Safety and Immunogenicity Study of GSK Biologicals' Malaria Vaccine 257049, When Incorporated Into an EPI Regimen

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00436007
First received: February 15, 2007
Last updated: May 23, 2013
Last verified: May 2013
  Purpose

This study is being done to assess the possibility of the potential integration of malaria vaccine into the EPI regimen. It will evaluate whether the malaria vaccine is safe and immunogenic in infants aged 6 to 10 weeks at first dose, when co-administered with other EPI vaccine antigens. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.


Condition Intervention Phase
Malaria Vaccines
Biological: GSK 257049
Biological: Tritanrix™ HepB/Hib
Biological: Rouvax™
Biological: Stamaril™
Biological: Polio Sabin™
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity Study of GSK Biologicals' Investigational Vaccination Regimen Malaria Vaccine 257049, When Incorporated Into an Expanded Program on Immunization (EPI) Regimen That Includes Tritanrix HepB/Hib, OPV, Measles and Yellow Fever Vaccination in Infants

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Serious Adverse Events (SAEs). [ Time Frame: From Month 0 to Month 8 ] [ Designated as safety issue: No ]
    SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.


Secondary Outcome Measures:
  • Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). [ Time Frame: At Months 0, 1, 3 and 7. ] [ Designated as safety issue: No ]
    Anti-HB antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seroprotection assay cut-off was 10 mIU/mL. This outcome only covers results for the GSK 257049 1 Group.

  • Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). [ Time Frame: At Months 0, 3, 7 and 8. ] [ Designated as safety issue: No ]
    Anti-HB antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seroprotection assay cut-off was 10 mIU/mL. This outcome only covers results for the GSK 257049 2 Group.

  • Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies). [ Time Frame: At Months 0, 3, 7 and 8. ] [ Designated as safety issue: No ]
    Anti-HB antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seroprotection assay cut-off was 10 mIU/mL. This outcome only covers results for the Tritanrix™ HepB/Hiberix™ Group.

  • Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies. [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    Anti-D and Anti-T antibody concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The seroprotection assay cut-off was 0.1 IU/mL.

  • Number of Subjects With Serious Adverse Events (SAEs). [ Time Frame: From Month 8 to Month 19 ] [ Designated as safety issue: No ]
    SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

  • Concentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies. [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    Anti-PRP antibody concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The seroprotection assay cut-off was 0.15 µg/mL.

  • Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies). [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    Anti-Polio 1, 2 and 3 antibody titers were expressed as geometric mean titers (GMTs). The seroprotection assay cut-off was 8.

  • Concentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies. [ Time Frame: At Month 3 ] [ Designated as safety issue: No ]
    Anti-BPT antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The seropositivity assay cut-off was 15 EL.U/mL.

  • Concentrations of Anti-measles Antibodies. [ Time Frame: At Months 7 and 8. ] [ Designated as safety issue: No ]
    Anti-measles antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The seropositivity assay cut-off was 150 mIU/mL. The analysis was only performed on subjects from the GSK 257049 2 and Tritanrix™ HepB/Hiberix™ groups.

  • Titers for Anti-yellow Fever Antibodies. [ Time Frame: At Months 7 and 8. ] [ Designated as safety issue: No ]

    Anti-yellow fever antibody titers were expressed as geometric mean titers (GMTs). The seroprotection assay cut-off was 10. The analysis was only performed on subjects from the GSK 257049 2 and Tritanrix™ HepB/Hiberix™ groups.

    The analysis was only performed on subjects from the GSK 257049 2 and Tritanrix™ HepB/Hiberix™ groups.


  • Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. [ Time Frame: At Months 0, 1, 3 and 7. ] [ Designated as safety issue: No ]
    Anti-CS antibody antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The seropositivity assay cut-off was 0.5 EL.U/mL. This outcome only covers results for the GSK 257049 1 Group.

  • Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. [ Time Frame: At Months 0, 3, 7 and 8. ] [ Designated as safety issue: No ]
    Anti-CS antiibodies were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The seropositivity assay cut-off was 0.5 EL.U/mL. This outcome only covers results for the GSK 257049 2 Group.

  • Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies. [ Time Frame: At Months 0, 3, 7 and 8. ] [ Designated as safety issue: No ]
    Anti-CS antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The seropositivity assay cut-off was 0.5 EL.U/mL. This outcome only covers results for the Tritanrix™ HepB/Hiberix™ Group.

