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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00289185
• Collaborator: (none)
• Enrollment: 340
• Location: 1
• Arms: 2
• Actual Duration (Months): 27.6
• Patients Per Site Per Month: 12.3

Study Details

Study Description

Brief Summary

GSK Biologicals in partnership with the Malaria Vaccine Initiative at PATH is developing a candidate malaria vaccine GSK 257049 for the routine immunization of infants and children living in malaria endemic areas. The vaccine would offer protection against malaria disease due to the parasite Plasmodium falciparum. The vaccine would also provide protection against infection with hepatitis B virus (HBV).

In order to integrate the malaria vaccine into the EPI regimen in malaria-endemic regions, a new variant RTS,S/AS02D (0.5 mL dose) has been developed.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Condition or Disease	Intervention/Treatment	Phase
Malaria; Malaria Vaccines	Biological: RTS,S/AS02D; Biological: Engerix-B®; Biological: TETRActHib™	Phase 2

Detailed Description

This is a phase 2b trial designed to evaluate the safety and immunogenicity of RTS,S/AS02D when co-administered with a multivalent DTPw/Hib (Aventis Pasteur's TETRActHib vaccine). Infants randomized to the control group will receive a licensed hepatitis B vaccine, Engerix-B in place of RTS,S/AS02D.

Data pertaining to RTS,S/AS02D or Engerix-B will be collected in a double blinded manner; data relating to TETRActHib will be collected in an open fashion.

Oral polio vaccine (OPV) will be administered at birth, 8, 12, 16 weeks in co-administration with other vaccines and will not be administered as part of this protocol. Antibody titers to OPV will not be assessed as part of this protocol.

Study Design

• Study Type: Interventional
• Actual Enrollment: 340 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase IIb Randomized, Double-blind, Controlled Study of the Safety, Immunogenicity and Proof-of-concept of RTS,S/AS02D, a Candidate Malaria Vaccine, When Incorporated Into an Expanded Program on Immunization (EPI) Regimen That Includes DTPw/Hib in Infants Living in a Malaria-endemic Region.
• Actual Study Start Date: Sep 27, 2006
• Actual Primary Completion Date: Feb 11, 2008
• Actual Study Completion Date: Jan 15, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RTS,S/AS02D Group Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Biological: RTS,S/AS02D; 3-dose intramuscular injection in the thigh; Other Names: GSK 257146 RTS S/AS02D ; Biological: TETRActHib™; 3-dose intramuscular injection in the thigh.; Other Names: DTPw/Hib
Active Comparator: Engerix-B Group Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh..	Biological: Engerix-B®; 3-dose intramuscular injection in the thigh.; Biological: TETRActHib™; 3-dose intramuscular injection in the thigh.; Other Names: DTPw/Hib

Outcome Measures

Primary Outcome Measures

1. Concentrations of Antibodies Against Hepatitis B (Anti-HB) [Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.]

   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.

2. Number of Subjects With Serious Adverse Events (SAEs) [From Week 0 to Month 9.]

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

3. Concentrations of Antibodies Against Diphtheria (Anti-D) [Prior to vaccination at Week 0 (PRE), and at Month 3.]

   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.

4. Concentrations of Antibodies Against Tetanus (Anti-T) [Prior to vaccination at Week 0 (PRE), and at Month 3.]

   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.

5. Concentrations of Anti-polyribosyl Ribitol Phosphate Antibodies (Anti-PRP). [Prior to vaccination at Week 0 (PRE), and at Month 3.]

   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.

6. Number of Subjects With Serious Adverse Events (SAEs) [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.

7. Concentrations of Anti-Bordetella Pertussis Toxin Antibodies (Anti-BPT). [Prior to vaccination at Week 0 (PRE), and at Month 3.]

   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.

8. Number of Subjects With Hepatitis B Antibody (Anti-HB) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value [Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.]

   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.

9. Number of Subjects With Anti-diphtheria Antibody (Anti-D) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value [Prior to vaccination at Week 0 (PRE), and at Month 3.]

   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.

10. Number of Subjects With Anti-tetanus Antibody (Anti-T) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value [Prior to vaccination at Week 0 (PRE), and at Month 3.]

    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.

11. Number of Subjects With Anti-polyribosyl Ribitol Phosphate Antibody (Anti-PRP) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value [Prior to vaccination at Week 0 (PRE), and at Month 3.]

