 14, post-dose 2 at Day 42, at DoC PP (Day of CHMI = Day 217), at DoC PP (Day 217) + 7, 28, 84, 159 days (Days 224, 245, 301, 376).]

   Frequency of CD8 polypositives T-cells with at least 2 cytokines/activation markers between CD40-L, INF-g, IL-2 and TNF-a was assessed for PBMC with ICS.

8. Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) [7 days before vaccination (D-7), post-dose 1 at Day 28, post-dose 2 at Days 42, 56, 98, 196 after first dose, at DoC PP (Day of CHMI = Day 217), at DoC PP (Day 217)+ 7, 14, 28, 42, 56, 70, 84, 159 days (Days 224, 231, 245, 259, 273, 287, 301, 376).]

   Anti-HBs antibody concentrations were determined by Chemiluminometric Immunoassay (CLIA) and expressed as miliinternation units per mililier (mIU/mL).

9. Anti-HBs Antibody Concentrations for Rechallenge Phase [At Day 0 of rechallenge (pre-booster dose) and at DoC PP (Day 217 = Day of rechallenge)]

   Anti-HBs antibody concentrations were determined by Chemiluminometric Immunoassay (CLIA).

10. Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase [Post-dose 1 at Day 28, post-dose 2 at Days 56, and 196, DoC PP (DoC = the day of CHMI, Day 217), DoC PP (Day 217) + 84 days (Day 301) and DoC PP (Day 217) +159 days (Day 376)]

    The avidity index percentage was calculated by anti-CS repeat region concentration under chaotropic reagent/anti-CS repeat region concentration without chaotropic reagent. The median and inter-quartile (Q1 and Q3) range was reported at the prespecified time-points.

11. Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase [Pre-booster dose (Booster phase Day 0) and at DoC Booster/rechallenge phase (Day of Controlled Human Malaria Infection - Day 21)]

    The avidity index percentage was calculated by anti-CS repeat region titer under chaotropic reagent/anti-CS repeat region titer without chaotropic reagent. The median and inter-quartile (Q1 and Q3) range was reported at the prespecified time-points.

12. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses]

    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

13. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses]

    Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (nausea, vomiting and/or abdominal pain), headache and fever [defined as axillary temperature equal to or above (≥) 38.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

14. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [Within the 7-day (Days 0-6) post- booster vaccination period]

    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

15. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [Within the 7-day (Days 0-6) post- booster vaccination period]

    Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache and fever [defined as axillary temperature equal to or above (≥) 38.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

16. Number of Subjects With Any Unsolicited Adverse Events (AEs) [Within 30-days (Days 0-29) post-primary vaccination]

    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.

17. Number of Subjects With Any Unsolicited Adverse Events (AEs) [Within 30-days (Days 0-29) post- booster vaccination]

    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.

18. Number of Subjects With Any Unsolicited Adverse Events (AEs) [Within 30-days (Days 0-29) post-first CHMI]

    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.

19. Number of Subjects With Any Unsolicited Adverse Events (AEs) [Within 30-days (Days 0-29) post- second CHMI]

    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.

20. Number of Subjects With Serious Adverse Events (SAEs) [From study start to end of Primary Phase (Study Day 245)]

    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.

21. Number of Subjects With Serious Adverse Events (SAEs) [During the entire study period (Up to Day 105 of Booster Phase)]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Inclusion criteria for enrolment to the primary phase:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.

• A male or non-pregnant female 18 to 50 years of age at the time of first vaccination.

• Written informed consent obtained from the subject before screening procedures.

• Free of obvious health problems as established by medical history and clinical examination before entering into the study.

• Available to participate for the duration of the study (approximately 15 months per vaccinated subject in the delayed fractional dose group, approximately 10 months per vaccinated subject in the 0, 1, 2-month schedule and approximately 7 months per subject in the infectivity control group).

• Female subjects of non-childbearing potential may be enrolled in the study.

• Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.

• Female subjects of childbearing potential may be enrolled in the study, if the subject:

• has practiced adequate FDA-approved contraception for 30 days prior to vaccination, and

• has a negative pregnancy test on the day of vaccination, and

• has agreed to continue adequate FDA-approved contraception during the entire treatment period and for 2 months after completion of the vaccination series and/or malaria challenge.

Inclusion criteria for enrolment to the booster phase:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.

• Written informed consent obtained from the subject before screening procedures.

• Subjects vaccinated in the primary phase of the study (not applicable to new infectivity controls), having undergone sporozoite challenge during the primary phase of the study.

• Available to participate for the duration of the booster phase of the study (approximately 3 months).

• Female subjects of non-childbearing potential may be enrolled in the study.

• Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.

• Female subjects of childbearing potential may be enrolled in the booster phase of the study, if the subject:

• has practiced adequate FDA-approved contraception for 30 days prior to day of booster vaccination, and

• has a negative pregnancy test on the day of booster vaccination, and

• has agreed to continue adequate FDA-approved contraception during the entire treatment period and for 2 months after completion of the booster vaccination and/or malaria rechallenge.

Exclusion Criteria:

For enrolment to the primary & booster phase:

• Any confirmed or suspected immunosuppressive or immunodeficient condition, including immunodeficiency virus (HIV) infection.

• Acute disease and/or fever at the time of enrolment to booster phase.

• Acute disease is defined as the presence of a moderate or severe illness with or without fever. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.

• Fever is defined as temperature ≥ 38.0°C (100.4°F) on oral, axillary or tympanic setting. The preferred route for recording temperature in this study will be oral.

• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.

• Evidence of increased cardiovascular disease risk, "moderate" or "high", according to the National health and nutrition examination survey I (NHANES I) criteria.

Note: NHANES I criteria will be applied for all subjects including subjects aged 18-35 years old.

