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

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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

Tracking Information
First Submitted Date  ICMJE September 25, 2006
First Posted Date  ICMJE September 26, 2006
Results First Submitted Date  ICMJE August 25, 2017
Results First Posted Date  ICMJE July 3, 2018
Last Update Posted Date July 3, 2018
Actual Study Start Date  ICMJE January 3, 2007
Actual Primary Completion Date August 15, 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 25, 2006)
Time to 1st case of malaria (P. fal infection >2500 parasites/mcL & fever >=37.5 C) over a period starting 14 days post-Dose 3 & extending for 4 mths; safety
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2018)
  • 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.
  • 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.
  • 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.
  • 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) ]
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
  • 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).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of RTS,S/AS01 Vaccine Against Episodes of Malaria Due to P. Falciparum Infection in Children.
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Care Provider, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Malaria
Intervention  ICMJE
  • Biological: GSK malaria vaccine 257049 Vaccine
    3 dose intramuscular injection
    Other Names:
    • RTS
    • S/AS01E vaccine
  • Biological: Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine
    3 dose intramuscular injection
Study Arms  ICMJE
  • 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.
    Intervention: Biological: GSK malaria vaccine 257049 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.
    Intervention: Biological: Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 4, 2018)
894
Original Enrollment  ICMJE
 (submitted: September 25, 2006)
890
Actual Study Completion Date  ICMJE November 11, 2008
Actual Primary Completion Date August 15, 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Months to 17 Months   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Kenya,   Tanzania
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00380393
Other Study ID Numbers  ICMJE 106464
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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.
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP