MalariaPhase 2NCT01366534

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

A Phase 2 study testing Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01), GSK Biologicals' malaria vaccine 257049 (2 doses) and GSK Biologicals' malaria vaccine 257049 (3 doses) 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

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. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Malaria
What is being tested?: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01), GSK Biologicals' malaria vaccine 257049 (2 doses) and GSK Biologicals' malaria vaccine 257049 (3 doses)
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 67 participants
Where: 1 siteUnited States
Study dates: 10 Aug 2011to 3 Jul 2012
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 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

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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.

Who cannot join

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.

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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.

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: 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

Read the 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.

Conditions: Malaria
Being tested: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01), GSK Biologicals' malaria vaccine 257049 (2 doses), GSK Biologicals' malaria vaccine 257049 (3 doses), Sporozoite challenge
Keywords: safety, Vaccine, Phase 1/2, immunogenicity, Malaria, efficacy, sporozoite challenge
Medical subject headings: Malaria

What participants receive

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

Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01)Biological
One dose will be administered intramuscularly at Study Day 0.
GSK Biologicals' malaria vaccine 257049 (2 doses)Biological
Two doses will be administered intramuscularly at monthly intervals
GSK Biologicals' malaria vaccine 257049 (3 doses)Biological
Three doses will be administered intramuscularly at monthly intervals
Sporozoite challengeOther
Subjects were challenged with sporozoite-infected mosquitoes to determine whether immune protective response had been induced by vaccination.

Study groups in NCT01366534
Study group	Role	What they receive
Ad35.CS.01 Group	Experimental	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. Receives: Biological: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01); Biological: GSK Biologicals' malaria vaccine 257049 (2 doses)
GSK257049 Group	Experimental	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. Receives: Biological: GSK Biologicals' malaria vaccine 257049 (3 doses)
Control Group	Experimental	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. Receives: Other: Sporozoite challenge

What is being measured

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

Number of Subjects With Plasmodium Falciparum Parasitemia Following Sporozoite Challenge
1. falciparum parasitemia was defined as a positive blood slide.
Measured: 28 days following sporozoite challenge (Day 105)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, pain that prevented normal every day activities. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Measured: Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
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.
Measured: Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination
Number of Subjects With Any Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Measured: Within the 30-day (Day 0 - Day 29) follow-up period post-vaccination
Number of Subjects With Any Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Measured: Within the 30-day (Day 0 - Day 29) follow-up period post-challenge
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Measured: Throughout the study period (Day 0 - Day 236)

Secondary outcomes (9)

Number of Days Until the Onset of P. Falciparum Parasitemia Following Sporozoite Challenge
The onset of P. falciparum parasitemia was defined by a positive blood slide.
Measured: From day of challenge (Day 0) up to 159 days post-challenge
Anti-circumsporozoite Protein (Anti-CS) Antibody Titers
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.
Measured: 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)
Anti-hepatitis B (Anti-HBs) Antibody Titers
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.
Measured: 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)
Anti-Adenovirus Type 35 (Ad35) Neutralizing Antibody Titers at Specified Time Points
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.
Measured: 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)
Frequency of CS (Total CS or Repeat)-Specific CD4+ T-cells
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.
Measured: 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)
Frequency of CS (Total CS or Repeat)-Specific CD8+ T Cells
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.
Measured: 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)
Frequency of HBs-specific CD4+ T-cells
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.
Measured: 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)
Frequency of CS-specific T-cells Producing IFN-γ
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.
Measured: 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)
Frequency of CS-specific T-cells Producing IFN-γ
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).
Measured: 14 days post-dose 1 (Day 14)

Timeline

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

10 Aug 20113 Jul 2012

First posted6 Jun 2011 (estimated)
Study start10 Aug 2011
Primary completion27 Feb 2012
Study completion3 Jul 2012

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 (3)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: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 67 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01366534
Sponsor's protocol ID: 114460
Status last verified: Jun 2019
First submitted: 2 Jun 2011
Last updated: 18 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: Yes: Patient-level data for this study is available via the Clinical Study Data Request site (click on the link provided below)

