Study to Evaluate Immunogenicity of the Hepatitis B Antigen of the GSK Biologicals' Candidate Malaria Vaccine (257049)

Malaria Clinical Trial

Official title:

Immunogenicity of the Hepatitis B Antigen of the GSK Biologicals' Candidate Malaria Vaccine (257049)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01345240
• Other study ID #: 113681
• Secondary ID: 2011-001508-37
• Status: Completed
• Phase: Phase 3
• Start date: November 17, 2011
• Est. completion date: February 9, 2017

Study information

• Verified date: July 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study has been designed to support the indication of the candidate vaccine (also referred to as GSK 257049 or RTS,S in this record) against hepatitis B virus infection, when administered as a primary vaccination integrated into an Expanded Program on Immunization (EPI) regimen to infants living in sub-Saharan Africa.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 705
• Est. completion date: February 9, 2017
• Est. primary completion date: January 9, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Weeks to 12 Weeks

Eligibility

Inclusion Criteria:

All subjects must satisfy ALL the following criteria at study entry:

• A male or female infant aged between 8 and 12 weeks inclusive at the time of first vaccination

• Signed or thumb-printed informed consent obtained from the parent(s)/Legally Acceptable Representative [LAR(s)] of the child. Where parent(s)/LAR(s) are illiterate, the consent form will be countersigned by an independent witness

• Subjects who the investigator believes that their parent(s)/LAR(s) can and will comply with the requirements of the protocol

• Healthy subjects as established by medical history and clinical examination before entering into the study

• Born to a mother who is Hepatitis B surface antigen (HBsAg) negative

• Born to a mother who is Human Immunodeficiency Virus (HIV) negative

• Born after a normal gestation period of 36 to 42 weeks inclusive.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study:

• Child in care

• Acute disease and/or fever 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

• Previous vaccination with diphtheria, tetanus, pertussis, Haemophilus influenzae type b, Streptococcus pneumoniae, hepatitis B vaccine or rotavirus vaccines.

• Planned administration/administration of a licensed vaccine not foreseen by the study protocol within 7 days of the first dose of study vaccine.

• Use of a drug or vaccine that is not approved for that indication other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.

• Administration of immunoglobulins and/or any blood products in the period between birth and Dose 1 and within the three months preceding planned vaccine administration during the study period.

• Chronic administration of immunosuppressants or other immune-modifying drugs in the period between birth and Dose 1.

• Concurrently participating in another clinical study at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.

• Same sex twin

• Maternal death

• History of allergic reactions 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.

• Any other findings that the investigator feels would result in data collected being incomplete or of poor quality.

• Previous participation in any other malaria vaccine trial.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis B
• Malaria
• Malaria Vaccines

Intervention

Biological:
• GlaxoSmithKline (GSK) Biologicals' candidate Plasmodium falciparum malaria vaccine 257049
Children enrolled in 9 groups will receive 3 doses of the candidate malaria vaccine (Lot 1, 2 and 3) by intramuscular injection.
• Engerix-B™ vaccine
Children enrolled in 2 groups will receive 4 doses of Engerix-B™ vaccine by intramuscular injection. Children enrolled in all other groups will receive one dose of Engerix-B vaccine by intramuscular injection.
• Infanrix/Hib™ vaccine
Children enrolled in all 11 groups will receive 4 doses of Infanrix/Hib™ vaccine by intramuscular injection
• Polio Sabin™ vaccine
Children enrolled in all 11 groups will receive 3 doses of Polio Sabin™ by intramuscular injection.
• Rotarix™ vaccine
Children enrolled in all 11 groups will receive 2 doses of oral Rotarix™ vaccine.
• Synflorix™ vaccine
Children enrolled in all 11 groups will receive 4 doses of Synflorix™ vaccine by intramuscular injection.
• Measles vaccine
Children enrolled in all 11 groups will receive 1 dose of measles vaccine by intramuscular injection.
• Yellow fever vaccine
Children enrolled in all 11 groups will receive 1 dose of yellow fever vaccine by intramuscular injection.

