Back to resultsStudy to Evaluate Immunogenicity of the Hepatitis B Antigen of the GSK Biologicals' Candidate Malaria Vaccine (257049)
Primary Purpose
Malaria, Malaria Vaccines
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
GlaxoSmithKline (GSK) Biologicals' candidate Plasmodium falciparum malaria vaccine 257049
Engerix-B™ vaccine
Infanrix/Hib™ vaccine
Polio Sabin™ vaccine
Rotarix™ vaccine
Synflorix™ vaccine
Measles vaccine
Yellow fever vaccine
Sponsored by
About this trial
This is an interventional prevention trial for Malaria focused on measuring Africa, Plasmodium falciparum, Malaria vaccine, hepatitis B, EPI
Eligibility Criteria
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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Active Comparator
Active Comparator
Arm Label
RTS,S Regimen A Lot 1 Group
RTS,S Regimen A Lot 2 Group
RTS,S Regimen A Lot 3 Group
RTS,S Regimen B Lot 1 Group
RTS,S Regimen B Lot 2 Group
RTS,S Regimen B Lot 3 Group
RTS,S Regimen C Lot 1 Group
RTS,S Regimen C Lot 2 Group
RTS,S Regimen C Lot 3 Group
Engerix B Regimen A Group
Engerix B Regimen B Group
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen A, with the RTS,S vaccine administered in its Lot 1 formulation. This RTS,S Vaccination Regimen A included 3 doses of RTS,S vaccine, Lot 1, co-administered with Infanrix™-Hib, Polio Sabin™ and Synflorix™, at Weeks 0, 4 and 8, and 2 doses of Rotarix™ vaccine, at Weeks 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen A, with the RTS,S vaccine administered in its Lot 2 formulation. This RTS,S Vaccination Regimen A included 3 doses of RTS,S vaccine, Lot 2, co-administered with Infanrix™-Hib, Polio Sabin™ and Synflorix™, at Weeks 0, 4 and 8, and 2 doses of Rotarix™ vaccine, at Weeks 6 and 10. In addition, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen A, with the RTS,S vaccine administered in its Lot 3 formulation. This RTS,S Vaccination Regimen A included 3 doses of RTS,S vaccine, Lot 3, co-administered with Infanrix™-Hib, Polio Sabin™ and Synflorix™, at Weeks 0, 4 and 8, and 2 doses of Rotarix™ vaccine, at Weeks 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen B, with the RTS,S vaccine administered in its Lot 1 formulation. This RTS,S Vaccination Regimen B included 3 doses of RTS,S vaccine, Lot 1, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 4 and 8, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen B, with the RTS,S vaccine administered in its Lot 2 formulation. This RTS,S Vaccination Regimen B included 3 doses of RTS,S vaccine, Lot 2, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 4 and 8, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen B, with the RTS,S vaccine administered in its Lot 3 formulation. This RTS,S Vaccination Regimen B included 3 doses of RTS,S vaccine, Lot 3, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 4 and 8, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen C, with the RTS,S vaccine administered in its Lot 1 formulation. This RTS,S Vaccination Regimen C included 3 doses of RTS,S vaccine, Lot 1, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 6 and 10, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen C, with the RTS,S vaccine administered in its Lot 2 formulation. This RTS,S Vaccination Regimen C included 3 doses of RTS,S vaccine, Lot 2, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 6 and 10, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen C, with the RTS,S vaccine administered in its Lot 3 formulation. This RTS,S Vaccination Regimen C included 3 doses of RTS,S vaccine, Lot 3, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 6 and 10, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the Engerix-B Vaccination Regimen A. This regimen included 3 doses of Engerix B™ co-administered with Infanrix™-Hib, Polio Sabin™ and Synflorix™ at Weeks 0, 4 and 8, and 2 doses of Rotarix™, at Weeks 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. Engerix B™ was administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the Engerix-B Vaccination Regimen B. This regimen included 3 doses of Engerix B™ co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™ vaccine, at Weeks 4 and 8, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. Engerix B™ was administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Outcomes
Primary Outcome Measures
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).
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).
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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)
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01345240
Brief Title
Study to Evaluate Immunogenicity of the Hepatitis B Antigen of the GSK Biologicals' Candidate Malaria Vaccine (257049)
Official Title
Immunogenicity of the Hepatitis B Antigen of the GSK Biologicals' Candidate Malaria Vaccine (257049)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
November 17, 2011 (Actual)
Primary Completion Date
January 9, 2013 (Actual)
Study Completion Date
February 9, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria, Malaria Vaccines
Keywords
Africa, Plasmodium falciparum, Malaria vaccine, hepatitis B, EPI
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
705 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RTS,S Regimen A Lot 1 Group
Arm Type
Experimental
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen A, with the RTS,S vaccine administered in its Lot 1 formulation. This RTS,S Vaccination Regimen A included 3 doses of RTS,S vaccine, Lot 1, co-administered with Infanrix™-Hib, Polio Sabin™ and Synflorix™, at Weeks 0, 4 and 8, and 2 doses of Rotarix™ vaccine, at Weeks 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Arm Title
RTS,S Regimen A Lot 2 Group
Arm Type
Experimental
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen A, with the RTS,S vaccine administered in its Lot 2 formulation. This RTS,S Vaccination Regimen A included 3 doses of RTS,S vaccine, Lot 2, co-administered with Infanrix™-Hib, Polio Sabin™ and Synflorix™, at Weeks 0, 4 and 8, and 2 doses of Rotarix™ vaccine, at Weeks 6 and 10. In addition, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Arm Title
RTS,S Regimen A Lot 3 Group
Arm Type
Experimental
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen A, with the RTS,S vaccine administered in its Lot 3 formulation. This RTS,S Vaccination Regimen A included 3 doses of RTS,S vaccine, Lot 3, co-administered with Infanrix™-Hib, Polio Sabin™ and Synflorix™, at Weeks 0, 4 and 8, and 2 doses of Rotarix™ vaccine, at Weeks 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Arm Title
RTS,S Regimen B Lot 1 Group
Arm Type
Experimental
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen B, with the RTS,S vaccine administered in its Lot 1 formulation. This RTS,S Vaccination Regimen B included 3 doses of RTS,S vaccine, Lot 1, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 4 and 8, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Arm Title
RTS,S Regimen B Lot 2 Group
Arm Type
Experimental
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen B, with the RTS,S vaccine administered in its Lot 2 formulation. This RTS,S Vaccination Regimen B included 3 doses of RTS,S vaccine, Lot 2, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 4 and 8, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Arm Title
RTS,S Regimen B Lot 3 Group
Arm Type
Experimental
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen B, with the RTS,S vaccine administered in its Lot 3 formulation. This RTS,S Vaccination Regimen B included 3 doses of RTS,S vaccine, Lot 3, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 4 and 8, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Arm Title
RTS,S Regimen C Lot 1 Group
Arm Type
Experimental
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen C, with the RTS,S vaccine administered in its Lot 1 formulation. This RTS,S Vaccination Regimen C included 3 doses of RTS,S vaccine, Lot 1, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 6 and 10, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Arm Title
RTS,S Regimen C Lot 2 Group
Arm Type
Experimental
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen C, with the RTS,S vaccine administered in its Lot 2 formulation. This RTS,S Vaccination Regimen C included 3 doses of RTS,S vaccine, Lot 2, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 6 and 10, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Arm Title
RTS,S Regimen C Lot 3 Group
Arm Type
Experimental
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the RTS,S Vaccination Regimen C, with the RTS,S vaccine administered in its Lot 3 formulation. This RTS,S Vaccination Regimen C included 3 doses of RTS,S vaccine, Lot 3, co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™, at Weeks 6 and 10, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. The RTS,S vaccine and Engerix B™ were administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Arm Title
Engerix B Regimen A Group
Arm Type
Active Comparator
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the Engerix-B Vaccination Regimen A. This regimen included 3 doses of Engerix B™ co-administered with Infanrix™-Hib, Polio Sabin™ and Synflorix™ at Weeks 0, 4 and 8, and 2 doses of Rotarix™, at Weeks 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. Engerix B™ was administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Arm Title
Engerix B Regimen B Group
Arm Type
Active Comparator
Arm Description
Subjects, healthy male and female infants between 8 and 12 weeks of age inclusive at the time of first vaccination, received the Engerix-B Vaccination Regimen B. This regimen included 3 doses of Engerix B™ co-administered with Infanrix™-Hib and Polio Sabin™, at Weeks 0, 4 and 8, 2 doses of Rotarix™ vaccine, at Weeks 4 and 8, and 3 doses of Synflorix™ at Weeks 2, 6 and 10. Additionally, subjects also received one dose of vaccine against yellow fever and against measles, at Week 32, and one booster dose of Infanrix™-Hib and Synflorix™, at Month 16, and one booster dose of Engerix B™ vaccine, at Month 50. Engerix B™ was administered intramuscularly (IM) in the left anterolateral thigh, Infanrix™-Hib IM in the right deltoid, Synflorix™ IM in the right anterolateral thigh, and Rotarix™ and Polio Sabin™ orally. The measles and yellow fever vaccines were administered IM in the deltoid.