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-Naive Adults. PLoS One. 2015 Jul 6;10(7):e0131571. doi: 10.1371/journal.pone.0131571. eCollection 2015.
PubMed 26148007
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
Li K, Dodds M, Spreng RL, Abraha M, Huntwork RHC, Dahora LC, Nyanhete T, Dutta S, Wille-Reece U, Jongert E, Ewer KJ, Hill AVS, Jin C, Hill J, Pollard AJ, Munir Alam S, Tomaras GD, Dennison SM. A tool for evaluating heterogeneity in avidity of polyclonal antibodies. Front Immunol. 2023 Feb 16;14:1049673. doi: 10.3389/fimmu.2023.1049673. eCollection 2023.
PubMed 36875126

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 18 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01366534
Acronym / sponsor ID: 114460
Conditions: Malaria
Keywords: safety, Vaccine, Phase 1/2, immunogenicity, Malaria, efficacy, sporozoite challenge
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 67 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Collaborators: The PATH Malaria Vaccine Initiative (MVI), Crucell Holland BV
Study start: 10 Aug 2011 (actual)
Primary completion: 27 Feb 2012 (actual)
Study completion: 3 Jul 2012 (actual)
First posted: 6 Jun 2011 (estimated)
Results: Posted 9 Jun 2017

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: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Ad35.CS.01 Group	Experimental	Biological: Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01), Biological: GSK Biologicals' malaria vaccine 257049 (2 doses)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.
GSK257049 Group	Experimental	Biological: GSK Biologicals' malaria vaccine 257049 (3 doses)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.
Control Group	Experimental	Other: Sporozoite challengeHealthy 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.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

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.

Key exclusion criteria (35 listed)

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.

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
Crucell's replication deficient adenovirus type 35 circumsporozoite malaria vaccine (Ad35.CS.01)One dose will be administered intramuscularly at Study Day 0.	Biological	Ad35.CS.01 Group
GSK Biologicals' malaria vaccine 257049 (2 doses)Two doses will be administered intramuscularly at monthly intervals	Biological	Ad35.CS.01 Group
GSK Biologicals' malaria vaccine 257049 (3 doses)Three doses will be administered intramuscularly at monthly intervals	Biological	GSK257049 Group
Sporozoite challengeSubjects were challenged with sporozoite-infected mosquitoes to determine whether immune protective response had been induced by vaccination.	Other	Control Group

Primary outcome

Number of Subjects With Plasmodium Falciparum Parasitemia Following Sporozoite Challenge
Time frame: 28 days following sporozoite challenge (Day 105)
P. falciparum parasitemia was defined as a positive blood slide.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: 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.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: 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.
Number of Subjects With Any Unsolicited Adverse Events (AEs)
Time frame: 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.
Number of Subjects With Any Unsolicited Adverse Events (AEs)
Time frame: 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.
Number of Subjects With Serious Adverse Events (SAEs)
Time frame: 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.

9 secondary outcomes

Number of Days Until the Onset of P. Falciparum Parasitemia Following Sporozoite Challenge
Time frame: From day of challenge (Day 0) up to 159 days post-challenge
Anti-circumsporozoite Protein (Anti-CS) Antibody Titers
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)
Anti-hepatitis B (Anti-HBs) Antibody Titers
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)
Anti-Adenovirus Type 35 (Ad35) Neutralizing Antibody Titers at Specified Time Points
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)
Frequency of CS (Total CS or Repeat)-Specific CD4+ T-cells
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)
Frequency of CS (Total CS or Repeat)-Specific CD8+ T Cells
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)
Frequency of HBs-specific CD4+ T-cells
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)
Frequency of CS-specific T-cells Producing IFN-γ
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)
Frequency of CS-specific T-cells Producing IFN-γ
Time frame: 14 days post-dose 1 (Day 14)

Results and safety

Results posted to the registry on 9 Jun 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ad35.CS.01 Group	28	26
GSK257049 Group	27	25
Control Group	12	12

