MalariaPhase 2NCT03162614

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

A Phase 2 study testing RTS,S/AS01E, RTS,S/AS01B and Sporozoite-infected mosquitoes challenge. in people with Malaria, run by GlaxoSmithKline at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Malaria
What is being tested?: RTS,S/AS01E, RTS,S/AS01B and Sporozoite-infected mosquitoes challenge.
Type of treatment: Vaccines, Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 154 participants
Where: 1 siteUnited States
Study dates: 24 May 2017to 24 Sep 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
Written informed consent obtained from the subject prior to performing of any study specific procedure.
A male or female between, and including, 18 and 55 years of age at the time of enrolment.
Healthy subjects as established by medical history and clinical examination before entering into the study.
Available to participate for the duration of the study.
Female subjects of non-childbearing potential may be enrolled in the study.

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Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
Female subjects of childbearing potential may be enrolled in the study, if the subject:
has practiced adequate contraception for 30 days prior to vaccination, and
has a negative pregnancy test at enrolment, and
has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series and/or malaria challenge.

Who cannot join

Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 0), or planned use during the study period.
Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
Administration of long-acting immune-modifying drugs at any time during the study period.
Chronic use of antibiotics with antimalarial effects.
Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before the first dose.

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Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
Documented HIV-positive subject.
Previous vaccination against malaria.
History of malaria chemoprophylaxis within 60 days prior to vaccination.
Any history of malaria (for the vaccine groups).
Planned travel to malaria endemic areas during the study period.
History of splenectomy.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
Family history of congenital or hereditary immunodeficiency.
History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
History of anaphylaxis post-vaccination.
Hypersensitivity to latex.
History of any reaction or hypersensitivity likely to be exacerbated by chloroquine.
History of psoriasis and porphyria, which may be exacerbated after chloroquine treatment.
Current use of medications known to cause drug reactions to chloroquine.
History of severe reactions to mosquito bites.
Major congenital defects.
Serious chronic illness.
History of any neurological disorders or seizures.
Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route.
Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
Any abnormal baseline laboratory screening tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, hemoglobin, platelet count, total white blood cells (WBC), out of normal range as defined in the protocol.
Evidence of increased cardiovascular disease risk, "moderate" or "high", according to the National health and nutrition examination survey I criteria.
Hepatomegaly, right upper quadrant abdominal pain or tenderness.
Personal history of autoimmune disease.
Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period.
Pregnant or lactating female.
History of chronic alcohol consumption and/or drug abuse.
Female planning to become pregnant or planning to discontinue contraceptive precautions.
History of blood donation within 56 days preceding enrolment.
Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

GSK Investigational Site
Silver Spring, Maryland, 20910

Other trials in United States

About this study

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

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

Read the detailed description

Protocol Amendment 1 incorporated: additional blood sampling for assessment of parasitemia (polymerase chain reaction [PCR] testing); clarification that blood samples for both peripheral blood mononuclear cells (PBMC) and plasma will be collected for repository storage; revision of volume of whole blood samples to be taken for parasitemia assessment; clarification that urine pregnancy tests will be conducted for all females and not just those of childbearing potential; deletion of visit at Day 1 post day of challenge; clarification that RNA sequencing and not deep sequencing will be performed in this study.

Note that as a result of internal change in data standards terminology, the study data collected was converted to cDISC and the statistical analysis plan was amended accordingly. "Day 0" in the study design was replaced by "Day 1"; consequently, "Day n" was replaced by "Day n+1". Thus, the timeframes (Day 0, Day n) of Outcome Measures described in this study record are different to that denoted in the full protocol document posted.

Conditions: Malaria
Being tested: RTS,S/AS01E, RTS,S/AS01B, Sporozoite-infected mosquitoes challenge.
Keywords: healthy volunteers, Malaria, malaria vaccine, controlled human challenge, RTS,S/AS01
Medical subject headings: Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RTS,S/AS01EBiological
Subjects will receive intramuscular injection of RTS,S/AS01E.
RTS,S/AS01BBiological
Subjects will receive intramuscular injection of RTS,S/AS01B.
Sporozoite-infected mosquitoes challenge.Procedure or surgery
Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed.
The challenge occurs approximately 90 days (three months) after the last vaccination.
Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.

