Safety, Immunogenicity and Efficacy Against of a Combined Malaria Vaccine in Healthy Malaria-naïve Adults

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01366534
• Collaborator: The PATH Malaria Vaccine Initiative (MVI) (Other), Crucell Holland BV (Industry)
• Enrollment: 67
• Location: 1
• Arms: 3
• Actual Duration (Months): 10.8
• Patients Per Site Per Month: 6.2

Study Details

Study Description

Brief Summary

This study will evaluate whether administration of two investigational malaria vaccines (257049 and Ad35.CS.01 vaccines) combined in one immunization schedule increases protection against malaria infection as compared to protection induced by the 257049 vaccine alone. The study will also evaluate the safety and the immune response to the new combination of the two experimental malaria vaccines.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Biological: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01); Biological: GSK Biologicals' malaria vaccine 257049 (2 doses); Biological: GSK Biologicals' malaria vaccine 257049 (3 doses); Other: Sporozoite challenge	Phase 2

Detailed Description

Approximately 168 healthy, malaria-naïve volunteers aged 18 - 50 years, divided into 2 groups (84 in each group), will receive either one dose of Ad35.CS.01 followed by two doses of 257049 at monthly intervals or 3 doses of 257049 vaccine at monthly intervals. Of these, a maximum of 138 vaccinated volunteers will be challenged with P. falciparum infected mosquitoes. The challenge will occur 2 weeks following the third immunization. A group of up to 18 infectivity controls will begin participation in the study at the challenge stage. These controls receive no vaccine and are enrolled for malaria-challenge only in order to provide comparison group for vaccinated individuals.

Study Design

• Study Type: Interventional
• Actual Enrollment: 67 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Safety, Immunogenicity and Efficacy Against Malaria in the Sporozoite Challenge Model of One Dose of Ad35.CS.01 Malaria Vaccine Followed by Two Doses of Malaria 257049 Vaccine in Healthy Malaria-naïve Adults
• Actual Study Start Date: Aug 10, 2011
• Actual Primary Completion Date: Feb 27, 2012
• Actual Study Completion Date: Jul 3, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ad35.CS.01 Group Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Biological: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01); One dose will be administered intramuscularly at Study Day 0.; Biological: GSK Biologicals' malaria vaccine 257049 (2 doses); Two doses will be administered intramuscularly at monthly intervals
Experimental: GSK257049 Group Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Biological: GSK Biologicals' malaria vaccine 257049 (3 doses); Three doses will be administered intramuscularly at monthly intervals
Experimental: Control Group Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.	Other: Sporozoite challenge; Subjects were challenged with sporozoite-infected mosquitoes to determine whether immune protective response had been induced by vaccination.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Plasmodium Falciparum Parasitemia Following Sporozoite Challenge [28 days following sporozoite challenge (Day 105)]

   P. falciparum parasitemia was defined as a positive blood slide.

2. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination]

   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, pain that prevented normal every day activities. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

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

   Assessed solicited general symptoms were chills, fatigue, gastrointestinal symptoms, headache and temperature [defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade.Grade 3 Chills = rigors [uncontrollable shivering more than (>) 15 seconds]. Grade 3 Fatigue, Gastrointestinal symptoms and Headache = symptoms that prevented normal activity. Grade 3 fever = fever higher than (>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

4. Number of Subjects With Any Unsolicited Adverse Events (AEs) [Within the 30-day (Day 0 - Day 29) follow-up period post-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.

5. Number of Subjects With Any Unsolicited Adverse Events (AEs) [Within the 30-day (Day 0 - Day 29) follow-up period post-challenge]

   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.

6. Number of Subjects With Serious Adverse Events (SAEs) [Throughout the study period (Day 0 - Day 236)]

   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.

Secondary Outcome Measures

1. Number of Days Until the Onset of P. Falciparum Parasitemia Following Sporozoite Challenge [From day of challenge (Day 0) up to 159 days post-challenge]

   The onset of P. falciparum parasitemia was defined by a positive blood slide.

2. Anti-circumsporozoite Protein (Anti-CS) Antibody Titers [28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)]

   Titers are presented as geometric mean titers (GMTs) and are measured in titers. Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore GMTs for this group are presented as from Day 77.