    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.

12. Number of Subjects With Anti-Bordetella Pertussis Toxin Antibody (Anti-BPT) Concentrations Equal to or Above (>=) the Seropositivity Cut-off Value [Prior to vaccination at Week 0 (PRE), and at Month 3.]

    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.

Secondary Outcome Measures

1. Concentrations of Anti-Circumsporozoite Protein (Anti-CS) Antibodies [Prior to vaccination at Week 0 (PRE), at Month 2, at Month 3 and at Month 9.]

   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.

2. Number of Subjects With Solicited Local Symptoms. [Within 7 days (Days 0-6) after vaccination with the RTS,S/AS02D or Engerix-B vaccine.]

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

3. Number of Subjects With Solicited Local Symptoms. [Within 7 days (Days 0-6) after vaccination with the TETRActHib vaccine.]

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

4. Number of Subjects With Solicited General Symptoms. [Within 7 days (Days 0-6) after vaccination]

   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).

5. Number of Subjects With Unsolicited Adverse Events (AEs). [Within 30 days (Days 0-29) after vaccination]

   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.

6. Number of Subjects With Serious Adverse Events (SAEs) [Throughout the entire study, from Week 0 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.

7. Time to First Malaria Infection [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).]

   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.

8. Number of Subjects Prevalent for Parasitemia [At Month 9]

   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.

9. Plasmodium Falciparum (P. Falciparum) Parasite Density in Subjects Prevalent for Parasitemia [At Month 9]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Weeks to 10 Weeks
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

• A male or female infant between 6 and 10 weeks of age at the time of first vaccination.

• Written or oral, signed or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child.

• Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits).

• Born to a mother who is HBsAg negative & HIV negative.

• Born after a normal gestation period (between 36 and 42 weeks).

• Subjects who live within a 5 km radius of a dispensary.

Exclusion criteria:

• Acute disease at the time of enrolment.

• Serious acute or chronic illness determined by clinical or physical examination and laboratory screening tests.

• Laboratory screening tests out of range for haemoglobin, total white cell count, platelets, ALT and creatinine.

• Previous vaccination with diphtheria, tetanus, pertussis (whole-cell or acellular), Hemophilus influenzae type b or hepatitis B vaccines.

• BCG administration within one week of proposed administration of a study vaccine.

• Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s).

• Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.

• Administration of immunoglobulins, blood transfusions or other blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.

• Previous participation in any other malaria vaccine trial.

• Simultaneous participation in any other clinical trial.

• Same sex twin.

• Maternal death.

• History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunizations.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.

• Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Dar-es-Salaam		Tanzania

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Abdulla S, Oberholzer R, Juma O, Kubhoja S, Machera F, Membi C, Omari S, Urassa A, Mshinda H, Jumanne A, Salim N, Shomari M, Aebi T, Schellenberg DM, Carter T, Villafana T, Demoitié MA, Dubois MC, Leach A, Lievens M, Vekemans J, Cohen J, Ballou WR, Tanner M. Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. N Engl J Med. 2008 Dec 11;359(24):2533-44. doi: 10.1056/NEJMoa0807773. Epub 2008 Dec 8.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00289185
• Other Study ID Numbers: 104298; 2015-001539-19
• First Posted: Feb 9, 2006
• Last Update Posted: Oct 29, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Coccidiosis; Parasitic Diseases; Malaria, Falciparum; Malaria
• Additional relevant MeSH terms: Malaria

Study Results

Participant Flow

Recruitment Details	A total of 340 subjects were enrolled for this study. The study comprised 2 phases, a double-blind phase, from Week 0 to Month 9 (2 months after the administration of the last vaccine dose), followed by a single-blind safety phase, from Month 9 to study end at Month 20.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Period Title: Overall Study
STARTED	170	170
COMPLETED	142	144
NOT COMPLETED	28	26

Baseline Characteristics

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group	Total
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Total of all reporting groups
Overall Participants	170	170	340
Age (Weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Weeks]	7.87 (0.83)	7.82 (0.77)	7.85 (0.80)
Sex: Female, Male (Count of Participants)
Female	85 50%	91 53.5%	176 51.8%
Male	85 50%	79 46.5%	164 48.2%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	148	149
Anti-HB - PRE (N=134;116)	13.0	14.3
Anti-HB - Month 2 (N=148;149)	16.9	111.8
Anti-HB - Month 3 (N=141;141)	113.8	667.4