Locations

Country	Name	City	State
Burkina Faso	GSK Investigational Site	Ouagadougou 01
Ghana	GSK Investigational Site	Kumasi

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Burkina Faso,  Ghana, 

References & Publications (1)

Valéa I, Adjei S, Usuf E, Traore O, Ansong D, Tinto H, Owusu Boateng H, Leach A, Mwinessobaonfou Some A, Buabeng P, Vekemans J, Nana LA, Kotey A, Vandoolaeghe P, Ouedraogo F, Sambian D, Lievens M, Tahita MC, Rettig T, Jongert E, Lompo P, Idriss A, Borys D, Ouedraogo S, Prempeh F, Habib MA, Schuerman L, Sorgho H, Agbenyega T. Immune response to the hepatitis B antigen in the RTS,S/AS01 malaria vaccine, and co-administration with pneumococcal conjugate and rotavirus vaccines in African children: A randomized controlled trial. Hum Vaccin Immunother. 2018 Jun 3;14(6):1489-1500. doi: 10.1080/21645515.2018.1442996. Epub 2018 Apr 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Seroprotected Subjects Against Anti-Hepatitis B (HBs) Antigen	A seroprotected subject was defined as a subject with anti-HBs antibody titers greater than or equal to (>=) the cut-off of 10 mili-international units per mililiter (mIU/mL). A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis, with study groups pooled by primary vaccine administered (RTS,S vs Engerix -B).	At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Primary	Anti-Hepatitis B (HBs) Antibody Concentrations for RTS,S Group and Engerix B Group	Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (>=) 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis, with study groups pooled by primary vaccine administered (RTS,S vs Engerix-B).	At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Primary	Anti-Hepatitis B (HBs) Antibody Concentrations for All Study Groups	Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (>=) 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis, for each RTS,S Regimen A, B, C and each Engerix B Regimen A and B study groups.	At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Secondary	Anti-Hepatitis B (HBs) Antibody Concentrations at Month 3	Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (>=) 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis. Results presented are for the study groups receiving the RTS,S vaccine, pooled by vaccine lot, that is, for the RTS,S Lot 1, RTS,S Lot 2, and RTS,S Lot 3 groups, as defined below.	At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Secondary	Anti-Hepatitis B (HBs) Antibody Concentrations at Month 14 and 26	Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (>=) 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis. Results presented are for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.	At Months 14 and 26, aka at 12 and 24 months post Dose 3 of RTS,S vaccine or Engerix-B
Secondary	Anti-Hepatitis B (HBs) Antibody Concentrations at Month 38, 50 and 51	Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (>=) 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis. Results presented are for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.	At Months 38, 50 and 51, aka 36 and 48 months post Dose 3 of RTS,S vaccine or Engerix-B and one month post the Month 50 booster dose of Engerix-B
Secondary	Concentrations of Antibodies to the Hepatitis B RF1 Surface Antigen (Anti-HBs RF1) at Month 3	Anti-HBs RF1 antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (>=) 33 EL.U/mL. The table shows results for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.	At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Secondary	Concentrations of Antibodies to the Hepatitis B RF1 Surface Antigen (Anti-HBs RF1) at Month 51	Anti-HBs RF1 antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (>=) 33 EL.U/mL. The table shows results for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.	At Month 51, aka one month post the Month 50 booster dose of Engerix-B
Secondary	Anti-circumsporozoite Protein (Anti-CS) Antibody Concentrations at Month 3	Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (>=) 0.5 EL.U/mL. The table shows results for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.	At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Secondary	Anti-circumsporozoite Protein (Anti-CS) Antibody Concentrations at Month 14	Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (>=) 0.5 EL.U/mL. The table shows results for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups. No anti-CS results are available for the time point 24 months post Dose 3 (Month 26) because the quantity of serum available for the anti-CS assay was insufficient for many samples.	At Month 14, aka at 12 months post Dose 3 of RTS,S vaccine or Engerix-B
Secondary	Anti-circumsporozoite Protein (Anti-CS) Antibody Concentrations at Month 38 and 50	Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (>=) 1.9 EL.U/mL. The table shows results for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.	At Months 38 and 50, aka 36 and 48 months post Dose 3 of RTS,S vaccine or Engerix-B
Secondary	Pneumococcal Antibody Concentrations Against Synflorix Pneumococcal Vaccine Serotypes at Month 3	Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), and expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The pneumococcal vaccine serotypes assessed were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The cut-off of the assay, by GSK assay, was greater than or equal to (>=) 0.2 µg/mL. This corresponds to the standard ELISA value of 0.35 µg/mL. This outcome concerns the subjects who received the RTS,S or Engerix-B vaccine co-administered with Synflorix. Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix-B Regimen A groups.	At Month 3, aka at one month post Dose 3 of Synflorix
Secondary	Pneumococcal Antibody Concentrations Against Synflorix Pneumococcal Vaccine Serotypes at Month 17	Antibody concentrations were measured by GSK assay, and expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The pneumococcal vaccine serotypes assessed were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The cut-off of the assay, by GSK assay, was greater than or equal to (>=) 0.2 µg/mL. This corresponds to the standard ELISA value of 0.35 µg/mL. This outcome concerns the subjects who received the RTS,S or Engerix -B vaccine co-administered with Synflorix. Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix -B Regimen A groups.	At Month 17, aka one month post the Month 16 booster dose of Synflorix
Secondary	Titers for Opsonophagocytic Activity Against Synflorix Pneumococcal Vaccine Serotypes at Month 3	The pneumococcal vaccine serotypes assessed were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Streptococcus pneumoniae opsonophagocytic activity was presented as the dilution of serum (opsonic titer) able to sustain 50 % killing of live pneumococci under the assay conditions, expressed as geometric mean titers (GMTs). The cut-off of the assay was an opsonic dilution >= 8. This outcome concerns the subjects who received the RTS,S or Engerix-B vaccine co-administered with Synflorix. Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix-B Regimen A groups.	At Month 3, aka at one month (1M) post Dose 3 of Synflorix
Secondary	Titers for Opsonophagocytic Activity Against Synflorix Pneumococcal Vaccine Serotypes at Month 17	The pneumococcal vaccine serotypes assessed were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Streptococcus pneumoniae opsonophagocytic activity was presented as the dilution of serum (opsonic titer) able to sustain 50 % killing of live pneumococci under the assay conditions, expressed as geometric mean titers (GMTs). The cut-off of the assay was an opsonic dilution >= 8. This outcome concerns the subjects who received the RTS,S or Engerix -B vaccine co-administered with Synflorix . Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix -B Regimen A groups.	At Month 17, aka one month post the Month 16 booster dose of Synflorix
Secondary	Anti-protein D (PD) Antibody Concentrations at Month 3	Anti-PD antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off value of greater than or equal to 100 EL.U/mL. This outcome concerns the subjects who received the RTS,S or Engerix-B vaccine co-administered with Synflorix. Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix-B Regimen A groups.	At Month 3, aka at one month post Dose 3 of Synflorix
Secondary	Anti-protein D (PD) Antibody Concentrations at Month 17	Anti-PD antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off value of greater than or equal to 100 EL.U/mL. This outcome concerns the subjects who received the RTS,S or Engerix -B vaccine co-administered with Synflorix. Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix -B Regimen A groups.	At Month 17, aka one month post the Month 16 booster dose of Synflorix
Secondary	Concentrations of Antibodies Against Acellular B-pertussis (BPT) at Day 0 and at Month 3	The antibodies against BPT assessed were against pertussis toxoid (anti-PT), against filamentous haemagglutinin (anti-FHA), and against pertactin (anti-PRN). Concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off value of greater than or equal to (>=) 5 EL.U/mL. The table shows results for study groups pooled by primary vaccine administered (RTS,S vs Engerix -B)	At Day 0 and at Month 3 (one month post Dose 3 of Infanrix-Hib)
Secondary	Anti-Rotavirus (Anti-RV) Antibody Concentrations	Anti-Rotavirus (anti-RV) antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs). The cut-off of the assay was the seropositive cut-off value of greater than or equal to (>=) 20 units per milliliter (U/mL). This outcome measure was assessed in subjects who were administered Rotarix as part of an EPI regimen, with and without RTS,S vaccine co-administration. This outcome concerns the subjects who received the RTS,S or Engerix-B vaccine co-administered with Rotarix. Results presented are for the study groups pooled by RTS,S or Engerix-B vaccine co-administration, that is, for the RTS,S Regimen B and Engerix-B Regimen B groups.	At Month 3, aka one month post Dose 2 of Rotarix
Secondary	Number of Subjects With Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling at the site of injection. All solicited local symptoms assessed were considered by the investigator as causally related to the study vaccination. Analysis for this outcome was performed solely for the 7-days follow-up periods following the primary vaccination with RTS,S vaccine or Engerix-B (at Day 0, and Months 1 and 2). Data presented are those for any occurrence of the assessed solicited local symptoms, that is, the occurrences of these symptoms regardless of their intensity grade.	Within the 7-day follow-up period (Days 0-6) after administration of Dose (D) 1, 2 and 3, respectively, with RTS,S or Engerix-B vaccine