Study groups in NCT03162614
Study group	Role	What they receive
AduFx Group	Active comparator	Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and Month 1 and 1/5th of RTS,S/AS01B full dose at Month 7, and underwent sporozoite challenge. Receives: Biological: RTS,S/AS01B; Procedure: Sporozoite-infected mosquitoes challenge.
2PedFx Group	Experimental	Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E double dose at Month 0 and Month 1, and 1/5th of double dose RTS,S/AS01E at Month 7, and underwent sporozoite challenge. Receives: Biological: RTS,S/AS01E; Procedure: Sporozoite-infected mosquitoes challenge.
PedFx Group	Experimental	Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E full dose at Month 0 and Month 1, and 1/5th of RTS,S/AS01E full dose at Month 7, and underwent sporozoite challenge. Receives: Biological: RTS,S/AS01E; Procedure: Sporozoite-infected mosquitoes challenge.
Adu2Fx Group	Experimental	Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose at Month 1 and Month 7, and underwent sporozoite challenge. Receives: Biological: RTS,S/AS01B; Procedure: Sporozoite-infected mosquitoes challenge.
Adu1Fx Group	Active comparator	Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose administered at Month 7, and underwent sporozoite challenge. Receives: Biological: RTS,S/AS01B; Procedure: Sporozoite-infected mosquitoes challenge.
Control Group	Other	Healthy subjects, between, and including, 18 and 55 years of age, who did not receive any immunization but underwent sporozoite challenge. Receives: Procedure: Sporozoite-infected mosquitoes challenge.

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (14)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 May 201724 Sep 2018

First posted22 May 2017
Study start24 May 2017
Primary completion9 Jul 2018
Study completion24 Sep 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for MalariaStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 154 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03162614
Sponsor's protocol ID: 205081
Status last verified: Oct 2020
First submitted: 15 May 2017
Last updated: 27 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study is available via the Clinical Study Data Request site.

Publications

Moon JE, Ockenhouse C, Regules JA, Vekemans J, Lee C, Chuang I, Traskine M, Jongert E, Ivinson K, Morelle D, Komisar JL, Lievens M, Sedegah M, Garver LS, Sikaffy AK, Waters NC, Ballou WR, Ofori-Anyinam O; RTS,S Malaria Vaccine Working Group. A Phase IIa Controlled Human Malaria Infection and Immunogenicity Study of RTS,S/AS01E and RTS,S/AS01B Delayed Fractional Dose Regimens in Malaria-Naive Adults. J Infect Dis. 2020 Oct 13;222(10):1681-1691. doi: 10.1093/infdis/jiaa421.
PubMed 32687161
Spreng RL, Seaton KE, Lin L, Hilliard S, Horn GQ, Abraha M, Deal AW, Li K, Carnacchi AJ, Feeney E, Shabbir S, Zhang L, Bekker V, Mudrak SV, Dutta S, Mercer LD, Gregory S, King CR, Wille-Reece U, Jongert E, Kisalu NK, Tomaras GD, Dennison SM. Identification of RTS,S/AS01 vaccine-induced humoral biomarkers predictive of protection against controlled human malaria infection. JCI Insight. 2024 Oct 8;9(19):e178801. doi: 10.1172/jci.insight.178801.
PubMed 39377226

