Malaria
Conditions
Keywords
Efficacy, Sporozoite challenge model, Malaria, Immunogenicity, Malaria- naïve adults, Safety
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.
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.
Interventions
BIOLOGICALGSK257049 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.
BIOLOGICALGSK257049 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.
PROCEDURESporozoite-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).
Sponsors
Walter Reed Army Institute of Research (WRAIR)
The PATH Malaria Vaccine Initiative (MVI)
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 a fractional dose of GSK257049 vaccine and underwent sporozoite challenge (CHMI). | 34 |
| GSK257049-0,1,2M Group Subjects receiving 3 doses of GSK257049 vaccine given one month apart (0,1 and 2 months) and underwent sporozoite challenge (CHMI). | 17 |
| Infectivity Control Group Volunteers who did not receive any immunization but underwent sporozoite challenge (CHMI). | 12 |
| GSK257049-0,1,7M P-NoBo Group 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. | 7 |
| GSK257049-0,1,7M P-Bo Group 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. | 10 |
| GSK257049-0,1,7M NP-Bo Group 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. | 2 |
| GSK257049-0,1,2M P-NoBo Group 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. | 5 |
| GSK257049-0,1,2M P-Bo Group 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. | 4 |
| GSK257049-0,1,2M NP-Bo Group 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. | 3 |
| Control Group Follow-up 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. | 6 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Booster/Rechallenge Phase | Volunteer took antibiotic pre-challenge | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Booster/Rechallenge Phase | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Primary/Challenge Phase | Lost to Follow-up | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Primary/Challenge Phase | Other | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Primary/Challenge Phase | Pregnancy | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Primary/Challenge Phase | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | GSK257049-0,1,7M Group | GSK257049-0,1,2M Group | Infectivity Control Group | Total |
|---|---|---|---|---|
| Age, Continuous | 34.4 Years STANDARD_DEVIATION 8.6 | 30.1 Years STANDARD_DEVIATION 7.9 | 36.4 Years STANDARD_DEVIATION 8.7 | 33.6 Years STANDARD_DEVIATION 8.6 |
| Race/Ethnicity, Customized Geographic ancestry African Heritage/African American | 15 Participants | 5 Participants | 5 Participants | 25 Participants |
| Race/Ethnicity, Customized Geographic ancestry Asian - Central/South Asian Heritage | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Geographic ancestry Asian - South East Asian Heritage | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Geographic ancestry Unspecified | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Geographic ancestry White - Caucasian/European Heritage | 13 Participants | 10 Participants | 5 Participants | 28 Participants |
| Sex: Female, Male Female | 15 Participants | 6 Participants | 7 Participants | 28 Participants |
| Sex: Female, Male Male | 19 Participants | 11 Participants | 5 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 17 | 0 / 12 |
| other Total, other adverse events | 34 / 34 | 17 / 17 | 0 / 12 |
| serious Total, serious adverse events | 1 / 34 | 0 / 17 | 0 / 12 |
Outcome results
Primary
Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Challenge
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)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Challenge | 4 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Challenge | 6 Participants |
| Infectivity Control Group | Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Challenge | 12 Participants |
Comparison: Vaccine efficacy (VE) was defined as 100\*(1-Relative Risk \[RR\]).p-value: 0.000995% CI: [29.4, 80.1]Mantel Haenszel
Comparison: Vaccine efficacy (VE) was defined as 100\*(1-Relative Risk \[RR\]).p-value: <0.000195% CI: [66.8, 94.6]Mantel Haenszel
Secondary
Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs)
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 70 after DoC PP (Day 217) | 23722.4 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At Day 98 | 12367.7 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 159 after DoC PP (Day 217) | 14459.9 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | 7 days before vaccination | 27.5 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At Day 196 | 9917.0 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At DoC PP (Day 217) | 33715.4 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 7 after DoC PP (Day 217) | 29902.6 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At Day 28 | 7223.0 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 14 after DoC PP (Day 217) | 35401.1 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 28 after DoC PP (Day 217) | 25553.8 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At Day 42 | 35016.9 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 42 after DoC PP (Day 217) | 23757.6 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 56 after DoC PP (Day 217) | 25917.3 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At Day 56 | 21013.0 mIU/mL |
| GSK257049-0,1,7M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 84 after DoC PP (Day 217) | 19155.1 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 70 after DoC PP (Day 217) | 23313.8 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At Day 56 | 20625.8 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 7 after DoC PP (Day 217) | 28989.2 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 84 after DoC PP (Day 217) | 19631.5 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At Day 42 | 27205.5 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 56 after DoC PP (Day 217) | 23199.5 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 159 after DoC PP (Day 217) | 13495.2 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 14 after DoC PP (Day 217) | 24952.2 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At Day 28 | 7318.2 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 42 after DoC PP (Day 217) | 20000.3 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At DoC PP (Day 217) | 31798.7 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | 7 days before vaccination | 28.5 mIU/mL |
| GSK257049-0,1,2M Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 28 after DoC PP (Day 217) | 25944.1 mIU/mL |
| Infectivity Control Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 159 after DoC PP (Day 217) | 26.2 mIU/mL |
| Infectivity Control Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | At DoC PP (Day 217) | 27.9 mIU/mL |
| Infectivity Control Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 7 after DoC PP (Day 217) | 32.5 mIU/mL |
| Infectivity Control Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 14 after DoC PP (Day 217) | 25.7 mIU/mL |
| Infectivity Control Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 28 after DoC PP (Day 217) | 27.5 mIU/mL |
| Infectivity Control Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 42 after DoC PP (Day 217) | 32.8 mIU/mL |
| Infectivity Control Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 56 after DoC PP (Day 217) | 34.6 mIU/mL |
| Infectivity Control Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 70 after DoC PP (Day 217) | 31.9 mIU/mL |
| Infectivity Control Group | Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Day 84 after DoC PP (Day 217) | 26.3 mIU/mL |
Secondary
Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations
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).
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 7 after DoC PP (Day 217) | 75.7 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | 7 days before vaccination | 0.3 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 70 after DoC PP (Day 217) | 46.9 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 14 after DoC PP (Day 217) | 68.9 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At Day 42 | 104.2 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 56 after DoC PP (Day 217) | 54.0 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 28 after DoC PP (Day 217) | 63.8 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At Day 56 | 83.3 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 42 after DoC PP (Day 217) | 57.6 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 159 after DoC PP (Day 217) | 32.8 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At Day 98 | 46.1 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At Day 196 | 18.3 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At DoC PP (Day 217) | 75.2 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At Day 28 | 13.1 EU/mL |
| GSK257049-0,1,7M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 84 after DoC PP (Day 217) | 45.6 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At Day 42 | 64.4 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 84 after DoC PP (Day 217) | 55.3 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | 7 days before vaccination | 0.3 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At Day 28 | 16.3 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At Day 56 | 57.9 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At DoC PP (Day 217) | 100.1 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 7 after DoC PP (Day 217) | 91.7 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 14 after DoC PP (Day 217) | 79.4 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 28 after DoC PP (Day 217) | 75.7 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 42 after DoC PP (Day 217) | 73.6 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 56 after DoC PP (Day 217) | 63.2 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 70 after DoC PP (Day 217) | 59.2 EU/mL |
| GSK257049-0,1,2M Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 159 after DoC PP (Day 217) | 34.6 EU/mL |
| Infectivity Control Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 84 after DoC PP (Day 217) | 0.5 EU/mL |
| Infectivity Control Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 56 after DoC PP (Day 217) | 0.5 EU/mL |