Secondary	Number of Subjects With Solicited General Symptoms	Assessed solicited general symptoms were fever, irritability/fussiness, drowsiness, and loss of appetite. Fever was defined as axillary temperature higher than (>) 37.5 degrees Celsius (°C). Analysis for this outcome was performed solely for the 7-days follow-up periods following the primary vaccination with RTS,S vaccine or Engerix-B (at Day 0, and Months 1 and 2). Data presented are those for any occurrence of the assessed solicited general symptoms, that is, the occurrences of these symptoms regardless of their intensity grade or relationship to vaccination.	Within the 7-day follow-up period (Days 0-6) after administration of Dose (D) 1, 2 and 3, respectively, with RTS,S or Engerix-B vaccine
Secondary	Number of Subjects With Potential Immune Mediated Disorders (pIMDs) From Day 0 to Month 8	A potential immune mediated disorder (pIMD) was defined as an event about which concerns arose that vaccination may have interfered with immunological self-tolerance of the subjects. IMDs assessed included among others neuroinflammatory disorders (such as optic neuritis, multiple sclerosis, or encephalitis), musculoskeletal disorders (such as cutaneous lupus, rheumatoid arthritis, juvenile arthritis, or psoriatic arthropathy), gastrointestinal disorders (ulcerative colitis and ulcerative proctitis, celiac disease), metabolic diseases (such as autoimmune thyroiditis, or diabetes Mellitus Type 1, Addison's disease), skin disorders (such as psoriasis or vitiligo), and other disorders such as vasculitis, pernicious anemia, or, sarcoidosis.	From Day 0 to Month 8
Secondary	Number of Subjects With Potential Immune Mediated Disorders (pIMDs) From Day 0 to Month 26	A potential immune mediated disorder (pIMD) was defined as an event about which concerns arose that vaccination may have interfered with immunological self-tolerance of the subjects. IMDs assessed included among others neuroinflammatory disorders (such as optic neuritis, multiple sclerosis, or encephalitis), musculoskeletal disorders (such as cutaneous lupus, rheumatoid arthritis, juvenile arthritis, or psoriatic arthropathy), gastrointestinal disorders (ulcerative colitis and ulcerative proctitis, celiac disease), metabolic diseases (such as autoimmune thyroiditis, or diabetes Mellitus Type 1, Addison's disease), skin disorders (such as psoriasis or vitiligo), and other disorders such as vasculitis, pernicious anemia, or, sarcoidosis.	From Day 0 to Month 26
Secondary	Number of Subjects With Potential Immune Mediated Disorders (pIMDs) From Day 0 up to Study End (Month 51)	A potential immune mediated disorder (pIMD) was defined as an event about which concerns arose that vaccination may have interfered with immunological self-tolerance of the subjects. IMDs assessed included among others neuroinflammatory disorders (such as optic neuritis, multiple sclerosis, or encephalitis), musculoskeletal disorders (such as cutaneous lupus, rheumatoid arthritis, juvenile arthritis, or psoriatic arthropathy), gastrointestinal disorders (ulcerative colitis and ulcerative proctitis, celiac disease), metabolic diseases (such as autoimmune thyroiditis, or diabetes Mellitus Type 1, Addison's disease), skin disorders (such as psoriasis or vitiligo), and other disorders such as vasculitis, pernicious anemia, or, sarcoidosis.	From Day 0 up to Study End (Month 51)
Secondary	Number of Subjects With Unsolicited Adverse Events (AEs)	An unsolicited AE was defined as an 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.	Within the 30-day follow-up periods (Days 0-29) after vaccination with RTS,S vaccine or Engerix-B
Secondary	Number of Subjects With Any and Fatal Serious Adverse Events (SAEs) Within the 30-day Follow-up Periods (Days 0-29)	A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or a reported adverse event of specific interest such as seizures occurring within a 30-day period of vaccination, immune-mediated disorders, and specific autoimmune diseases. A fatal SAE was defined as a SAE resulting in the death of the study subject.	Within the 30-day follow-up periods (Days 0-29) after vaccination with RTS,S vaccine or Engerix-B
Secondary	Number of Subjects With Any and Fatal Serious Adverse Events (SAEs) From Day 0 to Month 8	A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or a reported adverse event of specific interest such as seizures occurring within a 30-day period of vaccination, immune-mediated disorders, and specific autoimmune diseases. A fatal SAE was defined as a SAE resulting in the death of the study subject.	From Day 0 to Month 8
Secondary	Number of Subjects With Any and Fatal Serious Adverse Events (SAEs) From Day 0 to Month 26	A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or a reported adverse event of specific interest such as seizures occurring within a 30-day period of vaccination, immune-mediated disorders, and specific autoimmune diseases. A fatal SAE was defined as a SAE resulting in the death of the study subject.	From Day 0 to Month 26
Secondary	Number of Subjects With Any, Fatal and Related Serious Adverse Events (SAEs) From Day 0 up to Study End (Month 51)	A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or a reported adverse event of specific interest such as seizures occurring within a 30-day period of vaccination, immune-mediated disorders, and specific autoimmune diseases. A fatal SAE was defined as a SAE resulting in the death of the study subject. A related SAE was defined as a SAE assessed by the investigator as being causally related to vaccination.	From Day 0 up to Study End (Month 51)

External Links

•   IPD for this study will be made available via the Clinical Study Data Request site.