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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03824236
• Collaborator: PATH (Other)
• Enrollment: 61
• Location: 1
• Arms: 3
• Actual Duration (Months): 7.7
• Patients Per Site Per Month: 8

Study Details

Study Description

Brief Summary

MALARIA-092 (NCT03162614) study was designed to evaluate the efficacy, immunogenicity and safety of various dose schedules and formulations of GSK Biologicals' candidate malaria vaccine (RTS,S/AS01E) in healthy malaria-naïve subjects aged 18-55 years.

The purpose of this study (follow-up to MALARIA-092 [NCT03162614] study) is to evaluate if protection can be extended with an additional Fx booster dose and if unprotected subjects can be protected following a Fx booster dose.

In this booster study, subjects from MALARIA-092 (NCT03162614) study who completed vaccination and challenge will receive a Fx booster dose of RTS,S/AS01E and undergo a second controlled human malaria infection (CHMI) three to four weeks after vaccination. Additionally, subjects will be newly enrolled and will only undergo the sporozoite challenge as infectivity controls.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Biological: RTS,S/AS01E (SB257049)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Efficacy, Immunogenicity and Safety Study Evaluating a Fractional (Fx) Booster Dose of GSK Biologicals' Candidate Malaria Vaccine (SB257049) in a Sporozoite Challenge Model in Healthy Malaria-naïve Adults
• Actual Study Start Date: Feb 5, 2019
• Actual Primary Completion Date: Apr 30, 2019
• Actual Study Completion Date: Sep 26, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: P-Fx group Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Biological: RTS,S/AS01E (SB257049); Subjects from the P-Fx and NP-Fx groups will receive one Fx booster dose of RTS,S/AS01E at Day 1.
Experimental: NP-Fx group Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Biological: RTS,S/AS01E (SB257049); Subjects from the P-Fx and NP-Fx groups will receive one Fx booster dose of RTS,S/AS01E at Day 1.
No Intervention: InfectivityCtrl group Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Reporting Plasmodium Falciparum (P. Falciparum) Parasitemia (Defined by a Positive Blood Slide) Following Sporozoite Challenge (in All Study Groups Versus Infectivity Controls) [During the sporozoite challenge dose follow-up period (from Day 22 up to Day 50)]

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

Secondary Outcome Measures

1. Time to Onset of P. Falciparum Parasitemia (Defined by a Positive Blood Slide) Following Sporozoite Challenge [During the sporozoite challenge period starting at Day 22 (after the vaccine dose administered at Day 1), up to Day 50]

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

2. Anti- Circumsporozoite (CS) Repeat Region Antibody Concentrations [At Day 1, prior to challenge (Day 22), 28 days post-challenge (Day 50) and at study end (Day 190)]

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

3. Anti-Hepatitis B (HBs) Immunoglobulin G (IgG) Antibody Concentrations [At Day 1, prior to challenge (Day 22), 28 days post-challenge (Day 50) and at study end (Day 190)]

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

4. Number of Subjects With Any Solicited Local Adverse Events (AEs) in the Booster Vaccination Groups [Within 7 days after vaccination (day of vaccination and 6 subsequent days) in the booster vaccination groups]

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

5. Number of Subjects With Any Solicited General AEs in the Booster Vaccination Groups [Within 7 days after vaccination (day of vaccination and 6 subsequent days) in the booster vaccination groups]

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

6. Number of Subjects With Any Unsolicited AEs After Vaccination, in the Booster Vaccination Groups [Up to 21 days after booster vaccination period (day of vaccination and 20 subsequent days), after booster vaccination]

   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.

7. Number of Subjects With Any Unsolicited AEs After Challenge, in All Study Groups [Within 29 days after challenge (day of challenge and 28 subsequent days)]

   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.