• An abnormal baseline screening electrocardiogram (EKG), defined as one showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm excluding isolated premature atrial contractions; right or left bundle branch block; or advanced A-V heart block.

• Female who intends to become pregnant during the study or planning to discontinue contraceptive measures.

For enrolment to the primary phase:

• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.

• Planned administration/administration of a vaccine not foreseen by the study protocol within 7 days of the first dose of vaccines.

• Prior receipt of an investigational malaria vaccine.

• Chronic use of antibiotics with antimalarial effects.

• History of malaria chemoprophylaxis within 60 days prior to vaccination.

• Any history of malaria.

• Planned travel to malaria endemic areas during the study period.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s) including latex.

• History of allergic disease or reactions likely to be exacerbated by chloroquine.

• History of psoriasis and porphyria, which may be exacerbated after chloroquine treatment.

• Current use of medications known to cause drug reactions to chloroquine.

• Any history of anaphylaxis in reaction to any previous vaccination.

• History of severe reactions to mosquito bites.

• 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.

• Chronic administration of immunosuppressants or other immune modifying drugs within six months prior to first vaccine dose. For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 20 mg/day. Inhaled and topical steroids are allowed.

• Family history of congenital or hereditary immunodeficiency.

• History of splenectomy.

• Major congenital defects or serious chronic illness.

• History of any neurological disorders or seizures, except for a single episode of simple febrile seizure in childhood.

• Any abnormal baseline laboratory screening tests: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), creatinine, hemoglobin, platelet count, total white blood cell count, out of normal range as defined in the protocol.

• Hepatomegaly, right upper quadrant abdominal pain or tenderness.

• Personal history of autoimmune disease.

• Seropositive for hepatitis B surface antigen or Hepatitis C virus.

• Pregnant or lactating female.

• Suspected or known current alcohol abuse.

• Chronic or active intravenous drug use.

• History of blood donation within 56 days preceding enrolment.

• Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.

For enrolment to the booster phase:

• Planned use of any investigational or non-registered product other than the study vaccine during the study period.

• Planned administration/administration of a vaccine not foreseen by the study protocol within 7 days of booster dose of study vaccine.

• Planned administration of immunoglobulins and/or any blood products during the study period.

• An abnormal baseline laboratory screening test, graded 2 or more as defined in the protocol.

• Any abnormal baseline laboratory screening tests out of normal range as defined in the protocol and of clinical concern according to the Principal Investigator.

• Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in the booster phase of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Silver Spring	Maryland	United States	20910

Sponsors and Collaborators

• GlaxoSmithKline
• Walter Reed Army Institute of Research (WRAIR)
• The PATH Malaria Vaccine Initiative (MVI)

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Regules JA, Cicatelli SB, Bennett JW, Paolino KM, Twomey PS, Moon JE, Kathcart AK, Hauns KD, Komisar JL, Qabar AN, Davidson SA, Dutta S, Griffith ME, Magee CD, Wojnarski M, Livezey JR, Kress AT, Waterman PE, Jongert E, Wille-Reece U, Volkmuth W, Emerling D, Robinson WH, Lievens M, Morelle D, Lee CK, Yassin-Rajkumar B, Weltzin R, Cohen J, Paris RM, Waters NC, Birkett AJ, Kaslow DC, Ballou WR, Ockenhouse CF, Vekemans J. Fractional Third and Fourth Dose of RTS,S/AS01 Malaria Candidate Vaccine: A Phase 2a Controlled Human Malaria Parasite Infection and Immunogenicity Study. J Infect Dis. 2016 Sep 1;214(5):762-71. doi: 10.1093/infdis/jiw237. Epub 2016 Jun 13.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01857869
• Other Study ID Numbers: 117014
• First Posted: May 20, 2013
• Last Update Posted: Jun 26, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Efficacy; Sporozoite challenge model; Malaria; Immunogenicity; Malaria- naïve adults; Safety
• Additional relevant MeSH terms: Malaria

