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Clinical Trial Results:
A phase 2, open, randomized, controlled, multi-center study to evaluate the safety and immunogenicity of 7 infant immunization schedules of the RTS,S/AS01E candidate vaccine against P. falciparum.

Summary
EudraCT number	2012-005718-20
Trial protocol	Outside EU/EEA
Global end of trial date	23 Dec 2014

Results information
Results version number	v3(current)
This version publication date	14 Sep 2016
First version publication date	03 Jul 2015
Other versions	v1 , v2
Version creation reason	New data added to full data set Additional primary and secondary results were added to dataset.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

111315

ISRCTN number

US NCT number

NCT01231503

WHO universal trial number (UTN)

Other trial identifiers

IND: 12937

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

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

15 Apr 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

23 Dec 2014

Was the trial ended prematurely?

Main objective of the trial

1) To describe the safety of 7 infant immunization schedules of RTS,S/AS01E (RTS,S) integrated with an expanded program on immunization (EPI) regimen comprising Polio Sabin™, Bacille Calmette Guerin tuberculosis vaccine, Tritanrix HepB/Hib and Rouvax™ with and without a neonatal dose of Engerix™-B from study start until month 10. 2) To describe the anti-Plasmodium falciparum cir-cumsporozoite (CS) antigen response induced by 7 infant immunization schedules of RTS,S, integrated with an EPI regimen comprising Polio Sabin™, Bacille Calmette Guerin tuberculosis vaccine, Tritanrix HepB/Hib and Rouvax™, with and without a neonatal dose of Engerix™-B, at 1 month post Dose 3 of RTS,S.

Protection of trial subjects

All subjects were supervised for 60 min after vaccination/product administration with appropriate medical treatment readily available. Vaccines/products were administered by qualified and trained personnel. Vaccines/products were administered only to eligible subjects that had no contraindications to any components of the vaccines/products. Subjects were followed-up for xx days after the last vaccination/product administration. In addition, this trial was overseen by a Independent data monitoring committee (IDMC) operating under a charter assisted by a Local Safety Monitor (LSM) at each site. The role of the IDMC included the review of the implementation and progress of the study. It provided initial, regular, and closing advice on safety-related issues to GSK Biologicals. The IDMC also reviewed the Protocol and Report and Analysis Plan (RAP) and safety reports. The IDMC was in the capability, if deemed necessary, convene a meeting with, or request further information from the Principal Investigators, the Medical Monitor/Local Safety Monitors and GSK Biologicals’ and MVI’s designated project representatives at any stage of the study. If applicable, the IDMC was in the capacity to recommend to the sponsor to suspend the enrollment to the trial and/or vaccination across all sites based on their review of safety data arising in this trial or other relevant trials of the same product.

Background therapy

Evidence for comparator

Actual start date of recruitment

13 Jan 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Malawi: 480

Worldwide total number of subjects

480

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

240

Infants and toddlers (28 days-23 months)

240

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

480 subjects were enrolled into the study. Out of these 480 subjects, 479 were vaccinated and 1 was allocated a subject number but was not vaccinated.

Number of subjects started

480

Number of subjects completed

479

Reason: Number of subjects

Protocol deviation: 1

Period 1 title

Overall period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

RTS,S Neo-10-14 Group

Arm description

Subjects received 3 doses of RTS,S/AS01E (GSK257049) when ≤ 7 days of age and at 10 and 14 weeks of age. In addition, all subjects received a 3-doses course of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, 4 doses of Polio Sabin™, administered when ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax™, administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The Tritanrix™HepB/Hib and Rouvax™ vaccines were administered IM in the right antero-lateral thigh and the Polio Sabin™ vaccine orally. The Bacille Calmette Guerin tuberculosis vaccine was administered via intradermal route in the shoulder.

Arm type

Experimental

Investigational medicinal product name

Candidate Plasmodium falciparum malaria vaccine

Investigational medicinal product code

RTS,S+AS01E

Other name

RTS,S/AS01E, GSK257049

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of RTS,S/AS01E (GSK257049) when ≤ 7 days of age and at 10 and 14 weeks of age, administered intramuscularly (IM) in the left antero-lateral thigh.

Investigational medicinal product name

Tritanrix HB + Hib

Investigational medicinal product code

Tritanrix HB + Hib

Other name

Tritanrix™HepB/Hib, DTPwHepB/Hib

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, intramuscularly in the right antero-lateral thigh.

Investigational medicinal product name

BCG Vaccines SSI

Investigational medicinal product code

Other name

Bacille Calmette Guerin tuberculosis vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, via intradermal route in the shoulder.

Investigational medicinal product name

Polio Sabin (Oral)

Investigational medicinal product code

OPV

Other name

Polio Sabin™, OPV

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 4 doses of Polio Sabin™, administered orally when ≤ 7 days of age and at 6, 10 and 14 weeks of age.

Investigational medicinal product name

Rouvax

Investigational medicinal product code

Other name

Rouvax™, Measles vaccine

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Rouvax™, administered at 9 months of age, intramuscularly in the right antero-lateral thigh.

RTS,S Neo-10-26 Group

Arm description

Subjects received 3 doses of RTS,S/AS01E (GSK257049) when ≤ 7 days of age and at 10 and 26 weeks of age. In addition, all subjects received a 3-doses course of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, 4 doses of Polio Sabin™, administered when below ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax™, administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The Tritanrix™HepB/Hib and Rouvax™ vaccines were administered IM in the right antero-lateral thigh and the Polio Sabin™ vaccine orally. The Bacille Calmette Guerin tuberculosis vaccine was administered via intradermal route in the shoulder.

Arm type

Experimental

Investigational medicinal product name

Candidate Plasmodium falciparum malaria vaccine

Investigational medicinal product code

RTS,S+AS01E

Other name

RTS,S/AS01E, GSK257049

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of RTS,S/AS01E (GSK257049) when ≤ 7 days of age and at 10 and 26 weeks of age, administered intramuscularly (IM) in the left antero-lateral thigh.

Investigational medicinal product name

Tritanrix HB + Hib

Investigational medicinal product code

Tritanrix HB + Hib

Other name

Tritanrix™HepB/Hib, DTPwHepB/Hib

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, intramuscularly in the right antero-lateral thigh.

Investigational medicinal product name

BCG Vaccines SSI

Investigational medicinal product code

Other name

Bacille Calmette Guerin tuberculosis vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, via intradermal route in the shoulder.

Investigational medicinal product name

Polio Sabin (Oral)

Investigational medicinal product code

OPV

Other name

Polio Sabin™, OPV

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 4 doses of Polio Sabin™, administered orally when ≤ 7 days of age and at 6, 10 and 14 weeks of age.

Investigational medicinal product name

Rouvax

Investigational medicinal product code

Other name

Rouvax™, Measles vaccine

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Rouvax™, administered at 9 months of age, intramuscularly in the right antero-lateral thigh.

RTS,S 6-10-14 Group

Arm description

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 6, 10 and 14 weeks of age. In addition, all subjects received a 3-doses course of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, 4 doses of Polio Sabin™, administered when ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax™, administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The Tritanrix™HepB/Hib and Rouvax™ vaccines were administered IM in the right antero-lateral thigh and the Polio Sabin™ vaccine orally. The Bacille Calmette Guerin tuberculosis vaccine was administered via intradermal route in the shoulder.

Arm type

Experimental

Investigational medicinal product name

Candidate Plasmodium falciparum malaria vaccine

Investigational medicinal product code

RTS,S+AS01E

Other name

RTS,S/AS01E, GSK257049

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 6, 10 and 14 weeks of age, administered intramuscularly (IM) in the left antero-lateral thigh.