Primary outcome: Number of Subjects With Plasmodium Falciparum Parasitemia Following Sporozoite Challenge

Time frame: 28 days following sporozoite challenge (Day 105). Count of participants. Unit: Participants

Measure	Ad35.CS.01 Group n = 25	GSK257049 Group n = 21	Control Group n = 12
Value	14	10	12

Ad35.CS.01 Group vs GSK257049 Group: Vaccine Efficacy Maentel-Haenzel Method: -17.6 (95% CI -107.4 to 33.3), p = 0.7675, 2-sided Fisher Exact test
Ad35.CS.01 Group vs Control Group: Vaccine Efficacy: Maentel-Haenzel Method: 44.0 (95% CI 20.7 to 60.4), p = 0.0066, 2-sided Fisher Exact test
GSK257049 Group vs Control Group: Vaccine Efficacy: Maentel-Haenzel Method: 52.4 (95% CI 25.4 to 69.6), p = 0.0021, 2-sided Fisher Exact test

Population analysed: 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.

Primary outcome: Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Time frame: Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination. Count of participants. Unit: Participants

Measure	Ad35.CS.01 Group n = 28	GSK257049 Group n = 27
Any Pain, Dose 1	25	25
Grade 3 Pain, Dose 1	0	1
Any Redness, Dose 1	7	4
Grade 3 Redness, Dose 1	0	0
Any Swelling, Dose 1	6	6
Grade 3 Swelling, Dose 1	0	0
Any Pain, Dose 2	26	20
Grade 3 Pain, Dose 2	1	0

Population analysed: 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.

Primary outcome: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

Time frame: Within the 7-day (Day 0 - Day 6) follow-up period post-vaccination. Count of participants. Unit: Participants

Measure	Ad35.CS.01 Group n = 28	GSK257049 Group n = 27
Any Chills, Dose 1	7	3
Related Chills, Dose 1	7	3
Grade 3 Chills, Dose 1	2	1
Any Fatigue, Dose 1	9	11
Related Fatigue, Dose 1	9	8
Grade 3 Fatigue, Dose 1	0	1
Any Gastrointestinal symptoms, Dose 1	3	4
Related Gastrointestinal symptoms, Dose 1	3	3

Primary outcome: Number of Subjects With Any Unsolicited Adverse Events (AEs)

Time frame: Within the 30-day (Day 0 - Day 29) follow-up period post-vaccination. Count of participants. Unit: Participants

Measure	Ad35.CS.01 Group n = 28	GSK257049 Group n = 27
Value	23	21

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

9 secondary outcomes are reported in the full results.

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).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ad35.CS.01 Group	0 of 28 (0%)	27 of 28 (96.4%)	0 of 28
GSK257049 Group	0 of 27 (0%)	27 of 27 (100%)	0 of 27
Control Group	0 of 12 (0%)	12 of 12 (100%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26148007Ockenhouse 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-Naive Adults. PLoS One. 2015 Jul 6;10(7):e0131571. doi: 10.1371/journal.pone.0131571. eCollection 2015.
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.
Derived from this study: PubMed 36875126Li K, Dodds M, Spreng RL, Abraha M, Huntwork RHC, Dahora LC, Nyanhete T, Dutta S, Wille-Reece U, Jongert E, Ewer KJ, Hill AVS, Jin C, Hill J, Pollard AJ, Munir Alam S, Tomaras GD, Dennison SM. A tool for evaluating heterogeneity in avidity of polyclonal antibodies. Front Immunol. 2023 Feb 16;14:1049673. doi: 10.3389/fimmu.2023.1049673. eCollection 2023.
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Patient-level data for this study is available via the Clinical Study Data Request site (click on the link provided below)

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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?

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 35 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 18 Jun 2019. 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 9 Jun 2017). 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 Plasmodium Falciparum Parasitemia Following Sporozoite Challenge (time frame: 28 days following sporozoite challenge (Day 105)). The study lists 6 primary outcomes in all. 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 NCT01366534, which also lists 3 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 18 Jun 2019.