Efficacy, Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine Evaluating Different Dose Schedules in a Sporozoite Challenge Model in Healthy Malaria-naïve Adults

Efficacy, Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Various Dose Schedules in a Sporozoite Challenge Model in Healthy Malaria-naïve Adults

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03162614

Enrollment

154

Registered

2017-05-22

Start date

2017-05-24

Completion date

2018-09-24

Last updated

2020-10-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Malaria

Keywords

healthy volunteers, Malaria, malaria vaccine, controlled human challenge, RTS,S/AS01

Brief summary

This study is designed to evaluate efficacy, immunogenicity and safety of various dose schedules of GSK Biologicals' candidate malaria vaccines RTS,S/AS01B (adult formulation) and RTS,S/AS01E (pediatric formulation) in healthy malaria-naïve subjects aged 18-55 years. The purpose of this study is to investigate whether changes in dosing schedule are associated with increased or equivalent protection, and to evaluate the immune mechanisms associated with vaccine efficacy under varying dosing schedules.

Detailed description

Protocol Amendment 1 incorporated: additional blood sampling for assessment of parasitemia (polymerase chain reaction \[PCR\] testing); clarification that blood samples for both peripheral blood mononuclear cells (PBMC) and plasma will be collected for repository storage; revision of volume of whole blood samples to be taken for parasitemia assessment; clarification that urine pregnancy tests will be conducted for all females and not just those of childbearing potential; deletion of visit at Day 1 post day of challenge; clarification that RNA sequencing and not deep sequencing will be performed in this study. Note that as a result of internal change in data standards terminology, the study data collected was converted to cDISC and the statistical analysis plan was amended accordingly. Day 0 in the study design was replaced by Day 1; consequently, Day n was replaced by Day n+1. Thus, the timeframes (Day 0, Day n) of Outcome Measures described in this study record are different to that denoted in the full protocol document posted.

Interventions

BIOLOGICALRTS,S/AS01E

Subjects will receive intramuscular injection of RTS,S/AS01E.

BIOLOGICALRTS,S/AS01B

Subjects will receive intramuscular injection of RTS,S/AS01B.

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 subjects. For each subject, 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. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed. The challenge occurs approximately 90 days (three months) after the last vaccination. Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* 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 prior to performing of any study specific procedure. * A male or female between, and including, 18 and 55 years of age at the time of enrolment. * Healthy subjects as established by medical history and clinical examination before entering into the study. * Available to participate for the duration of the study. * 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 contraception for 30 days prior to vaccination, and * has a negative pregnancy test at enrolment, and * has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series and/or malaria challenge.

Exclusion criteria

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 0), or planned use during the study period. * Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. * Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed. * Administration of long-acting immune-modifying drugs at any time during the study period. * Chronic use of antibiotics with antimalarial effects. * Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before the first dose. * Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product. * Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV). * Documented HIV-positive subject. * Previous vaccination against malaria. * History of malaria chemoprophylaxis within 60 days prior to vaccination. * Any history of malaria (for the vaccine groups). * Planned travel to malaria endemic areas during the study period. * History of splenectomy. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * Family history of congenital or hereditary immunodeficiency. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. * History of anaphylaxis post-vaccination. * Hypersensitivity to latex. * History of any reaction or hypersensitivity 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. * History of severe reactions to mosquito bites. * Major congenital defects. * Serious chronic illness. * History of any neurological disorders or seizures. * Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route. \- Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. * Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. * Any abnormal baseline laboratory screening tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, hemoglobin, platelet count, total white blood cells (WBC), out of normal range as defined in the protocol. * Evidence of increased cardiovascular disease risk, moderate or high, according to the National health and nutrition examination survey I criteria. * Hepatomegaly, right upper quadrant abdominal pain or tenderness. * Personal history of autoimmune disease. * Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period. * Pregnant or lactating female. * History of chronic alcohol consumption and/or drug abuse. * Female planning to become pregnant or planning to discontinue contraceptive precautions. * 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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Subjects With at Least One Occurrence of Plasmodium Falciparum (P. Falciparum) Parasitemia for Each Vaccination Schedule Versus Infectivity Controls	Following sporozoite challenge starting 3 months after the last vaccine dose (Day 287) for up to 28 days post-challenge (Day 315).	Occurrence of P. falciparum parasitemia (defined by a positive blood slide) following sporozoite challenge. Post-challenge, parasitemia was determined by microscopy of Giemsa-stained thick blood films (smear). Microscopy was performed on thick smears using a validated standard operation procedure. For the analysis of proportion affected (relative risk), all subjects included in the analysis were considered at risk of infection and no censoring or elimination was applied for subjects not completing the entire protocol defined post challenge follow-up (Day 315 - 28 days post challenge).