Investigational medicinal product name

Tritanrix HB + Hib

Investigational medicinal product code

Tritanrix HB + Hib

Other name

Tritanrix™HepB/Hib, DTPwHepB/Hib

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, intramuscularly in the right antero-lateral thigh.

Investigational medicinal product name

BCG Vaccines SSI

Investigational medicinal product code

Other name

Bacille Calmette Guerin tuberculosis vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, via intradermal route in the shoulder.

Investigational medicinal product name

Polio Sabin (Oral)

Investigational medicinal product code

OPV

Other name

Polio Sabin™, OPV

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 4 doses of Polio Sabin™, administered orally when ≤ 7 days of age and at 6, 10 and 14 weeks of age.

Investigational medicinal product name

Rouvax

Investigational medicinal product code

Other name

Rouvax™, Measles vaccine

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Rouvax™, administered at 9 months of age, intramuscularly in the right antero-lateral thigh.

RTS,S 6-10-26 Group

Arm description

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 6, 10 and 26 weeks of age. In addition, all subjects received a 3-doses course of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, 4 doses of Polio Sabin™, administered when ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax™, administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The Tritanrix™HepB/Hib and Rouvax™ vaccines were administered IM in the right antero-lateral thigh and the Polio Sabin™ vaccine orally. The Bacille Calmette Guerin tuberculosis vaccine was administered via intradermal route in the shoulder.

Arm type

Experimental

Investigational medicinal product name

Candidate Plasmodium falciparum malaria vaccine

Investigational medicinal product code

RTS,S+AS01E

Other name

RTS,S/AS01E, GSK257049

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 6, 10 and 26 weeks of age, administered intramuscularly (IM) in the left antero-lateral thigh.

Investigational medicinal product name

Tritanrix HB + Hib

Investigational medicinal product code

Tritanrix HB + Hib

Other name

Tritanrix™HepB/Hib, DTPwHepB/Hib

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, intramuscularly in the right antero-lateral thigh.

Investigational medicinal product name

BCG Vaccines SSI

Investigational medicinal product code

Other name

Bacille Calmette Guerin tuberculosis vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, via intradermal route in the shoulder.

Investigational medicinal product name

Polio Sabin (Oral)

Investigational medicinal product code

OPV

Other name

Polio Sabin™, OPV

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 4 doses of Polio Sabin™, administered orally when ≤ 7 days of age and at 6, 10 and 14 weeks of age.

Investigational medicinal product name

Rouvax

Investigational medicinal product code

Other name

Rouvax™, Measles vaccine

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Rouvax™, administered at 9 months of age, intramuscularly in the right antero-lateral thigh.

Engerix-B Neo/RTS,S 6-10-26 Group

Arm description

Subjects received one dose of Engerix™-B when ≤ 7 days of age followed by 3 doses of RTS,S/AS01E (GSK257049) at 6, 10 and 26 weeks of age. In addition, all subjects received a 3-doses course of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, 4 doses of Polio Sabin™, administered when ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax™, administered at 9 months of age. The RTS,S/AS01E and Engerix™-B vaccines were administered intramuscularly (IM) in the left antero-lateral thigh. The Tritanrix™HepB/Hib and Rouvax™ vaccines were administered IM in the right antero-lateral thigh and the Polio Sabin™ vaccine orally. The Bacille Calmette Guerin tuberculosis vaccine was administered via intradermal route in the shoulder.

Arm type

Experimental

Investigational medicinal product name

Candidate Plasmodium falciparum malaria vaccine

Investigational medicinal product code

RTS,S+AS01E

Other name

RTS,S/AS01E, GSK257049

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 6, 10 and 26 weeks of age, administered intramuscularly (IM) in the left antero-lateral thigh.

Investigational medicinal product name

Tritanrix HB + Hib

Investigational medicinal product code

Tritanrix HB + Hib

Other name

Tritanrix™HepB/Hib, DTPwHepB/Hib

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, intramuscularly in the right antero-lateral thigh.

Investigational medicinal product name

BCG Vaccines SSI

Investigational medicinal product code

Other name

Bacille Calmette Guerin tuberculosis vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, via intradermal route in the shoulder.

Investigational medicinal product name

Polio Sabin (Oral)

Investigational medicinal product code

OPV

Other name

Polio Sabin™, OPV

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 4 doses of Polio Sabin™, administered orally when ≤ 7 days of age and at 6, 10 and 14 weeks of age.

Investigational medicinal product name

Rouvax

Investigational medicinal product code

Other name

Rouvax™, Measles vaccine

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Rouvax™, administered at 9 months of age, intramuscularly in the right antero-lateral thigh.

Investigational medicinal product name

Engerix-B Junior

Investigational medicinal product code

HBV Paediatric 10

Other name

Engerix™-B, HBV

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Engerix™-B when ≤ 7 days of age, administered intramuscularly (IM) in the left antero-lateral thigh.

RTS,S 10-14-26 Group

Arm description

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 10, 14 and 26 weeks of age. In addition, all subjects received a 3-doses course of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, 4 doses of Polio Sabin™, administered when below ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax™, administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The Tritanrix™HepB/Hib and Rouvax™ vaccines were administered IM in the right antero-lateral thigh and the Polio Sabin™ vaccine orally. The Bacille Calmette Guerin tuberculosis vaccine was administered via intradermal route in the shoulder.

Arm type

Experimental

Investigational medicinal product name

Candidate Plasmodium falciparum malaria vaccine

Investigational medicinal product code

RTS,S+AS01E

Other name

RTS,S/AS01E, GSK257049

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 10, 14 and 26 weeks of age, administered intramuscularly (IM) in the left antero-lateral thigh.

Investigational medicinal product name

Tritanrix HB + Hib

Investigational medicinal product code

Tritanrix HB + Hib

Other name

Tritanrix™HepB/Hib, DTPwHepB/Hib

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, intramuscularly in the right antero-lateral thigh.

Investigational medicinal product name

BCG Vaccines SSI

Investigational medicinal product code

Other name

Bacille Calmette Guerin tuberculosis vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, via intradermal route in the shoulder.

Investigational medicinal product name

Polio Sabin (Oral)

Investigational medicinal product code

OPV

Other name

Polio Sabin™, OPV

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 4 doses of Polio Sabin™, administered orally when ≤ 7 days of age and at 6, 10 and 14 weeks of age.

Investigational medicinal product name

Rouvax

Investigational medicinal product code

Other name

Rouvax™, Measles vaccine

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Rouvax™, administered at 9 months of age, intramuscularly in the right antero-lateral thigh.

RTS,S 14-26-9M Group

Arm description

Subjects received 3 doses of RTS,S/AS01E (or GSK257049) at 14 and 26 weeks of age and at 9 months of age. In addition, all subjects received a 3-doses course of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when below ≤ 7 days of age, 4 doses of Polio Sabin™, administered when below ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax™, administered at 9 months of age. The RTS,S/AS01E vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The Tritanrix™HepB/Hib and Rouvax™ vaccines were administered IM in the right antero-lateral thigh and the Polio Sabin™ vaccine orally. The Bacille Calmette Guerin tuberculosis vaccine was administered via intradermal route in the shoulder.

Arm type

Experimental

Investigational medicinal product name

Candidate Plasmodium falciparum malaria vaccine

Investigational medicinal product code

RTS,S+AS01E

Other name

RTS,S/AS01E, GSK257049

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of RTS,S/AS01E (GSK257049) at 14 and 26 weeks of age and at 9 months of age, administered intramuscularly (IM) in the left antero-lateral thigh.

