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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00380393
Recruitment Status : Completed
First Posted : September 26, 2006
Results First Posted : July 3, 2018
Last Update Posted : July 3, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief 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.


Condition or disease Intervention/treatment Phase
Malaria Biological: GSK malaria vaccine 257049 Vaccine Biological: Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 894 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Care Provider, Outcomes Assessor)
Primary Purpose: Prevention
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
Actual Study Start Date : January 3, 2007
Actual Primary Completion Date : August 15, 2008
Actual Study Completion Date : November 11, 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: GSK257049 Group
Male 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.
Biological: GSK malaria vaccine 257049 Vaccine
3 dose intramuscular injection
Other Names:
  • RTS
  • S/AS01E vaccine

Active Comparator: Rabipur Group
Male 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.
Biological: Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine
3 dose intramuscular injection




Primary Outcome Measures :
  1. 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) ]
    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.


Secondary Outcome Measures :
  1. Frequency of First Case Malaria Meeting the Secondary Case Definition [ Time Frame: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months) ]
    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.

  2. Multiple Events 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) ]
    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.

  3. Multiple Events of Malaria Meeting the Secondary Case Definition [ Time Frame: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months) ]
    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.

  4. Number of Subjects Positive for P. Falciparum Parasitaemia [ Time Frame: 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 [ Time Frame: 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) ]
    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).

  6. Haemoglobin Values at Cross-Sectional Visit [ Time Frame: 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 are expressed in grams per deciliter (g/dL).

  7. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses ]
    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.

  8. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses ]
    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.

  9. Number of Subjects With Any Unsolicited Adverse Events (AEs) [ Time Frame: Within the 30-day (Days 0-29) post-vaccination follow-up period ]
    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.

  10. Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: Throughout the study period (Day 0 - Month 14) ]
    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.

  11. Number of Subjects With Hemoglobin Values Outside Normal Ranges With Toxicity Grades [ Time Frame: 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) ]
    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.

  12. Number of Subjects With White Blood Cell (WBC) Values Outside Normal Ranges With Toxicity Grades [ Time Frame: 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) ]
    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.

  13. Number of Subjects With Platelet Values Outside Normal Ranges With Toxicity Grades [ Time Frame: 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) ]
    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.

  14. Number of Subjects With Alanine Aminotransferase (ALT) Values Outside Normal Ranges With Toxicity Grades [ Time Frame: 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) ]
    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.

  15. Number of Subjects With Creatinine Values Outside Normal Ranges With Toxicity Grades [ Time Frame: 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) ]
    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.

  16. Concentration of Antibodies Against the P. Falciparum Circumsporozoite (CS) Repeat Domain (Anti-CS) [ Time Frame: 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) ]
    Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL).

  17. Concentration of Antibodies Against Hepatitis B Surface Antigen (Anti-HBs) [ Time Frame: At Day 0 and at Month 3 ]
    Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL).

  18. Frequency of Cluster of Differentiation 4 (CD4+) CS-specific T-cells [ Time Frame: Prior to vaccination (Day 0) ]
    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).

  19. Frequency of Cluster of Differentiation 8 (CD8+) CS-specific T-cells [ Time Frame: Prior to vaccination (Day 0) ]
    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).

  20. Frequency of Cluster of Differentiation 4 (CD4+) CS-specific T-cells [ Time Frame: At Month 3 ]
    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).

  21. Frequency of Cluster of Differentiation 8 (CD8+) CS-specific T-cells [ Time Frame: At Month 3 ]
    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).



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Ages Eligible for Study:   5 Months to 17 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00380393


Locations
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Kenya
GSK Investigational Site
Kilifi, Kenya, 80108
Tanzania
GSK Investigational Site
Amani, Tanga, Tanzania
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline

Additional Information:
Study Data/Documents: Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 106464
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 106464
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 106464
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 106464
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 106464
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 106464
For additional information about this study please refer to the GSK Clinical Study Register

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00380393     History of Changes
Other Study ID Numbers: 106464
First Posted: September 26, 2006    Key Record Dates
Results First Posted: July 3, 2018
Last Update Posted: July 3, 2018
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:
Malaria
Plasmodium
RTS
S/AS01
Falciparum

Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs