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CompletedNCT00436007Updated Aug 16, 2018Results posted

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

A Phase 2 interventional study of GSK 257049 and Tritanrix™ HepB/Hib in Malaria, sponsored by GlaxoSmithKline. Completed at 3 sites in 3 countries. Open to participants aged 6 Weeks to 10 Weeks, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-08-16.

Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
511
Allocation
Randomized
Ages
6 Weeks to 10 Weeks
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Malaria

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Keywords

  • Africa
  • Plasmodium falciparum
  • Malaria
03

Who can participate

Ages eligible
6 Weeks to 10 Weeks
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
511 participants (actual)

Study arms

  • 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 · Biological: Tritanrix™ HepB/Hib · Biological: Rouvax™ · Biological: Stamaril™ · Biological: Polio Sabin™

  • 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 · Biological: Tritanrix™ HepB/Hib · Biological: Rouvax™ · Biological: Stamaril™ · Biological: Polio Sabin™

  • 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 · Biological: Rouvax™ · Biological: Stamaril™ · Biological: Polio Sabin™

Interventions

  • BiologicalGSK 257049

    GlaxoSmithKline (GSK) Biologicals' candidate Plasmodium falciparum malaria vaccine

  • BiologicalTritanrix™ HepB/Hib

    GSK Biologicals' re-constituted diphtheria, tetanus, pertussis, hepatitis B vaccine (Tritanrix™ HepB) and Haemophilus influenzae type B vaccine (Hiberix™)

    Also known as: DTPwHepB/Hib vaccine

  • BiologicalRouvax™

    Aventis Pasteur's attenuated measles vaccine.

  • BiologicalStamaril™

    Aventis Pasteur's attenuated yellow fever vaccine.

    Also known as: Yellow Fever Vaccine

  • BiologicalPolio Sabin™

    GSK Biologicals' oral polio virus vaccine

    Also known as: Oral Polio vaccine (OPV).

05

What researchers measure

Primary outcomes

  1. Number of Subjects With Serious Adverse Events (SAEs).

    SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

    Time frame: From Month 0 to Month 8

Secondary outcomes

  1. Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).

    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.

    Time frame: At Months 0, 1, 3 and 7.

  2. Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).

    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.

    Time frame: At Months 0, 3, 7 and 8.

  3. Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).

    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.

    Time frame: At Months 0, 3, 7 and 8.

  4. Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies.

    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.

    Time frame: At Month 3

  5. Number of Subjects With Serious Adverse Events (SAEs).

    SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

    Time frame: From Month 8 to Month 19

  6. Concentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies.

    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.

    Time frame: At Month 3

  7. Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies).

    Anti-Polio 1, 2 and 3 antibody titers were expressed as geometric mean titers (GMTs). The seroprotection assay cut-off was 8.

    Time frame: At Month 3

  8. Concentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies.

    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.

    Time frame: At Month 3

  9. Concentrations of Anti-measles Antibodies.

    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.

    Time frame: At Months 7 and 8.

  10. Titers for Anti-yellow Fever Antibodies.

    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.

    Time frame: At Months 7 and 8.

  11. Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.

    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.

    Time frame: At Months 0, 1, 3 and 7.

  12. Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.

    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.

    Time frame: At Months 0, 3, 7 and 8.

  13. Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.

    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.

    Time frame: At Months 0, 3, 7 and 8.

  14. Number of Subjects With Solicited Local Symptoms.

    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.

    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.

  15. Number of Subjects With Solicited General Symptoms.

    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.

    Time frame: During the 7-day (Days 0-6) follow-up period after any vaccination

  16. Number of Subjects With Unsolicited Adverse Events (AEs)

    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.

    Time frame: During the 30-day (Days 0-29) follow-up period after any vaccination

  17. Number of Subjects With Serious Adverse Events (SAEs).

    SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

    Time frame: From Month 0 to Month 19

06

Results

Posted May 27, 2013

Participant flow

Participant flow — Overall Study
MilestoneGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Started170170171
Completed151156148
Not completed191423
Withdrew: Withdrawal by subject534
Withdrew: Lost to follow-up141013
Withdrew: Physician decision002
Withdrew: Death013
Withdrew: Other001

Outcome measures

PrimaryNumber of Subjects With Serious Adverse Events (SAEs).

SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

Time frame:
From Month 0 to Month 8
Reported as:
Number · subjects
Number of Subjects With Serious Adverse Events (SAEs).
subjectsGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Number of Subjects With Serious Adverse Events (SAEs).382833
SecondaryConcentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).

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.