3. Anti-hepatitis B (Anti-HBs) Antibody Titers [28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)]

   Titers are presented as geometric mean titers (GMTs) and are measured in titers. Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore GMTs for this group are presented as from Day 77.

4. Anti-Adenovirus Type 35 (Ad35) Neutralizing Antibody Titers at Specified Time Points [28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)]

   Titers are presented as geometric mean titers (GMTs) and are measured in titers. Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore GMTs for this group are presented as from Day 77.

5. Frequency of CS (Total CS or Repeat)-Specific CD4+ T-cells [14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)]

   CS-specific CD4+ T-cells expressing at least 2 cytokines/activation markers between IL-2, IFN-γ, TNF-α and CD40-L are presented here. Analysis was performed via intra-cellular staining (ICS) assays, data are presented as frequency of T-cells per million peripheral blood mononuclear cells (PBMCs).Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.

6. Frequency of CS (Total CS or Repeat)-Specific CD8+ T Cells [14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)]

   CS-specific CD8+ T-cells expressing at least 2 cytokines/activation markers between IL-2, IFN-γ, TNF-α and CD40-L are presented here. Analysis was performed via intra-cellular staining (ICS) assays, data are presented as frequency of T-cells per million peripheral blood mononuclear cells (PBMC). Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.

7. Frequency of HBs-specific CD4+ T-cells [14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)]

   HB-specific CD4+ T-cells expressing at least 2 cytokines/activation markers between IL-2, IFN-γ, TNF-α and CD40-L are presented here. Analysis was performed via intra-cellular staining (ICS) assays, data are presented as frequency of T-cells per million peripheral blood mononuclear cells (PBMCs). Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.

8. Frequency of CS-specific T-cells Producing IFN-γ [14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)]

   The analysis was performed via Enzyme-Linked Immunospot (ELISPOT) full length assay. Data are presented as the number of spots per million peripheral blood mononuclear cells (PBMCs). Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.

9. Frequency of CS-specific T-cells Producing IFN-γ [14 days post-dose 1 (Day 14)]

   The analysis was performed via Enzyme-Linked Immunospot (ELISPOT) N-terminal assay. Data are presented as the number of spots per million peripheral blood mononuclear cells (PBMCs).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Subjects who the investigator believes 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.

• Female subjects of non-childbearing potential.

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

• has practiced adequate Food and Drug Administration (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.

• Pass a comprehension assessment test.

Exclusion Criteria:

• Use of any investigational or non-registered product within 30 days preceding the first dose of study vaccine, or planned use of any investigational or non-registered product other than the study vaccines 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 or adenovirus 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, such as antacids and kaolin.

• 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.

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

• Family history of congenital or hereditary immunodeficiency.

• History of splenectomy.

• Major congenital defects or serious chronic illness.

• History of any neurological disorders or seizures.

• Acute disease and/or fever at the time of enrollment.

• 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.

• 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.

• Evidence of increased cardiovascular disease risk, "moderate" or "high", according to the NHANES I criteria.

• An abnormal baseline screening electrocardiogram (EKG).

• Hepatomegaly, right upper quadrant abdominal pain or tenderness.

• Personal history of autoimmune disease.

• Seropositive for hepatitis B surface antigen or Hepatitis C virus (antibodies to HCV).

• Pregnant or lactating female.

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

• 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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• GlaxoSmithKline
• The PATH Malaria Vaccine Initiative (MVI)
• Crucell Holland BV

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

• Ockenhouse CF, Regules J, Tosh D, Cowden J, Kathcart A, Cummings J, Paolino K, Moon J, Komisar J, Kamau E, Oliver T, Chhoeu A, Murphy J, Lyke K, Laurens M, Birkett A, Lee C, Weltzin R, Wille-Reece U, Sedegah M, Hendriks J, Versteege I, Pau MG, Sadoff J, Vanloubbeeck Y, Lievens M, Heerwegh D, Moris P, Guerra Mendoza Y, Jongert E, Cohen J, Voss G, Ballou WR, Vekemans J. Ad35.CS.01-RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naïve Adults. PLoS One. 2015 Jul 6;10(7):e0131571. doi: 10.1371/journal.pone.0131571. eCollection 2015.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01366534
• Other Study ID Numbers: 114460
• First Posted: Jun 6, 2011
• Last Update Posted: Jun 18, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: safety; Vaccine; Phase 1/2; immunogenicity; Malaria; efficacy; sporozoite challenge
• Additional relevant MeSH terms: Malaria; Vaccines

Study Results

Participant Flow

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Period Title: Overall Study
STARTED	28	27	12
COMPLETED	26	25	12
NOT COMPLETED	2	2	0

Baseline Characteristics

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group	Total
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.	Total of all reporting groups
Overall Participants	28	27	12	67
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	29.9 (7.03)	30.3 (7.83)	29.8 (6.86)	30.04 (7.23)
Sex: Female, Male (Count of Participants)
Female	16 57.1%	10 37%	6 50%	32 47.8%
Male	12 42.9%	17 63%	6 50%	35 52.2%
Race/Ethnicity, Customized (Count of Participants)
African heritage/African American	9 32.1%	16 59.3%	5 41.7%	30 44.8%
American Indian or Alaskan native	0 0%	1 3.7%	0 0%	1 1.5%
Asian - Central/South Asian heritage	1 3.6%	1 3.7%	1 8.3%	3 4.5%
White - Caucasian/European heritage	15 53.6%	9 33.3%	5 41.7%	29 43.3%
Mixed Origin	3 10.7%	0 0%	1 8.3%	4 6%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Plasmodium Falciparum Parasitemia Following Sporozoite Challenge
Description	P. falciparum parasitemia was defined as a positive blood slide.
Time Frame	28 days following sporozoite challenge (Day 105)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-to-Protocol (ATP) cohort for Efficacy, which included all evaluable subjects who did not use any medication or blood products forbidden by the protocol, who did not report any under lying medical condition influencing immune responses, for whom efficacy data were available.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	25	21	12
Count of Participants [Participants]	14 50%	10 37%	12 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ad35.CS.01 Group, GSK257049 Group
	Comments	Comparison of the efficacy (occurrence of P. falciparum parasitemia, assessed by blood slide) of an immunization regimen comprising of one dose of Ad35.CS.01 vaccine followed one month later by 2 doses of GSK257049 vaccine administered at one month intervals, with that of 3 doses of GSK257049 vaccine administered at one month intervals, in healthy malaria-naïve volunteers aged 18-50 years in the sporozoite challenge model.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7675
	Comments
	Method	2-sided Fisher Exact test
	Comments
Method of Estimation	Estimation Parameter	Vaccine Efficacy Maentel-Haenzel Method
	Estimated Value	-17.6
	Confidence Interval	(2-Sided) 95%; -107.4 to 33.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Pre-defined futility criteria for efficacy: point estimate of increase of VE in Ad35.CS.01 Group over GSK257049 Group less than 0%

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ad35.CS.01 Group, Control Group
	Comments	Comparison of the efficacy (occurrence of P. falciparum parasitemia, assessed by blood slide) of an immunization regimen comprising of one dose of Ad35.CS.01 vaccine followed one month later by 2 doses of GSK257049 vaccine administered at 1 month intervals, with that of 3 doses of GSK257049 vaccine administered at one month intervals, in healthy malaria-naïve volunteers aged 18-50 years in the sporozoite challenge model.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0066
	Comments
	Method	2-sided Fisher Exact test
	Comments
Method of Estimation	Estimation Parameter	Vaccine Efficacy: Maentel-Haenzel Method
	Estimated Value	44.0
	Confidence Interval	(2-Sided) 95%; 20.7 to 60.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GSK257049 Group, Control Group
	Comments	Comparison of the efficacy (occurrence of P. falciparum parasitemia, assessed by blood slide) of an immunization regimen comprising of one dose of Ad35.CS.01 vaccine followed one month later by 2 doses of GSK257049 vaccine administered at 1 month intervals, with that of 3 doses of GSK257049 vaccine administered at one month intervals, in healthy malaria-naïve volunteers aged 18-50 years in the sporozoite challenge model.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	2-sided Fisher Exact test
	Comments
Method of Estimation	Estimation Parameter	Vaccine Efficacy: Maentel-Haenzel Method
	Estimated Value	52.4
	Confidence Interval	(2-Sided) 95%; 25.4 to 69.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Intention-to-treat (ITT) cohort, which included all subjects with at least one vaccine administration documented, who had their symptoms sheet filled in.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.
Measure Participants	28	27
Any Pain, Dose 1	25 89.3%	25 92.6%
Grade 3 Pain, Dose 1	0 0%	1 3.7%
Any Redness, Dose 1	7 25%	4 14.8%
Grade 3 Redness, Dose 1	0 0%	0 0%
Any Swelling, Dose 1	6 21.4%	6 22.2%
Grade 3 Swelling, Dose 1	0 0%	0 0%
Any Pain, Dose 2	26 92.9%	20 74.1%
Grade 3 Pain, Dose 2	1 3.6%	0 0%
Any Redness, Dose 2	8 28.6%	7 25.9%
Grade 3 Redness, Dose 2	1 3.6%	0 0%
Any Swelling, Dose 2	6 21.4%	3 11.1%
Grade 3 Swelling, Dose 2	0 0%	0 0%
Any Pain, Dose 3	20 71.4%	15 55.6%
Grade 3 Pain, Dose 3	1 3.6%	0 0%
Any Redness, Dose 3	11 39.3%	8 29.6%
Grade 3 Redness, Dose 3	0 0%	1 3.7%
Any Swelling, Dose 3	10 35.7%	6 22.2%
Grade 3 Swelling, Dose 3	0 0%	0 0%
Any Pain, Across Doses	27 96.4%	26 96.3%
Grade 3 Pain, Across Doses	2 7.1%	1 3.7%
Any Redness, Across Doses	15 53.6%	11 40.7%
Grade 3 Redness, Across Doses	1 3.6%	1 3.7%
Any Swelling, Across Doses	13 46.4%	11 40.7%
Grade 3 Swelling, Across Doses	0 0%	0 0%

