Study of Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine in Tanzanian Infants

Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The cut-off of the assay was the seroprotection cut-off of 0.1 IU/mL. Month 3 results are the specific results for this primary outcome measure.

Time frame: Prior to vaccination at Week 0 (PRE), and at Month 3.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

Concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The cut-off of the assay was the seroprotection cut-off of 10 mIU/mL. Month 3 results are the specific results for this primary outcome measure.

Time frame: Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The cut-off of the assay was the seroprotection cut-off of 0.1 IU/mL. Month 3 results are the specific results for this primary outcome measure.

Time frame: Prior to vaccination at Week 0 (PRE), and at Month 3.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off of 15 EL.U/mL. Month 3 results are the specific results for this primary outcome measure.

Time frame: Prior to vaccination at Week 0 (PRE), and at Month 3.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The cut-off of the assay is the seroprotection cut-off value of 0.15 µg/mL. Month 3 results are the specific results for this primary outcome measure.

Time frame: Prior to vaccination at Week 0 (PRE), and at Month 3.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seropositivity cut-off value was 15 ELISA units per milliliter (EL.U/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.

Time frame: Prior to vaccination at Week 0 (PRE), and at Month 3.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.1 international unit per milliliter (IU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.

Time frame: Prior to vaccination at Week 0 (PRE), and at Month 3.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.15 microgram per milliliter (µg/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.

Time frame: Prior to vaccination at Week 0 (PRE), and at Month 3.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.1 international unit per milliliter (IU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.

Time frame: Prior to vaccination at Week 0 (PRE), and at Month 3.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

The seroprotection cut-off value was 10 milli-international units per milliliter (mIU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3. Month 3 results are the specific results for this primary outcome measure.

Time frame: Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Time frame: From Month 9 to Month 20.

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Time frame: From Week 0 to Month 9.

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.

Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations are expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off value of 0.5 EL.U/mL.

Time frame: Prior to vaccination at Week 0 (PRE), at Month 2, at Month 3 and at Month 9.

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity outcome variables were available.

Subjects prevalent for P. falciparum parasitemia were defined as subjects with the presence of P. falciparum asexual parasitemia above 0 per microliter (µL) on Giemsa stained thick blood films.

Time frame: At Month 9

Population: The analysis was performed on the According-to-Protocol cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome variables were available.

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Time frame: Throughout the entire study, from Week 0 to Month 20.

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.

Assessed solicited general symptoms were drowsiness, fever, irritability, and loss of appetite. Fever was defined as axillary temperature above or equal to (\>=) 37.5 degrees Celsius (°C).

Time frame: Within 7 days (Days 0-6) after vaccination

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.

Assessed solicited local symptoms were pain and swelling following vaccination with the TETRActHib vaccine..

Time frame: Within 7 days (Days 0-6) after vaccination with the TETRActHib vaccine.

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.

Assessed solicited local symptoms were pain and swelling following vaccination with the RTS,S/AS02D or Engerix-B vaccine.

Time frame: Within 7 days (Days 0-6) after vaccination with the RTS,S/AS02D or Engerix-B vaccine.

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.

An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

Time frame: Within 30 days (Days 0-29) after vaccination

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.

The parasite density in subjects prevalent for P. falciparum parasitemia (Subjects with the presence of P. falciparum asexual parasitemia above 0 per microliter (µL) on Giemsa stained thick blood films), was detected at a cross sectional time point 7 months after administration of Dose 3 of RTS,S or HBV vaccine (Month 9). Parasite density is expressed as mean, minimum and maximum density in parasite per µL. This outcome for solely assessed in the Engerix-B Group, as no subject in the RTS,S/AS02D was assessed as prevalent for parasitemia.

Time frame: At Month 9

Population: The analysis was performed on the According-to-Protocol cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome variables were available.

Malaria infection by Plasmodium falciparum (P. falciparum) was detected by active detection of infection (ADI) and passive case detection (PCD), and was defined as the presence of P. falciparum asexual parasitemia above 0 per microliter (µL) on Giemsa stained thick blood films. The time to first malaria infection is expressed in terms of rate of first malaria infection, that is, the number of malaria infection events reported (n) over the period elapsed until the event occurred (i.e. events per Persons Year at Risk \[PYAR\]) for each group.

Time frame: Over the period starting 14 days after Dose 3 of RTS,S or HBV vaccine and extending for 6 months thereafter (from Month 2.5 up to Month 9).

Population: The analysis was performed on the According-to-Protocol cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome variables were available.