| Infectivity Control Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 7 after DoC PP (Day 217) | 0.4 EU/mL |
| Infectivity Control Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 159 after DoC PP (Day 217) | 0.5 EU/mL |
| Infectivity Control Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 70 after DoC PP (Day 217) | 0.5 EU/mL |
| Infectivity Control Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 28 after DoC PP (Day 217) | 0.5 EU/mL |
| Infectivity Control Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | At DoC PP (Day 217) | 0.4 EU/mL |
| Infectivity Control Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 42 after DoC PP (Day 217) | 0.6 EU/mL |
| Infectivity Control Group | Anti-circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations | Day 14 after DoC PP (Day 217) | 0.4 EU/mL |
Secondary
Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase
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)
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK257049-0,1,7M Group | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At DoC PP (Day 217) | 25.7 EU/mL |
| GSK257049-0,1,2M Group | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At Day 0 of rechallenge | 30.7 EU/mL |
| GSK257049-0,1,2M Group | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At DoC PP (Day 217) | 86.6 EU/mL |
| Infectivity Control Group | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At DoC PP (Day 217) | 81.2 EU/mL |
| Infectivity Control Group | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At Day 0 of rechallenge | 7.2 EU/mL |
| GSK257049-0,1,2M P-NoBo Group | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At DoC PP (Day 217) | 39.2 EU/mL |
| GSK257049-0,1,2M P-Bo Group | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At Day 0 of rechallenge | 35.9 EU/mL |
| GSK257049-0,1,2M P-Bo Group | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At DoC PP (Day 217) | 61.7 EU/mL |
| GSK257049-0,1,2M NP-Bo Group | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At Day 0 of rechallenge | 24.5 EU/mL |
| GSK257049-0,1,2M NP-Bo Group | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At DoC PP (Day 217) | 53.5 EU/mL |
| Control Group Follow-up | Anti-CS Repeat Region Antibody Concentrations for the Rechallenge Phase | At DoC PP (Day 217) | 0.3 EU/mL |
Secondary
Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GSK257049-0,1,7M Group | Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase | DoC Booster/rechallenge phase (Day 21) | 35.00 Avidity index |
| GSK257049-0,1,2M Group | Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase | Pre-booster dose | 41.15 Avidity index |
| GSK257049-0,1,2M Group | Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase | DoC Booster/rechallenge phase (Day 21) | 46.55 Avidity index |
| Infectivity Control Group | Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase | DoC Booster/rechallenge phase (Day 21) | 50.60 Avidity index |
| Infectivity Control Group | Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase | Pre-booster dose | 43.30 Avidity index |
| GSK257049-0,1,2M P-NoBo Group | Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase | DoC Booster/rechallenge phase (Day 21) | 31.30 Avidity index |
| GSK257049-0,1,2M P-Bo Group | Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase | DoC Booster/rechallenge phase (Day 21) | 36.80 Avidity index |
| GSK257049-0,1,2M P-Bo Group | Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase | Pre-booster dose | 21.25 Avidity index |
| GSK257049-0,1,2M NP-Bo Group | Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase | DoC Booster/rechallenge phase (Day 21) | 31.20 Avidity index |
| GSK257049-0,1,2M NP-Bo Group | Anti-CS Repeat Region IgG Avidity Index for the Rechallenge Phase | Pre-booster dose | 30.40 Avidity index |
Secondary
Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GSK257049-0,1,7M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | At Day 28 | 25.65 Avidity index |
| GSK257049-0,1,7M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | Day 84 after DoC PP (Day 217) | 37.40 Avidity index |
| GSK257049-0,1,7M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | At Day 56 | 37.40 Avidity index |
| GSK257049-0,1,7M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | Day 159 after DoC PP (Day 217) | 36.10 Avidity index |
| GSK257049-0,1,7M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | At Day 196 | 28.10 Avidity index |
| GSK257049-0,1,7M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | At DoC PP (Day 217) | 40.40 Avidity index |
| GSK257049-0,1,2M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | At DoC PP (Day 217) | 29.00 Avidity index |
| GSK257049-0,1,2M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | At Day 28 | 17.90 Avidity index |
| GSK257049-0,1,2M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | At Day 56 | 31.10 Avidity index |
| GSK257049-0,1,2M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | Day 84 after DoC PP (Day 217) | 28.30 Avidity index |
| GSK257049-0,1,2M Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | Day 159 after DoC PP (Day 217) | 28.90 Avidity index |
| Infectivity Control Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | Day 159 after DoC PP (Day 217) | 32.05 Avidity index |