Secondary

Measure	Time frame	Description
Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 1, Day 59, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from AduFx, 2PedFx, PedFx, and Adu2Fx Groups. At Day 1, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from Adu1Fx Group	Anti-CS antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in Enzyme-linked immunosorbent assay Unit per milliliter (EU/mL). The cut-off for the assay was 1.9 EU/mL. The GMC calculations were performed by taking the anti-log of the mean of the log transformations (base 10). Antibody concentrations below the cut-off of the assay were given an arbitrary value of half the cut-off (=1.0) for the purpose of GMC calculation.
Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 1, Day 59, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from AduFx, 2PedFx, PedFx, and Adu2Fx Groups. At Day 1, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from Adu1Fx Group	Anti-HBs IgG antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milli-International Unit per milliliter (mIU/ml). The cut-off for the assay was 6.2 mIU/mL.
Number of Subjects With Any Solicited Local Symptoms	Within the 7-day period (Days 1-7) after dose 1, dose 2 (except for Adu1Fx Group) and dose 3.	Solicited local symptoms assessed are pain, redness and swelling. Any occurrence of symptom regardless of intensity grade. Any Redness or any Swelling symptom = any symptom greater than (\>) 0 millimeter (mm).
Number of Subjects With Any Solicited General Symptoms	Within the 7-day period (Days 1-7) after dose 1, dose 2 (except for Adu1Fx Group) and dose 3.	Solicited general symptoms assessed are fatigue, gastrointestinal symptoms, headache and fever. Any occurrence of symptom regardless of intensity grade. Fever was defined as temperature equal or greater than (≥) 37.5 degrees Celsius (°C) for oral route, axillary or tympanic route or 38.0°C for rectal route.
Number of Subjects With Any Unsolicited Adverse Events (AEs) After Any Vaccination	Within the 30-day period (Days 1-30), after any vaccination (across doses)	An unsolicited adverse event is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited adverse event is any event reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Number of Subjects With Any Unsolicited AEs After Challenge	Within the 30-day (Days 1-30) period post-challenge	An adverse event is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.
Time to Onset of P. Falciparum Parasitemia After Sporozoite Challenge for Each Vaccination Schedule	Following sporozoite challenge starting 3 months after the last vaccine dose (at Day 287) for up to 28 days post-challenge (at Day 315).	For the analyses of time to onset of parasitemia, time at risk started on first day of challenge. Time at risk was censored on Day 315 (28 days post challenge), drop-out date, start date of antimalarial treatment or date meeting an endpoint, whichever occurs first.
Number of Subjects With Any, Fatal or Related SAEs During the Whole Study Period	From Day 1 up to study conclusion (Day 377)	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Number of Subjects With Any AE and SAE Leading to Withdrawal From Further Vaccination	From Day 1 up to study conclusion (Day 377)	An adverse event is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Number of Subjects With Potential Immune Mediated Diseases (pIMDs)	From Day 1 up to study conclusion (Day 377)	Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Number of Subjects With Meningitis	From Day 1 up to study conclusion (Day 377)	Meningitis is to be reported as an adverse event of specific interest and tabulated per study group.
Number of Subjects With Abnormal Laboratory Values Gradings	At Visit 1 Screening (Day -89 to Day 1), Day 36, Day 59, Day 204, Day 227, between Day 292 & Day 313, and Day 315 for each vaccinated subject.For Infectivity Control subjects at Visit 1b Screening (Day 231 to Day 287),between Day 292 & Day 313,and Day 315	Biochemistry (Alanine Aminotransferase \[ALT\], Aspartate Aminotransferase \[AST\] and creatinine) and hematological (hemoglobin, platelets, White Blood Cells \[WBC\] decrease and WBC increase) laboratory values were presented according to toxicity grading scales (Grade 0 \[GR0\], Grade 1 \[GR1\], Grade 2 \[GR2\] Grade 3 \[GR3\]) and tabulated by group. Grading scale is taken from the \[FDA guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials (September 2007)\].
Number of Subjects With Any, Fatal or Related SAE, After Challenge	From day of challenge (Day 287) to the end of the challenge phase (Day 315)	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Number of Subjects With Any, Fatal or Related Serious Adverse Events (SAEs) After Each Vaccination	Within the 30-day period (Days 1-30) after any vaccination (across doses)	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Countries