Study Results

Participant Flow

Recruitment Details	Out of the 64 subjects originally enrolled in the study, 1 subject was not included in the Intention-to-Treat Cohort. The design of the study included 4 epochs (see pre-assignment details).
Pre-assignment Detail	Primary Phase (screening, vaccination [delayed fractional dose group and 0, 1, 2-month group] & challenge): Study Day (D) 217 to D245 - Follow-up: D259 to D376 - Booster (Bst) Phase (re-screening [delayed fractional dose group and 0, 1, 2-month group], vaccination & re-challange): Bst Phase Study D20 to D49 - Follow-up: Bst Phase Study D77 to D105.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group	GSK257049-0,1,7M P-NoBo Group	GSK257049-0,1,7M P-Bo Group	GSK257049-0,1,7M NP-Bo Group	GSK257049-0,1,2M P-NoBo Group	GSK257049-0,1,2M P-Bo Group	GSK257049-0,1,2M NP-Bo Group	Control Group Follow-up
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (controlled human malaria infection [CHMI]).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallenge.	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,7M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received a booster fractional (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were not protected (NP) during first CHMI and who received a booster fractional (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from Control Group in Primary Phase who remained uninfected with P. falciparum malaria and enrolled as infectivity controls for Follow-up Phase to undergo sporozoite rechallange.
Period Title: Primary/Challenge Phase
STARTED	34	17	12	0	0	0	0	0	0	0
COMPLETED	29	16	12	0	0	0	0	0	0	0
NOT COMPLETED	5	1	0	0	0	0	0	0	0	0
Period Title: Primary/Challenge Phase
STARTED	0	0	0	9	10	2	5	4	3	6
COMPLETED	0	0	0	7	10	2	5	4	3	6
NOT COMPLETED	0	0	0	2	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group	GSK257049-0,1,7M P-NoBo Group	GSK257049-0,1,7M P-Bo Group	GSK257049-0,1,7M NP-Bo Group	GSK257049-0,1,2M P-NoBo Group	GSK257049-0,1,2M P-Bo Group	GSK257049-0,1,2M NP-Bo Group	Control Group Follow-up	Total
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallenge.	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,7M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from Control Group in Primary Phase who remained uninfected with P. falciparum malaria and enrolled as infectivity controls for Follow-up Phase to undergo sporozoite rechallange.	Total of all reporting groups
Overall Participants	34	17	12	7	10	2	5	4	3	6	100
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.4 (8.6)	30.1 (7.9)	36.4 (8.7)	33.6 (8.6)
Sex: Female, Male (Count of Participants)
Female	15 44.1%	6 35.3%	7 58.3%	28 400%
Male	19 55.9%	11 64.7%	5 41.7%	35 500%
Race/Ethnicity, Customized (Count of Participants)
African Heritage/African American	15 44.1%	5 29.4%	5 41.7%	25 357.1%
Asian - Central/South Asian Heritage	1 2.9%	0 0%	0 0%	1 14.3%
Asian - South East Asian Heritage	2 5.9%	0 0%	0 0%	2 28.6%
White - Caucasian/European Heritage	13 38.2%	10 58.8%	5 41.7%	28 400%
Unspecified	3 8.8%	2 11.8%	2 16.7%	7 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Challenge
Description	The definition of malaria for primary and secondary efficacy outcomes is the appearance of asexual blood stage P. falciparum parasites detected by blood slide at any time post challenge/rechallenge up to 28 days.
Time Frame	28 days post-challenge (Study Day 245)

Outcome Measure Data

Analysis Population Description

The analysis was based on the According-to-Protocol (ATP) population for immunogenicity and efficacy, which included all subjects who complied with the protocol requirements and underwent P. falciparum CHMI.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
Measure Participants	30	16	12
Count of Participants [Participants]	4 11.8%	6 35.3%	12 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK257049-0,1,7M Group, Infectivity Control Group
	Comments	Vaccine efficacy (VE) was defined as 100*(1-Relative Risk [RR]).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two-sided Fisher Exact test was used for the comparison of malaria incidence after first/second CHMI between the compared groups.
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	1-Relative Risk
	Estimated Value	86.7
	Confidence Interval	(2-Sided) 95%; 66.8 to 94.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK257049-0,1,2M Group, Infectivity Control Group
	Comments	Vaccine efficacy (VE) was defined as 100*(1-Relative Risk [RR]).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0009
	Comments	Two-sided Fisher Exact test was used for the comparison of malaria incidence after first/second CHMI between the compared groups.
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	1-Relative Risk
	Estimated Value	62.5
	Confidence Interval	(2-Sided) 95%; 29.4 to 80.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Challenge
Description	The time to onset was expressed in days. The definition of malaria infection for primary and secondary efficacy outcomes is the appearance of asexual blood stage P. falciparum parasites detected by blood slide at any time post challenge/rechallenge up to 28 days.
Time Frame	Up to 28 days post-challenge (Study Day 245)

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy, which included all subjects who complied with the protocol requirements and underwent P. falciparum CHMI. This analysis included those subjects with a positive blood slide.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
Measure Participants	4	6	12
Mean (Standard Deviation) [Days]	17 (6)	15 (5)	13 (1)

3. Secondary Outcome

Title	Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge
Description	The definition of malaria infection for primary and secondary efficacy outcomes is the appearance of asexual blood stage P. falciparum parasites detected by blood slide at any time post challenge/rechallenge up to 28 days.
Time Frame	Up to 28 days post rechallenge (Booster Phase Day 49)

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy for the rechallenge Phase, which included all subjects from the ATP population for immunogenicity and efficacy who consented to the rechallenge.

Arm/Group Title	GSK257049-0,1,7M P-NoBo Group	GSK257049-0,1,7M P-Bo Group	GSK257049-0,1,7M NP-Bo Group	GSK257049-0,1,2M P-NoBo Group	GSK257049-0,1,2M P-Bo Group	GSK257049-0,1,2M NP-Bo Group	Control Group Follow-up
Arm/Group Description	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallenge.	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,7M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from Control Group in Primary Phase who remained uninfected with P. falciparum malaria and enrolled as infectivity controls for Follow-up Phase to undergo sporozoite rechallange.
Measure Participants	7	10	2	5	4	3	6
Count of Participants [Participants]	4 11.8%	1 5.9%	0 0%	4 57.1%	3 30%	1 50%	6 120%

4. Secondary Outcome

Title	Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Rechallenge
Description	The time to onset was expressed in days. The definition of malaria infection for primary and secondary efficacy outcomes is the appearance of asexual blood stage P. falciparum parasites detected by blood slide at any time post challenge/rechallenge up to 28 days.
Time Frame	Up to 28 days post rechallenge (Booster Phase Day 49)

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy for the rechallenge Phase, which included all subjects from the ATP population for immunogenicity and efficacy who consented to the rechallenge. This analysis included those subjects with a positive blood slide.

Arm/Group Title	GSK257049-0,1,7M P-NoBo Group	GSK257049-0,1,7M P-Bo Group	GSK257049-0,1,2M P-NoBo Group	GSK257049-0,1,2M P-Bo Group	GSK257049-0,1,2M NP-Bo Group	Control Group Follow-up
Arm/Group Description	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallenge.	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from Control Group in Primary Phase who remained uninfected with P. falciparum malaria and enrolled as infectivity controls for Follow-up Phase to undergo sporozoite rechallange.
Measure Participants	4	1	4	3	1	6
Mean (Standard Deviation) [Days]	14 (1)	14 (0)	15 (1)	14 (2)	14 (0)	12 (1)

5. Secondary Outcome

Title	Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations
Description	Anti-CS antibody concentrations were determined by Enzyme Linked Immunosorbent Assay (ELISA) and expressed as EU/mL.
Time Frame	7 days before vaccination (D-7), post-dose 1 at Day 28, post-dose 2 at Days 42, 56, 98, 196, at DoC Primary Phase (PP) (Day of CHMI = Day 217), at DoC PP (Day 217) + 7, 14, 28, 42, 56, 70, 84, 159 days (Days 224, 231, 245, 259, 273, 287, 301, 376).

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy, which included all subjects who complied with the protocol requirements and underwent P. falciparum CHMI.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
Measure Participants	30	16	12
7 days before vaccination	0.3	0.3
At Day 28	13.1	16.3
At Day 42	104.2	64.4
At Day 56	83.3	57.9
At Day 98	46.1
At Day 196	18.3
At DoC PP (Day 217)	75.2	100.1	0.4
Day 7 after DoC PP (Day 217)	75.7	91.7	0.4
Day 14 after DoC PP (Day 217)	68.9	79.4	0.4
Day 28 after DoC PP (Day 217)	63.8	75.7	0.5
Day 42 after DoC PP (Day 217)	57.6	73.6	0.6
Day 56 after DoC PP (Day 217)	54.0	63.2	0.5
Day 70 after DoC PP (Day 217)	46.9	59.2	0.5
Day 84 after DoC PP (Day 217)	45.6	55.3	0.5
Day 159 after DoC PP (Day 217)	32.8	34.6	0.5

6. Secondary Outcome

Title	Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase
Description	Anti-CS antibody concentrations were determined by Enzyme Linked Immunosorbent Assay (ELISA) and expressed as EU/mL.
Time Frame	At Day 0 of rechallenge (pre-booster dose) and at DoC PP (Day 217 = Day of rechallenge)

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy for the rechallenge, which included all subjects from the ATP population for immunogenicity and efficacy who consented to the rechallenge.

Arm/Group Title	GSK257049-0,1,7M P-NoBo Group	GSK257049-0,1,7M P-Bo Group	GSK257049-0,1,7M NP-Bo Group	GSK257049-0,1,2M P-NoBo Group	GSK257049-0,1,2M P-Bo Group	GSK257049-0,1,2M NP-Bo Group	Control Group Follow-up
Arm/Group Description	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallenge.	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,7M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from Control Group in Primary Phase who remained uninfected with P. falciparum malaria and enrolled as infectivity controls for Follow-up Phase to undergo sporozoite rechallange.
Measure Participants	7	10	2	5	4	3	6
At Day 0 of rechallenge	30.7	7.2	35.9	24.5
At DoC PP (Day 217)	25.7	86.6	81.2	39.2	61.7	53.5	0.3

7. Secondary Outcome

Title	Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells
Description	Frequency of Cluster of Differentiation 4 (CD4) polypositives T-cells with at least 2 cytokines/activation markers between CD40-Ligand (CD40-L), interferon gamma (INF-g), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-a) was assessed for peripheral blood mononuclear cells (PBMC) with intracellular cytokine staining (ICS).
Time Frame	7 days before vaccination (D-7), post-dose 1 at Day 14, post-dose 2 at Day 42, at DoC PP (Day of CHMI = Day 217), at DoC PP (Day 217) + 7, 28, 84, 159 days (Days 224, 245, 301, 376).

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy, which included all subjects who complied with the protocol requirements and underwent P. falciparum CHMI, with cellular mediated immunity data available.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
Measure Participants	29	16	12
7 days before vaccination	61.38 (95.16)	83.31 (79.40)
At Day 14	168.89 (205.87)	242.53 (262.97)
At Day 42	1306.11 (1962.03)	866.87 (779.25)
At DoC PP (Day 217)	596.15 (636.60)	555.86 (487.16)	57.17 (102.19)
Day 7 after DoC PP (Day 217)	661.61 (711.86)	539.40 (416.68)	39.25 (42.40)
Day 28 after DoC PP (Day 217)	626.29 (586.16)	472.63 (287.64)	162.22 (275.51)
Day 84 after DoC PP (Day 217)	481.44 (392.44)	472.63 (287.64)	90.67 (121.47)
Day 159 after DoC PP (Day 217)	490.00 (401.39)	307.87 (231.91)	32.55 (51.06)

8. Secondary Outcome

Title	Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells
Description	Frequency of CD8 polypositives T-cells with at least 2 cytokines/activation markers between CD40-L, INF-g, IL-2 and TNF-a was assessed for PBMC with ICS.
Time Frame	7 days before vaccination (D-7), post-dose 1 at Day 14, post-dose 2 at Day 42, at DoC PP (Day of CHMI = Day 217), at DoC PP (Day 217) + 7, 28, 84, 159 days (Days 224, 245, 301, 376).