| Infectivity Control Group | Anti-CS Repeat Region Immunoglobulin G (IgG) Avidity Index for the Challenge Phase | Day 84 after DoC PP (Day 217) | 32.10 Avidity index |
Secondary
Anti-HBs Antibody Concentrations for Rechallenge Phase
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)
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GSK257049-0,1,7M Group | Anti-HBs Antibody Concentrations for Rechallenge Phase | At DoC PP (Day 217) | 19592.4 mIU/mL |
| GSK257049-0,1,2M Group | Anti-HBs Antibody Concentrations for Rechallenge Phase | At Day 9 of rechallenge | 9270.9 mIU/mL |
| GSK257049-0,1,2M Group | Anti-HBs Antibody Concentrations for Rechallenge Phase | At DoC PP (Day 217) | 24261.5 mIU/mL |
| Infectivity Control Group | Anti-HBs Antibody Concentrations for Rechallenge Phase | At DoC PP (Day 217) | 36809.8 mIU/mL |
| Infectivity Control Group | Anti-HBs Antibody Concentrations for Rechallenge Phase | At Day 9 of rechallenge | 6928.3 mIU/mL |
| GSK257049-0,1,2M P-NoBo Group | Anti-HBs Antibody Concentrations for Rechallenge Phase | At DoC PP (Day 217) | 6051.9 mIU/mL |
| GSK257049-0,1,2M P-Bo Group | Anti-HBs Antibody Concentrations for Rechallenge Phase | At Day 9 of rechallenge | 23259.5 mIU/mL |
| GSK257049-0,1,2M P-Bo Group | Anti-HBs Antibody Concentrations for Rechallenge Phase | At DoC PP (Day 217) | 38175.5 mIU/mL |
| GSK257049-0,1,2M NP-Bo Group | Anti-HBs Antibody Concentrations for Rechallenge Phase | At Day 9 of rechallenge | 15620.0 mIU/mL |
| GSK257049-0,1,2M NP-Bo Group | Anti-HBs Antibody Concentrations for Rechallenge Phase | At DoC PP (Day 217) | 34470.4 mIU/mL |
| Control Group Follow-up | Anti-HBs Antibody Concentrations for Rechallenge Phase | At DoC PP (Day 217) | 35.7 mIU/mL |
Secondary
Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells
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).
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 159 after DoC PP (Day 217) | 26.74 CD8+ T-cells/million CD8 T-cells | Standard Deviation 52.22 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 7 after DoC PP (Day 217) | 19.54 CD8+ T-cells/million CD8 T-cells | Standard Deviation 42.55 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | 7 days before vaccination | 14.10 CD8+ T-cells/million CD8 T-cells | Standard Deviation 20.6 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 84 after DoC PP (Day 217) | 19.89 CD8+ T-cells/million CD8 T-cells | Standard Deviation 54.19 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 28 after DoC PP (Day 217) | 19.96 CD8+ T-cells/million CD8 T-cells | Standard Deviation 27.35 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | At Day 14 | 24.61 CD8+ T-cells/million CD8 T-cells | Standard Deviation 43.01 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | At DoC PP (Day 217) | 32.52 CD8+ T-cells/million CD8 T-cells | Standard Deviation 57.64 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | At Day 42 | 18.7 CD8+ T-cells/million CD8 T-cells | Standard Deviation 46.69 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 7 after DoC PP (Day 217) | 32.07 CD8+ T-cells/million CD8 T-cells | Standard Deviation 56.77 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | 7 days before vaccination | 9.56 CD8+ T-cells/million CD8 T-cells | Standard Deviation 15.31 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | At Day 14 | 17.20 CD8+ T-cells/million CD8 T-cells | Standard Deviation 30.03 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | At Day 42 | 27.60 CD8+ T-cells/million CD8 T-cells | Standard Deviation 40.4 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | At DoC PP (Day 217) | 28.86 CD8+ T-cells/million CD8 T-cells | Standard Deviation 28.73 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 28 after DoC PP (Day 217) | 34.81 CD8+ T-cells/million CD8 T-cells | Standard Deviation 66.56 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 84 after DoC PP (Day 217) | 20.23 CD8+ T-cells/million CD8 T-cells | Standard Deviation 26.25 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 159 after DoC PP (Day 217) | 24.40 CD8+ T-cells/million CD8 T-cells | Standard Deviation 44.3 |
| Infectivity Control Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 159 after DoC PP (Day 217) | 22.00 CD8+ T-cells/million CD8 T-cells | Standard Deviation 33.01 |
| Infectivity Control Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 84 after DoC PP (Day 217) | 12.17 CD8+ T-cells/million CD8 T-cells | Standard Deviation 22.91 |
| Infectivity Control Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | At DoC PP (Day 217) | 15.33 CD8+ T-cells/million CD8 T-cells | Standard Deviation 29.06 |
| Infectivity Control Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 28 after DoC PP (Day 217) | 17.67 CD8+ T-cells/million CD8 T-cells | Standard Deviation 36.31 |
| Infectivity Control Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific CD8 T-cells | Day 7 after DoC PP (Day 217) | 32.00 CD8+ T-cells/million CD8 T-cells | Standard Deviation 53.81 |
Secondary
Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells
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).
