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MalariaPhase 2NCT00380393

Efficacy of RTS,S/AS01 Vaccine Against Episodes of Malaria Due to P. Falciparum Infection in Children.

A Phase 2 study testing GSK malaria vaccine 257049 Vaccine and Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine in people with Malaria, run by GlaxoSmithKline at 2 sites in 2 countries.

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 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. Read more about this study

Who is it for?
Ages 5 to 17 monthsHealthy volunteers can take part
Conditions the study is for
Malaria
What is being tested?
GSK malaria vaccine 257049 Vaccine and Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
894 participants
Where
2 sitesin 2 countries
Study dates
3 Jan 2007to 11 Nov 2008
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 5 to 17 months
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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 locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Kenya1 site
  • GSK Investigational Site

    Kilifi, 80108

Other trials in Kenya

Tanzania1 site
  • GSK Investigational Site

    Amani, Tanga

Other trials in Tanzania

About this study

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

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.

Conditions
Malaria
Being tested
GSK malaria vaccine 257049 Vaccine, Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine
Keywords
Malaria, Plasmodium, RTS, S/AS01, Falciparum
Medical subject headings
Malaria

What participants receive

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

  • GSK malaria vaccine 257049 VaccineBiological

    Also called RTS, S/AS01E vaccine

    3 dose intramuscular injection

  • Sanofi-Pasteur's Human Diploid Cell Rabies VaccineBiological

    3 dose intramuscular injection

Study groups in NCT00380393
Study groupRoleWhat they receive
GSK257049 GroupExperimentalMale or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Receives: Biological: GSK malaria vaccine 257049 Vaccine
Rabipur GroupActive comparatorMale or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Receives: Biological: Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine

What is being measured

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

  1. Frequency of First Case of Malaria Meeting the Primary Case Definition

    The first case of malaria meeting the primary case definition was defined as the first or only episodes with the presence of Plasmodium falciparum asexual parasitemia above (>) 2500 per microliter (μL) and the presence of fever greater than or equal to (≥) 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of first case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

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

Secondary outcomes (21)
  1. Frequency of First Case Malaria Meeting the Secondary Case Definition

    The first case of malaria meeting the secondary case definition was defined as the first or only episodes with the presence of P.falciparum asexual parasitemia > 0 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of first case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

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

  2. Multiple Events of Malaria Meeting the Primary Case Definition

    Multiple episodes of malaria meeting the primary case definition was defined as episodes with the presence of P.falciparum asexual parasitemia > 25000 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of primary case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

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

  3. Multiple Events of Malaria Meeting the Secondary Case Definition

    Multiple episodes of malaria meeting the secondary case definition was defined as episodes with the presence of P.falciparum asexual parasitemia > 0 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of secondary case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

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

  4. Number of Subjects Positive for P. Falciparum Parasitaemia

    Measured: 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)

  5. Geometric Mean Density of Asexual P. Falciparum Parasite

    Estimates of asexual P. falciparum parasite density were made at the investigator's sites according to laboratory standard operating procedures. Parasite density was presented as a geometric mean (GMean), expressed in parasite per microliters (μL).

    Measured: 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)

  6. Haemoglobin Values at Cross-Sectional Visit

    Haemoglobin values are expressed in grams per deciliter (g/dL).

    Measured: 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)

  7. Number of Subjects With Any and Grade 3 Solicited Local Symptoms

    Assessed solicited local symptoms were pain and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 swelling = swelling spreading beyond 20 millimeters (mm) of injection site.

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

  8. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

    Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom 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: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

  9. 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 (Days 0-29) post-vaccination follow-up period

  10. 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 - Month 14)

  11. Number of Subjects With Hemoglobin Values Outside Normal Ranges With Toxicity Grades

    Definitions for toxicity grading for hemoglobin were: Normal Hemoglobin = equal to or above (≥) 8.0 g/dL; Grade 1 Hemoglobin = under (<) 8.0 g/dL and above (>) 6.0 g/dL.; Grade 2 Hemoglobin = under (<) 6.0 g/dL.

    Measured: 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)

  12. Number of Subjects With White Blood Cell (WBC) Values Outside Normal Ranges With Toxicity Grades

    Definitions for toxicity grading for WBC were: Normal WBC = ≥ 4.0 x 10^3 cells per microliters (cells/μL) or < 17 x 10^3 cells /μL; Grade 1 WBC = 2.5 to 4.0 x 10^3 cells/μL.

    Measured: 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)

  13. Number of Subjects With Platelet Values Outside Normal Ranges With Toxicity Grades

    Definitions for toxicity grading for platelets were: Normal Platelets = ≥ 75 x 10^3 cells/μL; Grade 1 Platelets = 50 to 74 x 10^3 /μL; Grade 2 Platelets = 25 to 49 x 10^3 /μL; Grade 3 Platelets = < 25 x 10^3 /μL.

    Measured: 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)

  14. Number of Subjects With Alanine Aminotransferase (ALT) Values Outside Normal Ranges With Toxicity Grades

    Definition for toxicity grading for ALT were: Normal ALT = ≤ 60 international units per liter (IU/L); Grade 1 ALT = 1.1 to 2.5 x Upper Limit of Normal (ULN); Grade 2 ALT = 2.6 to 5.0 x ULN.