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy, which included all subjects who complied with the protocol requirements and underwent P. falciparum CHMI, with cellular mediated immunity data available.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
Measure Participants	29	16	12
7 days before vaccination	14.10 (20.60)	9.56 (15.31)
At Day 14	24.61 (43.01)	17.20 (30.03)
At Day 42	18.7 (46.69)	27.60 (40.40)
At DoC PP (Day 217)	32.52 (57.64)	28.86 (28.73)	15.33 (29.06)
Day 7 after DoC PP (Day 217)	19.54 (42.55)	32.07 (56.77)	32.00 (53.81)
Day 28 after DoC PP (Day 217)	19.96 (27.35)	34.81 (66.56)	17.67 (36.31)
Day 84 after DoC PP (Day 217)	19.89 (54.19)	20.23 (26.25)	12.17 (22.91)
Day 159 after DoC PP (Day 217)	26.74 (52.22)	24.40 (44.30)	22.00 (33.01)

9. Secondary Outcome

Title	Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs)
Description	Anti-HBs antibody concentrations were determined by Chemiluminometric Immunoassay (CLIA) and expressed as miliinternation units per mililier (mIU/mL).
Time Frame	7 days before vaccination (D-7), post-dose 1 at Day 28, post-dose 2 at Days 42, 56, 98, 196 after first dose, at DoC PP (Day of CHMI = Day 217), at DoC PP (Day 217)+ 7, 14, 28, 42, 56, 70, 84, 159 days (Days 224, 231, 245, 259, 273, 287, 301, 376).

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy, which included all subjects who complied with the protocol requirements and underwent P. falciparum CHMI.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
Measure Participants	30	16	12
7 days before vaccination	27.5	28.5
At Day 28	7223.0	7318.2
At Day 42	35016.9	27205.5
At Day 56	21013.0	20625.8
At Day 98	12367.7
At Day 196	9917.0
At DoC PP (Day 217)	33715.4	31798.7	27.9
Day 7 after DoC PP (Day 217)	29902.6	28989.2	32.5
Day 14 after DoC PP (Day 217)	35401.1	24952.2	25.7
Day 28 after DoC PP (Day 217)	25553.8	25944.1	27.5
Day 42 after DoC PP (Day 217)	23757.6	20000.3	32.8
Day 56 after DoC PP (Day 217)	25917.3	23199.5	34.6
Day 70 after DoC PP (Day 217)	23722.4	23313.8	31.9
Day 84 after DoC PP (Day 217)	19155.1	19631.5	26.3
Day 159 after DoC PP (Day 217)	14459.9	13495.2	26.2

10. Secondary Outcome

Title	Anti-HBs Antibody Concentrations for Rechallenge Phase
Description	Anti-HBs antibody concentrations were determined by Chemiluminometric Immunoassay (CLIA).
Time Frame	At Day 0 of rechallenge (pre-booster dose) and at DoC PP (Day 217 = Day of rechallenge)

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy for the rechallenge, which included all subjects from the ATP population for immunogenicity and efficacy who consented to the rechallenge.

Arm/Group Title	GSK257049-0,1,7M P-NoBo Group	GSK257049-0,1,7M P-Bo Group	GSK257049-0,1,7M NP-Bo Group	GSK257049-0,1,2M P-NoBo Group	GSK257049-0,1,2M P-Bo Group	GSK257049-0,1,2M NP-Bo Group	Control Group Follow-up
Arm/Group Description	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallenge.	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,7M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from Control Group in Primary Phase who remained uninfected with P. falciparum malaria and enrolled as infectivity controls for Follow-up Phase to undergo sporozoite rechallange.
Measure Participants	7	10	2	5	4	3	6
At Day 9 of rechallenge	9270.9	6928.3	23259.5	15620.0
At DoC PP (Day 217)	19592.4	24261.5	36809.8	6051.9	38175.5	34470.4	35.7

11. Secondary Outcome

Title	Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase
Description	The avidity index percentage was calculated by anti-CS repeat region concentration under chaotropic reagent/anti-CS repeat region concentration without chaotropic reagent. The median and inter-quartile (Q1 and Q3) range was reported at the prespecified time-points.
Time Frame	Post-dose 1 at Day 28, post-dose 2 at Days 56, and 196, DoC PP (DoC = the day of CHMI, Day 217), DoC PP (Day 217) + 84 days (Day 301) and DoC PP (Day 217) +159 days (Day 376)

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy, which included all subjects who complied with the protocol requirements and underwent P. falciparum CHMI.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
Measure Participants	30	16	2
At Day 28	25.65	17.90
At Day 56	37.40	31.10
At Day 196	28.10
At DoC PP (Day 217)	40.40	29.00
Day 84 after DoC PP (Day 217)	37.40	28.30	32.10
Day 159 after DoC PP (Day 217)	36.10	28.90	32.05

12. Secondary Outcome

Title	Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase
Description	The avidity index percentage was calculated by anti-CS repeat region titer under chaotropic reagent/anti-CS repeat region titer without chaotropic reagent. The median and inter-quartile (Q1 and Q3) range was reported at the prespecified time-points.
Time Frame	Pre-booster dose (Booster phase Day 0) and at DoC Booster/rechallenge phase (Day of Controlled Human Malaria Infection - Day 21)

Outcome Measure Data

Analysis Population Description

The analysis was based on the ATP population for immunogenicity and efficacy for the rechallenge, which included all subjects from the ATP population for immunogenicity and efficacy who consented to the rechallenge. Results were not reported for the Control Group Follow-up, since subjects from this group did not receive any immunization.

Arm/Group Title	GSK257049-0,1,7M P-NoBo Group	GSK257049-0,1,7M P-Bo Group	GSK257049-0,1,7M NP-Bo Group	GSK257049-0,1,2M P-NoBo Group	GSK257049-0,1,2M P-Bo Group	GSK257049-0,1,2M NP-Bo Group
Arm/Group Description	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallenge.	Subjects from GSK257049-0,1,7M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,7M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received no booster dose (NoBo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were protected (P) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.	Subjects from GSK257049-0,1,2M Group who were not protected (NP) during first CHMI and who received a booster fractional low-formulated (Bo) of GSK257049 vaccine and underwent sporozoite rechallange.
Measure Participants	7	10	2	5	4	3
Pre-booster dose	41.15	43.30	21.25	30.40
DoC Booster/rechallenge phase (Day 21)	35.00	46.55	50.60	31.30	36.80	31.20

13. Secondary Outcome

Title	Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Time Frame	Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses

Outcome Measure Data

Analysis Population Description

The analysis was based on the Intention-to-Treat (ITT) population, which included all subjects with at least one vaccine administration documented, who had their symptom sheets filled in. Results were not reported for the Infectivity Control Group, since subjects from this group did not receive any immunization.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).
Measure Participants	34	17
Any Pain, Dose 1	30 88.2%	16 94.1%
Grade 3 Pain, Dose 1	0 0%	0 0%
Any Redness, Dose 1	7 20.6%	8 47.1%
Grade 3 Redness, Dose 1	0 0%	0 0%
Any Swelling, Dose 1	8 23.5%	1 5.9%
Grade 3 Swelling, Dose 1	0 0%	0 0%
Any Pain, Dose 2	28 82.4%	13 76.5%
Grade 3 Pain, Dose 2	0 0%	0 0%
Any Redness, Dose 2	13 38.2%	6 35.3%
Grade 3 Redness, Dose 2	0 0%	0 0%
Any Swelling, Dose 2	10 29.4%	2 11.8%
Grade 3 Swelling, Dose 2	0 0%	0 0%
Any Pain, Dose 3	21 61.8%	12 70.6%
Grade 3 Pain, Dose 3	0 0%	0 0%
Any Redness, Dose 3	23 67.6%	7 41.2%
Grade 3 Redness, Dose 3	0 0%	0 0%
Any Swelling, Dose 3	17 50%	3 17.6%
Grade 3 Swelling, Dose 3	0 0%	0 0%
Any Pain, Across doses	32 94.1%	16 94.1%
Grade 3 Pain, Across doses	0 0%	0 0%
Any Redness, Across doses	26 76.5%	12 70.6%
Grade 3 Redness, Across doses	0 0%	0 0%
Any Swelling, Across doses	21 61.8%	4 23.5%
Grade 3 Swelling, Across doses	0 0%	0 0%

14. Secondary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description	Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (nausea, vomiting and/or abdominal pain), headache and fever [defined as axillary temperature equal to or above (≥) 38.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Time Frame	Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses

Outcome Measure Data

Analysis Population Description

The analysis was based on the ITT population, which included all subjects with at least one vaccine administration documented, who had their symptom sheets filled in. Results were not reported for the Infectivity Control Group, since subjects from this group did not receive any immunization.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).
Measure Participants	34	17
Any Fatigue, Dose 1	10 29.4%	3 17.6%
Related Fatigue, Dose 1	9 26.5%	3 17.6%
Grade 3 Fatigue, Dose 1	1 2.9%	0 0%
Any Gastrointestinal symptoms, Dose 1	4 11.8%	2 11.8%
Related Gastrointestinal symptoms, Dose 1	4 11.8%	2 11.8%
Grade 3 Gastrointestinal symptoms, Dose 1	0 0%	0 0%
Any Headache, Dose 1	9 26.5%	9 52.9%
Related Headache, Dose 1	8 23.5%	9 52.9%
Grade 3 Headache, Dose 1	1 2.9%	0 0%
Any Temperature, Dose 1	3 8.8%	3 17.6%
Related Temperature, Dose 1	3 8.8%	0 0%
Grade 3 Temperature, Dose 1	0 0%	0 0%
Any Fatigue, Dose 2	15 44.1%	5 29.4%
Related Fatigue, Dose 2	15 44.1%	5 29.4%
Grade 3 Fatigue, Dose 2	1 2.9%	0 0%
Any Gastrointestinal symptoms, Dose 2	3 8.8%	5 29.4%
Related Gastrointestinal symptoms, Dose 2	3 8.8%	5 29.4%
Grade 3 Gastrointestinal symptoms, Dose 2	0 0%	0 0%
Any Headache, Dose 2	15 44.1%	9 52.9%
Related Headache, Dose 2	15 44.1%	8 47.1%
Grade 3 Headache, Dose 2	0 0%	0 0%
Any Temperature, Dose 2	6 17.6%	1 5.9%
Related Temperature, Dose 2	6 17.6%	1 5.9%
Grade 3 Temperature, Dose 2	3 8.8%	0 0%
Any Fatigue, Dose 3	8 23.5%	7 41.2%
Related Fatigue, Dose 3	8 23.5%	6 35.3%
Grade 3 Fatigue, Dose 3	0 0%	0 0%
Any Gastrointestinal symptoms, Dose 3	6 17.6%	2 11.8%
Related Gastrointestinal symptoms, Dose 3	3 8.8%	2 11.8%
Grade 3 Gastrointestinal symptoms, Dose 3	0 0%	0 0%
Any Headache, Dose 3	9 26.5%	6 35.3%
Related Headache, Dose 3	7 20.6%	6 35.3%
Grade 3 Headache, Dose 3	0 0%	0 0%
Any Temperature, Dose 3	0 0%	0 0%
Related Temperature, Dose 3	0 0%	0 0%
Grade 3 Temperature, Dose 3	0 0%	0 0%
Any Fatigue, Across doses	18 52.9%	9 52.9%
Related Fatigue, Across doses	18 52.9%	8 47.1%
Grade 3 Fatigue, Across doses	2 5.9%	0 0%
Any Gastrointestinal symptoms, Across doses	7 20.6%	5 29.4%
Related Gastrointestinal symptoms, Across doses	7 20.6%	5 29.4%
Grade 3 Gastrointestinal symptoms, Across doses	0 0%	0 0%
Any Headache, Across doses	18 52.9%	11 64.7%
Related Headache, Across doses	18 52.9%	11 64.7%
Grade 3 Headache, Across doses	1 2.9%	0 0%
Any Temperature, Across doses	8 23.5%	4 23.5%
Related Temperature, Across doses	8 23.5%	1 5.9%
Grade 3 Temperature, Across doses	3 8.8%	0 0%

15. Secondary Outcome

Title	Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Time Frame	Within the 7-day (Days 0-6) post- booster vaccination period

Outcome Measure Data

Analysis Population Description

The analysis was based on the ITT population for the rechallenge, which included subjects from the ITT population consenting to the rechallenge. For the purpose of the analysis, subjects who received a low fractional formulation booster dose of GSK257049 vaccine have been pooled into a single group and results were tabulated accordingly.

