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    Clinical Trial Results:
    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.

    Summary
    EudraCT number
    		 2015-001539-19
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    15 Jan 2009

    Results information
    Results version number
    		 v3(current)
    This version publication date
    22 Oct 2020
    First version publication date
    08 Jul 2015
    Other versions
    		 v1 , v2
    Version creation reason
    • Correction of full data set
    Results have been amended to account for consistency with other registries.

    Trial information

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    Trial identification
    Sponsor protocol code
    104298
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00289185
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND number: 10514
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l'Institut, 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Dec 2009
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Jan 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    -To describe the safety and reactogenicity of RTS,S/AS02D + TETRActHib (vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type B) co-administered as 3 doses intramuscularly in separate thighs to infants at 8, 12 and 16 weeks of age. -To demonstrate the non-inferiority of antibody responses to antigens D (diphteria), T (tetanus), Pw (whole-cell pertussis), Hib (Haemophilus influenzae type B) and HBs (hepatitis B), when administered as 3 doses of RTS,S/AS02D + TETRActHib at 8, 12 and 16 weeks of age compared to a regimen of 3 doses of Engerix-B (hepatitis B vaccine) + TETRActHib at the same age when assessed at 1 month post Dose 3.
    Protection of trial subjects
    Vaccinations took place the expanded program of immunization (EPI) clinic of the Bagamoyo District Hospital (BDH). All subjects were supervised closely for at least one hour following vaccination with appropriate medical treatment readily available to evaluate and treat any acute adverse events. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines. Subjects were followed-up for one month (minimum 30 days) following administration of the last dose of study vaccines. Subjects who could not be vaccinated on the originally scheduled were vaccinated within 7 days and undergo all study procedures for the visit on the same day as vaccination. In the particular case of any child found to be febrile (axillary temperature  37.5C), a blood slide was taken to investigate for malaria. Children were treated as appropriate for their condition and were followed up until resolution of any symptoms and vaccinated if their clinical symptoms resolved within 7 days. Those who could not be re-vaccinated within 7 days of their scheduled date continued all study procedures apart from receiving further study vaccinations. The parent(s)/guardian(s) of infants who are withdrawn from the study will be advised on an appropriate method of completing the infants’ vaccination regimen. In addition to above, subjects were followed-up for post-vaccination adverse events (AEs) and serious AEs (SAEs) according to the following timeframes: 7-day (Days 0-6) and 21-day (Days 0-20) periods post vaccination for solicited symptoms and unsolicited AES, respectively; SAEs were assessed throughout the entire study period, from Week 0 to Month 20.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Sep 2006
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 11 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Tanzania, United Republic of: 340
    Worldwide total number of subjects
    340
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    340
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    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.

    Pre-assignment
    Screening details
    		 Screening included the following: routine antenatal care to counsel/test for HIV infection in pregnancy, check for inclusion/exclusion criteria, vaccination contraindications/precautions & subjects’ medical history, & signing informed consent forms.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    The study was run as a double blind to Month 9, then as a single blind to Month 20. To Month 9, data pertaining to RTS,S/AS02D or Engerix-B were collected in a double blinded manner and data relating to TETRActHib in an open fashion. ‘Double blinded’ meant that the vaccine recipient and their parent(s)/guardian(s) as well as those responsible for the evaluation of safety, immunogenicity and efficacy endpoints were unaware which treatment, RTS,S/AS02D or Engerix-B, was administered to a subject.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Engerix-B Group
    Arm 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.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Engerix-B Junior
    Investigational medicinal product code
    HBV Paediatric 10
    Other name
    HBV, Engerix-B
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3-dose intramuscular injection in the thigh.

    Investigational medicinal product name
    TETRActHib
    Investigational medicinal product code
    DTPw+Hib
    Other name
    DTPw/Hib
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3-dose intramuscular injection in the thigh.

    Arm title
    		 RTS,S/AS02D Group
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TETRActHib
    Investigational medicinal product code
    DTPw+Hib
    Other name
    DTPw/Hib
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3-dose intramuscular injection in the thigh.