Time frame:
At Months 0, 1, 3 and 7.
Reported as:
Geometric mean · mIU/mL
Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).
mIU/mLGSK 257049 1 Group
Anti-HB, Month 0 [N=145]12.5 (9.9 to 15.7)
Anti-HB, Month 1 [N=133]173.4 (131.9 to 228.0)
Anti-HB, Month 3 [N=130]1355.7 (1100.6 to 1669.9)
Anti-HB, Month 7 [N=137]1555.5 (1315.8 to 1839.0)
SecondaryConcentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).

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.

Time frame:
At Months 0, 3, 7 and 8.
Reported as:
Geometric mean · mIU/mL
Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).
mIU/mLGSK 257049 2 Group
Anti-HB, Month 0 [N=131]9.6 (7.8 to 11.8)
Anti-HB, Month 3 [N=119]651.2 (541.1 to 783.8)
Anti-HB, Month 7 [N=126]1133.1 (972.3 to 1320.6)
Anti-HB, Month 8 [N=125]59813.5 (47050.5 to 76038.6)
SecondaryConcentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).

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.

Time frame:
At Months 0, 3, 7 and 8.
Reported as:
Geometric mean · mIU/mL
Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).
mIU/mLTritanrix™ HepB/Hiberix™ Group
Anti-HB, Month 0 [N=143]8.7 (7.3 to 10.5)
Anti-HB, Month 3 [N=126]338.0 (266.3 to 429.0)
Anti-HB, Month 7 [N=131]159.9 (127.0 to 201.3)
Anti-HB, Month 8 [N=133]162.4 (127.9 to 206.3)
SecondaryConcentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies.

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.

Time frame:
At Month 3
Reported as:
Geometric mean · IU/mL
Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies.
IU/mLGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Anti-D1.0 (0.9 to 1.2)1.1 (0.9 to 1.3)1.4 (1.2 to 1.7)
Anti-T2.8 (2.3 to 3.3)2.6 (2.2 to 3.1)3.7 (3.2 to 4.3)
SecondaryNumber of Subjects With Serious Adverse Events (SAEs).

SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

Time frame:
From Month 8 to Month 19
Reported as:
Number · subjects
Number of Subjects With Serious Adverse Events (SAEs).
subjectsGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Number of Subjects With Serious Adverse Events (SAEs).282427
SecondaryConcentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies.

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.

Time frame:
At Month 3
Reported as:
Geometric mean · µg/mL
Concentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies.
µg/mLGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Concentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies.13.3 (10.5 to 16.7)15.7 (12.6 to 19.4)18.6 (14.8 to 23.5)
SecondaryTiters for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies).

Anti-Polio 1, 2 and 3 antibody titers were expressed as geometric mean titers (GMTs). The seroprotection assay cut-off was 8.

Time frame:
At Month 3
Reported as:
Geometric mean · titers
Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies).
titersGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Anti-Polio 1 [N=136;125;131]463.6 (342.8 to 627.0)485.5 (342.5 to 688.3)500.0 (365.0 to 684.9)
Anti-Polio 2 [N=135;124;131]494.0 (389.7 to 626.2)563.2 (457.3 to 693.6)406.8 (329.1 to 502.9)
Anti-Polio 3 [N=135;125;133]123.5 (92.1 to 165.6)148.7 (112.2 to 197.0)205.1 (156.5 to 268.7)
SecondaryConcentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies.

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.

Time frame:
At Month 3
Reported as:
Geometric mean · EL.U/mL
Concentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies.
EL.U/mLGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Concentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies.85.3 (76.8 to 94.6)104.4 (94.8 to 115.0)106.5 (96.1 to 118.1)
SecondaryConcentrations of Anti-measles Antibodies.

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.

Time frame:
At Months 7 and 8.
Reported as:
Geometric mean · mIU/mL
Concentrations of Anti-measles Antibodies.
mIU/mLGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Anti-measles, Month 7 [N=112;120]75.0 (75.0 to 75.0)1295.2 (1052.1 to 1594.5)
Anti-measles, Month 8 [N=119;122]76.2 (73.8 to 78.6)1299.0 (1038.8 to 1624.4)
SecondaryTiters for Anti-yellow Fever Antibodies.

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.

Time frame:
At Months 7 and 8.
Reported as:
Geometric mean · titers
Titers for Anti-yellow Fever Antibodies.
titersGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Anti-yellow fever, Month 7 [N=41;62]5.3 (4.8 to 5.8)5.9 (5.1 to 6.9)
Anti-yellow fever, Month 8 [N=46;64]172.2 (135.9 to 236.3)183.4 (134.0 to 250.9)
SecondaryConcentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.

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.

Time frame:
At Months 0, 1, 3 and 7.
Reported as:
Geometric mean · EL.U/mL
Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.
EL.U/mLGSK 257049 1 Group
Anti-CS, Month 0 [N=153]0.4 (0.3 to 0.4)
Anti-CS, Month 2 [N=137]86.6 (66.5 to 112.7)
Anti-CS, Month 3 [N=131]190.3 (154.3 to 234.7)
Anti-CS, Month 7 [N=137]35.3 (28.5 to 43.8)
SecondaryConcentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.

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.

Time frame:
At Months 0, 3, 7 and 8.
Reported as:
Geometric mean · EL.U/mL
Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.
EL.U/mLGSK 257049 2 Group
Anti-CS, Month 0 [N=141]0.4 (0.3 to 0.4)
Anti-CS, Month 3 [N=121]57.7 (43.7 to 76.2)
Anti-CS, Month 7 [N=127]6.1 (4.6 to 7.9)
Anti-CS, Month 8 [N=127]107.8 (81.1 to 143.4)
SecondaryConcentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.

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.

Time frame:
At Months 0, 3, 7 and 8.
Reported as:
Geometric mean · EL.U/mL
Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.
EL.U/mLTritanrix™ HepB/Hiberix™ Group
Anti-CS, Month 0 [N=156]0.4 (0.3 to 0.4)
Anti-CS, Month 3 [N=129]0.3 (0.3 to 0.3)
Anti-CS, Month 7 [N=132]0.3 (0.3 to 0.3)
Anti-CS, Month 8 [N=135]0.3 (0.3 to 0.3)
SecondaryNumber of Subjects With Solicited Local Symptoms.

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.

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.
Reported as:
Number · subjects
Number of Subjects With Solicited Local Symptoms.
subjectsGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Pain - GSK 257049 [N=170;170;0]126116NA
Swelling - GSK 257049 [N=170;170;0]2844NA
Pain - Rouvax™ [N=163;161;159]525447
Swelling - Rouvax™ [N=163;161;159]202116
Pain - Stamaril™ [N=95;94;94]272
Swelling - Stamaril™ [N=95;94;94]010
Pain - Tritanrix™ HepB/Hib [N=170;170;171]127133140
Swelling - Tritanrix™ HepB/Hib [N=170;170;171]476868
SecondaryNumber of Subjects With Solicited General Symptoms.

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.

Time frame:
During the 7-day (Days 0-6) follow-up period after any vaccination
Reported as:
Number · subjects
Number of Subjects With Solicited General Symptoms.
subjectsGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Drowsiness829772
Fever (axillary temperature ≥ 37.5°C)1029575
Irritability124131118
Loss of appetite688370
SecondaryNumber of Subjects With Unsolicited Adverse Events (AEs)

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.

Time frame:
During the 30-day (Days 0-29) follow-up period after any vaccination
Reported as:
Number · subjects
Number of Subjects With Unsolicited Adverse Events (AEs)
subjectsGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Number of Subjects With Unsolicited Adverse Events (AEs)160161164
SecondaryNumber of Subjects With Serious Adverse Events (SAEs).

SAEs were defined as medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

Time frame:
From Month 0 to Month 19
Reported as:
Number · subjects
Number of Subjects With Serious Adverse Events (SAEs).
subjectsGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
Number of Subjects With Serious Adverse Events (SAEs).574749

Adverse events

Collected over SAEs: entire study period (Months 0-19); Solicited local/general symptoms and Unsolicited AEs: during the 7- and 30-day (Days 0-29) post-vaccination period, respectively.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
GSK 257049 1 Group—57/170 (33.5%)169/170 (99.4%)
GSK 257049 2 Group—47/170 (27.6%)169/170 (99.4%)
Tritanrix™ HepB/Hiberix™ Group—49/171 (28.7%)171/171 (100%)
Most frequent serious events
Showing 10 of 76
Most frequent serious events
EventGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
GastroenteritisInfections and infestations17/17010/17014/171
Plasmodium falciparum infectionInfections and infestations6/1706/17014/171
Plasmodium falciparum infectionInfections and infestations5/17010/17013/171
PneumoniaInfections and infestations11/1709/1708/171
AnaemiaBlood and lymphatic system disorders6/17010/17010/171
AnaemiaBlood and lymphatic system disorders6/1706/17010/171
PneumoniaInfections and infestations5/1707/1707/171
Upper respiratory tract infectionInfections and infestations7/1704/1705/171
GastroenteritisInfections and infestations7/1706/1702/171
Upper respiratory tract infectionInfections and infestations5/1704/1704/171
Most frequent other events
Showing 10 of 23
Most frequent other events
EventGSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ Group
PainGeneral disorders127/170133/170140/171
IrritabilityGeneral disorders124/170131/170118/171
PainGeneral disorders126/170116/170—
FeverGeneral disorders102/17095/17075/171
DrowsinessGeneral disorders82/17097/17072/171
Loss of appetiteGeneral disorders68/17083/17070/171
NasopharyngitisInfections and infestations53/17062/17071/171
SwellingGeneral disorders47/17068/17068/171
Upper respiratory tract infectionInfections and infestations66/17066/17065/171
PainGeneral disorders52/16354/16147/159