Arm/Group Title	Boosted Group
Arm/Group Description	Pooled group comprising subjects from the GSK257049-0,1,7M P-Bo Group; GSK257049-0,1,7M NP-Bo Group; GSK257049-0,1,2M P-Bo Group and GSK257049-0,1,2M NP-Bo Group (protected and not protected subjects from the Primary Phase groups, that received a low fractional formulation booster dose of GSK257049 vaccine).
Measure Participants	19
Any Pain	11 32.4%
Grade 3 Pain	0 0%
Any Redness	8 23.5%
Grade 3 Redness	0 0%
Any Swelling	4 11.8%
Grade 3 Swelling	0 0%

16. Secondary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description	Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache and fever [defined as axillary temperature equal to or above (≥) 38.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Time Frame	Within the 7-day (Days 0-6) post- booster vaccination period

Outcome Measure Data

Analysis Population Description

The analysis was based on the ITT population for the rechallenge, which included subjects from the ITT population consenting to the rechallenge. For the purpose of the analysis, subjects who received a low fractional formulation booster dose of GSK257049 vaccine have been pooled into a single group and results were tabulated accordingly.

Arm/Group Title	Boosted Group
Arm/Group Description	Pooled group comprising subjects from the GSK257049-0,1,7M P-Bo Group; GSK257049-0,1,7M NP-Bo Group; GSK257049-0,1,2M P-Bo Group and GSK257049-0,1,2M NP-Bo Group (protected and not protected subjects from the Primary Phase groups, that received a low fractional formulation booster dose of GSK257049 vaccine).
Measure Participants	19
Any Fatigue	8 23.5%
Related Fatigue	5 14.7%
Grade 3 Fatigue	0 0%
Any Gastrointestinal symptoms	4 11.8%
Related Gastrointestinal symptoms	3 8.8%
Grade 3 Gastrointestinal symptoms	0 0%
Any Headache	8 23.5%
Related Headache	6 17.6%
Grade 3 Headache	1 2.9%
Any Temperature	0 0%
Related Temperature	0 0%
Grade 3 Temperature	0 0%

17. Secondary Outcome

Title	Number of Subjects With Any Unsolicited Adverse Events (AEs)
Description	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.
Time Frame	Within 30-days (Days 0-29) post-primary vaccination

Outcome Measure Data

Analysis Population Description

The analysis was based on the ITT population, which included all subjects with at least one vaccine administration documented. Results were not reported for the Infectivity Control Group, since subjects from this group did not receive any immunization.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).
Measure Participants	34	17
Count of Participants [Participants]	25 73.5%	16 94.1%

18. Secondary Outcome

Title	Number of Subjects With Any Unsolicited Adverse Events (AEs)
Description	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.
Time Frame	Within 30-days (Days 0-29) post- booster vaccination

Outcome Measure Data

Analysis Population Description

The analysis was based on the ITT population for the rechallenge, which included subjects from the ITT population consenting to the rechallenge. For the purpose of the analysis, subjects who received a low fractional formulation booster dose of GSK257049 vaccine have been pooled into a single group and results were tabulated accordingly.

Arm/Group Title	Boosted Group
Arm/Group Description	Pooled group comprising subjects from the GSK257049-0,1,7M P-Bo Group; GSK257049-0,1,7M NP-Bo Group; GSK257049-0,1,2M P-Bo Group and GSK257049-0,1,2M NP-Bo Group (protected and not protected subjects from the Primary Phase groups, that received a low fractional formulation booster dose of GSK257049 vaccine).
Measure Participants	19
Count of Participants [Participants]	10 29.4%

19. Secondary Outcome

Title	Number of Subjects With Any Unsolicited Adverse Events (AEs)
Description	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.
Time Frame	Within 30-days (Days 0-29) post-first CHMI

Outcome Measure Data

Analysis Population Description

The analysis was based on the ITT population, which included all subjects with at least one vaccine administration documented and who had post-first CHMI available results.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
Measure Participants	30	16	12
Count of Participants [Participants]	25 73.5%	13 76.5%	12 100%

20. Secondary Outcome

Title	Number of Subjects With Any Unsolicited Adverse Events (AEs)
Description	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.
Time Frame	Within 30-days (Days 0-29) post- second CHMI

Outcome Measure Data

Analysis Population Description

The analysis was based on the ITT population for the rechallenge, which included subjects from the ITT population consenting to the rechallenge.