8. Number of Subjects With AEs of Specific Interest (Potential Immune-mediated Diseases [pIMDs] and Meningitis), in All Study Groups [From Day 1 up to study conclusion (Day 190)]

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

9. Number of Subjects With Serious Adverse Events (SAEs) (Any, Fatal or Related to Investigational Vaccine) During the Whole Study Period, in All Study Groups [From Day 1 up to study conclusion (Day 190)]

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

10. Number of Subjects With Abnormal Laboratory Values [At screening, Day(D)1, D8, D22 (day of first parasitemia) and D50 (28 days post-challenge) for the booster vaccination groups; and at screening, D22 (day of first parasitemia) and D50 (28 days post-challenge) for the infectivity control subjects]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Only for subjects from MALARIA-092 study (NCT03162614):

• Subjects vaccinated and having undergone sporozoite challenge during the primary study (MALARIA-092 [NCT03162614]).

For all subjects:

• 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 any study-specific procedure.

• 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.

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

• Has practiced adequate contraception for 30 days prior to Day 1, and has agreed to continue adequate contraception during the entire treatment period and for two months after malaria challenge (only for subjects from the MALARIA-092 study [NCT03162614]).

• Has practiced adequate contraception for 30 days prior to malaria challenge, and has agreed to continue adequate contraception up to two months after malaria challenge (only for the infectivity control subjects).

• Has a negative pregnancy test at enrollment.

For the infectivity control subjects:

• Male or female subjects between, and including, 18 and 55 years of age.

Exclusion Criteria:

For all subjects except the infectivity control subjects:

• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.

• History of anaphylaxis post-vaccination.

For all subjects:

• Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before Day 1 (Day -29 to Day 1) (for P-Fx and NP-Fx groups)/before the malaria challenge (for infectivity control subjects), or planned use during the study period.

• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to Day 1 (for P-Fx and NP-Fx groups) or malaria challenge (for infectivity control subjects). 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 anti-malarial effects.

• Planned administration/administration of a vaccine not foreseen by the study protocol in the period within seven days of Day 1 (for P-Fx and NP-Fx groups) or the malaria challenge (for infectivity control subjects).

• 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 Human Immunodeficiency Virus, Hepatitis B surface antigen or Hepatitis C Virus.

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

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

• History of any reaction or hypersensitivity that would prevent the subject from utilizing all of the following: chloroquine, atovaquone/proguanil, artemether/lumefantrine.

• Current use of medications known to cause drug reactions that would prevent the subject from utilizing any of the following: chloroquine, atovaquone/proguanil, artemether/lumefantrine.

• History of severe reactions to mosquito bites.

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

• Fever is defined as temperature ≥37.5°C/99.5°F for oral, axillary or tympanic route.

• Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.

• Hepatomegaly, right upper quadrant abdominal pain or tenderness.

• Any abnormal baseline laboratory screening tests: ALT, AST, creatinine, hemoglobin, platelet count, total WBC, out of normal range.

• Personal history of auto-immune disease.

• Administration of immunoglobulins and/or any blood products during the period starting three months before Day 1 (for P-Fx and NP-Fx groups)/the malaria challenge (for infectivity control subjects), or planned administration during the study period.

• Pregnant or lactating female.

• Female planning to become pregnant or planning to discontinue contraceptive precautions.

• History of chronic alcohol consumption and/or drug abuse.

• History of blood donation within 56 days preceding enrollment.

• 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.

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

• Evidence of increased cardiovascular disease risk, "moderate" or "high", according to the National Health And Nutrition Examination Survey I (NHANES I) criteria.

Only for infectivity control subjects:

• Previous vaccination against malaria.

• History of splenectomy.

• Family history of congenital or hereditary immunodeficiency.

• Major congenital defects.

• Serious chronic illness.

• History of any neurological disorders or seizures.

• Diagnosed with malaria within the last 5 years (inclusive).

Contacts and Locations

Locations

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

Sponsors and Collaborators

• GlaxoSmithKline
• PATH

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Study Documents (Full-Text)

• Study Protocol - Sep 26, 2018
• Statistical Analysis Plan - Dec 20, 2018

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03824236
• Other Study ID Numbers: 209003; 17337
• First Posted: Jan 31, 2019
• Last Update Posted: Aug 14, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Malaria; RTS,S/AS01E vaccine; Fractional dose; Sporozoite challenge
• Additional relevant MeSH terms: Malaria

Study Results

Participant Flow

Arm/Group Title	P-Fx Group	NP-Fx Group	Infectivity Control Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge.
Period Title: Overall Study
STARTED	25	24	12
COMPLETED	25	24	11
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	P-Fx Group	NP-Fx Group	Infectivity Control Group	Total
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge.	Total of all reporting groups
Overall Participants	25	24	12	61
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	35.7 (10.2)	35.5 (10.1)	31.7 (10.8)	34.8 (10.2)
Sex: Female, Male (Count of Participants)
Female	10 40%	10 41.7%	4 33.3%	24 39.3%
Male	15 60%	14 58.3%	8 66.7%	37 60.7%
Race/Ethnicity, Customized (Count of Participants)
AMERICAN INDIAN OR ALASKA NATIVE	1 4%	1 4.2%	0 0%	2 3.3%
ASIAN	2 8%	1 4.2%	2 16.7%	5 8.2%
BLACK OR AFRICAN AMERICAN	7 28%	11 45.8%	4 33.3%	22 36.1%
OTHER, Not specified	0 0%	0 0%	1 8.3%	1 1.6%
WHITE	15 60%	11 45.8%	5 41.7%	31 50.8%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Reporting Plasmodium Falciparum (P. Falciparum) Parasitemia (Defined by a Positive Blood Slide) Following Sporozoite Challenge (in All Study Groups Versus Infectivity Controls)
Description	Occurrence of P. falciparum parasitemia (defined by a positive blood slide) following sporozoite challenge. Post-challenge, parasitemia was determined by microscopy of Giemsa-stained thick blood films (smear). Microscopy was performed on thick smears using a validated standard operation procedure. P. falciparum infection was defined as asexual blood stage P. falciparum parasite density greater than (>) 0 detected by blood slide reading. For the analysis of proportion affected (relative risk), all subjects included in the analysis were considered at risk of infection and no censoring or elimination was applied for subjects not completing the entire protocol-defined post-challenge follow-up (Day 50 - 28 days post challenge).
Time Frame	During the sporozoite challenge dose follow-up period (from Day 22 up to Day 50)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group	Infectivity Control Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge.
Measure Participants	25	24	11
Count of Participants [Participants]	12 48%	11 45.8%	11 91.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	P-Fx Group, Infectivity Control Group
	Comments	Efficacy analysis aimed at comparing P. falciparum parasitemia incidence after sporozoite challenge between P-Fx group and the Infectivity Control group.
	Type of Statistical Test	Other
	Comments	Vaccine efficacy rate was calculated as 100*(1-RR) with RR=relative risk of developing the disease for vaccinated people (P-Fx Group) compared to unvaccinated people (Infectivity Control Group).
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy rate
	Estimated Value	52
	Confidence Interval	(2-Sided) 95%; 28 to 68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	NP-Fx Group, Infectivity Control Group
	Comments	Efficacy analysis aimed at comparing P. falciparum parasitemia incidence after sporozoite challenge between NP-Fx group and the Infectivity Control group.
	Type of Statistical Test	Other
	Comments	Vaccine efficacy rate was calculated as 100*(1-RR) with RR=relative risk of developing the disease for vaccinated people (NP-Fx Group) compared to unvaccinated people (Infectivity Control Group).
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy rate
	Estimated Value	54
	Confidence Interval	(2-Sided) 95%; 29 to 70
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to Onset of P. Falciparum Parasitemia (Defined by a Positive Blood Slide) Following Sporozoite Challenge
Description	For the analyses of time to onset of parasitemia (Kaplan-Meyer and log-rank), time at risk started on first day of challenge. Time at risk was censored on Day 50 (28 days post challenge), drop-out date, start date of anti-malarial treatment or date meeting an endpoint, whichever occured first. Time-at-risk was calculated as: censor date - date challenge + 1.
Time Frame	During the sporozoite challenge period starting at Day 22 (after the vaccine dose administered at Day 1), up to Day 50