    Measured: 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)

  15. Number of Subjects With Creatinine Values Outside Normal Ranges With Toxicity Grades

    Definition for toxicity grading for creatinine were: Normal Creatinine = ≤ 60 micromols per liter (μmol/L); Grade 1 Creatinine = 1.1 to 1.5 x ULN; Grade 2 Creatinine = 1.6 to 3.0 x ULN.

    Measured: 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)

  16. Concentration of Antibodies Against the P. Falciparum Circumsporozoite (CS) Repeat Domain (Anti-CS)

    Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL).

    Measured: 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)

  17. Concentration of Antibodies Against Hepatitis B Surface Antigen (Anti-HBs)

    Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL).

    Measured: At Day 0 and at Month 3

  18. Frequency of Cluster of Differentiation 4 (CD4+) CS-specific T-cells

    T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).

    Measured: Prior to vaccination (Day 0)

  19. Frequency of Cluster of Differentiation 8 (CD8+) CS-specific T-cells

    T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).

    Measured: Prior to vaccination (Day 0)

  20. Frequency of Cluster of Differentiation 4 (CD4+) CS-specific T-cells

    T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).

    Measured: At Month 3

  21. Frequency of Cluster of Differentiation 8 (CD8+) CS-specific T-cells

    T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).

    Measured: At Month 3

Timeline

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

  1. First posted26 Sep 2006 (estimated)
  2. Study start3 Jan 2007
  3. Primary completion15 Aug 2008
  4. Study completion11 Nov 2008

Resources

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
Double blind
Who is masked
Care provider, Outcomes assessor
Enrolment
894 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00380393
Sponsor's protocol ID
106464
Status last verified
Nov 2017
First submitted
25 Sep 2006
Last updated
3 Jul 2018
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • Bejon P, Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, Mshamu S, Lang T, Gould J, Dubois MC, Demoitie MA, Stallaert JF, Vansadia P, Carter T, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Ballou WR, Cohen J, Riley EM, Lemnge MM, Marsh K, von Seidlein L. Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. N Engl J Med. 2008 Dec 11;359(24):2521-32. doi: 10.1056/NEJMoa0807381. Epub 2008 Dec 8.

    PubMed 19064627
  • Lang TA, Gould J, von Seidlein L, Lusingu JP, Mshamu S, Ismael S, Liheluka E, Kamuya D, Mwachiro D, Olotu A, Njuguna P, Bejon P, Marsh V, Molyneux C. Approaching the community about screening children for a multicentre malaria vaccine trial. Int Health. 2012 Mar;4(1):47-54. doi: 10.1016/j.inhe.2011.10.003.

    PubMed 24030880
  • Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, Olivier A, Benns S, Olomi R, Msham S, Lang T, Gould J, Hallez K, Guerra Y, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Dekker D, Malle L, Ismael S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Ballou WR, Cohen J, Riley EM, Lemnge MM, Marsh K, Bejon P, von Seidlein L. Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children. PLoS One. 2010 Nov 29;5(11):e14090. doi: 10.1371/journal.pone.0014090.

    PubMed 21124768
  • Olotu A, Lusingu J, Leach A, Lievens M, Vekemans J, Msham S, Lang T, Gould J, Dubois MC, Jongert E, Vansadia P, Carter T, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Lapierre D, Ballou WR, Cohen J, Lemnge MM, Peshu N, Marsh K, Riley EM, von Seidlein L, Bejon P. 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. 2011 Feb;11(2):102-9. doi: 10.1016/S1473-3099(10)70262-0. Epub 2011 Jan 13.

    PubMed 21237715
  • Olotu A, Clement F, Jongert E, Vekemans J, Njuguna P, Ndungu FM, Marsh K, Leroux-Roels G, Bejon P. Avidity of anti-circumsporozoite antibodies following vaccination with RTS,S/AS01E in young children. PLoS One. 2014 Dec 15;9(12):e115126. doi: 10.1371/journal.pone.0115126. eCollection 2014.

    PubMed 25506706
  • Warimwe GM, Fletcher HA, Olotu A, Agnandji ST, Hill AV, Marsh K, Bejon P. Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data. BMC Med. 2013 Aug 21;11:184. doi: 10.1186/1741-7015-11-184.

    PubMed 23962071
  • Horowitz A, Hafalla JC, King E, Lusingu J, Dekker D, Leach A, Moris P, Cohen J, Vekemans J, Villafana T, Corran PH, Bejon P, Drakeley CJ, von Seidlein L, Riley EM. Antigen-specific IL-2 secretion correlates with NK cell responses after immunization of Tanzanian children with the RTS,S/AS01 malaria vaccine. J Immunol. 2012 May 15;188(10):5054-62. doi: 10.4049/jimmunol.1102710. Epub 2012 Apr 13.

    PubMed 22504653

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK malaria vaccine 257049 Vaccine and Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine in people with Malaria, run by GlaxoSmithKline at 2 sites in 2 countries.

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 3 inclusion and 13 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 3 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Kenya, Tanzania. 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 3 Jul 2018). 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?

Frequency of First Case of Malaria Meeting the Primary Case Definition (time frame: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)). 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 NCT00380393, which also lists 7 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 3 Jul 2018.

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