United States

Participant flow

Participants by arm

Arm	Count
AduFx Group Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and Month 1 and 1/5th of RTS,S/AS01B full dose at Month 7, and underwent sporozoite challenge.	26
2PedFx Group Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E double dose at Month 0 and Month 1, and 1/5th of double dose RTS,S/AS01E at Month 7, and underwent sporozoite challenge.	26
PedFx Group Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E full dose at Month 0 and Month 1, and 1/5th of RTS,S/AS01E full dose at Month 7, and underwent sporozoite challenge.	26
Adu2Fx Group Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose at Month 1 and Month 7, and underwent sporozoite challenge.	26
Adu1Fx Group Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose administered at Month 7, and underwent sporozoite challenge.	26
Control Group Healthy subjects, between, and including, 18 and 55 years of age, who did not receive any immunization but underwent sporozoite challenge	24
Total	154

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Lost to Follow-up	2	1	1	1	2
Overall Study	Missed vaccination, exclusion criteria	2	2	2	4	3
Overall Study	Protocol Violation	0	1	0	1	0
Overall Study	Withdrawal by Subject	2	1	1	1	0

Baseline characteristics

Characteristic	AduFx Group	2PedFx Group	PedFx Group	Adu2Fx Group	Adu1Fx Group	Control Group	Total
Age, Continuous	31.7 Years STANDARD_DEVIATION 8.4	30.8 Years STANDARD_DEVIATION 9.6	32.0 Years STANDARD_DEVIATION 10.4	32.4 Years STANDARD_DEVIATION 10.9	32.2 Years STANDARD_DEVIATION 10.3	34.6 Years STANDARD_DEVIATION 11.9	32.3 Years STANDARD_DEVIATION 10.2
Race/Ethnicity, Customized Asian	1 Participants	3 Participants	2 Participants	2 Participants	1 Participants	0 Participants	9 Participants
Race/Ethnicity, Customized Black Or African American	8 Participants	6 Participants	10 Participants	9 Participants	7 Participants	8 Participants	48 Participants
Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Other, Not Specified	0 Participants	1 Participants	2 Participants	2 Participants	4 Participants	1 Participants	10 Participants
Race/Ethnicity, Customized White	17 Participants	16 Participants	12 Participants	13 Participants	14 Participants	14 Participants	86 Participants
Sex: Female, Male Female	11 Participants	10 Participants	12 Participants	4 Participants	10 Participants	10 Participants	57 Participants
Sex: Female, Male Male	15 Participants	16 Participants	14 Participants	22 Participants	16 Participants	14 Participants	97 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	0 / 26	0 / 26	0 / 26	0 / 26	0 / 26	0 / 24
other Total, other adverse events	26 / 26	25 / 26	23 / 26	25 / 26	24 / 26	0 / 24
serious Total, serious adverse events	0 / 26	0 / 26	0 / 26	0 / 26	0 / 26	0 / 24

Outcome results

Primary

Number of Subjects With at Least One Occurrence of Plasmodium Falciparum (P. Falciparum) Parasitemia for Each Vaccination Schedule Versus Infectivity Controls

Occurrence of P. falciparum parasitemia (defined by a positive blood slide) following sporozoite challenge. Post-challenge, parasitemia was determined by microscopy of Giemsa-stained thick blood films (smear). Microscopy was performed on thick smears using a validated standard operation procedure. For the analysis of proportion affected (relative risk), all subjects included in the analysis were considered at risk of infection and no censoring or elimination was applied for subjects not completing the entire protocol defined post challenge follow-up (Day 315 - 28 days post challenge).