Baseline characteristics

Age, Continuous
Age, Continuous(Weeks)GSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ GroupTotal
Mean7.0 ± 0.977.1 ± 1.057.0 ± 0.977.0 ± 1.00
Sex: Female, Male
Sex: Female, Male(Participants)GSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ GroupTotal
Female908478252
Male808693259
Region of Enrollment
Region of Enrollment(Subjects)GSK 257049 1 GroupGSK 257049 2 GroupTritanrix™ HepB/Hiberix™ GroupTotal
Gabon737374220
Ghana27272781
Tanzania707070210
07

Study locations

3 sites
  • GSK Investigational Site
    Lambaréné, Gabon
  • GSK Investigational Site
    Kintampo, Ghana
  • GSK Investigational Site
    Dar-es-Salaam, Tanzania
08

References and documents

Publications

  • Ajua A, Lell B, Agnandji ST, Asante KP, Owusu-Agyei S, Mwangoka G, Mpina M, Salim N, Tanner M, Abdulla S, Vekemans J, Jongert E, Lievens M, Cambron P, Ockenhouse CF, Kremsner PG, Mordmuller B. The effect of immunization schedule with the malaria vaccine candidate RTS,S/AS01E on protective efficacy and anti-circumsporozoite protein antibody avidity in African infants. Malar J. 2015 Feb 13;14:72. doi: 10.1186/s12936-015-0605-7. PubMed 25885325 ↗
  • 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 ↗
  • Asante KP, Abdulla S, Agnandji S, Lyimo J, Vekemans J, Soulanoudjingar S, Owusu R, Shomari M, Leach A, Jongert E, Salim N, Fernandes JF, Dosoo D, Chikawe M, Issifou S, Osei-Kwakye K, Lievens M, Paricek M, Moller T, Apanga S, Mwangoka G, Dubois MC, Madi T, Kwara E, Minja R, Hounkpatin AB, Boahen O, Kayan K, Adjei G, Chandramohan D, Carter T, Vansadia P, Sillman M, Savarese B, Loucq C, Lapierre D, Greenwood B, Cohen J, Kremsner P, Owusu-Agyei S, Tanner M, Lell B. Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial. Lancet Infect Dis. 2011 Oct;11(10):741-9. doi: 10.1016/S1473-3099(11)70100-1. Epub 2011 Jul 22. Erratum In: Lancet Infect Dis. 2011 Oct;11(10):727. PubMed 21782519 ↗
  • Agnandji ST, Asante KP, Lyimo J, Vekemans J, Soulanoudjingar SS, Owusu R, Shomari M, Leach A, Fernandes J, Dosoo D, Chikawe M, Issifou S, Osei-Kwakye K, Lievens M, Paricek M, Apanga S, Mwangoka G, Okissi B, Kwara E, Minja R, Lange J, Boahen O, Kayan K, Adjei G, Chandramohan D, Jongert E, Demoitie MA, Dubois MC, Carter T, Vansadia P, Villafana T, Sillman M, Savarese B, Lapierre D, Ballou WR, Greenwood B, Tanner M, Cohen J, Kremsner PG, Lell B, Owusu-Agyei S, Abdulla S. Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization. J Infect Dis. 2010 Oct 1;202(7):1076-87. doi: 10.1086/656190. Erratum In: J Infect Dis. 2011 May 1;203(9):1344. PubMed 20735271 ↗

Individual participant data

Plan to share: Yes — Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

09

Registry details

Key details

Study ID
NCT00436007
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Feb 16, 2007
Start date
Apr 30, 2007
Primary completion
Sep 15, 2008
Completion
Oct 7, 2009
Results posted
May 27, 2013
Last update
Aug 16, 2018

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline
View the source record on ClinicalTrials.gov ↗

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