  • Number of Subjects With Solicited Local Symptoms. [ Time Frame: During the 7-day (Days 0-6) follow-up period after any vaccination with the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049 and Stamaril™ vaccines. ] [ Designated as safety issue: No ]
    Assessed solicited local symptoms were pain and swelling at injection site following vaccination with each of the following study vaccines administered intramuscularly, e. a. the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049 and Stamaril™ vaccines. The numbers of subjects with each of the assessed solicited local symptoms reported were tabulated for each vaccine administered, separately.

  • Number of Subjects With Solicited General Symptoms. [ Time Frame: During the 7-day (Days 0-6) follow-up period after any vaccination ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were drowsiness, fever [axillary temperature equal or above (≥) 37.5 degrees Celsius (°C)], irritability and loss of appetite following any vaccination with any of the study vaccines, e. a. the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049, Stamaril™ and Polio Sabin™ vaccines.

  • Number of Subjects With Unsolicited Adverse Events (AEs) [ Time Frame: During the 30-day (Days 0-29) follow-up period after any vaccination ] [ Designated as safety issue: No ]
    An unsolicited AE is any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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. Unsolicited AEs were assessed following vaccination with any of the study vaccines, e. a. the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049, Stamaril™ and Polio Sabin™ vaccines.

  • Number of Subjects With Serious Adverse Events (SAEs). [ Time Frame: From Month 0 to Month 19 ] [ Designated as safety issue: No ]
    SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.


Enrollment: 511
Study Start Date: April 2007
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK 257049 1 Group

Subjects aged 6 to 10 weeks at the time of first vaccination received 3 doses of Tritanrix™ HepB/Hib, Polio Sabin™ and GSK 257049 vaccines at Months 0, 1 and 2, and a single dose of Rouvax™ and Stamaril™ vaccines at Month 7.

The GSK 257049 and Tritanrix™ HepB/Hib vaccines were administered intramuscularly in the left and right antero-lateral thigh, respectively. Rouvax™ and Stamaril™ were administered intramuscularly in the left and right arm respectively. Polio Sabin™ was administered orally. The Stamaril™ vaccine was not administered to subjects from Tanzania as this vaccine was not foreseen at the time to be introduced to the EPI vaccination schedule in Tanzania.

Biological: GSK 257049
GlaxoSmithKline (GSK) Biologicals' candidate Plasmodium falciparum malaria vaccine
Biological: Tritanrix™ HepB/Hib
GSK Biologicals' re-constituted diphtheria, tetanus, pertussis, hepatitis B vaccine (Tritanrix™ HepB) and Haemophilus influenzae type B vaccine (Hiberix™)
Other Name: DTPwHepB/Hib vaccine
Biological: Rouvax™
Aventis Pasteur's attenuated measles vaccine.
Biological: Stamaril™
Aventis Pasteur's attenuated yellow fever vaccine.
Other Name: Yellow Fever Vaccine
Biological: Polio Sabin™
GSK Biologicals' oral polio virus vaccine
Other Name: Oral Polio vaccine (OPV).
Experimental: GSK 257049 2 Group
Subjects aged 6 to 10 weeks at the time of first vaccination received 3 doses of Tritanrix™ HepB/Hib and Polio Sabin™ at Months 0, 1 and 2, 3 doses of GSK 257049 vaccine at Months 0, 1 and 7, and a single dose of Rouvax™ and Stamaril™ at Month 7. The GSK 257049 and Tritanrix™ HepB/Hib vaccines were administered intramuscularly in the left and right antero-lateral thigh, respectively. Rouvax™ and Stamaril™ were administered intramuscularly in the left and right arm respectively. Polio Sabin™ was administered orally. Stamaril™ was not administered to subjects from Tanzania as this vaccine was not foreseen at the time to be introduced to the EPI vaccination schedule in Tanzania.
Biological: GSK 257049
GlaxoSmithKline (GSK) Biologicals' candidate Plasmodium falciparum malaria vaccine
Biological: Tritanrix™ HepB/Hib
GSK Biologicals' re-constituted diphtheria, tetanus, pertussis, hepatitis B vaccine (Tritanrix™ HepB) and Haemophilus influenzae type B vaccine (Hiberix™)
Other Name: DTPwHepB/Hib vaccine
Biological: Rouvax™
Aventis Pasteur's attenuated measles vaccine.
Biological: Stamaril™
Aventis Pasteur's attenuated yellow fever vaccine.
Other Name: Yellow Fever Vaccine
Biological: Polio Sabin™
GSK Biologicals' oral polio virus vaccine
Other Name: Oral Polio vaccine (OPV).
Active Comparator: Tritanrix™ HepB/Hiberix™ Group
Subjects aged 6 to 10 weeks at the time of first vaccination received 3 doses of Tritanrix™ HepB/Hib and Polio Sabin™ at Months 0, 1 and 2, and a single dose of Rouvax™ and Stamaril™ at Month 7. The GSK 257049 and Tritanrix™ HepB/Hib vaccines were administered intramuscularly in the left and right antero-lateral thigh, respectively. Rouvax™ and Stamaril™ were administered intramuscularly in the left and right arm respectively. Polio Sabin™ was administered orally. The Stamaril™ vaccine was not administered to subjects from Tanzania as this vaccine was not foreseen at the time to be introduced to the EPI vaccination schedule in Tanzania.
Biological: Tritanrix™ HepB/Hib
GSK Biologicals' re-constituted diphtheria, tetanus, pertussis, hepatitis B vaccine (Tritanrix™ HepB) and Haemophilus influenzae type B vaccine (Hiberix™)
Other Name: DTPwHepB/Hib vaccine
Biological: Rouvax™
Aventis Pasteur's attenuated measles vaccine.
Biological: Stamaril™
Aventis Pasteur's attenuated yellow fever vaccine.
Other Name: Yellow Fever Vaccine
Biological: Polio Sabin™
GSK Biologicals' oral polio virus vaccine
Other Name: Oral Polio vaccine (OPV).