3. Primary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description	Assessed solicited general symptoms were chills, fatigue, gastrointestinal symptoms, headache and temperature [defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade.Grade 3 Chills = rigors [uncontrollable shivering more than (>) 15 seconds]. Grade 3 Fatigue, Gastrointestinal symptoms and Headache = symptoms that prevented normal activity. Grade 3 fever = fever higher than (>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Time Frame	Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Intention-to-treat (ITT) cohort, which included all subjects with at least one vaccine administration documented, who had their symptoms sheet filled in.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.
Measure Participants	28	27
Any Chills, Dose 1	7 25%	3 11.1%
Related Chills, Dose 1	7 25%	3 11.1%
Grade 3 Chills, Dose 1	2 7.1%	1 3.7%
Any Fatigue, Dose 1	9 32.1%	11 40.7%
Related Fatigue, Dose 1	9 32.1%	8 29.6%
Grade 3 Fatigue, Dose 1	0 0%	1 3.7%
Any Gastrointestinal symptoms, Dose 1	3 10.7%	4 14.8%
Related Gastrointestinal symptoms, Dose 1	3 10.7%	3 11.1%
Grade 3 Gastrointestinal symptoms, Dose 1	0 0%	1 3.7%
Any Headache, Dose 1	12 42.9%	10 37%
Related Headache, Dose 1	11 39.3%	7 25.9%
Grade 3 Headache, Dose 1	0 0%	2 7.4%
Any Temperature, Dose 1	3 10.7%	2 7.4%
Related Temperature, Dose 1	2 7.1%	2 7.4%
Grade 3 Temperature, Dose 1	0 0%	0 0%
Any Chills, Dose 2	6 21.4%	11 40.7%
Related Chills, Dose 2	6 21.4%	11 40.7%
Grade 3 Chills, Dose 2	0 0%	1 3.7%
Any Fatigue, Dose 2	9 32.1%	11 40.7%
Related Fatigue, Dose 2	8 28.6%	11 40.7%
Grade 3 Fatigue, Dose 2	0 0%	0 0%
Any Gastrointestinal symptoms, Dose 2	0 0%	1 3.7%
Related Gastrointestinal symptoms, Dose 2	0 0%	1 3.7%
Grade 3 Gastrointestinal symptoms, Dose 2	0 0%	0 0%
Any Headache, Dose 2	10 35.7%	12 44.4%
Related Headache, Dose 2	9 32.1%	11 40.7%
Grade 3 Headache, Dose 2	0 0%	0 0%
Any Temperature, Dose 2	1 3.6%	3 11.1%
Related Temperature, Dose 2	1 3.6%	3 11.1%
Grade 3 Temperature, Dose 2	0 0%	0 0%
Any Chills, Dose 3	8 28.6%	7 25.9%
Related Chills, Dose 3	8 28.6%	7 25.9%
Grade 3 Chills, Dose 3	2 7.1%	1 3.7%
Any Fatigue, Dose 3	8 28.6%	10 37%
Related Fatigue, Dose 3	8 28.6%	9 33.3%
Grade 3 Fatigue, Dose 3	1 3.6%	0 0%
Any Gastrointestinal symptoms, Dose 3	3 10.7%	2 7.4%
Related Gastrointestinal symptoms, Dose 3	3 10.7%	1 3.7%
Grade 3 Gastrointestinal symptoms, Dose 3	0 0%	0 0%
Any Headache, Dose 3	14 50%	6 22.2%
Related Headache, Dose 3	14 50%	6 22.2%
Grade 3 Headache, Dose 3	1 3.6%	0 0%
Any Temperature, Dose 3	2 7.1%	5 18.5%
Related Temperature, Dose 3	2 7.1%	4 14.8%
Grade 3 Temperature, Dose 3	1 3.6%	0 0%
Any Chills, Across doses	15 53.6%	13 48.1%
Related Chills, Across doses	15 53.6%	13 48.1%
Grade 3 Chills, Across doses	4 14.3%	3 11.1%
Any Fatigue, Across doses	15 53.6%	17 63%
Related Fatigue, Across doses	15 53.6%	14 51.9%
Grade 3 Fatigue, Across doses	1 3.6%	1 3.7%
Any Gastrointestinal symptoms, Across doses	5 17.9%	6 22.2%
Related Gastrointestinal symptoms, Across doses	5 17.9%	5 18.5%
Grade 3 Gastrointestinal symptoms, Across doses	0 0%	1 3.7%
Any Headache, Across doses	21 75%	14 51.9%
Related Headache, Across doses	21 75%	13 48.1%
Grade 3 Headache, Across doses	1 3.6%	2 7.4%
Any Temperature, Across doses	6 21.4%	9 33.3%
Related Temperature, Across doses	5 17.9%	8 29.6%
Grade 3 Temperature, Across doses	1 3.6%	0 0%

4. Primary Outcome

Title	Number of Subjects With Any Unsolicited Adverse Events (AEs)
Description	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time Frame	Within the 30-day (Day 0 - Day 29) follow-up period post-vaccination

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Intention-to-treat (ITT) cohort, which included all subjects with at least one vaccine administration documented.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.
Measure Participants	28	27
Count of Participants [Participants]	23 82.1%	21 77.8%

5. Primary Outcome

Title	Number of Subjects With Any Unsolicited Adverse Events (AEs)
Description	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time Frame	Within the 30-day (Day 0 - Day 29) follow-up period post-challenge

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Intention-to-treat (ITT) cohort, which included all subjects with at least one vaccine administration documented. All challenged infectivity controls were also included in this cohort and presented as a separate group.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	25	21	12
Count of Participants [Participants]	22 78.6%	18 66.7%	12 100%

6. Primary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame	Throughout the study period (Day 0 - Day 236)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Intention-to-treat (ITT) cohort, which included all subjects with at least one vaccine administration documented. All challenged infectivity controls were also included in this cohort and presented as a separate group.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	28	27	12
Count of Participants [Participants]	0 0%	0 0%	0 0%

7. Secondary Outcome

Title	Number of Days Until the Onset of P. Falciparum Parasitemia Following Sporozoite Challenge
Description	The onset of P. falciparum parasitemia was defined by a positive blood slide.
Time Frame	From day of challenge (Day 0) up to 159 days post-challenge

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-to-Protocol (ATP) cohort for Efficacy, which included all evaluable subjects who did not use any medication or blood products forbidden by the protocol, who did not report any under lying medical condition influencing immune responses, for whom efficacy data were available.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	14	10	12
Mean (Standard Deviation) [Days]	14 (1)	14 (2)	12 (2)

8. Secondary Outcome

Title	Anti-circumsporozoite Protein (Anti-CS) Antibody Titers
Description	Titers are presented as geometric mean titers (GMTs) and are measured in titers. Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore GMTs for this group are presented as from Day 77.
Time Frame	28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-to-Protocol (ATP) cohort for Immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements, who did not report any underlying medical condition influencing immune responses and for whom immunogenicity data were available.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	26	27	12
D28	0.9	14.7
D56	14.3	79.2
D77	55.5	115.9	0.3
D105	50.0	96.6	0.5
D140	40.5	62.3	0.4
D236	21.4	29.2	0.3

9. Secondary Outcome

Title	Anti-hepatitis B (Anti-HBs) Antibody Titers
Description	Titers are presented as geometric mean titers (GMTs) and are measured in titers. Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore GMTs for this group are presented as from Day 77.
Time Frame	28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-to-Protocol (ATP) cohort for Immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements, who did not report any underlying medical condition influencing immune responses and for whom immunogenicity data were available.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	26	27	12
D28	53.0	26596.6
D56	15845.4	59388.2
D77	30877.5	103746.8	35.6
D105	28180.7	77659.2	47.4
D140	29307.7	47932.8	41.2
D236	15589.7	40727.8	34.2

10. Secondary Outcome

Title	Anti-Adenovirus Type 35 (Ad35) Neutralizing Antibody Titers at Specified Time Points
Description	Titers are presented as geometric mean titers (GMTs) and are measured in titers. Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore GMTs for this group are presented as from Day 77.
Time Frame	28 days post-dose 1 (Day 28), 28 days post-dose 2 (Day 56), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-to-Protocol (ATP) cohort for Immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements, who did not report any underlying medical condition influencing immune responses and for whom immunogenicity data were available.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	26	27	12
D28	27.3	16.3
D56	25.5	16.5
D77	26.3	17.0	23.2
D105	22.1	17.2	25.9
D140	20.8	16.0	23.4
D236	21.3	16.5	24.2

11. Secondary Outcome

Title	Frequency of CS (Total CS or Repeat)-Specific CD4+ T-cells
Description	CS-specific CD4+ T-cells expressing at least 2 cytokines/activation markers between IL-2, IFN-γ, TNF-α and CD40-L are presented here. Analysis was performed via intra-cellular staining (ICS) assays, data are presented as frequency of T-cells per million peripheral blood mononuclear cells (PBMCs).Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.
Time Frame	14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-to-Protocol (ATP) cohort for Immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements, who did not report any underlying medical condition influencing immune responses and for whom immunogenicity data were available.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	26	24	11
D14	143.23 (170.19)	220.25 (188.34)
D42	1693.38 (1268.50)	854.29 (911.56)
D77	1364.95 (1025.92)	608.59 (744.99)	96.00 (94.72)
D105	1149.29 (560.47)	622.27 (448.50)	80.90 (88.40)
D140	893.68 (933.95)	492.14 (424.34)	36.40 (75.39)
D236	750.95 (676.98)	363.69 (272.73)	59.55 (65.07)

12. Secondary Outcome

Title	Frequency of CS (Total CS or Repeat)-Specific CD8+ T Cells
Description	CS-specific CD8+ T-cells expressing at least 2 cytokines/activation markers between IL-2, IFN-γ, TNF-α and CD40-L are presented here. Analysis was performed via intra-cellular staining (ICS) assays, data are presented as frequency of T-cells per million peripheral blood mononuclear cells (PBMC). Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.
Time Frame	14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-to-Protocol (ATP) cohort for Immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements, who did not report any underlying medical condition influencing immune responses and for whom immunogenicity data were available.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	26	24	11
D14	37.04 (64.66)	18.29 (33.10)
D42	76.81 (107.06)	25.29 (37.31)
D77	94.86 (153.45)	31.35 (34.89)	19.00 (32.21)
D105	131.47 (153.24)	32.27 (40.73)	8.50 (16.43)
D140	99.95 (159.19)	26.18 (34.99)	44.60 (93.49)
D236	42.74 (47.54)	28.00 (51.66)	48.45 (68.98)

13. Secondary Outcome

Title	Frequency of HBs-specific CD4+ T-cells
Description	HB-specific CD4+ T-cells expressing at least 2 cytokines/activation markers between IL-2, IFN-γ, TNF-α and CD40-L are presented here. Analysis was performed via intra-cellular staining (ICS) assays, data are presented as frequency of T-cells per million peripheral blood mononuclear cells (PBMCs). Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.
Time Frame	14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-to-Protocol (ATP) cohort for Immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements, who did not report any underlying medical condition influencing immune responses and for whom immunogenicity data were available.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	25	25	11
D14	373.67 (613.02)	1400.80 (2449.05)
D42	1518.36 (1526.01)	1836.33 (2264.88)
D77	1163.77 (1022.03)	1023.58 (936.22)	232.13 (301.75)
D105	1265.00 (863.73)	1310.53 (747.79)	569.70 (489.67)
D140	1158.47 (804.40)	1181.00 (603.43)	531.90 (407.21)
D236	940.16 (564.66)	1244.38 (833.86)	498.36 (313.94)

14. Secondary Outcome

Title	Frequency of CS-specific T-cells Producing IFN-γ
Description	The analysis was performed via Enzyme-Linked Immunospot (ELISPOT) full length assay. Data are presented as the number of spots per million peripheral blood mononuclear cells (PBMCs). Volunteers from Control Group did not receive any immunization, but were subjected to the sporozoite challenge, therefore the frequency for this group is presented as from Day 77.
Time Frame	14 days post-dose 1 (Day 14), 14 days post-dose 2 (Day 42), 21 days post-dose 3 (Day 77 = Day of challenge), 28 days post-challenge (Day 105), 63 days post-challenge (Day 140), 159 days post-challenge (Day 236)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-to-Protocol (ATP) cohort for Immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements, who did not report any underlying medical condition influencing immune responses and for whom immunogenicity data were available.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group	Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
Measure Participants	26	27	12
D14	51.05 (61.89)	63.20 (100.85)
D42	297.97 (243.24)	54.27 (53.52)
D77	225.98 (161.51)	64.54 (87.40)	66.68 (124.31)
D105	232.35 (175.77)	58.04 (76.86)	90.75 (219.50)
D140	208.97 (125.45)	50.77 (71.69)	75.74 (135.72)
D236	167.91 (153.79)	38.85 (56.36)	105.12 (255.20)

15. Secondary Outcome

Title	Frequency of CS-specific T-cells Producing IFN-γ
Description	The analysis was performed via Enzyme-Linked Immunospot (ELISPOT) N-terminal assay. Data are presented as the number of spots per million peripheral blood mononuclear cells (PBMCs).
Time Frame	14 days post-dose 1 (Day 14)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-to-Protocol (ATP) cohort for Immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements, who did not report any underlying medical condition influencing immune responses and for whom immunogenicity data were available.

Arm/Group Title	Ad35.CS.01 Group	GSK257049 Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.
Measure Participants	25	27
Mean (Standard Deviation) [spots/million PBMCs]	18.88 (19.97)	14.57 (18.39)