    Investigational medicinal product name
    Candidate Plasmodium falciparum Malaria vaccines
    Investigational medicinal product code
    RTS,S/AS02D
    Other name
    GSK 257146; RTS,S/AS02D
    Pharmaceutical forms
    Powder and suspension for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3-dose intramuscular injection in the thigh

    Number of subjects in period 1
    		Engerix-B Group RTS,S/AS02D Group
    Started
    170
    170
    Completed
    142
    144
    Not completed
    28
    26
         Consent withdrawn by subject
    4
    8
         Death
    1
    1
         Lost to follow-up
    23
    17

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Engerix-B Group
    Reporting 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.

    Reporting group title
    RTS,S/AS02D Group
    Reporting 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 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.

    Reporting group values
    		 Engerix-B Group RTS,S/AS02D Group Total
    Number of subjects
    		 170 170 340
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 170 170 340
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: weeks
        arithmetic mean (standard deviation)
    		 7.87 ( 0.83 ) 7.82 ( 0.77 ) -
    Gender categorical
    Units: Subjects
        Female
    		 85 91 176
        Male
    		 85 79 164

    End points

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    End points reporting groups
    Reporting group title
    Engerix-B Group
    Reporting 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.

    Reporting group title
    RTS,S/AS02D Group
    Reporting 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 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.

    Primary: Concentrations of antibodies against hepatitis B (Anti-HB)

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    End point title
    		 Concentrations of antibodies against hepatitis B (Anti-HB) [1]
    End point 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.
    End point type
    Primary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    148
    149
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        Anti-HB – PRE (N=134;116)
    13 (9.8 to 17.2)
    14.3 (10.8 to 19)
        Anti-HB – Month 2 (N=148;149)
    16.9 (13.5 to 21.2)
    111.8 (89.9 to 139)
        Anti-HB – Month 3 (N=141;141)
    113.8 (91.3 to 141.8)
    667.4 (533.8 to 834.4)
    No statistical analyses for this end point

    Primary: Number of subjects with serious adverse events (SAEs)

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    End point title
    		 Number of subjects with serious adverse events (SAEs) [2]
    End point description
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
    End point type
    Primary
    End point timeframe
    From Week 0 to Month 9.
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    170
    170
    Units: Subject
    42
    31
    No statistical analyses for this end point

    Primary: Concentrations of antibodies against diphtheria (Anti-D)

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    End point title
    		 Concentrations of antibodies against diphtheria (Anti-D) [3]
    End point 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. An arbitrary value is provided for GMC values for Week 0 time point because concentrations fell below the seroprotection cut-off of 0.1 IU/mL.
    End point type
    Primary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), and at Month 3.
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    165
    162
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Anti-D – PRE (N=165;162)
    0.1 (0.1 to 0.1)
    0.1 (0.1 to 0.1)
        Anti-D – Month 3 (N=151;149)
    1.3 (1.1 to 1.5)
    1.1 (1 to 1.3)
    No statistical analyses for this end point

    Primary: Concentrations of antibodies against tetanus (Anti-T)

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    End point title
    		 Concentrations of antibodies against tetanus (Anti-T) [4]
    End point 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.
    End point type
    Primary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), and at Month 3.
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    165
    162
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Anti-T – PRE (N=165;162)
    1.1 (0.9 to 1.4)
    1.2 (1 to 1.6)
        Anti-T – Month 3 (N=151;149)
    4.2 (3.6 to 4.8)
    3 (2.6 to 3.4)
    No statistical analyses for this end point

    Primary: Concentrations of anti-polyribosyl ribitol phosphate antibodies (Anti-PRP).

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    End point title
    		 Concentrations of anti-polyribosyl ribitol phosphate antibodies (Anti-PRP). [5]
    End point 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.
    End point type
    Primary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), and at Month 3.
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    165
    162
    Units: µg/mL
    geometric mean (confidence interval 95%)
        Anti-PRP – PRE (N=165;162)
    0.2 (0.2 to 0.2)
    0.2 (0.2 to 0.2)
        Anti-PRP – Month 3 (N=151;148)
    19.3 (15.6 to 24)
    14.3 (11.5 to 17.9)
    No statistical analyses for this end point

    Primary: Number of subjects with serious adverse events (SAEs)

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    End point title
    		 Number of subjects with serious adverse events (SAEs) [6]
    End point description
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
    End point type
    Primary
    End point timeframe
    From Month 9 to Month 20.
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    170
    170
    Units: Subjects
    34
    34
    No statistical analyses for this end point

    Primary: Concentrations of anti-Bordetella pertussis toxin antibodies (Anti-BPT).

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    End point title
    		 Concentrations of anti-Bordetella pertussis toxin antibodies (Anti-BPT).
    End point 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.
    End point type
    Primary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), and at Month 3.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    162
    165
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-BPT – PRE (N=165;162)
    7.6 (7.4 to 7.8)
    7.6 (7.4 to 7.7)
        Anti-BPT – Month 3 (N=144;148)
    101.4 (92.5 to 111.2)
    82.3 (75.4 to 89.9)
    Statistical analysis title
    		 Non-inferiority - Anti-BPT immune response
    Statistical analysis description
    The aim was to test the non-inferiority (NI) of 3 doses of RTS,S/AS02D vs 3 doses of HBV, both co-administered with DTPw/Hib, as regards antigens for BPT. NI was demonstrated if - ALL criteria to be met: 1) difference between groups in percent of seroprotection (SPR) < 10% for anti-PRP antibodies AND 2) geometric mean concentration (GMC) ratio between groups < 1.5 for anti-BPT antibodies.
    Comparison groups
    RTS,S/AS02D Group v Engerix-B Group
    Number of subjects included in analysis
    327
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.08
         upper limit
    		 1.4
    Notes
    [7] - This analysis concerns the NI assessment for anti-BPT immune response. GMC ratio between groups (Engerix-B over RTS,S/AS02D) as anti BPT antibody concentrations (expressed in %) was calculated as well as the 95% CI (standardized asymptotic) (criteria for success = lower limit of 95% CI of GMC ratio between groups < 1.5). Results from this analysis are to be combined with those for NI assessment for antigens for BPT to obtain an overall assessment of NI.

    Primary: Number of subjects with Hepatitis B Antibody (Anti-HB) concentrations equal to or above (>=) the seroprotection cut-off value

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    End point title
    		 Number of subjects with Hepatitis B Antibody (Anti-HB) concentrations equal to or above (>=) the seroprotection cut-off value
    End point 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.
    End point type
    Primary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    148
    149
    Units: Subjects
        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
    Statistical analysis title
    		 Non-inferiority - Anti-HB SPR immune response
    Statistical analysis description
    The aim was to test the non-inferiority (NI) of 3 doses of RTS,S/AS02D vs 3 doses of HBV, both co-administered with DTPw/Hib, as regards antigens for HB, D, T, PRP and BPT as assessed at Month 3. NI was demonstrated if - ALL criteria to be met: 1) difference between groups in percent of seroprotection (SPR) < 10% for anti-HB, -D, -T and PRP antibodies AND 2) geometric mean concentration (GMC) ratio between groups < 1.5 for anti-BPT antibodies.
    Comparison groups
    Engerix-B Group v RTS,S/AS02D Group
    Number of subjects included in analysis
    297
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    Parameter type
    		 Difference in %
    Point estimate
    -5.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.8
         upper limit
    		 2.9
    Notes
    [8] - This analysis assesses NI as regards anti-HB immune response. The difference between groups (Engerix-B minus RTS,S/AS02D) as regards SPR (expressed in %) was calculated as well as the 95% CI (standardized asymptotic) around this difference (criteria for success = lower limit of 95% CI of difference between groups in percent of SPR < 10%). Results from this analysis are to be combined with those for NI assessment for antigens for HB, D, T, PRP and BPT to obtain an overall assessment of NI.

    Primary: Number of subjects with anti-diphtheria antibody (Anti-D) concentrations equal to or above (>=) the seroprotection cut-off value

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    End point title
    		 Number of subjects with anti-diphtheria antibody (Anti-D) concentrations equal to or above (>=) the seroprotection cut-off value
    End point 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.
    End point type
    Primary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), and at Month 3.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    165
    162
    Units: Subjects
        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
    Statistical analysis title
    		 Non-inferiority - Anti-D SPR immune response
    Statistical analysis description
    The aim was to test the non-inferiority (NI) of 3 doses of RTS,S/AS02D vs 3 doses of HBV, both co-administered with DTPw/Hib, as regards antigens for HB, D, T, PRP and BPT as assessed at Month 3. NI was demonstrated if - ALL criteria to be met: 1) difference between groups in percent of seroprotection (SPR) < 10% for anti-HB, -D, -T and PRP antibodies AND 2) geometric mean concentration (GMC) ratio between groups < 1.5 for anti-BPT antibodies.
    Comparison groups
    Engerix-B Group v RTS,S/AS02D Group
    Number of subjects included in analysis
    327
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [9]
    Method
    Parameter type
    		 Difference in %
    Point estimate
    -1.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.09
         upper limit
    		 1.9
    Notes
    [9] - This analysis assesses NI as regards anti-D immune response. The difference between groups (Engerix-B minus RTS,S/AS02D) as regards SPR (expressed in %) was calculated as well as the 95% CI (standardized asymptotic) around this difference (criteria for success = lower limit of 95% CI of difference between groups in percent of SPR < 10%). Results from this analysis are to be combined with those for NI assessment for antigens for HB, D, T, PRP and BPT to obtain an overall assessment of NI.

    Primary: Number of subjects with anti-tetanus antibody (Anti-T) concentrations equal to or above (>=) the seroprotection cut-off value

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    End point title
    		 Number of subjects with anti-tetanus antibody (Anti-T) concentrations equal to or above (>=) the seroprotection cut-off value
    End point 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.
    End point type
    Primary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), and at Month 3.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    165
    162
    Units: Subjects
        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
    Statistical analysis title
    		 Non-inferiority - Anti-T SPR immune response
    Statistical analysis description
    The aim was to test the non-inferiority (NI) of 3 doses of RTS,S/AS02D vs 3 doses of HBV, both co-administered with DTPw/Hib, as regards antigens for HB, D, T, PRP and BPT as assessed at Month 3. NI was demonstrated if - ALL criteria to be met: 1) difference between groups in percent of seroprotection (SPR) < 10% for anti-HB, -D, -T and PRP antibodies AND 2) geometric mean concentration (GMC) ratio between groups < 1.5 for anti-BPT antibodies.
    Comparison groups
    Engerix-B Group v RTS,S/AS02D Group
    Number of subjects included in analysis
    327
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [10]
    Method
    Parameter type
    		 Difference in %
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.48
         upper limit
    		 2.51
    Notes
    [10] - This analysis assesses NI as regards anti-T immune response. The difference between groups (Engerix-B minus RTS,S/AS02D) as regards SPR (expressed in %) was calculated as well as the 95% CI (standardized asymptotic) around this difference (criteria for success = lower limit of 95% CI of difference between groups in percent of SPR < 10%). Results from this analysis are to be combined with those for NI assessment for antigens for HB, D, T, PRP and BPT to obtain an overall assessment of NI.