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group	Infectivity Control Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge.
Measure Participants	12	11	11
Mean (Standard Deviation) [Days]	14.6 (1.9)	14.1 (1.6)	11.6 (0.9)

3. Secondary Outcome

Title	Anti- Circumsporozoite (CS) Repeat Region Antibody Concentrations
Description	Anti-CS antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in Enzyme-linked immunosorbent assay Unit per milliliter (EU/mL). The cut-off for the assay was equal to 1.9 EU/mL. GMC calculations are performed by taking the inverse logarithm of the mean of the log concentration transformations. Antibody concentrations below the cut-off of the assay will be given an arbitrary value of half the cut-off of the assay for the purpose of GMC calculation.
Time Frame	At Day 1, prior to challenge (Day 22), 28 days post-challenge (Day 50) and at study end (Day 190)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.
Measure Participants	25	24
Day 1	32.8	7.2
Day 22	87.3	37.3
Day 50	77.8	25.7
Day 190	49.7	12.7

4. Secondary Outcome

Title	Anti-Hepatitis B (HBs) Immunoglobulin G (IgG) Antibody Concentrations
Description	Anti-HBs IgG antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in milli-International Unit per milliliter (mIU/mL). The cut-off for the assay was equal to 6.2 mIU/mL. GMC calculations are performed by taking the inverse logarithm of the mean of the log concentration transformations. Antibody concentrations below the cut-off of the assay will be given an arbitrary value of half the cut-off of the assay for the purpose of GMC calculation.
Time Frame	At Day 1, prior to challenge (Day 22), 28 days post-challenge (Day 50) and at study end (Day 190)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.
Measure Participants	25	24
Day 1	7788	6608.1
Day 22	25344.5	29271.3
Day 50	21203.1	19894.8
Day 190	11593.9	9092.5

5. Secondary Outcome

Title	Number of Subjects With Any Solicited Local Adverse Events (AEs) in the Booster Vaccination Groups
Description	Solicited local AEs assessed are erythema, pain and swelling. Any occurrence of AE regardless of intensity grade are reported. Any Erythema or any Swelling symptom = any symptom recorded with a surface diameter greater than 0 millimeter.
Time Frame	Within 7 days after vaccination (day of vaccination and 6 subsequent days) in the booster vaccination groups

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.
Measure Participants	25	24
Erythema	8 32%	4 16.7%
Pain	11 44%	10 41.7%
Swelling	4 16%	4 16.7%

6. Secondary Outcome

Title	Number of Subjects With Any Solicited General AEs in the Booster Vaccination Groups
Description	Solicited general AEs assessed are fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhea and/or abdominal pain), headache and fever. Any occurrence of symptom regardless of intensity grade and relationship to the vaccination. Fever was defined as temperature equal or greater than 37.5 °C (preferably oral route measure).
Time Frame	Within 7 days after vaccination (day of vaccination and 6 subsequent days) in the booster vaccination groups

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.
Measure Participants	25	24
Fatigue	7 28%	4 16.7%
Gastrointestinal symptoms	2 8%	0 0%
Headache	6 24%	5 20.8%
Fever	3 12%	0 0%

7. Secondary Outcome

Title	Number of Subjects With Any Unsolicited AEs After Vaccination, in the Booster Vaccination Groups
Description	An unsolicited adverse event is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited adverse event is any event reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time Frame	Up to 21 days after booster vaccination period (day of vaccination and 20 subsequent days), after booster vaccination

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.
Measure Participants	25	24
Count of Participants [Participants]	5 20%	1 4.2%

8. Secondary Outcome

Title	Number of Subjects With Any Unsolicited AEs After Challenge, in All Study Groups
Description	An adverse event is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame	Within 29 days after challenge (day of challenge and 28 subsequent days)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group	Infectivity Control Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge.
Measure Participants	25	24	12
Count of Participants [Participants]	19 76%	19 79.2%	12 100%