Investigational medicinal product name

Tritanrix HB + Hib

Investigational medicinal product code

Tritanrix HB + Hib

Other name

Tritanrix™HepB/Hib, DTPwHepB/Hib

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, intramuscularly in the right antero-lateral thigh.

Investigational medicinal product name

BCG Vaccines SSI

Investigational medicinal product code

Other name

Bacille Calmette Guerin tuberculosis vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, via intradermal route in the shoulder.

Investigational medicinal product name

Polio Sabin (Oral)

Investigational medicinal product code

OPV

Other name

Polio Sabin™, OPV

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 4 doses of Polio Sabin™, administered orally when ≤ 7 days of age and at 6, 10 and 14 weeks of age.

Investigational medicinal product name

Rouvax

Investigational medicinal product code

Other name

Rouvax™, Measles vaccine

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Rouvax™, administered at 9 months of age, intramuscularly in the right antero-lateral thigh.

Engerix-B Neo Group

Arm description

Subjects in this group received one dose of Engerix™-B ≤ 7 days of age. In addition, all subjects received a 3-doses course of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when below ≤ 7 days of age, 4 doses of Polio Sabin™, administered when ≤ 7 days of age and at 6, 10 and 14 weeks of age, and one dose of Rouvax™, administered at 9 months of age. The Engerix™-B vaccine was administered intramuscularly (IM) in the left antero-lateral thigh. The Tritanrix™HepB/Hib and Rouvax™ vaccines were administered IM in the right antero-lateral thigh and the Polio Sabin™ vaccine orally. The Bacille Calmette Guerin tuberculosis vaccine was administered via intradermal route in the shoulder.

Arm type

Active comparator

Investigational medicinal product name

Engerix-B Junior

Investigational medicinal product code

HBV Paediatric 10

Other name

Engerix™-B, HBV

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Engerix™-B when ≤ 7 days of age, administered intramuscularly (IM) in the left antero-lateral thigh.

Investigational medicinal product name

Tritanrix HB + Hib

Investigational medicinal product code

Tritanrix HB + Hib

Other name

Tritanrix™HepB/Hib, DTPwHepB/Hib

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of Tritanrix™HepB/Hib, administered at 6, 10 and 14 weeks of age, intramuscularly in the right antero-lateral thigh.

Investigational medicinal product name

BCG Vaccines SSI

Investigational medicinal product code

Other name

Bacille Calmette Guerin tuberculosis vaccine

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Bacille Calmette Guerin tuberculosis vaccine, administered when ≤ 7 days of age, via intradermal route in the shoulder.

Investigational medicinal product name

Polio Sabin (Oral)

Investigational medicinal product code

OPV

Other name

Polio Sabin™, OPV

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received 4 doses of Polio Sabin™, administered orally when ≤ 7 days of age and at 6, 10 and 14 weeks of age.

Investigational medicinal product name

Rouvax

Investigational medicinal product code

Other name

Rouvax™, Measles vaccine

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one dose of Rouvax™, administered at 9 months of age, intramuscularly in the right antero-lateral thigh.

Number of subjects in period 1 ^[1]	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Started	60	59	60	60	60	60	60	60
Completed	46	46	48	52	50	44	53	52
Not completed	14	13	12	8	10	16	7	8
Adverse event, serious fatal	-	-	-	1	-	1	-	-
Consent withdrawn by subject	6	3	3	1	3	5	1	2
Adverse event, non-fatal	-	-	-	-	-	1	-	-
Lost to follow-up	8	10	8	5	7	9	6	6
Protocol deviation	-	-	1	1	-	-	-	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 480 subjects were enrolled into the study. Out of these 480 subjects, 479 were vaccinated and 1 was allocated a subject number but was not vaccinated.

Baseline characteristics

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Reporting group title

RTS,S Neo-10-14 Group

Reporting group description

Reporting group title

RTS,S Neo-10-26 Group

Reporting group description

Reporting group title

RTS,S 6-10-14 Group

Reporting group description

Reporting group title

RTS,S 6-10-26 Group

Reporting group description

Reporting group title

Engerix-B Neo/RTS,S 6-10-26 Group

Reporting group description

Reporting group title

RTS,S 10-14-26 Group

Reporting group description

Reporting group title

RTS,S 14-26-9M Group

Reporting group description

Reporting group title

Engerix-B Neo Group

Reporting group description

Reporting group values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group	Total
Number of subjects	60	59	60	60	60	60	60	60	479
Age categorical
Units: Subjects
In utero									0
Preterm newborn infants (gestational age < 37 wks)									0
Newborns (0-27 days)									0
Infants and toddlers (28 days-23 months)									0
Children (2-11 years)									0
Adolescents (12-17 years)									0
Adults (18-64 years)									0
From 65-84 years									0
85 years and over									0
Age continuous
Units: days
arithmetic mean (standard deviation)	0.4 ( 1.1 )	0.4 ( 1.2 )	0.2 ( 1 )	0.2 ( 0.8 )	0.5 ( 1.4 )	0.2 ( 0.8 )	0.2 ( 0.9 )	0.4 ( 1.2 )	-
Gender categorical
Units: Subjects
Female	30	32	28	35	31	29	24	28	237
Male	30	27	32	25	29	31	36	32	242

End points

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Reporting group title

RTS,S Neo-10-14 Group

Reporting group description

Reporting group title

RTS,S Neo-10-26 Group

Reporting group description

Reporting group title

RTS,S 6-10-14 Group

Reporting group description

Reporting group title

RTS,S 6-10-26 Group

Reporting group description

Reporting group title

Engerix-B Neo/RTS,S 6-10-26 Group

Reporting group description

Reporting group title

RTS,S 10-14-26 Group

Reporting group description

Reporting group title

RTS,S 14-26-9M Group

Reporting group description

Reporting group title

Engerix-B Neo Group

Reporting group description

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

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End point title

Number of subjects reported with serious adverse events (SAEs) ^[1]

End point description

An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. “Any” is defined as incidence of an SAE regardless of intensity/severity.

End point type

Primary

End point timeframe

From study start at Month 0 up to Month 10

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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	60	59	60	60	60	60	60	60
Units: Subjects
SAEs to Month 10	5	4	5	7	5	10	4	3

No statistical analyses for this end point

Primary: Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

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End point title

Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies) ^[2]

End point description

Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (≥) 0.5 EL.U/mL.

End point type

Primary

End point timeframe

At 1 month post Dose 3 of RTS,S/AS01E

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: The scope of this primary end point was descriptive, no statistical hypothesis test was performed.

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	47	43	45	46	43	41	47	48
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-CS, PIV(M5) [N=47,0,45,0,0,0,0,48]	128.2 (92.2 to 178.2)	0 (0 to 0)	218.3 (160.1 to 297.6)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.3 (0.3 to 0.3)
Anti-CS, PV(M7) [N=0,43,0,46,43,41,0,0]	0 (0 to 0)	136.6 (93 to 200.7)	0 (0 to 0)	156.5 (100.4 to 244)	170.6 (114.6 to 254.1)	392.6 (323.3 to 476.7)	0 (0 to 0)	0 (0 to 0)
Anti-CS, PVI(M10) [N=0,0,0,0,0,0,47,0]	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	269.9 (183.3 to 397.5)	0 (0 to 0)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

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End point title

Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

End point description

End point type

Secondary

End point timeframe

At Screening (SCR), at Month 5 (M5), at Month 7 (M7) and at Month 10 (M10), according to the vaccination scheduling

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	43	42	45	43	45	42	51	45
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-CS, Screening [N=43,42,45,43,45,42,51,45]	0.5 (0.4 to 7)	0.4 (0.3 to 0.5)	0.4 (0.3 to 0.5)	0.4 (0.3 to 0.5)	0.4 (0.3 to 0.6)	0.4 (0.3 to 0.5)	0.4 (0.3 to 0.5)	0.5 (0.4 to 0.7)
Anti-CS, PIII(M4) [N=30,32,31,37,39,0,0,36]	33.6 (18.5 to 61.3)	72.8 (44.6 to 118.7)	112.2 (76 to 165.8)	99.7 (61.3 to 162)	88 (55.4 to 139.8)	0 (0 to 0)	0 (0 to 0)	0.3 (0.3 to 0.3)
Anti-CS PIV(M5) [N=47,0,45,0,0,44,0,48]	128.2 (92.2 to 178.2)	0 (0 to 0)	218.3 (160.1 to 297.6)	0 (0 to 0)	0 (0 to 0)	167.6 (133.2 to 210.9)	0 (0 to 0)	0.3 (0.3 to 0.3)
Anti-CS, PV(M7) [N=0,43,0,46,43,42,36,47]	0 (0 to 0)	136.6 (93 to 200.7)	0 (0 to 0)	156.5 (100.4 to 244)	170.6 (170.6 to 254.1)	392.6 (323.3 to 476.7)	141.7 (97 to 207.1)	0.3 (0.3 to 0.3)
Anti-CS, PVI(M10) [N=39,37,36,40,39,38,47,40]	13.8 (8.5 to 22.6)	39.5 (22.4 to 69.6)	30.1 (18.8 to 48.2)	44.2 (23.8 to 82.2)	43.3 (24.6 to 76)	121 (89.4 to 163.7)	269.9 (183.3 to 397.5)	0.3 (0.2 to 0.4)

No statistical analyses for this end point

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

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End point title

Number of subjects reported with unsolicited adverse events (AEs)

End point description

An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. “Any” is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. Please note that, for this outcome measure, analysis was performed only on subjects with at least one administered dose of RTS,S/AS01E and/or Tritanrix™HepB/Hib for the Engerix-B Neo Group.

End point type

Secondary

End point timeframe

During the 30-day (Days 0-29) post vaccination period following 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	60	59	54	57	57	52	57	52
Units: Subjects
Unsolicited AEs	36	35	28	29	35	36	47	31

No statistical analyses for this end point

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

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End point title

Number of subjects reported with serious adverse events (SAEs)

End point description

End point type

Secondary

End point timeframe

From study start at Month 0 up to Month 18 (corresponding data lock point = 23 March 2015)

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	60	59	60	60	60	60	60	60
Units: Subjects
SAEs to Month 18	7	5	6	9	8	12	5	4

No statistical analyses for this end point

Secondary: Number of subjects reported with biochemical abnormalities, for the alanine aminotransferase (ALT) parameter

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End point title

Number of subjects reported with biochemical abnormalities, for the alanine aminotransferase (ALT) parameter

End point description

This outcome measure concerns biochemical abnormalities, for the alanine aminotransferase (ALT) parameter. Subjects’ levels were assessed as either normal, Grade 1, Grade 2, Grade 3, Grade 4, Missing or Out of range (OOR). Normal ALT level was defined as ALT< 60 International units per milliliter (IU/mL). Grade 1 ALT level was defined as 1.1 to 2.5 times the upper limit of normal (ULN). Grade 2 ALT level was defined as 2.6 to 5.0 times the ULN. Grade 3 ALT level was defined as 5.1 to 10.0 times the ULN. Grade 4 ALT level was defined as > 10.0 times the ULN.

End point type

Secondary

End point timeframe

At screening (SCR), at Study Day 6 (D6), at 6 days post Study Week 6 (W6+6D), at 6 days post Study Week 10 (W10+6D), at 6 days post Study Week 14 (W14+6D), at Month 5 (M5), at Month 7 (M7) and at Month 10 (M10).

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	60	59	60	60	60	60	60	60
Units: Subjects
SCR, Normal (N=60;59,60;60;60;60;60;60)	60	59	60	60	60	60	60	60
SCR, Grade 1 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 2 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 3 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 4 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Missing (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, OOR (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
D6, Normal (N=58;57;0;0;0;0;0;58)	56	55	0	0	0	0	0	57
D6, Grade 1 (N=58;57;0;0;0;0;0;58)	1	0	0	0	0	0	0	0
D6, Grade 2 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Grade 3 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Grade 4 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Missing (N=58;57;0;0;0;0;0;58)	1	2	0	0	0	0	0	0
D6, OOR (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	1
W6+6D, Normal (N=0;0;53;57;57;54;0;0)	0	0	51	55	55	52	0	0
W6+6D, Grade 1 (N=0;0;53;57;57;54;0;0)	0	0	0	0	2	2	0	0
W6+6D, Grade 2 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Grade 3 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Grade 4 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Missing (N=0;0;53;57;57;54;0;0)	0	0	2	2	0	0	0	0
W6+6D, OOR (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W10+6D, Normal (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	50	0	0
W10+6D, Grade 1 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Grade 2 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Grade 3 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Grade 4 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Missing (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	1	0	0
W10+6D, OOR (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	1	0	0
W14+6D, Normal (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	56	0
W14+6D, Grade 1 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	1	0
W14+6D, Grade 2 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 3 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 4 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Missing (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, OOR (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
M5, Normal (N=51;0;50;0;0;0;0;51)	48	0	49	0	0	0	0	50
M5, Grade 1 (N=51;0;50;0;0;0;0;51)	1	0	0	0	0	0	0	0
M5, Grade 2 (N=51;0;50;0;0;0;0;51)	0	0	0	0	0	0	0	0
M5, Grade 3 (N=51;0;50;0;0;0;0;51)	0	0	0	0	0	0	0	0
M5, Grade 4 (N=51;0;50;0;0;0;0;51)	0	0	0	0	0	0	0	0
M5, Missing (N=51;0;50;0;0;0;0;51)	2	0	1	0	0	0	0	1
M5, OOR (N=51;0;50;0;0;0;0;51)	0	0	0	0	0	0	0	0
M7, Normal (N=0;49;0;54;53;47;0;52)	0	49	0	52	52	47	0	52
M7, Grade 1 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Grade 2 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Grade 3 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Grade 4 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Missing (N=0;49;0;54;53;47;0;52)	0	0	0	2	1	0	0	0
M7, OOR (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M10, Normal (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	51	48
M10, Grade 1 (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	0	1
M10, Grade 2 (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	0	0
M10, Grade 3 (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	0	0
M10, Grade 4 (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	0	0
M10, Missing (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	2	3
M10, OOR (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects reported with biochemical abnormalities, for the creatinine (CREA) parameter

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End point title

Number of subjects reported with biochemical abnormalities, for the creatinine (CREA) parameter

End point description

This outcome measure concerns biochemical abnormalities, for the creatinine (CREA) parameter. Subjects’ levels were assessed as either normal, Grade 1, Grade 2, Grade 3, Grade 4, Missing or Out of range (OOR). Normal CREA level was defined as CREA ≤ 106, 88 and 71 micromoles per liter (µmol/L) for subjects 1, 2 or ≥ 2 days of age, respectively. Grade 1 CREA level was defined as 1.1 to 1.3 times the upper limit of normal (ULN). Grade 2 CREA level was defined as 1.4 to 1.8 times the ULN. Grade 3 CREA level was defined as 1.9 to 3.4 times the ULN. Grade 4 CREA level was defined as ≥ 3.5 times the ULN.

