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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Malaria

Intervention / Treatment
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* Biological: GSK 257049
* Biological: Tritanrix™ HepB/Hib
* Biological: Rouvax™
* Biological: Stamaril™
* Biological: Polio Sabin™


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 10 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK 257049 1 Group<br>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<br>* GlaxoSmithKline (GSK) Biologicals' candidate Plasmodium falciparum malaria vaccine<br>Biological: Tritanrix™ HepB/Hib<br>* GSK Biologicals' re-constituted diphtheria, tetanus, pertussis, hepatitis B vaccine (Tritanrix™ HepB) and Haemophilus influenzae type B vaccine (Hiberix™)<br>* Other names: DTPwHepB/Hib vaccine;Biological: Rouvax™<br>* Aventis Pasteur's attenuated measles vaccine.<br>Biological: Stamaril™<br>* Aventis Pasteur's attenuated yellow fever vaccine.<br>* Other names: Yellow Fever Vaccine;Biological: Polio Sabin™<br>* GSK Biologicals' oral polio virus vaccine<br>* Other names: Oral Polio vaccine (OPV).;|
| Experimental: GSK 257049 2 Group<br>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<br>* GlaxoSmithKline (GSK) Biologicals' candidate Plasmodium falciparum malaria vaccine<br>Biological: Tritanrix™ HepB/Hib<br>* GSK Biologicals' re-constituted diphtheria, tetanus, pertussis, hepatitis B vaccine (Tritanrix™ HepB) and Haemophilus influenzae type B vaccine (Hiberix™)<br>* Other names: DTPwHepB/Hib vaccine;Biological: Rouvax™<br>* Aventis Pasteur's attenuated measles vaccine.<br>Biological: Stamaril™<br>* Aventis Pasteur's attenuated yellow fever vaccine.<br>* Other names: Yellow Fever Vaccine;Biological: Polio Sabin™<br>* GSK Biologicals' oral polio virus vaccine<br>* Other names: Oral Polio vaccine (OPV).;|
| Active Comparator: Tritanrix™ HepB/Hiberix™ Group<br>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<br>* GSK Biologicals' re-constituted diphtheria, tetanus, pertussis, hepatitis B vaccine (Tritanrix™ HepB) and Haemophilus influenzae type B vaccine (Hiberix™)<br>* Other names: DTPwHepB/Hib vaccine;Biological: Rouvax™<br>* Aventis Pasteur's attenuated measles vaccine.<br>Biological: Stamaril™<br>* Aventis Pasteur's attenuated yellow fever vaccine.<br>* Other names: Yellow Fever Vaccine;Biological: Polio Sabin™<br>* GSK Biologicals' oral polio virus vaccine<br>* Other names: Oral Polio vaccine (OPV).;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From Month 0 to Month 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At Months 0, 1, 3 and 7. | 
| 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. | At Months 0, 3, 7 and 8. | 
| 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. | At Months 0, 3, 7 and 8. | 
| 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. | At Month 3 | 
| 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. | From Month 8 to Month 19 | 
| 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. | At Month 3 | 
| 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. | At Month 3 | 
| 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. | At Month 3 | 
| 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. | At Months 7 and 8. | 
| 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. | At Months 7 and 8. | 
| 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. | At Months 0, 1, 3 and 7. | 
| 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. | At Months 0, 3, 7 and 8. | 
| 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. | At Months 0, 3, 7 and 8. | 
| 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. | During the 7-day (Days 0-6) follow-up period after any vaccination with the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049 and Stamaril™ vaccines. | 
| 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. | During the 7-day (Days 0-6) follow-up period after any vaccination | 
| 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. | During the 30-day (Days 0-29) follow-up period after any vaccination | 
| 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. | From Month 0 to Month 19 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Africa, Plasmodium falciparum, Malaria