    Primary: Number of subjects with anti-polyribosyl ribitol phosphate antibody (Anti-PRP) concentrations equal to or above (>=) the seroprotection cut-off value

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    End point title
    		 Number of subjects with anti-polyribosyl ribitol phosphate antibody (Anti-PRP) concentrations equal to or above (>=) the seroprotection cut-off value
    End point 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.
    End point type
    Primary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), and at Month 3.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    165
    162
    Units: Subjects
        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
    Statistical analysis title
    		 Non-inferiority - Anti-PRP SPR immune response
    Statistical analysis description
    The aim was to test the non-inferiority (NI) of 3 doses of RTS,S/AS02D vs 3 doses of HBV, both co-administered with DTPw/Hib, as regards antigens for HB, D, T, PRP and BPT as assessed at Month 3. NI was demonstrated if - ALL criteria to be met: 1) difference between groups in percent of seroprotection (SPR) < 10% for anti-HB, -D, -T and PRP antibodies AND 2) geometric mean concentration (GMC) ratio between groups < 1.5 for anti-BPT antibodies.
    Comparison groups
    Engerix-B Group v RTS,S/AS02D Group
    Number of subjects included in analysis
    327
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [11]
    Method
    Parameter type
    		 Difference in %
    Point estimate
    0.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.04
         upper limit
    		 3.12
    Notes
    [11] - This analysis assesses NI as regards anti-PRP immune response. The difference between groups (Engerix-B minus RTS,S/AS02D) as regards SPR (expressed in %) was calculated as well as the 95% CI (standardized asymptotic) around this difference (criteria for success = lower limit of 95% CI of difference between groups in percent of SPR < 10%). Results from this analysis are to be combined with those for NI assessment for antigens for HB, D, T, PRP and BPT to obtain an overall assessment of NI.

    Primary: Number of subjects with anti-Bordetella pertussis toxin antibody (Anti-BPT) concentrations equal to or above (>=) the seropositivity cut-off value

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    End point title
    		 Number of subjects with anti-Bordetella pertussis toxin antibody (Anti-BPT) concentrations equal to or above (>=) the seropositivity cut-off value [12]
    End point 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.
    End point type
    Primary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), and at Month 3.
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    165
    162
    Units: Subjects
        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
    No statistical analyses for this end point

    Secondary: Concentrations of anti-Circumsporozoite protein (Anti-CS) antibodies

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    End point title
    		 Concentrations of anti-Circumsporozoite protein (Anti-CS) antibodies
    End point 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. Values below the cut-off of 0.5 EL.U/mL are considered arbitrary as concentrations fell off the seroprotection cut-off limit for all specified time points for the Engerix-B Group and for Week 0 in the RTS,S/AS02D Group.
    End point type
    Secondary
    End point timeframe
    Prior to vaccination at Week 0 (PRE), at Month 2, at Month 3 and at Month 9.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    156
    151
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-CS – PRE (N=152;141)
    0.4 (0.3 to 0.4)
    0.3 (0.3 to 0.4)
        Anti-CS – Month 2 (N=156;151)
    0.3 (0.3 to 0.3)
    28.9 (22.4 to 37.3)
        Anti-CS – Month 3 (N=144;143)
    0.3 (0.2 to 0.3)
    69.5 (53.9 to 89.6)
        Anti-CS – Month 9 (N=147;143)
    0.3 (0.3 to 0.3)
    6.2 (4.6 to 8.3)
    No statistical analyses for this end point

    Secondary: Number of subjects with solicited local symptoms.

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    End point title
    		 Number of subjects with solicited local symptoms.
    End point description
    Assessed solicited local symptoms were pain and swelling following vaccination with the RTS,S/AS02D or Engerix-B vaccine.
    End point type
    Secondary
    End point timeframe
    Within 7 days (Days 0-6) after vaccination with the RTS,S/AS02D or Engerix-B vaccine.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    170
    170
    Units: Subjects
        Pain
    167
    161
        Swelling
    17
    19
    No statistical analyses for this end point

    Secondary: Number of subjects with solicited local symptoms.

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    End point title
    		 Number of subjects with solicited local symptoms.
    End point description
    Assessed solicited local symptoms were pain and swelling following vaccination with the TETRActHib vaccine.
    End point type
    Secondary
    End point timeframe
    Within 7 days (Days 0-6) after vaccination with the TETRActHib vaccine.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    170
    170
    Units: Subjects
        Pain
    169
    168
        Swelling
    68
    67
    No statistical analyses for this end point

    Secondary: Number of subjects with solicited general symptoms.