End point type

Secondary

End point timeframe

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	60	59	60	60	60	60	60	60
Units: Subjects
SCR, Normal (N=60;59,60;60;60;60;60;60)	60	59	60	60	60	60	60	60
SCR, Grade 1 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 2 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 3 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 4 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Missing (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, OOR (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
D6, Normal (N=58;57;0;0;0;0;0;58)	55	55	0	0	0	0	0	56
D6, Grade 1 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Grade 2 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Grade 3 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Grade 4 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Missing (N=58;57;0;0;0;0;0;58)	3	2	0	0	0	0	0	2
D6, OOR (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
W6+6D, Normal (N=0;0;53;57;57;54;0;0)	0	0	53	57	57	53	0	0
W6+6D, Grade 1 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Grade 2 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Grade 3 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Grade 4 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Missing (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	1	0	0
W6+6D, OOR (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W10+6D, Normal (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	51	0	0
W10+6D, Grade 1 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Grade 2 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Grade 3 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Grade 4 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Missing (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	1	0	0
W10+6D, OOR (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W14+6D, Normal (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	57	0
W14+6D, Grade 1 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 2 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 3 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 4 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Missing (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, OOR (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
M5, Normal (N=51;0;50;0;0;0;0;51)	50	0	50	0	0	0	0	50
M5, Grade 1 (N=51;0;50;0;0;0;0;51)	0	0	0	0	0	0	0	0
M5, Grade 2 (N=51;0;50;0;0;0;0;51)	0	0	0	0	0	0	0	0
M5, Grade 3 (N=51;0;50;0;0;0;0;51)	0	0	0	0	0	0	0	0
M5, Grade 4 (N=51;0;50;0;0;0;0;51)	0	0	0	0	0	0	0	0
M5, Missing (N=51;0;50;0;0;0;0;51)	1	0	0	0	0	0	0	1
M5, OOR (N=51;0;50;0;0;0;0;51)	0	0	0	0	0	0	0	0
M7, Normal (N=0;49;0;54;53;47;0;52)	0	49	0	52	53	47	0	52
M7, Grade 1 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Grade 2 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Grade 3 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Grade 4 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Missing (N=0;49;0;54;53;47;0;52)	0	0	0	2	0	0	0	0
M7, OOR (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M10, Normal (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	52	52
M10, Grade 1 (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	0	0
M10, Grade 2 (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	0	0
M10, Grade 3 (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	0	0
M10, Grade 4 (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	0	0
M10, Missing (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	1	0
M10, OOR (N=0;0,0;0;0;0;53;52)	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects reported with haematological abnormalities, for the haemoglobin (HAE) parameter

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End point title

Number of subjects reported with haematological abnormalities, for the haemoglobin (HAE) parameter

End point description

This outcome measure concerns haematological abnormalities, for the haemoglobin (HAE) parameter. Subjects’ levels were assessed as either normal, Grade (G) 1, G2, G3, G4, Missing or Out of range (OOR). Normal HAE level was defined as HAE > 13.0 and 10.5 grams per deciliter (g/dL) for subjects aged 1 to 21 and 22 to 35 days respectively. Grades were defined as follows: 1) In subjects aged 1 to 21 days: G1 = HAE as 12.0 to 13.0 g/dL, G2 = HAE as 10.0 to 11.9 g/dL, G3 = HAE as 9.0 to 9.9 g/dL, G4 = HAE < 9.0 g/dL; 2) In subjects aged 22 to 35 days: G1 = HAE as 9.5 to 10.5 g/dL, G2 = HAE as 8.0 to 9.4 g/dL, G3 = HAE as 7.0 to 7.9 g/dL, G4 = HAE < 7.0 g/dL; 3) In subjects aged 36 to 56 days: G1 = HAE as 8.5 to 9.4 g/dL, G2 = HAE as 7.0 to 8.4 g/dL, G3 = HAE as 6.0 to 6.9 g/dL, G4 = HAE < 6.0 g/dL; 4) In subjects aged ≥ 57 days: G1 = HAE as 10.0 to 10.9 g/dL, G2 = HAE as 9.0 to 9.9 g/dL, G3 = HAE as 7.0 to 8.9 g/dL, G4 = HAE < 7.0 g/dL.

End point type

Secondary

End point timeframe

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	60	59	60	60	60	60	60	60
Units: Subjects
SCR, Normal (N=60;59,60;60;60;60;60;60)	60	59	60	60	60	60	60	60
SCR, Grade 1 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 2 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 3 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 4 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Missing (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, OOR (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
D6, Normal (N=58;57;0;0;0;0;0;58)	51	47	0	0	0	0	0	48
D6, Grade 1 (N=58;57;0;0;0;0;0;58)	1	5	0	0	0	0	0	3
D6, Grade 2 (N=58;57;0;0;0;0;0;58)	5	4	0	0	0	0	0	3
D6, Grade 3 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	3
D6, Grade 4 (N=58;57;0;0;0;0;0;58)	0	1	0	0	0	0	0	1
D6, Missing (N=58;57;0;0;0;0;0;58)	1	0	0	0	0	0	0	0
D6, OOR (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
W6+6D, Normal (N=0;0;53;57;57;54;0;0)	0	0	43	50	48	45	0	0
W6+6D, Grade 1 (N=0;0;53;57;57;54;0;0)	0	0	5	5	7	6	0	0
W6+6D, Grade 2 (N=0;0;53;57;57;54;0;0)	0	0	2	0	2	2	0	0
W6+6D, Grade 3 (N=0;0;53;57;57;54;0;0)	0	0	1	1	0	1	0	0
W6+6D, Grade 4 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Missing (N=0;0;53;57;57;54;0;0)	0	0	2	1	0	0	0	0
W6+6D, OOR (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W10+6D, Normal (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	18	0	0
W10+6D, Grade 1 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	15	0	0
W10+6D, Grade 2 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	10	0	0
W10+6D, Grade 3 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	7	0	0
W10+6D, Grade 4 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Missing (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	2	0	0
W10+6D, OOR (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W14+6D, Normal (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	25	0
W14+6D, Grade 1 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	21	0
W14+6D, Grade 2 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	9	0
W14+6D, Grade 3 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	2	0
W14+6D, Grade 4 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Missing (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, OOR (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
M5, Normal (N=51;0;50;0;0;0;0;52)	25	0	23	0	0	0	0	20
M5, Grade 1 (N=51;0;50;0;0;0;0;52)	16	0	16	0	0	0	0	24
M5, Grade 2 (N=51;0;50;0;0;0;0;52)	7	0	10	0	0	0	0	6
M5, Grade 3 (N=51;0;50;0;0;0;0;52)	3	0	0	0	0	0	0	2
M5, Grade 4 (N=51;0;50;0;0;0;0;52)	0	0	1	0	0	0	0	0
M5, Missing (N=51;0;50;0;0;0;0;52)	0	0	0	0	0	0	0	0
M5, OOR (N=51;0;50;0;0;0;0;52)	0	0	0	0	0	0	0	0
M7, Normal (N=0;49;0;54;53;47;0;52)	0	17	0	15	12	6	0	10
M7, Grade 1 (N=0;49;0;54;53;47;0;52)	0	15	0	18	26	15	0	23
M7, Grade 2 (N=0;49;0;54;53;47;0;52)	0	11	0	13	11	18	0	12
M7, Grade 3 (N=0;49;0;54;53;47;0;52)	0	6	0	7	4	8	0	6
M7, Grade 4 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	1
M7, Missing (N=0;49;0;54;53;47;0;52)	0	0	0	1	0	0	0	0
M7, OOR (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M10, Normal (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	15	8
M10, Grade 1 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	19	16
M10, Grade 2 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	12	17
M10, Grade 3 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	8	11
M10, Grade 4 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0
M10, Missing (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0
M10, OOR (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects reported with haematological abnormalities, for the platelets (PLA) parameter

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End point title

Number of subjects reported with haematological abnormalities, for the platelets (PLA) parameter

End point description

This outcome measure concerns haematological abnormalities, for the platelets (PLA) parameter. Subjects’ levels were assessed as either normal, Grade (G) 1, G2, G3, G4, Missing or Out of range (OOR). Normal PLA level was defined as > 125 x 109 PLA per liter (Billions PLA/L). Grade 1 PLA level was defined as 100 to 125 Billions PLA/L. Grade 2 PLA level was defined as 50 to 99 Billions PLA/L. Grade 3 PLA level was defined as 25 to 49 Billions PLA/L. Grade 4 PLA level was defined as < 25 Billions PLA/L.

