Last updated: 11/03/2018 09:03:46

Efficacy of RTS,S/AS01 vaccine against episodes of malaria due to P. falciparum infection in children.

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GSK study ID
106464
See study documents
Clinicaltrials.gov ID
NCT00380393
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A study of the efficacy against episodes of clinical malaria due to P. falciparum infection of GSK Biologicals candidate vaccine RTS,S/AS01, administered according to a 0,1,2-months schedule in children aged 5 to 17 months living in Tanzania & Kenya
Trial description: This phase IIb trial is being done to find out if the RTS,S/AS01 vaccine helps to prevent children from falling ill with malaria and to evaluate vaccine safety.
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Primary purpose:
Prevention
Trial design:
Parallel Assignment
Masking:
Double (Care Provider, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:

Frequency of first case of malaria meeting the primary case definition

Timeframe: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Secondary outcomes:

Frequency of first case malaria meeting the secondary case definition

Timeframe: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Multiple events of malaria meeting the primary case definition

Timeframe: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Multiple events of malaria meeting the secondary case definition

Timeframe: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Number of subjects positive for P. falciparum parasitaemia

Timeframe: At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Geometric mean density of asexual P. falciparum parasite

Timeframe: At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Haemoglobin values at Cross-Sectional Visit

Timeframe: At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Number of subjects with any and Grade 3 solicited local symptoms

Timeframe: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

Number of subjects with any, Grade 3 and related solicited general symptoms

Timeframe: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

Number of subjects with any unsolicited adverse events (AEs)

Timeframe: Within the 30-day (Days 0-29) post-vaccination follow-up period

Number of subjects with serious adverse events (SAEs)

Timeframe: Throughout the study period (Day 0 - Month 14)

Number of subjects with hemoglobin values outside normal ranges with toxicity grades

Timeframe: At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Number of subjects with white blood cell (WBC) values outside normal ranges with toxicity grades

Timeframe: At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Number of subjects with platelet values outside normal ranges with toxicity grades

Timeframe: At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Number of subjects with Alanine aminotransferase (ALT) values outside normal ranges with toxicity grades

Timeframe: At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Number of subjects with Creatinine values outside normal ranges with toxicity grades

Timeframe: At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Concentration of antibodies against the P. falciparum circumsporozoite (CS) repeat domain (anti-CS)

Timeframe: At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Concentration of antibodies against hepatitis B surface antigen (anti-HBs)

Timeframe: At Day 0 and at Month 3

Frequency of cluster of differentiation 4 (CD4+) CS-specific T-cells

Timeframe: Prior to vaccination (Day 0)

Frequency of cluster of differentiation 8 (CD8+) CS-specific T-cells

Timeframe: Prior to vaccination (Day 0)

Frequency of cluster of differentiation 4 (CD4+) CS-specific T-cells

Timeframe: At Month 3

Frequency of cluster of differentiation 8 (CD8+) CS-specific T-cells

Timeframe: At Month 3

Interventions:
  • Biological/vaccine: GSK malaria vaccine 257049 Vaccine
  • Biological/vaccine: Sanofi-Pasteur’s Human Diploid Cell Rabies Vaccine
    • Enrollment:
    894
    Primary completion date:
    2008-15-08
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Bejon P et al. (2008) Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. N Engl J Med. 359(24): 2521-2532.
    Lang TA et al. (2012) Approaching the community about screening children for a multicentre malaria vaccine trial. International Health Journal. 4(1):47-54.
    Lusingu J et al. (2010) Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian children. PLoS One. 5(11):e14090.
    Olotu A et al. (2011) Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial. Lancet Infect Dis. 11(2):102-109. Epub
    Bejon P et al. (2011) Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children. J Infect Dis. 204(1):9-18.
    Bejon P et al. (2011) Serological evidence of discrete spatial clusters of Plasmodium falciparum parasites. PLoS One. 6(6):e21711.
    Miura K et al. (2014) Effect of ingested human antibodies induced by RTS, S/AS01 malaria vaccination in children on Plasmodium falciparum oocyst formation and sporogony in mosquitoes. Malar J. 13:263.
    Olotu A et al. (2011) Circumsporozoite-specific T cell responses in children vaccinated with RTS,S/AS01E and protection against P falciparum clinical malaria. PLoS One. 6(10):e25786.
    Olotu A et al. (2011) Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial. Lancet Infect Dis. 11(2):102-109.
    Olotu A et al. (2014) Avidity of Anti-Circumsporozoite antibodies following vaccination with RTS,S/AS01E in young children. PLoS One. 9(12):e115126.
    Olotu A et al. (2016) Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children. N Engl J Med. 374(26):2519-2529.
    Medical condition
    Malaria
    Product
    SB257049
    Collaborators
    Not applicable
    Study date(s)
    January 2007 to November 2008
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    5 - 17 months
    Accepts healthy volunteers
    Yes
    • A male or female child of between 5 months and 17 months of age at the time of first vaccination.
    • Written or oral, signed or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child..
    • Acute disease at the time of enrolment.
    • Serious acute or chronic illness determined by clinical or physical examination and laboratory screening tests.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • A male or female child of between 5 months and 17 months of age at the time of first vaccination.
    • Written or oral, signed or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child..
    • Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
    Exclusion criteria:
    • Acute disease at the time of enrolment.
    • Serious acute or chronic illness determined by clinical or physical examination and laboratory screening tests.
    • Laboratory screening tests for haemoglobin, total white cell count, platelets, ALT and creatinine out of acceptable limits.
    • Planned administration/administration of a vaccine not foreseen by the study within 30 days of the first dose of vaccine(s) with the exception of tetanus toxoid or scheduled diphtheria, pertussis or measles vaccine.
    • Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
    • Administration of immunoglobulins, blood transfusions or other blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
    • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose
    • Previous participation in any other malaria vaccine trial.
    • Simultaneous participation in any other clinical trial.
    • Same sex twin.
    • History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunizations.
    • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
    • Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    Amani, Tanga, Tanzania
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Kilifi, Kenya, 80108
    Status
    Study Complete
    Contact us

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2008-15-08
    Actual study completion date
    2008-11-11

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

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