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 28 after DoC PP (Day 217) | 626.29 CD4+ T-cells/million CD4 T-cells | Standard Deviation 586.16 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | At Day 14 | 168.89 CD4+ T-cells/million CD4 T-cells | Standard Deviation 205.87 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 159 after DoC PP (Day 217) | 490.00 CD4+ T-cells/million CD4 T-cells | Standard Deviation 401.39 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | At Day 42 | 1306.11 CD4+ T-cells/million CD4 T-cells | Standard Deviation 1962.03 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 84 after DoC PP (Day 217) | 481.44 CD4+ T-cells/million CD4 T-cells | Standard Deviation 392.44 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | At DoC PP (Day 217) | 596.15 CD4+ T-cells/million CD4 T-cells | Standard Deviation 636.6 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 7 after DoC PP (Day 217) | 661.61 CD4+ T-cells/million CD4 T-cells | Standard Deviation 711.86 |
| GSK257049-0,1,7M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | 7 days before vaccination | 61.38 CD4+ T-cells/million CD4 T-cells | Standard Deviation 95.16 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 28 after DoC PP (Day 217) | 472.63 CD4+ T-cells/million CD4 T-cells | Standard Deviation 287.64 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 84 after DoC PP (Day 217) | 472.63 CD4+ T-cells/million CD4 T-cells | Standard Deviation 287.64 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 159 after DoC PP (Day 217) | 307.87 CD4+ T-cells/million CD4 T-cells | Standard Deviation 231.91 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | 7 days before vaccination | 83.31 CD4+ T-cells/million CD4 T-cells | Standard Deviation 79.4 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | At Day 14 | 242.53 CD4+ T-cells/million CD4 T-cells | Standard Deviation 262.97 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | At Day 42 | 866.87 CD4+ T-cells/million CD4 T-cells | Standard Deviation 779.25 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | At DoC PP (Day 217) | 555.86 CD4+ T-cells/million CD4 T-cells | Standard Deviation 487.16 |
| GSK257049-0,1,2M Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 7 after DoC PP (Day 217) | 539.40 CD4+ T-cells/million CD4 T-cells | Standard Deviation 416.68 |
| Infectivity Control Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 159 after DoC PP (Day 217) | 32.55 CD4+ T-cells/million CD4 T-cells | Standard Deviation 51.06 |
| Infectivity Control Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 28 after DoC PP (Day 217) | 162.22 CD4+ T-cells/million CD4 T-cells | Standard Deviation 275.51 |
| Infectivity Control Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 7 after DoC PP (Day 217) | 39.25 CD4+ T-cells/million CD4 T-cells | Standard Deviation 42.4 |
| Infectivity Control Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | Day 84 after DoC PP (Day 217) | 90.67 CD4+ T-cells/million CD4 T-cells | Standard Deviation 121.47 |
| Infectivity Control Group | Frequency of CS Repeat and T-cell Epitope (RT)-Specific Cluster of Differentiation 4 (CD4) T-cells | At DoC PP (Day 217) | 57.17 CD4+ T-cells/million CD4 T-cells | Standard Deviation 102.19 |
Secondary
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain, Dose 2 | 28 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain, Dose 1 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness, Dose 1 | 7 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness, Dose 1 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling, Dose 1 | 8 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling, Dose 1 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain, Dose 1 | 30 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain, Dose 2 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness, Dose 2 | 13 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness, Dose 2 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling, Dose 2 | 10 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling, Dose 2 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain, Dose 3 | 21 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain, Dose 3 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness, Dose 3 | 23 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness, Dose 3 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling, Dose 3 | 17 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling, Dose 3 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain, Across doses | 32 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain, Across doses | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness, Across doses | 26 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness, Across doses | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling, Across doses | 21 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling, Across doses | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling, Across doses | 4 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain, Dose 1 | 16 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain, Dose 3 | 12 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain, Dose 1 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain, Across doses | 16 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness, Dose 1 | 8 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain, Dose 3 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness, Dose 1 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness, Across doses | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling, Dose 1 | 1 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness, Dose 3 | 7 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling, Dose 1 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain, Across doses | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain, Dose 2 | 13 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness, Dose 3 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain, Dose 2 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling, Across doses | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness, Dose 2 | 6 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling, Dose 3 | 3 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness, Dose 2 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness, Across doses | 12 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling, Dose 2 | 2 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling, Dose 3 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling, Dose 2 | 0 Participants |