Detailed Description:

Two vaccination schedules will be studied, which constitutes the two alternative three dose regimens for the malaria candidate vaccine 257049 integration into EPI. The co-administered EPI vaccines include GSK Biologicals' Tritanrix™-HepB/Hiberix™, a measles vaccine (depending on the supply availability), Aventis Pasteur's Yellow Fever vaccine Stamaril™ and GSK Biologicals' Oral Polio vaccine Polio Sabin™. Tuberculosis vaccine (Bacillus of Calmette and Guerin, BCG) will be administered according to national medical practice and will not be administered as part of this protocol, but will be documented.

  Eligibility

Ages Eligible for Study:   6 Weeks to 10 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • A male or female infant between 6 and 10 weeks of age at the time of first vaccination.
  • Signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child. Where parent(s)/guardian(s) are illiterate, the consent form will be countersigned by a witness.
  • Subjects who have received one previous dose of OPV and BCG.
  • Subjects who are born after a normal gestation period (between 36 and 42 weeks).

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 out of range, specifically: ALT and creatinine above acceptable limit; Hemoglobin, Platelet count and Total white cell count below acceptable limit.
  • Previous vaccination with diphtheria, tetanus, pertussis (whole-cell or acellular), Hemophilus influenzae type b or hepatitis B vaccines.
  • BCG administration within one week of proposed administration of a study vaccine.
  • OPV administration within four weeks of proposed administration of a study vaccine.
  • Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s).
  • 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 since birth to 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 six months prior to the first vaccine dose.
  • Simultaneous participation in any other clinical trial.
  • Twins (to avoid misidentification).
  • Maternal death.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00436007

Locations
Gabon
GSK Investigational Site
Lambaréné, Gabon
Ghana
GSK Investigational Site
Kintampo, Ghana
Tanzania
GSK Investigational Site
Dar-es-Salaam, Tanzania
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Owusu Agyei S et al. Randomized, controlled phase 2 study assessing the safety and immunogenicity of the RTS,S/AS01E candidate malaria vaccine, when incorporated into an EPI regimen including DTPwHepB/Hib, OPV, measles and yellow fever vaccination. Abstract presented at the 5th Multilateral Initiative on Malaria Pan-African Malaria Conference (MIM). Nairobi, Kenya, 2-6 November 2009.
Owusu Agyei S et al. Safety and efficacy the RTS,S/AS01E malaria vaccine: extended follow up of a randomized controlled Phase 2 trial. Abstract presented at the 59th Annual Meeting on American Society of Tropical Medicine and Hygiene (ASTMH). Philadelphia, USA, 4-8 November 2010.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00436007     History of Changes
Other Study ID Numbers: 106369
Study First Received: February 15, 2007
Results First Received: December 19, 2012
Last Updated: May 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Africa
Plasmodium falciparum
Malaria

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on August 25, 2014