Intervention Type
Biological
Intervention Name(s)
GlaxoSmithKline (GSK) Biologicals' candidate Plasmodium falciparum malaria vaccine 257049
Intervention Description
Children enrolled in 9 groups will receive 3 doses of the candidate malaria vaccine (Lot 1, 2 and 3) by intramuscular injection.
Intervention Type
Biological
Intervention Name(s)
Engerix-B™ vaccine
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Infanrix/Hib™ vaccine
Intervention Description
Children enrolled in all 11 groups will receive 4 doses of Infanrix/Hib™ vaccine by intramuscular injection
Intervention Type
Biological
Intervention Name(s)
Polio Sabin™ vaccine
Intervention Description
Children enrolled in all 11 groups will receive 3 doses of Polio Sabin™ by intramuscular injection.
Intervention Type
Biological
Intervention Name(s)
Rotarix™ vaccine
Intervention Description
Children enrolled in all 11 groups will receive 2 doses of oral Rotarix™ vaccine.
Intervention Type
Biological
Intervention Name(s)
Synflorix™ vaccine
Intervention Description
Children enrolled in all 11 groups will receive 4 doses of Synflorix™ vaccine by intramuscular injection.
Intervention Type
Biological
Intervention Name(s)
Measles vaccine
Intervention Description
Children enrolled in all 11 groups will receive 1 dose of measles vaccine by intramuscular injection.
Intervention Type
Biological
Intervention Name(s)
Yellow fever vaccine
Intervention Description
Children enrolled in all 11 groups will receive 1 dose of yellow fever vaccine by intramuscular injection.
Primary Outcome Measure Information:
Title
Percentage of Seroprotected Subjects Against Anti-Hepatitis B (HBs) Antigen
Description
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).
Time Frame
At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Title
Anti-Hepatitis B (HBs) Antibody Concentrations for RTS,S Group and Engerix B Group
Description
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).
Time Frame
At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Title
Anti-Hepatitis B (HBs) Antibody Concentrations for All Study Groups
Description
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.
Time Frame
At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Secondary Outcome Measure Information:
Title
Anti-Hepatitis B (HBs) Antibody Concentrations at Month 3
Description
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.
Time Frame
At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Title
Anti-Hepatitis B (HBs) Antibody Concentrations at Month 14 and 26
Description
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.
Time Frame
At Months 14 and 26, aka at 12 and 24 months post Dose 3 of RTS,S vaccine or Engerix-B
Title
Anti-Hepatitis B (HBs) Antibody Concentrations at Month 38, 50 and 51
Description
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.
Time Frame
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
Title
Concentrations of Antibodies to the Hepatitis B RF1 Surface Antigen (Anti-HBs RF1) at Month 3
Description
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.
Time Frame
At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Title
Concentrations of Antibodies to the Hepatitis B RF1 Surface Antigen (Anti-HBs RF1) at Month 51
Description
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.
Time Frame
At Month 51, aka one month post the Month 50 booster dose of Engerix-B
Title
Anti-circumsporozoite Protein (Anti-CS) Antibody Concentrations at Month 3
Description
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.
Time Frame
At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Title
Anti-circumsporozoite Protein (Anti-CS) Antibody Concentrations at Month 14
Description
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.
Time Frame
At Month 14, aka at 12 months post Dose 3 of RTS,S vaccine or Engerix-B
Title
Anti-circumsporozoite Protein (Anti-CS) Antibody Concentrations at Month 38 and 50
Description
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.