2. Primary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	170	170
Number [Subject]	42	31

3. Primary Outcome

Title	Concentrations of Antibodies Against Diphtheria (Anti-D)
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in left anterolateral thigh, and the TETRActHib vaccine in the right anterolateral thigh.
Measure Participants	165	162
Anti-D - PRE (N=165;162)	NA	NA
Anti-D - Month 3 (N=151;149)	1.3	1.1

4. Primary Outcome

Title	Concentrations of Antibodies Against Tetanus (Anti-T)
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	165	162
Anti-T - PRE (N=165;162)	1.1	1.2
Anti-T - Month 3 (N=151;149)	4.2	3.0

5. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	165	162
Anti-PRP - PRE (N=165;162)	0.2	0.2
Anti-PRP - Month 3 (N=151;148)	19.3	14.3

6. Primary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	170	170
Number [Subject]	34	34

7. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	162	165
Anti-BPT - PRE (N=165;162)	7.6	7.6
Anti-BPT - Month 3 (N=144;148)	101.4	82.3

8. Primary Outcome

Title	Number of Subjects With Hepatitis B Antibody (Anti-HB) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	148	149
Anti-HB >= 10 mIU/mL - PRE (N=134;116)	45	44
Anti-HB >= 10 mIU/mL - Month 2 (N=148;149)	82	141
Anti-HB >= 10 mIU/mL - Month 3 (N=141;141)	133	141

9. Primary Outcome

Title	Number of Subjects With Anti-diphtheria Antibody (Anti-D) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	165	162
Anti-D >= 0.1 IU/mL - PRE (N=165;162)	27	24
Anti-D >= 0.1 IU/mL - Month 3 (N=151;149)	148	148

10. Primary Outcome

Title	Number of Subjects With Anti-tetanus Antibody (Anti-T) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	165	162
Anti-T >= 0.1 IU/mL - PRE (N=165;162)	156	155
Anti-T >= 0.1 IU/mL - Month 3 (N=151;149)	151	149

11. Primary Outcome

Title	Number of Subjects With Anti-polyribosyl Ribitol Phosphate Antibody (Anti-PRP) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	165	162
Anti-PRP >= 0.15 µg/mL - PRE (N=165;162)	86	78
Anti-PRP >= 0.15 µg/mL - Month 3 (N=151;148)	150	147

12. Primary Outcome

Title	Number of Subjects With Anti-Bordetella Pertussis Toxin Antibody (Anti-BPT) Concentrations Equal to or Above (>=) the Seropositivity Cut-off Value
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	165	162
Anti-BPT >= 15 EL.U/mL - PRE (N=165;162)	2	1
Anti-BPT >= 15 EL.U/mL - Month 3 (N=144;148)	142	148

13. Secondary Outcome

Title	Concentrations of Anti-Circumsporozoite Protein (Anti-CS) Antibodies
Description	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	156	151
Anti-CS - PRE (N=152;141)	NA	NA
Anti-CS - Month 2 (N=156;151)	NA	28.9
Anti-CS - Month 3 (N=144;143)	NA	69.5
Anti-CS - Month 9 (N=147;143)	NA	6.2

14. Secondary Outcome

Title	Number of Subjects With Solicited Local Symptoms.
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	170	170
Pain	167	161
Swelling	17	19

15. Secondary Outcome

Title	Number of Subjects With Solicited Local Symptoms.
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	170	170
Pain	169	168
Swelling	68	67

16. Secondary Outcome

Title	Number of Subjects With Solicited General Symptoms.
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	170	170
Drowsiness	4	3
Fever (Temperature ≥ 37.5°C)	52	103
Irritability	71	81
Loss of Appetite	5	5

17. Secondary Outcome

Title	Number of Subjects With Unsolicited Adverse Events (AEs).
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	170	170
Number [Subjects]	141	137

18. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	170	170
Number [Subjects]	62	57

19. Secondary Outcome

Title	Time to First Malaria Infection
Description	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).