Secondary
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Pain | 11 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Pain | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Redness | 8 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Redness | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Any Swelling | 4 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Grade 3 Swelling | 0 Participants |
Secondary
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fatigue | 8 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fatigue | 5 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fatigue | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Gastrointestinal symptoms | 4 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Gastrointestinal symptoms | 3 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Gastrointestinal symptoms | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Headache | 8 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Headache | 6 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Headache | 1 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature | 0 Participants |
Secondary
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature, Dose 3 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fatigue, Dose 1 | 9 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fatigue, Dose 1 | 1 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Gastrointestinal symptoms, Dose 1 | 4 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Gastrointestinal symptoms, Dose 1 | 4 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Gastrointestinal symptoms, Dose 1 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Headache, Dose 1 | 9 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Headache, Dose 1 | 8 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Headache, Dose 1 | 1 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature, Dose 1 | 3 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature, Dose 1 | 3 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature, Dose 1 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fatigue, Dose 2 | 15 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fatigue, Dose 2 | 15 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fatigue, Dose 2 | 1 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Gastrointestinal symptoms, Dose 2 | 3 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Gastrointestinal symptoms, Dose 2 | 3 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Gastrointestinal symptoms, Dose 2 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Headache, Dose 2 | 15 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Headache, Dose 2 | 15 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Headache, Dose 2 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature, Dose 2 | 6 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature, Dose 2 | 6 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature, Dose 2 | 3 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fatigue, Dose 3 | 8 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fatigue, Dose 3 | 8 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fatigue, Dose 3 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Gastrointestinal symptoms, Dose 3 | 6 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Gastrointestinal symptoms, Dose 3 | 3 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Gastrointestinal symptoms, Dose 3 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Headache, Dose 3 | 9 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Headache, Dose 3 | 7 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Headache, Dose 3 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature, Dose 3 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature, Dose 3 | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fatigue, Across doses | 18 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fatigue, Across doses | 18 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fatigue, Across doses | 2 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Gastrointestinal symptoms, Across doses | 7 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Gastrointestinal symptoms, Across doses | 7 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Gastrointestinal symptoms, Across doses | 0 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Headache, Across doses | 18 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Headache, Across doses | 18 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Headache, Across doses | 1 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature, Across doses | 8 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature, Across doses | 8 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature, Across doses | 3 Participants |
| GSK257049-0,1,7M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fatigue, Dose 1 | 10 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fatigue, Across doses | 9 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fatigue, Dose 1 | 3 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fatigue, Dose 3 | 7 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fatigue, Dose 1 | 3 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Headache, Across doses | 11 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fatigue, Dose 1 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fatigue, Dose 3 | 6 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Gastrointestinal symptoms, Dose 1 | 2 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fatigue, Across doses | 8 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Gastrointestinal symptoms, Dose 1 | 2 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fatigue, Dose 3 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Gastrointestinal symptoms, Dose 1 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature, Across doses | 4 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Headache, Dose 1 | 9 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Gastrointestinal symptoms, Dose 3 | 2 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Headache, Dose 1 | 9 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fatigue, Across doses | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Headache, Dose 1 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Gastrointestinal symptoms, Dose 3 | 2 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature, Dose 1 | 3 