Time Frame
At Months 38 and 50, aka 36 and 48 months post Dose 3 of RTS,S vaccine or Engerix-B
Title
Pneumococcal Antibody Concentrations Against Synflorix Pneumococcal Vaccine Serotypes at Month 3
Description
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.
Time Frame
At Month 3, aka at one month post Dose 3 of Synflorix
Title
Pneumococcal Antibody Concentrations Against Synflorix Pneumococcal Vaccine Serotypes at Month 17
Description
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.
Time Frame
At Month 17, aka one month post the Month 16 booster dose of Synflorix
Title
Titers for Opsonophagocytic Activity Against Synflorix Pneumococcal Vaccine Serotypes at Month 3
Description
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.
Time Frame
At Month 3, aka at one month (1M) post Dose 3 of Synflorix
Title
Titers for Opsonophagocytic Activity Against Synflorix Pneumococcal Vaccine Serotypes at Month 17
Description
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.
Time Frame
At Month 17, aka one month post the Month 16 booster dose of Synflorix
Title
Anti-protein D (PD) Antibody Concentrations at Month 3
Description
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.
Time Frame
At Month 3, aka at one month post Dose 3 of Synflorix
Title
Anti-protein D (PD) Antibody Concentrations at Month 17
Description
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.
Time Frame
At Month 17, aka one month post the Month 16 booster dose of Synflorix
Title
Concentrations of Antibodies Against Acellular B-pertussis (BPT) at Day 0 and at Month 3
Description
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)
Time Frame
At Day 0 and at Month 3 (one month post Dose 3 of Infanrix-Hib)
Title
Anti-Rotavirus (Anti-RV) Antibody Concentrations
Description
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.
Time Frame
At Month 3, aka one month post Dose 2 of Rotarix
Title
Number of Subjects With Solicited Local Symptoms
Description
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.
Time Frame
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
Title
Number of Subjects With Solicited General Symptoms
Description
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.
Time Frame
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
Title
Number of Subjects With Potential Immune Mediated Disorders (pIMDs) From Day 0 to Month 8
Description
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.
Time Frame
From Day 0 to Month 8
Title
Number of Subjects With Potential Immune Mediated Disorders (pIMDs) From Day 0 to Month 26
Description
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.
Time Frame
From Day 0 to Month 26
Title
Number of Subjects With Potential Immune Mediated Disorders (pIMDs) From Day 0 up to Study End (Month 51)
Description
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.
Time Frame
From Day 0 up to Study End (Month 51)
Title
Number of Subjects With Unsolicited Adverse Events (AEs)
Description
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.
Time Frame
Within the 30-day follow-up periods (Days 0-29) after vaccination with RTS,S vaccine or Engerix-B
Title
Number of Subjects With Any and Fatal Serious Adverse Events (SAEs) Within the 30-day Follow-up Periods (Days 0-29)
Description
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.
Time Frame
Within the 30-day follow-up periods (Days 0-29) after vaccination with RTS,S vaccine or Engerix-B
Title
Number of Subjects With Any and Fatal Serious Adverse Events (SAEs) From Day 0 to Month 8
Description
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.
Time Frame
From Day 0 to Month 8
Title
Number of Subjects With Any and Fatal Serious Adverse Events (SAEs) From Day 0 to Month 26
Description
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.
Time Frame
From Day 0 to Month 26
Title
Number of Subjects With Any, Fatal and Related Serious Adverse Events (SAEs) From Day 0 up to Study End (Month 51)
Description
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.
Time Frame
From Day 0 up to Study End (Month 51)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Weeks
Maximum Age & Unit of Time
12 Weeks
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Ouagadougou 01
Country
Burkina Faso
Facility Name
GSK Investigational Site
City
Kumasi
Country
Ghana
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD is available via the Clinical Study Data Request site (click on the link provided below).
IPD Sharing Time Frame
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
https://clinicalstudydatarequest.com
Citations:
PubMed Identifier
29630438
Citation
Valea 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.
Results Reference
background
Links:
URL
https://clinicalstudydatarequest.com
Description
IPD for this study will be made available via the Clinical Study Data Request site.
Learn more about this trial
Study to Evaluate Immunogenicity of the Hepatitis B Antigen of the GSK Biologicals' Candidate Malaria Vaccine (257049)
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