Arm/Group Title	Non Boosted Group	Boosted Group	Control Group Follow-up
Arm/Group Description	Pooled group comprising subjects from the GSK257049-0,1,7M P-NoBo and GSK257049-0,1,2M P-NoBo Group (protected subjects from the Primary Phase groups, that did not receive a booster dose of GSK257049 vaccine.	Pooled group comprising subjects from the GSK257049-0,1,7M P-Bo Group; GSK257049-0,1,7M NP-Bo Group; GSK257049-0,1,2M P-Bo Group and GSK257049-0,1,2M NP-Bo Group (protected and not protected subjects from the Primary Phase groups, that received a low fractional formulation booster dose of GSK257049 vaccine).	Subjects from Control Group in Primary Phase who remained uninfected with P. falciparum malaria and enrolled as infectivity controls for Follow-up Phase.
Measure Participants	12	19	6
Count of Participants [Participants]	11 32.4%	15 88.2%	6 50%

21. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	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.
Time Frame	From study start to end of Primary Phase (Study Day 245)

Outcome Measure Data

Analysis Population Description

The analysis was based on the ITT population, which included all subjects with at least one vaccine administration documented.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
Measure Participants	34	17	12
Count of Participants [Participants]	1 2.9%	0 0%	0 0%

22. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	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.
Time Frame	During the entire study period (Up to Day 105 of Booster Phase)

Outcome Measure Data

Analysis Population Description

The analysis was based on the ITT population, which included all subjects with at least one vaccine administration documented.

Arm/Group Title	GSK257049-0,1,7M Group	GSK257049-0,1,2M Group	Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).	Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).	Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
Measure Participants	34	17	12
Count of Participants [Participants]	1 2.9%	0 0%	0 0%

Adverse Events

Time Frame	Solicited local and general symptoms: within 7 days (Days 0-6) post-orimary vaccination. Unsolicited adverse events (AEs): within 30 days (Days 0-29) post-primary vaccination and post-CHMI. Serious adverse events (SAEs): during the entire study period (up to Day 105 of Booster Phase).
Adverse Event Reporting Description	Solicited and Unsolicited results were not reported for the Infectivity Control Group, since subjects from this group did not receive any immunization.
Arm/Group Title	GSK257049-0,1,7M Group		GSK257049-0,1,2M Group		Infectivity Control Group
Arm/Group Description	Subjects receiving 2 doses of GSK257049 vaccine given at 0 and 1 months and followed 6 months later (At Month 7) by a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI).		Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI).		Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI).
All Cause Mortality
	GSK257049-0,1,7M Group		GSK257049-0,1,2M Group		Infectivity Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/17 (0%)		0/12 (0%)
Serious Adverse Events
	GSK257049-0,1,7M Group		GSK257049-0,1,2M Group		Infectivity Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/34 (2.9%)		0/17 (0%)		0/12 (0%)
Injury, poisoning and procedural complications
Alcohol poisoning	1/34 (2.9%)	1	0/17 (0%)	0	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	GSK257049-0,1,7M Group		GSK257049-0,1,2M Group		Infectivity Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/34 (100%)		17/17 (100%)		0/12 (0%)
Ear and labyrinth disorders
Ear pain	1/34 (2.9%)	1	1/17 (5.9%)	1	0/12 (0%)	1
Gastrointestinal disorders
Abdominal pain	0/34 (0%)	0	1/17 (5.9%)	1	0/12 (0%)	1
Gastrointestinal disorder	8/34 (23.5%)	15	8/17 (47.1%)	12	0/12 (0%)	12
Gastrooesophageal reflux disease	0/34 (0%)	0	2/17 (11.8%)	2	0/12 (0%)	2
Nausea	3/34 (8.8%)	3	2/17 (11.8%)	2	0/12 (0%)	2
Toothache	0/34 (0%)	0	1/17 (5.9%)	2	0/12 (0%)	2
General disorders
Chills	4/34 (11.8%)	5	4/17 (23.5%)	5	0/12 (0%)	5
Fatigue	20/34 (58.8%)	39	10/17 (58.8%)	19	0/12 (0%)	19
Feeling hot	3/34 (8.8%)	3	2/17 (11.8%)	2	0/12 (0%)	2
Pain	32/34 (94.1%)	88	16/17 (94.1%)	43	0/12 (0%)	43
Pyrexia	8/34 (23.5%)	9	4/17 (23.5%)	4	0/12 (0%)	4
Swelling	23/34 (67.6%)	39	6/17 (35.3%)	8	0/12 (0%)	8
Infections and infestations
Gastroenteritis viral	0/34 (0%)	0	1/17 (5.9%)	1	0/12 (0%)	1
Tooth abscess	0/34 (0%)	0	1/17 (5.9%)	1	0/12 (0%)	1
Upper respiratory tract infection	5/34 (14.7%)	5	7/17 (41.2%)	7	0/12 (0%)	7
Viral infection	0/34 (0%)	0	2/17 (11.8%)	2	0/12 (0%)	2
Injury, poisoning and procedural complications
Arthropod bite	5/34 (14.7%)	5	3/17 (17.6%)	3	0/12 (0%)	3
Contusion	2/34 (5.9%)	2	0/17 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/34 (2.9%)	1	2/17 (11.8%)	2	0/12 (0%)	2
Myalgia	10/34 (29.4%)	12	4/17 (23.5%)	6	0/12 (0%)	6
Pain in extremity	1/34 (2.9%)	1	1/17 (5.9%)	1	0/12 (0%)	1
Nervous system disorders
Dizziness	0/34 (0%)	0	2/17 (11.8%)	2	0/12 (0%)	2
Headache	21/34 (61.8%)	44	12/17 (70.6%)	30	0/12 (0%)	30
Respiratory, thoracic and mediastinal disorders
Asthma	0/34 (0%)	0	1/17 (5.9%)	1	0/12 (0%)	1
Nasal congestion	1/34 (2.9%)	1	1/17 (5.9%)	1	0/12 (0%)	1
Oropharyngeal pain	0/34 (0%)	0	1/17 (5.9%)	1	0/12 (0%)	1
Sinus congestion	1/34 (2.9%)	1	2/17 (11.8%)	2	0/12 (0%)	2
Skin and subcutaneous tissue disorders
Erythema	27/34 (79.4%)	50	13/17 (76.5%)	23	0/12 (0%)	23
Pruritus	2/34 (5.9%)	2	0/17 (0%)	0	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.