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    End point title
    		 Number of subjects with solicited general symptoms.
    End point 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).
    End point type
    Secondary
    End point timeframe
    Within 7 days (Days 0-6) after vaccination
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    170
    170
    Units: Subjects
        Drowsiness
    4
    3
        Fever (Temperature ≥ 37.5°C)
    52
    103
        Irritability
    71
    81
        Loss of Appetite
    5
    5
    No statistical analyses for this end point

    Secondary: Number of subjects with unsolicited adverse events (AEs).

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    End point title
    		 Number of subjects with unsolicited adverse events (AEs).
    End point 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.
    End point type
    Secondary
    End point timeframe
    Within 30 days (Days 0–29) after vaccination
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    170
    170
    Units: Subjects
    141
    137
    No statistical analyses for this end point

    Secondary: Number of subjects with serious adverse events (SAEs)

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    End point title
    		 Number of subjects with serious adverse events (SAEs)
    End point description
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
    End point type
    Secondary
    End point timeframe
    Throughout the entire study, from Week 0 to Month 20.
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    170
    170
    Units: Subjects
    62
    57
    No statistical analyses for this end point

    Secondary: Time to first malaria infection

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    End point title
    		 Time to first malaria infection
    End point 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.
    End point type
    Secondary
    End point timeframe
    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).
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    151
    146
    Units: n/PYAR
        number (not applicable)
    0.29
    0.12
    No statistical analyses for this end point

    Secondary: Number of subjects prevalent for parasitemia

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    End point title
    		 Number of subjects prevalent for parasitemia
    End point 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.
    End point type
    Secondary
    End point timeframe
    At Month 9
    End point values
    		 Engerix-B Group RTS,S/AS02D Group
    Number of subjects analysed
    92
    93
    Units: Subjects
    1
    0
    No statistical analyses for this end point

    Secondary: Plasmodium falciparum (P. falciparum) parasite density in subjects prevalent for parasitemia

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    End point title
    		 Plasmodium falciparum (P. falciparum) parasite density in subjects prevalent for parasitemia [13]
    End point 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 Group was assessed as prevalent for parasitemia.
    End point type
    Secondary
    End point timeframe
    At Month 9
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Engerix-B Group
    Number of subjects analysed
    1
    Units: parasite/µL
        arithmetic mean (full range (min-max))
    23276 (23276 to 23276)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    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.
    Adverse event reporting additional description
    The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    12.1
    Reporting groups
    Reporting group title
    Engerix-B Group
    Reporting 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.

    Reporting group title
    RTS,S/AS02D Group
    Reporting 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 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.