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy, Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Various Dose Schedules in a Sporozoite Challenge Model in Healthy Malaria-naïve Adults
ClinicalTrials.gov ID: NCT03162614
Acronym / sponsor ID: 205081
Conditions: Malaria
Keywords: healthy volunteers, Malaria, malaria vaccine, controlled human challenge, RTS,S/AS01
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 154 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Collaborators: The PATH Malaria Vaccine Initiative (MVI)
Study start: 24 May 2017 (actual)
Primary completion: 9 Jul 2018 (actual)
Study completion: 24 Sep 2018 (actual)
First posted: 22 May 2017 (actual)
Results: Posted 24 Jul 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
AduFx Group	Active comparator	Biological: RTS,S/AS01B, Procedure: Sporozoite-infected mosquitoes challenge.Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and Month 1 and 1/5th of RTS,S/AS01B full dose at Month 7, and underwent sporozoite challenge.
2PedFx Group	Experimental	Biological: RTS,S/AS01E, Procedure: Sporozoite-infected mosquitoes challenge.Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E double dose at Month 0 and Month 1, and 1/5th of double dose RTS,S/AS01E at Month 7, and underwent sporozoite challenge.
PedFx Group	Experimental	Biological: RTS,S/AS01E, Procedure: Sporozoite-infected mosquitoes challenge.Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E full dose at Month 0 and Month 1, and 1/5th of RTS,S/AS01E full dose at Month 7, and underwent sporozoite challenge.
Adu2Fx Group	Experimental	Biological: RTS,S/AS01B, Procedure: Sporozoite-infected mosquitoes challenge.Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose at Month 1 and Month 7, and underwent sporozoite challenge.
Adu1Fx Group	Active comparator	Biological: RTS,S/AS01B, Procedure: Sporozoite-infected mosquitoes challenge.Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose administered at Month 7, and underwent sporozoite challenge.
Control Group	Other	Procedure: Sporozoite-infected mosquitoes challenge.Healthy subjects, between, and including, 18 and 55 years of age, who did not receive any immunization but underwent sporozoite challenge.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
Written informed consent obtained from the subject prior to performing of any study specific procedure.
A male or female between, and including, 18 and 55 years of age at the time of enrolment.
Healthy subjects as established by medical history and clinical examination before entering into the study.
Available to participate for the duration of the study.

Key exclusion criteria (39 listed)

Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 0), or planned use during the study period.
Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
Administration of long-acting immune-modifying drugs at any time during the study period.
Chronic use of antibiotics with antimalarial effects.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RTS,S/AS01ESubjects will receive intramuscular injection of RTS,S/AS01E.	Biological	2PedFx Group, PedFx Group
RTS,S/AS01BSubjects will receive intramuscular injection of RTS,S/AS01B.	Biological	Adu1Fx Group, Adu2Fx Group, AduFx Group
Sporozoite-infected mosquitoes challenge.Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed. The challenge occurs approximately 90 days (three months) after the last vaccination. Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.	Procedure or surgery	2PedFx Group, Adu1Fx Group, Adu2Fx Group, AduFx Group, Control Group, PedFx Group

Primary outcome

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

14 secondary outcomes

Time to Onset of P. Falciparum Parasitemia After Sporozoite Challenge for Each Vaccination Schedule
Time frame: Following sporozoite challenge starting 3 months after the last vaccine dose (at Day 287) for up to 28 days post-challenge (at Day 315).
Anti-Circumsporozoite (Anti-CS) Repeat Region Antibody Concentrations
Time frame: At Day 1, Day 59, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from AduFx, 2PedFx, PedFx, and Adu2Fx Groups. At Day 1, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from Adu1Fx Group
Anti-Hepatitis B (Anti-HBs) Immunoglobulin G (IgG) Antibody Concentrations
Time frame: At Day 1, Day 59, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from AduFx, 2PedFx, PedFx, and Adu2Fx Groups. At Day 1, Day 197, Day 227, Day 287, Day 315, and Day 377 for subjects from Adu1Fx Group
Number of Subjects With Any Solicited Local Symptoms
Time frame: Within the 7-day period (Days 1-7) after dose 1, dose 2 (except for Adu1Fx Group) and dose 3.
Number of Subjects With Any Solicited General Symptoms
Time frame: Within the 7-day period (Days 1-7) after dose 1, dose 2 (except for Adu1Fx Group) and dose 3.
Number of Subjects With Any Unsolicited Adverse Events (AEs) After Any Vaccination
Time frame: Within the 30-day period (Days 1-30), after any vaccination (across doses)
Number of Subjects With Any Unsolicited AEs After Challenge
Time frame: Within the 30-day (Days 1-30) period post-challenge
Number of Subjects With Any, Fatal or Related Serious Adverse Events (SAEs) After Each Vaccination
Time frame: Within the 30-day period (Days 1-30) after any vaccination (across doses)
Number of Subjects With Any, Fatal or Related SAEs During the Whole Study Period
Time frame: From Day 1 up to study conclusion (Day 377)
Number of Subjects With Any AE and SAE Leading to Withdrawal From Further Vaccination
Time frame: From Day 1 up to study conclusion (Day 377)
Number of Subjects With Potential Immune Mediated Diseases (pIMDs)
Time frame: From Day 1 up to study conclusion (Day 377)
Number of Subjects With Meningitis
Time frame: From Day 1 up to study conclusion (Day 377)
Number of Subjects With Abnormal Laboratory Values Gradings
Time frame: At Visit 1 Screening (Day -89 to Day 1), Day 36, Day 59, Day 204, Day 227, between Day 292 & Day 313, and Day 315 for each vaccinated subject.For Infectivity Control subjects at Visit 1b Screening (Day 231 to Day 287),between Day 292 & Day 313,and Day 315
Number of Subjects With Any, Fatal or Related SAE, After Challenge
Time frame: From day of challenge (Day 287) to the end of the challenge phase (Day 315)