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	151	146
Number [n/PYAR]	0.29	0.12

20. Secondary Outcome

Title	Number of Subjects Prevalent for Parasitemia
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group	RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	92	93
Number [Subjects]	1	0

21. Secondary Outcome

Title	Plasmodium Falciparum (P. Falciparum) Parasite Density in Subjects Prevalent for Parasitemia
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Engerix-B Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.
Measure Participants	1
Mean (Full Range) [Parasite per microliter (µL)]	23276

Adverse Events

Time Frame	Time frames for adverse events (AEs) reporting were the 7-day (Days 0-6) and 21-day (Days 0-20) periods post vaccination for solicited symptoms and unsolicited AES, respectively. Serious adverse events were assessed throughout, from Week 0 to Month 20.
Arm/Group Title	Engerix-B Group		RTS,S/AS02D Group
Arm/Group Description	Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.		Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in left anterolateral thigh, and the TETRActHib vaccine in the right anterolateral thigh.
All Cause Mortality
	Engerix-B Group		RTS,S/AS02D Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Engerix-B Group		RTS,S/AS02D Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/170 (36.5%)		57/170 (33.5%)
Blood and lymphatic system disorders
Anaemia	16/170 (9.4%)		16/170 (9.4%)
Lymphadenitis	0/170 (0%)		3/170 (1.8%)
General disorders
Pyrexia	0/170 (0%)		1/170 (0.6%)
Hepatobiliary disorders
Hepatitis toxic	0/170 (0%)		1/170 (0.6%)
Infections and infestations
Abscess	2/170 (1.2%)		2/170 (1.2%)
Abscess limb	1/170 (0.6%)		0/170 (0%)
Abscess neck	1/170 (0.6%)		0/170 (0%)
Acarodermatitis	2/170 (1.2%)		0/170 (0%)
Bronchiolitis	1/170 (0.6%)		2/170 (1.2%)
Cellulitis	1/170 (0.6%)		0/170 (0%)
Cerebral malaria	0/170 (0%)		1/170 (0.6%)
Dysentery	1/170 (0.6%)		0/170 (0%)
Gastroenteritis	12/170 (7.1%)		16/170 (9.4%)
Malaria	1/170 (0.6%)		0/170 (0%)
Measles	1/170 (0.6%)		0/170 (0%)
Meningitis viral	1/170 (0.6%)		1/170 (0.6%)
Plasmodium falciparum infection	25/170 (14.7%)		19/170 (11.2%)
Pneumonia	36/170 (21.2%)		25/170 (14.7%)
Pneumonia viral	2/170 (1.2%)		0/170 (0%)
Pyoderma	1/170 (0.6%)		0/170 (0%)
Sepsis	2/170 (1.2%)		2/170 (1.2%)
Upper respiratory tract infection	3/170 (1.8%)		2/170 (1.2%)
Urinary tract infection	3/170 (1.8%)		4/170 (2.4%)
Viral infection	0/170 (0%)		1/170 (0.6%)
Injury, poisoning and procedural complications
Poisoning	1/170 (0.6%)		1/170 (0.6%)
Thermal burn	1/170 (0.6%)		0/170 (0%)
Nervous system disorders
Convulsion	2/170 (1.2%)		2/170 (1.2%)
Febrile convulsion	2/170 (1.2%)		5/170 (2.9%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/170 (0%)		1/170 (0.6%)
Bronchial hyperreactivity	3/170 (1.8%)		0/170 (0%)
Loeffler's syndrome	0/170 (0%)		1/170 (0.6%)
Pneumonia aspiration	0/170 (0%)		1/170 (0.6%)
Pulmonary pneumatocele	0/170 (0%)		1/170 (0.6%)
Other (Not Including Serious) Adverse Events
	Engerix-B Group		RTS,S/AS02D Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	169/170 (99.4%)		170/170 (100%)
Eye disorders
Conjunctivitis	6/170 (3.5%)		12/170 (7.1%)
General disorders
Pain	169/170 (99.4%)		168/170 (98.8%)
Swelling	68/170 (40%)		67/170 (39.4%)
Fever	52/170 (30.6%)		103/170 (60.6%)
Irritability	71/170 (41.8%)		81/170 (47.6%)
Infections and infestations
Acarodermatitis	4/170 (2.4%)		13/170 (7.6%)
Pneumonia	54/170 (31.8%)		49/170 (28.8%)
Skin infection	3/170 (1.8%)		11/170 (6.5%)
Respiratory, thoracic and mediastinal disorders
Cough	80/170 (47.1%)		80/170 (47.1%)
Rhinorrhoea	73/170 (42.9%)		56/170 (32.9%)
Skin and subcutaneous tissue disorders
Rash	1/170 (0.6%)		12/170 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.