End point type

Secondary

End point timeframe

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	60	59	60	60	60	60	60	60
Units: Subjects
SCR, Normal (N=60;59,60;60;60;60;60;60)	60	59	60	60	60	60	60	60
SCR, Grade 1 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 2 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 3 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 4 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Missing (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, OOR (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
D6, Normal (N=58;57;0;0;0;0;0;58)	54	55	0	0	0	0	0	51
D6, Grade 1 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	5
D6, Grade 2 (N=58;57;0;0;0;0;0;58)	3	1	0	0	0	0	0	2
D6, Grade 3 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Grade 4 (N=58;57;0;0;0;0;0;58)	0	1	0	0	0	0	0	0
D6, Missing (N=58;57;0;0;0;0;0;58)	1	0	0	0	0	0	0	0
D6, OOR (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
W6+6D, Normal (N=0;0;53;57;57;54;0;0)	0	0	47	55	57	53	0	0
W6+6D, Grade 1 (N=0;0;53;57;57;54;0;0)	0	0	2	0	0	0	0	0
W6+6D, Grade 2 (N=0;0;53;57;57;54;0;0)	0	0	2	1	0	0	0	0
W6+6D, Grade 3 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Grade 4 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	1	0	0
W6+6D, Missing (N=0;0;53;57;57;54;0;0)	0	0	2	1	0	0	0	0
W6+6D, OOR (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W10+6D, Normal (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	47	0	0
W10+6D, Grade 1 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	2	0	0
W10+6D, Grade 2 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	1	0	0
W10+6D, Grade 3 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Grade 4 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Missing (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	2	0	0
W10+6D, OOR (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W14+6D, Normal (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	57	0
W14+6D, Grade 1 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 2 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 3 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 4 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Missing (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, OOR (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
M5, Normal (N=51;0;50;0;0;0;0;52)	51	0	46	0	0	0	0	51
M5, Grade 1 (N=51;0;50;0;0;0;0;52)	0	0	1	0	0	0	0	0
M5, Grade 2 (N=51;0;50;0;0;0;0;52)	0	0	1	0	0	0	0	1
M5, Grade 3 (N=51;0;50;0;0;0;0;52)	0	0	1	0	0	0	0	0
M5, Grade 4 (N=51;0;50;0;0;0;0;52)	0	0	1	0	0	0	0	0
M5, Missing (N=51;0;50;0;0;0;0;52)	0	0	0	0	0	0	0	0
M5, OOR (N=51;0;50;0;0;0;0;52)	0	0	0	0	0	0	0	0
M7, Normal (N=0;49;0;54;53;47;0;52)	0	49	0	53	51	45	0	50
M7, Grade 1 (N=0;49;0;54;53;47;0;52)	0	0	0	0	2	1	0	1
M7, Grade 2 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Grade 3 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	1
M7, Grade 4 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	1	0	0
M7, Missing (N=0;49;0;54;53;47;0;52)	0	0	0	1	0	0	0	0
M7, OOR (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M10, Normal (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	53	51
M10, Grade 1 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	1	0
M10, Grade 2 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0
M10, Grade 3 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	1
M10, Grade 4 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0
M10, Missing (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0
M10, OOR (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects reported with haematological abnormalities, for the white blood cells (WBC) parameter

Top of page

End point title

Number of subjects reported with haematological abnormalities, for the white blood cells (WBC) parameter

End point description

This outcome measure concerns haematological abnormalities, for the white blood cells (WBC) parameter. Subjects’ levels were assessed as either normal, Grade 1, Grade 2, Grade 3, Grade 4, Missing or Out of range (OOR). Normal WBC level was defined as > 2.5 x 109 WBC per liter (Billions WBC/L). Grade 1 WBC level was defined as 2.0 to 2.5 Billions WBC/L. Grade 2 WBC level was defined as 1.5 to 1.999 Billions WBC/L. Grade 3 WBC level was defined as 1.0 to 1.499 Billions WBC/L. Grade 4 WBC level was defined as < 1.0 Billions WBC/L.

End point type

Secondary

End point timeframe

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	60	59	60	60	60	60	60	60
Units: Subjects
SCR, Normal (N=60;59,60;60;60;60;60;60)	60	59	60	60	60	60	60	60
SCR, Grade 1 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 2 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 3 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Grade 4 (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, Missing (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
SCR, OOR (N=60;59,60;60;60;60;60;60)	0	0	0	0	0	0	0	0
D6, Normal (N=58;57;0;0;0;0;0;58)	57	57	0	0	0	0	0	58
D6, Grade 1 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Grade 2 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Grade 3 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Grade 4 (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
D6, Missing (N=58;57;0;0;0;0;0;58)	1	0	0	0	0	0	0	0
D6, OOR (N=58;57;0;0;0;0;0;58)	0	0	0	0	0	0	0	0
W6+6D, Normal (N=0;0;53;57;57;54;0;0)	0	0	50	56	57	54	0	0
W6+6D, Grade 1 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Grade 2 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Grade 3 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Grade 4 (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W6+6D, Missing (N=0;0;53;57;57;54;0;0)	0	0	3	1	0	0	0	0
W6+6D, OOR (N=0;0;53;57;57;54;0;0)	0	0	0	0	0	0	0	0
W10+6D, Normal (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	50	0	0
W10+6D, Grade 1 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Grade 2 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Grade 3 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Grade 4 (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W10+6D, Missing (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	2	0	0
W10+6D, OOR (N=0;0;0;0;0;52;0;0)	0	0	0	0	0	0	0	0
W14+6D, Normal (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	57	0
W14+6D, Grade 1 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 2 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 3 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Grade 4 (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, Missing (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
W14+6D, OOR (N=0;0;0;0;0;0;57;0)	0	0	0	0	0	0	0	0
M5, Normal (N=51;0;50;0;0;0;0;52)	51	0	50	0	0	0	0	52
M5, Grade 1 (N=51;0;50;0;0;0;0;52)	0	0	0	0	0	0	0	0
M5, Grade 2 (N=51;0;50;0;0;0;0;52)	0	0	0	0	0	0	0	0
M5, Grade 3 (N=51;0;50;0;0;0;0;52)	0	0	0	0	0	0	0	0
M5, Grade 4 (N=51;0;50;0;0;0;0;52)	0	0	0	0	0	0	0	0
M5, Missing (N=51;0;50;0;0;0;0;52)	0	0	0	0	0	0	0	0
M5, OOR (N=51;0;50;0;0;0;0;52)	0	0	0	0	0	0	0	0
M7, Normal (N=0;49;0;54;53;47;0;52)	0	49	0	53	53	47	0	51
M7, Grade 1 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Grade 2 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Grade 3 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	1
M7, Grade 4 (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M7, Missing (N=0;49;0;54;53;47;0;52)	0	0	0	1	0	0	0	0
M7, OOR (N=0;49;0;54;53;47;0;52)	0	0	0	0	0	0	0	0
M10, Normal (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	54	52
M10, Grade 1 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0
M10, Grade 2 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0
M10, Grade 3 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0
M10, Grade 4 (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0
M10, Missing (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0
M10, OOR (N=0;0,0;0;0;0;54;52)	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Anti-Hepatitis B surface antibody (anti-HBs) concentrations

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End point title

Anti-Hepatitis B surface antibody (anti-HBs) concentrations

End point description

Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The seropositivity and seroprotection cut-offs were greater than or equal to (≥) 6.2 and 10 mIU/mL, respectively.