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Headache, Across doses | 11 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature, Dose 1 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Gastrointestinal symptoms, Dose 3 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature, Dose 1 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Gastrointestinal symptoms, Across doses | 5 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Fatigue, Dose 2 | 5 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Headache, Dose 3 | 6 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Fatigue, Dose 2 | 5 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature, Across doses | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Fatigue, Dose 2 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Headache, Dose 3 | 6 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Gastrointestinal symptoms, Dose 2 | 5 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Gastrointestinal symptoms, Across doses | 5 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Gastrointestinal symptoms, Dose 2 | 5 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Headache, Dose 3 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Gastrointestinal symptoms, Dose 2 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Headache, Across doses | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Headache, Dose 2 | 9 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature, Dose 3 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Headache, Dose 2 | 8 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Gastrointestinal symptoms, Across doses | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Headache, Dose 2 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature, Dose 3 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Any Temperature, Dose 2 | 1 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature, Dose 3 | 0 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature, Dose 2 | 1 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Related Temperature, Across doses | 1 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Grade 3 Temperature, Dose 2 | 0 Participants |
Secondary
Number of Subjects With Any Unsolicited Adverse Events (AEs)
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
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 10 Participants |
Secondary
Number of Subjects With Any Unsolicited Adverse Events (AEs)
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
Population: The analysis was based on the ITT population for the rechallenge, which included subjects from the ITT population consenting to the rechallenge.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 11 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 15 Participants |
| Infectivity Control Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 6 Participants |
Secondary
Number of Subjects With Any Unsolicited Adverse Events (AEs)
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
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 25 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 13 Participants |
| Infectivity Control Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 12 Participants |
Secondary
Number of Subjects With Any Unsolicited Adverse Events (AEs)
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
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 25 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Any Unsolicited Adverse Events (AEs) | 16 Participants |
Secondary
Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge
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)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 4 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 1 Participants |
| Infectivity Control Group | Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 0 Participants |
| GSK257049-0,1,2M P-NoBo Group | Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 4 Participants |
| GSK257049-0,1,2M P-Bo Group | Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 3 Participants |
| GSK257049-0,1,2M NP-Bo Group | Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 1 Participants |
| Control Group Follow-up | Number of Subjects With Plasmodium Falciparum Parasitemia Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 6 Participants |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
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)
Population: The analysis was based on the ITT population, which included all subjects with at least one vaccine administration documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Serious Adverse Events (SAEs) | 1 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
| Infectivity Control Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
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)
Population: The analysis was based on the ITT population, which included all subjects with at least one vaccine administration documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK257049-0,1,7M Group | Number of Subjects With Serious Adverse Events (SAEs) | 1 Participants |
| GSK257049-0,1,2M Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
| Infectivity Control Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Challenge
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK257049-0,1,7M Group | Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Challenge | 17 Days | Standard Deviation 6 |
| GSK257049-0,1,2M Group | Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Challenge | 15 Days | Standard Deviation 5 |
| Infectivity Control Group | Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Challenge | 13 Days | Standard Deviation 1 |
Secondary
Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Rechallenge
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GSK257049-0,1,7M Group | Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 14 Days | Standard Deviation 1 |
| GSK257049-0,1,2M Group | Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 14 Days | Standard Deviation 0 |
| Infectivity Control Group | Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 15 Days | Standard Deviation 1 |
| GSK257049-0,1,2M P-NoBo Group | Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 14 Days | Standard Deviation 2 |
| GSK257049-0,1,2M P-Bo Group | Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 14 Days | Standard Deviation 0 |
| GSK257049-0,1,2M NP-Bo Group | Time to Onset of P. Falciparum Parasitemia Infection Defined by a Positive Blood Slide, Following Sporozoite Rechallenge | 12 Days | Standard Deviation 1 |