9. Secondary Outcome

Title	Number of Subjects With AEs of Specific Interest (Potential Immune-mediated Diseases [pIMDs] and Meningitis), in All Study Groups
Description	AEs of specific interest are potential immune-mediated diseases (pIMDs) and meningitis. pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Time Frame	From Day 1 up to study conclusion (Day 190)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group	Infectivity Control Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge.
Measure Participants	25	24	12
Count of Participants [Participants]	0 0%	0 0%	0 0%

10. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs) (Any, Fatal or Related to Investigational Vaccine) During the Whole Study Period, in All Study Groups
Description	An SAE is any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.
Time Frame	From Day 1 up to study conclusion (Day 190)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group	Infectivity Control Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge.
Measure Participants	25	24	12
Any SAEs	2 8%	0 0%	0 0%
Related SAEs	0 0%	0 0%	0 0%
Fatal SAEs	0 0%	0 0%	0 0%

11. Secondary Outcome

Title	Number of Subjects With Abnormal Laboratory Values
Description	Biochemistry (Alanine Aminotransferase [ALT], Aspartate Aminotransferase [AST] and Creatinine) and hematological (Hemoglobin, Platelets, White Blood Cells [WBC] decrease and WBC increase) laboratory values were presented according to toxicity grading scales and tabulated by group. Grading scale adapted from FDA guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials (September 2007).
Time Frame	At screening, Day(D)1, D8, D22 (day of first parasitemia) and D50 (28 days post-challenge) for the booster vaccination groups; and at screening, D22 (day of first parasitemia) and D50 (28 days post-challenge) for the infectivity control subjects

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	P-Fx Group	NP-Fx Group	Infectivity Control Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.	Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge.
Measure Participants	25	24	12
ALT, Screening, Grade 0	24 96%	23 95.8%	11 91.7%
ALT, Screening, Grade 1	1 4%	1 4.2%	1 8.3%
ALT, Day 1, Grade 0	25 100%	23 95.8%
ALT, Day 1, Grade 1	0 0%	1 4.2%
ALT, Day 8, Grade 0	24 96%	24 100%
ALT, Day 8, Grade 1	1 4%	0 0%
ALT, Day 22, Grade 0	23 92%	23 95.8%	12 100%
ALT, Day 22, Grade 1	2 8%	1 4.2%	0 0%
ALT, Day 50, Grade 0	23 92%	22 91.7%	10 83.3%
ALT, Day 50, Grade 1	2 8%	2 8.3%	1 8.3%
AST, Screening, Grade 0	25 100%	24 100%	11 91.7%
AST, Screening, Grade 1	0 0%	0 0%	1 8.3%
AST, Day 1, Grade 0	24 96%	24 100%
AST, Day 1, Grade 1	1 4%	0 0%
AST, Day 8, Grade 0	24 96%	24 100%
AST, Day 8, Grade 1	1 4%	0 0%
AST, Day 22, Grade 0	25 100%	23 95.8%	12 100%
AST, Day 22, Grade 1	0 0%	1 4.2%	0 0%
AST, Day 50, Grade 0	25 100%	24 100%	10 83.3%
AST, Day 50, Grade 1	0 0%	0 0%	1 8.3%
Creatinine, Screening, Grade 0	25 100%	24 100%	12 100%
Creatinine, Day 1, Grade 0	25 100%	24 100%
Creatinine, Day 8, Grade 0	25 100%	24 100%
Creatinine, Day 22, Grade 0	25 100%	24 100%	12 100%
Creatinine, Day 50, Grade 0	25 100%	24 100%	11 91.7%
Hemoglobin, Screening, Grade 0	24 96%	23 95.8%	12 100%
Hemoglobin, Screening, Grade 1	1 4%	1 4.2%	0 0%
Hemoglobin, Day 1, Grade 0	25 100%	22 91.7%
Hemoglobin, Day 1, Grade 1	0 0%	2 8.3%
Hemoglobin, Day 8, Grade 0	25 100%	22 91.7%
Hemoglobin, Day 8, Grade 1	0 0%	2 8.3%
Hemoglobin, Day 22, Grade 0	23 92%	21 87.5%	10 83.3%
Hemoglobin, Day 22, Grade 1	2 8%	2 8.3%	2 16.7%
Hemoglobin, Day 22, Grade 2	0 0%	1 4.2%	0 0%
Hemoglobin, Day 50, Grade 0	23 92%	22 91.7%	10 83.3%
Hemoglobin, Day 50, Grade 1	2 8%	2 8.3%	1 8.3%
Platelets, Screening, Grade 0	24 96%	24 100%	12 100%
Platelets, Screening, Grade 1	1 4%	0 0%	0 0%
Platelets, Day 1, Grade 0	24 96%	24 100%
Platelets, Day 1, Grade 2	1 4%	0 0%
Platelets, Day 8, Grade 0	25 100%	24 100%
Platelets, Day 22, Grade 0	24 96%	24 100%	12 100%
Platelets, Day 22, Grade 1	1 4%	0 0%	0 0%
Platelets, Day 50, Grade 0	25 100%	24 100%	11 91.7%
WBC Decrease, Screening, Grade 0	24 96%	24 100%	12 100%
WBC Decrease, Screening, Grade 1	1 4%	0 0%	0 0%
WBC Decrease, Day 1, Grade 0	24 96%	22 91.7%
WBC Decrease, Day 1, Grade 1	0 0%	2 8.3%
WBC Decrease, Day 1, Grade 2	1 4%	0 0%
WBC Decrease, Day 8, Grade 0	25 100%	23 95.8%
WBC Decrease, Day 8, Grade 1	0 0%	1 4.2%
WBC Decrease, Day 22, Grade 0	25 100%	24 100%	12 100%
WBC Decrease, Day 50, Grade 0	24 96%	23 95.8%	11 91.7%
WBC Decrease, Day 50, Grade 1	1 4%	1 4.2%	0 0%
WBC Increase, Screening, Grade 0	25 100%	24 100%	12 100%
WBC Increase, Day 1, Grade 0	25 100%	24 100%
WBC Increase, Day 8, Grade 0	25 100%	24 100%
WBC Increase, Day 22, Grade 0	25 100%	24 100%	12 100%
WBC Increase, Day 50, Grade 0	25 100%	24 100%	11 91.7%

Adverse Events

Time Frame	Solicited AEs were collected within the 7-day post-booster period. Unsolicited AEs were collected within the 21-day post-booster or within the 29-day post-challenge period. SAEs were collected from Day 1 up to study conclusion (Day 190).
Arm/Group Title	P-Fx Group		NP-Fx Group		Infectivity Control Group
Arm/Group Description	Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.		Healthy subjects, between and including 18 and 55 years of age, vaccinated with RTS,S/AS01 vaccine (different doses/formulations) and not protected following the first challenge at the time of the MALARIA-092 study (NCT03162614), who received, in the current study, a fractional (Fx) booster dose of RTS,S/AS01E 12 months after completion of the vaccination course in the Malaria-092 study, and underwent sporozoite challenge.		Healthy subjects, between and including 18 and 55 years of age, who did not receive, in the current study, any immunization but underwent sporozoite challenge.
All Cause Mortality
	P-Fx Group		NP-Fx Group		Infectivity Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/24 (0%)		0/12 (0%)
Serious Adverse Events
	P-Fx Group		NP-Fx Group		Infectivity Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/25 (8%)		0/24 (0%)		0/12 (0%)
Injury, poisoning and procedural complications
Hypobarism	1/25 (4%)	1	0/24 (0%)	0	0/12 (0%)	0
Injury	1/25 (4%)	1	0/24 (0%)	0	0/12 (0%)	0
Road traffic accident	1/25 (4%)	1	0/24 (0%)	0	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	P-Fx Group		NP-Fx Group		Infectivity Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/25 (84%)		22/24 (91.7%)		12/12 (100%)
Gastrointestinal disorders
Nausea	1/25 (4%)	2	3/24 (12.5%)	3	0/12 (0%)	0
Diarrhoea	2/25 (8%)	2	1/24 (4.2%)	1	0/12 (0%)	0
Abdominal pain	1/25 (4%)	1	1/24 (4.2%)	1	0/12 (0%)	0
Vomiting	1/25 (4%)	1	1/24 (4.2%)	1	0/12 (0%)	0
Gastrointestinal disorder	2/25 (8%)	2	0/24 (0%)	0	0/12 (0%)	0
Abdominal discomfort	0/25 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Dyspepsia	1/25 (4%)	1	0/24 (0%)	0	0/12 (0%)	0
General disorders
Injection site pain	11/25 (44%)	11	10/24 (41.7%)	10	0/12 (0%)	0
Fatigue	11/25 (44%)	11	7/24 (29.2%)	7	1/12 (8.3%)	1
Injection site erythema	8/25 (32%)	8	4/24 (16.7%)	4	0/12 (0%)	0
Injection site swelling	4/25 (16%)	4	4/24 (16.7%)	4	0/12 (0%)	0
Chills	3/25 (12%)	4	2/24 (8.3%)	2	0/12 (0%)	0
Feeling hot	2/25 (8%)	2	2/24 (8.3%)	2	0/12 (0%)	0
Pyrexia	3/25 (12%)	3	1/24 (4.2%)	1	0/12 (0%)	0
Malaise	1/25 (4%)	1	2/24 (8.3%)	2	0/12 (0%)	0
Peripheral swelling	1/25 (4%)	1	1/24 (4.2%)	1	0/12 (0%)	0
Thirst	0/25 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Infections and infestations
Malaria	12/25 (48%)	12	11/24 (45.8%)	11	11/12 (91.7%)	11
Upper respiratory tract infection	4/25 (16%)	4	0/24 (0%)	0	0/12 (0%)	0
Infection	0/25 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	0/25 (0%)	0	2/24 (8.3%)	2	0/12 (0%)	0
Post procedural discomfort	1/25 (4%)	1	0/24 (0%)	0	0/12 (0%)	0
Investigations
Aspartate aminotransferase increased	0/25 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	3/25 (12%)	4	0/24 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	3/25 (12%)	3	1/24 (4.2%)	1	1/12 (8.3%)	1
Myalgia	5/25 (20%)	5	0/24 (0%)	0	0/12 (0%)	0
Neck pain	1/25 (4%)	1	1/24 (4.2%)	2	0/12 (0%)	0
Musculoskeletal pain	2/25 (8%)	2	0/24 (0%)	0	0/12 (0%)	0
Joint swelling	0/25 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Muscle tightness	0/25 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Musculoskeletal stiffness	0/25 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Pain in extremity	0/25 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Joint warmth	1/25 (4%)	1	0/24 (0%)	0	0/12 (0%)	0
Nervous system disorders
Headache	9/25 (36%)	11	8/24 (33.3%)	8	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	0/25 (0%)	0	0/24 (0%)	0	2/12 (16.7%)	2
Nasal congestion	0/25 (0%)	0	2/24 (8.3%)	2	0/12 (0%)	0
Sneezing	0/25 (0%)	0	0/24 (0%)	0	1/12 (8.3%)	1
Cough	1/25 (4%)	1	1/24 (4.2%)	1	0/12 (0%)	0
Oropharyngeal pain	0/25 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Paranasal sinus discomfort	0/25 (0%)	0	1/24 (4.2%)	1	0/12 (0%)	0
Sinus congestion	1/25 (4%)	1	0/24 (0%)	0	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/25 (4%)	1	1/24 (4.2%)	1	0/12 (0%)	0
Pruritus	1/25 (4%)	1	0/24 (0%)	0	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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