End point type

Secondary

End point timeframe

At Screening (SCR), at Month 5 (M5), at Month 7 (M7) and at Month 10 (M10), according to the vaccination scheduling

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	33	37	37	38	37	34	37	38
Units: mIU/mL
geometric mean (confidence interval 95%)
SCR (N=27;25;32;34;32;32;37;31)	10.7 (4.2 to 27.3)	22.2 (6.6 to 74.6)	9.9 (4.4 to 22)	9.5 (4.4 to 20.6)	17.2 (7.1 to 41.8)	12.6 (4.9 to 32)	38.6 (13.6 to 109.5)	22.6 (8.5 to 59.8)
M5 (N=25;0;17;0;0;0;0;22)	6479 (3858.9 to 10878.2)	0 (0 to 0)	3831.6 (1783.4 to 8232.3)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	640.7 (381.3 to 1076.7)
M7 (N=0;35;0;37;30;34;0;38)	0 (0 to 0)	23218.5 (16670.1 to 32339.2)	0 (0 to 0)	29839.9 (20731.1 to 42951)	34589.1 (21299.2 to 56171.6)	44472.4 (31305.5 to 63177.1)	0 (0 to 0)	430.1 (277.8 to 666)
M10 (N=33;37;37;38;37;31;37;34)	2949.5 (2040.5 to 4263.4)	9630.8 (6472.2 to 14330.9)	3135 (2287.6 to 4296.2)	8581.8 (5974.8 to 12326.5)	12084.3 (8211.6 to 17783.5)	13360.1 (8195.5 to 21779.4)	75018 (54992.1 to 102336.5)	139.5 (77.2 to 252.1)

No statistical analyses for this end point

Secondary: Anti-diphtheria (Anti-D) and anti-tetanus toxoids (anti-TT) antibody concentrations

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End point title

Anti-diphtheria (Anti-D) and anti-tetanus toxoids (anti-TT) antibody concentrations

End point description

Anti-D and anti-TT antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in International units per milliliter (IU/mL), and tabulated. The seropositivity cut-off for the assay was ≥ 0.1 IU/mL.

End point type

Secondary

End point timeframe

At Month 5

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	48	46	45	48	47	44	54	47
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-D	3.1 (2.2 to 4.5)	3.9 (2.9 to 5.3)	3.2 (2.5 to 4)	4 (3.2 to 5.1)	3.6 (2.7 to 4.8)	4.3 (3.2 to 5.8)	4.3 (3.4 to 5.5)	4.6 (3.7 to 5.6)
Anti-TT	3.5 (2.6 to 4.6)	3.2 (2.3 to 4.4)	3.7 (2.8 to 4.8)	2.8 (2.2 to 3.7)	3.3 (2.4 to 4.4)	3.3 (2.4 to 4.6)	3.5 (2.6 to 4.6)	4.6 (3.5 to 6)

No statistical analyses for this end point

Secondary: Anti-polyribosyl ribitol phosphate (anti-PRP) antibody concentrations

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End point title

Anti-polyribosyl ribitol phosphate (anti-PRP) antibody concentrations

End point description

Anti-PRP antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in microgram per milliliter (g/mL), and tabulated. The seroprotection cut-off for the assay for the purpose of this endpoint was ≥ 0.15 g/mL.

End point type

Secondary

End point timeframe

At Month 5

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	47	44	44	48	47	43	52	47
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-PRP	6.8 (4.5 to 10.3)	11.1 (7.5 to 16.5)	11.4 (7.3 to 17.8)	13.6 (9.6 to 19.3)	10.9 (7.4 to 16)	11 (7.1 to 16.9)	15.6 (10.6 to 22.8)	13.8 (9.7 to 19.5)

No statistical analyses for this end point

Secondary: Anti-polio type 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody concentrations

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End point title

Anti-polio type 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody concentrations

End point description

Anti-Polio 1, 2 and 3 antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs) in International units per milliliter (IU/mL) and tabulated. The seroprotection cut-off of the assay was greater than or equal to (≥) 8 IU/mL.

End point type

Secondary

End point timeframe

At Month 5

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	31	16	25	25	19	29	25	30
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-Polio 1, M5 (N=25,13,20,14,13,20,20,19)	27.6 (16.5 to 46)	21.6 (10.3 to 45.2)	31.7 (17.2 to 58.7)	47.1 (21.5 to 102.8)	19.9 (4 to 98.3)	23.6 (8.4 to 66.5)	16.7 (7.9 to 35.4)	45.4 (18.9 to 109.4)
Anti-Polio 2, M5 (N=31,16,25,25,19,29,25,30)	27.5 (16.8 to 45.1)	35.1 (14.9 to 82.4)	56.6 (32.8 to 97.7)	37.9 (17 to 84.6)	42 (21.6 to 81.6)	27.6 (12.6 to 60.4)	40.1 (24.1 to 66.6)	25.9 (16.4 to 40.7)
Anti-Polio 3, M5 (N=27,11,23,18,16,24,24,26)	3.6 (1.6 to 7.9)	2.3 (0.6 to 8.7)	5.1 (2.6 to 10.2)	3.3 (1.3 to 8.4)	5.6 (2.6 to 12.2)	2.6 (1.2 to 5.7)	3 (1.6 to 5.5)	6 (3.3 to 10.8)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against acellular B-pertussis (BPT)

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End point title

Concentrations of antibodies against acellular B-pertussis (BPT)

End point description

Concentrations of anti-BPT antibodies were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off value of greater than or equal to (≥) 15 EL.U/mL.

End point type

Secondary

End point timeframe

At Month 5

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	43	42	41	46	42	42	50	41
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-BPT	82.9 (69.9 to 98.4)	102.3 (84.9 to 123.4)	86.7 (72.5 to 103.7)	81.2 (66.7 to 98.8)	99.2 (82.6 to 119.1)	86.1 (71.7 to 103.4)	91 (75.9 to 109)	109.8 (89.7 to 134.4)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against measles antigens

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End point title

Concentrations of antibodies against measles antigens ^[3]

End point description

The seropositivity cut-off for the assay was an anti-measles antibody (Anti-Measles Ab) concentration ≥ 150 milli-international units per millilitre (mIU/mL). Please note that this outcome measure was only assessed in subjects in the RTS,S 14-26-9M and Engerix-B Neo groups.

End point type

Secondary

End point timeframe

At Month 10

Notes
[3] - 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: Please note that this outcome measure was only assessed in subjects in the RTS,S 14-26-9M and Engerix-B Neo groups.

End point values	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	52	46
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-measles	1017.7 (751.9 to 1377.4)	1430.6 (996.9 to 2053.2)

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited local symptoms

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End point title

Number of subjects reported with solicited local symptoms

End point description

Solicited local symptoms assessed include pain, redness and swelling. “Any” about a specific symptom is defined as incidence of this symptom, regardless of its intensity. Please note that vaccines considered for the analyses of solicited local and general symptoms post vaccination were the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E and Tritanrix™HepB/Hib vaccines only.