Time frame: Following sporozoite challenge starting 3 months after the last vaccine dose (Day 287) for up to 28 days post-challenge (Day 315).

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
AduFx Group	Number of Subjects With at Least One Occurrence of Plasmodium Falciparum (P. Falciparum) Parasitemia for Each Vaccination Schedule Versus Infectivity Controls	9 Participants
2PedFx Group	Number of Subjects With at Least One Occurrence of Plasmodium Falciparum (P. Falciparum) Parasitemia for Each Vaccination Schedule Versus Infectivity Controls	5 Participants
PedFx Group	Number of Subjects With at Least One Occurrence of Plasmodium Falciparum (P. Falciparum) Parasitemia for Each Vaccination Schedule Versus Infectivity Controls	8 Participants
Adu2Fx Group	Number of Subjects With at Least One Occurrence of Plasmodium Falciparum (P. Falciparum) Parasitemia for Each Vaccination Schedule Versus Infectivity Controls	9 Participants
Adu1Fx Group	Number of Subjects With at Least One Occurrence of Plasmodium Falciparum (P. Falciparum) Parasitemia for Each Vaccination Schedule Versus Infectivity Controls	15 Participants
Control Group	Number of Subjects With at Least One Occurrence of Plasmodium Falciparum (P. Falciparum) Parasitemia for Each Vaccination Schedule Versus Infectivity Controls	22 Participants

Comparison: Efficacy analysis aimed at comparing RTS,S/AS01B administered as full doses at Month 0 and Month 1 and 1/5th dose at Month 7 (AduFx Group versus Control Group).p-value: <0.00195% CI: [27, 72]Fisher Exact

Comparison: Efficacy analysis aimed at comparing RTS,S/AS01E administered as double full doses at Month 0 and Month 1 and 1/5th double dose at Month 7 (2Ped Fx Group versus Control Group).p-value: <0.00195% CI: [49, 89]Fisher Exact

Comparison: Efficacy analysis aimed at comparing RTS,S/AS01E administered as full doses at Month 0 and Month 1 and 1/5th dose at Month 7 (PedFx Group versus Control Group).p-value: <0.00195% CI: [37, 79]Fisher Exact

Comparison: Efficacy analysis aimed at comparing RTS,S/AS01B administered as full dose at Month 0 and 1/5th dose at Month 1 and Month 7 (Adu2Fx Group versus Control Group).p-value: <0.00195% CI: [27, 72]Fisher Exact

Comparison: Efficacy analysis aimed at comparing RTS,S/AS01B administered as full dose at Month 0 and 1/5th dose at Month 7 (Adu1Fx Group versus Control Group).p-value: 0.00995% CI: [6, 46]Fisher Exact

Secondary

Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations

Anti-CS antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in Enzyme-linked immunosorbent assay Unit per milliliter (EU/mL). The cut-off for the assay was 1.9 EU/mL. The GMC calculations were performed by taking the anti-log of the mean of the log transformations (base 10). Antibody concentrations below the cut-off of the assay were given an arbitrary value of half the cut-off (=1.0) for the purpose of GMC calculation.