Results and safety

Results posted to the registry on 24 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AduFx Group	26	20
2PedFx Group	26	21
PedFx Group	26	22
Adu2Fx Group	26	19
Adu1Fx Group	26	21
Control Group	24	24

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

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

Measure	AduFx Group n = 20	2PedFx Group n = 21	PedFx Group n = 22	Adu2Fx Group n = 20	Adu1Fx Group n = 21	Control Group n = 22
Value	9	5	8	9	15	22

AduFx Group vs Control Group: Vaccine efficacy rate: 55 (95% CI 27 to 72), p <.001, Fisher Exact
2PedFx Group vs Control Group: Vaccine efficacy rate: 76 (95% CI 49 to 89), p <.001, Fisher Exact
PedFx Group vs Control Group: Vaccine efficacy rate: 64 (95% CI 37 to 79), p <.001, Fisher Exact

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

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: Solicited adverse events were reported during the 7-day follow-up period and unsolicited adverse events during the 30-day follow-up period after vaccination. Serious adverse events were reported during the whole study period (from Day 1 up to study conclusion at Day 377).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AduFx Group	0 of 26 (0%)	26 of 26 (100%)	0 of 26
2PedFx Group	0 of 26 (0%)	25 of 26 (96.2%)	0 of 26
PedFx Group	0 of 26 (0%)	23 of 26 (88.5%)	0 of 26
Adu2Fx Group	0 of 26 (0%)	25 of 26 (96.2%)	0 of 26
Adu1Fx Group	0 of 26 (0%)	24 of 26 (92.3%)	0 of 26
Control Group	0 of 24 (0%)	0 of 24 (0%)	0 of 24

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 32687161Moon JE, Ockenhouse C, Regules JA, Vekemans J, Lee C, Chuang I, Traskine M, Jongert E, Ivinson K, Morelle D, Komisar JL, Lievens M, Sedegah M, Garver LS, Sikaffy AK, Waters NC, Ballou WR, Ofori-Anyinam O; RTS,S Malaria Vaccine Working Group. A Phase IIa Controlled Human Malaria Infection and Immunogenicity Study of RTS,S/AS01E and RTS,S/AS01B Delayed Fractional Dose Regimens in Malaria-Naive Adults. J Infect Dis. 2020 Oct 13;222(10):1681-1691. doi: 10.1093/infdis/jiaa421.
Derived from this study: PubMed 39377226Spreng RL, Seaton KE, Lin L, Hilliard S, Horn GQ, Abraha M, Deal AW, Li K, Carnacchi AJ, Feeney E, Shabbir S, Zhang L, Bekker V, Mudrak SV, Dutta S, Mercer LD, Gregory S, King CR, Wille-Reece U, Jongert E, Kisalu NK, Tomaras GD, Dennison SM. Identification of RTS,S/AS01 vaccine-induced humoral biomarkers predictive of protection against controlled human malaria infection. JCI Insight. 2024 Oct 8;9(19):e178801. doi: 10.1172/jci.insight.178801.
Individual participant dataSharing planned: Yes. IPD for this study is available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RTS,S/AS01E, RTS,S/AS01B and Sporozoite-infected mosquitoes challenge. in people with Malaria, run by GlaxoSmithKline at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With at Least One Occurrence of Plasmodium Falciparum (P. Falciparum) Parasitemia for Each Vaccination Schedule Versus Infectivity Controls (time frame: Following sporozoite challenge starting 3 months after the last vaccine dose (Day 287) for up to 28 days post-challenge (Day 315).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03162614, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2020.