Adverse Events

Time Frame	Solicited local/general symptoms: during the 7-day post-vaccination period (Days 0-6). Unsolicited AEs: during the 31-day post-vaccination (Days 0-30). SAEs: during the entire study period (Day 0 - Day 236).
Arm/Group Title	Ad35.CS.01 Group		GSK257049 Group		Control Group
Arm/Group Description	Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered one dose of Ad35.CS.01 vaccine at Month 0, and 2 doses of GSK257049 at Months 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.		Healthy male or non-pregnant female subjects, aged 18 to 50 years, were administered 3 doses of GSK257049 vaccine at Months 0, 1 and 2 intramuscularly in the deltoid of the non-dominant arm. The duration of the study was approximately 11 months for vaccinated subjects.		Healthy male or non-pregnant female subjects, aged 18 to 50 years, were volunteers who did not receive any immunization but were subjected to the sporozoite challenge. The duration of the study was approximately 8 months for infectivity control subjects.
All Cause Mortality
	Ad35.CS.01 Group		GSK257049 Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/27 (0%)		0/12 (0%)
Serious Adverse Events
	Ad35.CS.01 Group		GSK257049 Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/27 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Ad35.CS.01 Group		GSK257049 Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/28 (96.4%)		27/27 (100%)		12/12 (100%)
Gastrointestinal disorders
Nausea (post-vaccination)	0/28 (0%)		2/27 (7.4%)		0/0 (NaN)
Nausea (post-challenge)	1/25 (4%)		2/21 (9.5%)		0/12 (0%)
General disorders
Fatigue (post-vaccination)	2/28 (7.1%)		0/27 (0%)		0/0 (NaN)
Malaise (post-vaccination)	2/28 (7.1%)		1/27 (3.7%)		0/0 (NaN)
Pain (post-vaccination)	5/28 (17.9%)		2/27 (7.4%)		0/0 (NaN)
Pain- solicited local (post-vaccination)	27/28 (96.4%)		26/27 (96.3%)		0/0 (NaN)
Redness (post-vaccination)	15/28 (53.6%)		11/27 (40.7%)		0/0 (NaN)
Swelling (post-vaccination)	13/28 (46.4%)		11/27 (40.7%)		0/0 (NaN)
Chills (post-vaccination)	15/28 (53.6%)		13/27 (48.1%)		0/0 (NaN)
Fatigue (post-vaccination)	15/28 (53.6%)		17/27 (63%)		0/0 (NaN)
Gastrointestinal symptoms (post-vaccination)	5/28 (17.9%)		6/27 (22.2%)		0/0 (NaN)
Headache- solicited general (post-vaccination)	21/28 (75%)		14/27 (51.9%)		0/0 (NaN)
Temperature (post-vaccination)	6/28 (21.4%)		9/27 (33.3%)		0/0 (NaN)
Infections and infestations
Nasopharyngitis (post-vaccination)	2/28 (7.1%)		5/27 (18.5%)		0/0 (NaN)
Upper respiratory tract infection (post-vaccination)	6/28 (21.4%)		5/27 (18.5%)		0/0 (NaN)
Malaria (post-challenge)	14/25 (56%)		10/21 (47.6%)		12/12 (100%)
Upper respiratory tract infection (post-challenge)	1/25 (4%)		2/21 (9.5%)		2/12 (16.7%)
Musculoskeletal and connective tissue disorders
Arthralgia (post-vaccination)	1/28 (3.6%)		2/27 (7.4%)		0/0 (NaN)
Back pain (post-vaccination)	4/28 (14.3%)		1/27 (3.7%)		0/0 (NaN)
Nervous system disorders
Headache (post-vaccination)	3/28 (10.7%)		4/27 (14.8%)		0/0 (NaN)
Headache (post-challenge)	5/25 (20%)		7/21 (33.3%)		2/12 (16.7%)
Reproductive system and breast disorders
Dysmenorrhoea (post-vaccination)	3/28 (10.7%)		1/27 (3.7%)		0/0 (NaN)
Respiratory, thoracic and mediastinal disorders
Nasal congestion (post-vaccination)	1/28 (3.6%)		4/27 (14.8%)		0/0 (NaN)
Throat irritation	2/28 (7.1%)		0/27 (0%)		0/0 (NaN)
Oropharyngeal pain(post-challenge)	3/25 (12%)		0/21 (0%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis (post-vaccination)	0/28 (0%)		3/27 (11.1%)		0/0 (NaN)
Pruritus (post-vaccination)	2/28 (7.1%)		2/27 (7.4%)		0/0 (NaN)
Pruritus (post-challenge)	1/25 (4%)		2/21 (9.5%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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