    Serious adverse events
    		 Engerix-B Group RTS,S/AS02D Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    62 / 170 (36.47%)
    57 / 170 (33.53%)
         number of deaths (all causes)
    1
    1
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Poisoning
         subjects affected / exposed
    1 / 170 (0.59%)
    1 / 170 (0.59%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    1 / 170 (0.59%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    2 / 170 (1.18%)
    2 / 170 (1.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Febrile convulsion
         subjects affected / exposed
    2 / 170 (1.18%)
    5 / 170 (2.94%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    16 / 170 (9.41%)
    16 / 170 (9.41%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    0 / 170 (0.00%)
    3 / 170 (1.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 170 (0.00%)
    1 / 170 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis toxic
         subjects affected / exposed
    0 / 170 (0.00%)
    1 / 170 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 170 (0.00%)
    1 / 170 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    3 / 170 (1.76%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loeffler’s syndrome
         subjects affected / exposed
    0 / 170 (0.00%)
    1 / 170 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 170 (0.00%)
    1 / 170 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary pneumatocele
         subjects affected / exposed
    0 / 170 (0.00%)
    1 / 170 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    2 / 170 (1.18%)
    2 / 170 (1.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 170 (0.59%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    1 / 170 (0.59%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acarodermatitis
         subjects affected / exposed
    2 / 170 (1.18%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    1 / 170 (0.59%)
    2 / 170 (1.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 170 (0.59%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral malaria
         subjects affected / exposed
    0 / 170 (0.00%)
    1 / 170 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dysentery
         subjects affected / exposed
    1 / 170 (0.59%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    12 / 170 (7.06%)
    16 / 170 (9.41%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaria
         subjects affected / exposed
    1 / 170 (0.59%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Measles
         subjects affected / exposed
    1 / 170 (0.59%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    1 / 170 (0.59%)
    1 / 170 (0.59%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasmodium falciparum infection
         subjects affected / exposed
    25 / 170 (14.71%)
    19 / 170 (11.18%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    36 / 170 (21.18%)
    25 / 170 (14.71%)
         occurrences causally related to treatment / all
    0 / 36
    0 / 25
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    2 / 170 (1.18%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyoderma
         subjects affected / exposed
    1 / 170 (0.59%)
    0 / 170 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 170 (1.18%)
    2 / 170 (1.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 170 (1.76%)
    2 / 170 (1.18%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 170 (1.76%)
    4 / 170 (2.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 170 (0.00%)
    1 / 170 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Engerix-B Group RTS,S/AS02D Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    169 / 170 (99.41%)
    170 / 170 (100.00%)
    General disorders and administration site conditions
    Pain
    alternative assessment type: Systematic
         subjects affected / exposed
    169 / 170 (99.41%)
    168 / 170 (98.82%)
         occurrences all number
    169
    168
    Swelling
    alternative assessment type: Systematic
         subjects affected / exposed
    68 / 170 (40.00%)
    67 / 170 (39.41%)
         occurrences all number
    68
    67
    Fever
    alternative assessment type: Systematic
         subjects affected / exposed
    52 / 170 (30.59%)
    103 / 170 (60.59%)
         occurrences all number
    52
    103
    Irritability
    alternative assessment type: Systematic
         subjects affected / exposed
    71 / 170 (41.76%)
    81 / 170 (47.65%)
         occurrences all number
    71
    81
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    6 / 170 (3.53%)
    12 / 170 (7.06%)
         occurrences all number
    6
    12
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    80 / 170 (47.06%)
    80 / 170 (47.06%)
         occurrences all number
    80
    80
    Rhinorrhoea
         subjects affected / exposed
    73 / 170 (42.94%)
    56 / 170 (32.94%)
         occurrences all number
    73
    56
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 170 (0.59%)
    12 / 170 (7.06%)
         occurrences all number
    1
    12
    Infections and infestations
    Acarodermatitis
         subjects affected / exposed
    4 / 170 (2.35%)
    13 / 170 (7.65%)
         occurrences all number
    4
    13
    Pneumonia
         subjects affected / exposed
    54 / 170 (31.76%)
    49 / 170 (28.82%)
         occurrences all number
    54
    49
    Skin infection
         subjects affected / exposed
    3 / 170 (1.76%)
    11 / 170 (6.47%)
         occurrences all number
    3
    11

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 May 2006
    At the request of National Institute of Medical Research (NIMR) and Malaria Vaccine Initiative (MVI) at Program for Appropriate Technology in Health (PATH), a number of operational and administrative details were made to the protocol. A number of errors in the final version of the protocol were corrected.
    15 Sep 2006
    Capillary puncture for obtaining blood samples was added as an alternative method to venous extraction with a needle and syringe in order to increase compliance with obtaining blood samples at the required visits. The minimum volume of blood to be obtained at each visit was also reviewed and decreased where appropriate.
    20 Aug 2007
    The study protocol was amended due to the low transmission rates observed in the community which would have resulted in an under-powered study to reach the efficacy objective. Efficacy data will be collected to 18 months post Dose 3 (Month 20) by passive case detection. It was proposed not to prolong active detection of infection visits given their intrusive nature for the families. Assessment of SAEs will be conducted for the duration of the study.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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