Time frame: At Day 1, Day 59, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from AduFx, 2PedFx, PedFx, and Adu2Fx Groups. At Day 1, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from Adu1Fx Group

Population: Analysis was performed on subjects fulfilling eligibility criteria, who received study vaccination according to protocol procedures (therefore, not on subjects from the Control Group), did not report any medical condition influencing the efficacy response, had data concerning immunogenicity outcome measures, and underwent P. falciparum challenge.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
AduFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 227	85.9 EU/mL
AduFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 315	56.6 EU/mL
AduFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 197	30 EU/mL
AduFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 287	61.4 EU/mL
AduFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 1	1 EU/mL
AduFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 59	108.2 EU/mL
AduFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 377	43.7 EU/mL
2PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 287	57.6 EU/mL
2PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 315	51 EU/mL
2PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 59	107.8 EU/mL
2PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 1	1 EU/mL
2PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 197	39.3 EU/mL
2PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 377	38.1 EU/mL
2PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 227	79.8 EU/mL
PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 59	53.8 EU/mL
PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 287	34.4 EU/mL
PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 227	50.2 EU/mL
PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 1	1 EU/mL
PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 315	31.3 EU/mL
PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 197	15.1 EU/mL
PedFx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 377	25 EU/mL
Adu2Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 227	64 EU/mL
Adu2Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 1	1 EU/mL
Adu2Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 59	61.7 EU/mL
Adu2Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 197	19.4 EU/mL
Adu2Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 287	38.1 EU/mL
Adu2Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 315	44.1 EU/mL
Adu2Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 377	31.7 EU/mL
Adu1Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 315	10.6 EU/mL
Adu1Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 227	22.1 EU/mL
Adu1Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 197	3.8 EU/mL
Adu1Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 1	1 EU/mL
Adu1Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 287	12.3 EU/mL
Adu1Fx Group	Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations	At Day 377	9.5 EU/mL

Secondary

Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations

Anti-HBs IgG antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milli-International Unit per milliliter (mIU/ml). The cut-off for the assay was 6.2 mIU/mL.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
AduFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 1	44.1 mIU/mL
AduFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 227	45959.9 mIU/mL
AduFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 197	19369.3 mIU/mL
AduFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 315	33027.7 mIU/mL
AduFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 287	36266.3 mIU/mL
AduFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 59	42616.7 mIU/mL
AduFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 377	27823 mIU/mL
2PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 287	20712.2 mIU/mL
2PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 315	18527.8 mIU/mL
2PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 59	28894.8 mIU/mL
2PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 197	15358.8 mIU/mL
2PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 1	68.8 mIU/mL
2PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 377	15083.7 mIU/mL
2PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 227	30994.5 mIU/mL
PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 1	45.7 mIU/mL
PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 287	19126.1 mIU/mL
PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 227	28560.6 mIU/mL
PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 59	26149.3 mIU/mL
PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 197	11269.1 mIU/mL
PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 315	17465.5 mIU/mL
PedFx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 377	13716 mIU/mL
Adu2Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 227	26717 mIU/mL
Adu2Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 1	21.8 mIU/mL
Adu2Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 59	14710.6 mIU/mL
Adu2Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 197	6846.7 mIU/mL
Adu2Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 287	13911.3 mIU/mL
Adu2Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 315	16685 mIU/mL
Adu2Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 377	11257.6 mIU/mL
Adu1Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 315	12609.9 mIU/mL
Adu1Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 227	35620.9 mIU/mL
Adu1Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 197	2031.7 mIU/mL
Adu1Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 1	16 mIU/mL
Adu1Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 287	16376.8 mIU/mL
Adu1Fx Group	Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations	At Day 377	10975.2 mIU/mL

Secondary

Number of Subjects With Abnormal Laboratory Values Gradings

Biochemistry (Alanine Aminotransferase \[ALT\], Aspartate Aminotransferase \[AST\] and creatinine) and hematological (hemoglobin, platelets, White Blood Cells \[WBC\] decrease and WBC increase) laboratory values were presented according to toxicity grading scales (Grade 0 \[GR0\], Grade 1 \[GR1\], Grade 2 \[GR2\] Grade 3 \[GR3\]) and tabulated by group. Grading scale is taken from the \[FDA guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials (September 2007)\].

Time frame: At Visit 1 Screening (Day -89 to Day 1), Day 36, Day 59, Day 204, Day 227, between Day 292 & Day 313, and Day 315 for each vaccinated subject.For Infectivity Control subjects at Visit 1b Screening (Day 231 to Day 287),between Day 292 & Day 313,and Day 315