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Week 0 vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	60	59	58	60	60	59	60	59
Units: Subjects
Any Pain	1	4	2	2	2	0	2	1
Any Redness	3	4	5	6	7	4	11	6
Any Swelling	2	4	5	6	5	5	8	6

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited local symptoms

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End point title

Number of subjects reported with solicited local symptoms

End point description

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Week 6 vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	55	55	54	57	57	55	58	51
Units: Subjects
Any Pain	2	2	7	7	3	6	4	6
Any Redness	3	2	6	4	4	5	4	4
Any Swelling	4	3	6	8	6	6	6	6

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited local symptoms

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End point title

Number of subjects reported with solicited local symptoms

End point description

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Week 10 vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	52	54	51	54	56	52	57	51
Units: Subjects
Any Pain	4	2	0	5	1	2	5	3
Any Redness	2	1	1	4	2	3	6	3
Any Swelling	4	1	3	6	3	3	6	3

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited local symptoms

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End point title

Number of subjects reported with solicited local symptoms

End point description

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Week 14 vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	51	53	51	54	55	50	57	52
Units: Subjects
Any Pain	4	5	4	1	4	3	1	3
Any Redness	4	5	4	1	3	2	2	3
Any Swelling	7	5	4	1	4	4	2	3

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited local symptoms

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End point title

Number of subjects reported with solicited local symptoms ^[4]

End point description

Solicited local symptoms assessed include pain, redness and swelling. “Any” about a specific symptom is defined as incidence of this symptom, regardless of its intensity. RTS,S Neo-10-14 Group, RTS,S 6-10-14 Group and Engerix-B Neo Group did not receive vaccination at this time point. Please note that vaccines considered for the analyses of solicited local and general symptoms post vaccination were the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E and Tritanrix™HepB/Hib vaccines only.

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Week 26 vaccination

Notes
[4] - 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: Groups considered were only those who received vaccination with either the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E or the Tritanrix™HepB/Hib vaccine(s) at Week 26.

End point values	RTS,S Neo-10-26 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group
Number of subjects analysed	49	54	54	46	56
Units: Subjects
Any Pain	0	0	0	0	0
Any Redness	0	0	0	0	0
Any Swelling	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited local symptoms

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End point title

Number of subjects reported with solicited local symptoms

End point description

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Month 9 vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	50	49	48	54	51	47	56	51
Units: Subjects
Any Pain	0	0	0	0	0	0	0	0
Any Redness	0	0	0	0	0	0	0	0
Any Swelling	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited general symptoms

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End point title

Number of subjects reported with solicited general symptoms

End point description

Solicited general symptoms assessed include Drowsiness, Fever (temperature by axillary route ≥ 37.5°C), Irritability/Fussiness and Loss of appetite. “Any” about a specific symptom is defined as incidence of this symptom, regardless of its intensity or relationship to vaccination. Please note that vaccines considered for the analyses of solicited local and general symptoms post vaccination were the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E and Tritanrix™HepB/Hib vaccines only.

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Week 0 vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	60	59	58	60	60	59	60	59
Units: Subjects
Any Drowsiness	0	0	0	0	0	1	0	1
Any Irritability/Fussiness	0	1	0	1	0	1	1	0
Any Loss of appetite	0	0	0	0	0	0	0	0
Any Fever	8	9	6	3	4	2	4	4

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited general symptoms

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End point title

Number of subjects reported with solicited general symptoms

End point description

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Week 6 vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	55	55	54	57	57	55	58	51
Units: Subjects
Any Drowsiness	0	0	0	0	0	0	0	0
Any Irritability/Fussiness	1	1	6	1	3	3	0	2
Any Loss of appetite	0	0	1	0	1	0	0	0
Any Fever	6	9	10	4	10	7	7	9

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited general symptoms

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End point title

Number of subjects reported with solicited general symptoms

End point description

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Week 10 vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	52	54	51	54	56	51	57	51
Units: Subjects
Any Drowsiness	0	0	0	0	0	0	0	0
Any Irritability/Fussiness	3	2	0	1	0	1	0	1
Any Loss of appetite	0	0	0	0	0	0	0	0
Any Fever	11	7	6	6	4	7	2	2

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited general symptoms

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End point title

Number of subjects reported with solicited general symptoms

End point description

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Week 14 vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	51	53	51	54	55	50	57	52
Units: Subjects
Any Drowsiness	0	0	0	0	0	0	0	0
Any Irritability/Fussiness	4	2	4	0	1	2	1	2
Any Loss of appetite	0	0	0	0	0	0	0	1
Any Fever	9	5	10	2	2	10	3	4

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited general symptoms

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End point title

Number of subjects reported with solicited general symptoms ^[5]

End point description

Solicited general symptoms assessed include Drowsiness, Fever (temperature by axillary route ≥ 37.5°C), Irritability/Fussiness and Loss of appetite. “Any” about a specific symptom is defined as incidence of this symptom, regardless of its intensity or relationship to vaccination. RTS,S Neo-10-14 Group, RTS,S 6-10-14 Group and Engerix-B Neo Group did not receive any vaccination at this time point. Please note that vaccines considered for the analyses of solicited local and general symptoms post vaccination were the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E and Tritanrix™HepB/Hib vaccines only.

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Week 26 vaccination

Notes
[5] - 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: Groups considered were only those who received vaccination with either the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E or the Tritanrix™HepB/Hib vaccine(s) at Week 26.

End point values	RTS,S Neo-10-26 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group
Number of subjects analysed	49	54	54	46	56
Units: Subjects
Any Drowsiness	0	0	0	0	0
Any Irritability/Fussiness	0	0	0	2	2
Any Loss of appetite	0	0	0	0	1
Any Fever	8	7	2	7	10

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited general symptoms

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End point title

Number of subjects reported with solicited general symptoms

End point description

End point type

Secondary

End point timeframe

Within 7 days (Days 0-6) after Month 9 vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	50	49	48	54	51	47	56	51
Units: Subjects
Any Drowsiness	0	0	0	0	1	0	1	0
Any Irritability/Fussiness	0	2	0	0	2	0	2	0
Any Loss of appetite	0	1	0	0	1	0	1	0
Any Fever	1	5	6	2	3	2	10	1

No statistical analyses for this end point

Other pre-specified: Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

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End point title

Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

End point description

Month 18 immunogenicity data were tertiary objectives, and although not required to be disclosed were included in this CTRS at the request of the study team to show the full study immunogenicity results.

End point type

Other pre-specified

End point timeframe

At Month 18 post vaccination

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	45	43	47	47	45	40	52	48
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-CS, M18	5.1 (3.1 to 8.3)	12.7 (7.2 to 22.3)	12 (8.3 to 17.4)	16.2 (9.4 to 28.1)	14.3 (8.7 to 23.6)	33.8 (24.7 to 46.4)	49.3 (36.2 to 67)	0.3 (0.2 to 0.3)

No statistical analyses for this end point

Other pre-specified: Anti-Hepatitis B surface antibody (anti-HBs) concentrations

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End point title

Anti-Hepatitis B surface antibody (anti-HBs) concentrations

End point description

At Month 18 post vaccination

End point type

Other pre-specified

End point timeframe

End point values	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Number of subjects analysed	40	41	45	45	43	39	47	42
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-HBs, M18	1656.6 (1180.1 to 2325.4)	3509.9 (2464.8 to 4998)	1823.1 (1260.6 to 2636.5)	4208.4 (3045.5 to 5815.5)	4725.7 (3508.7 to 6364.7)	7341.5 (5023.1 to 10729.9)	12045.3 (8881.5 to 16336.2)	78 (44.1 to 137.9)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited symptoms: 7 days post vaccination at Weeks 0, 6, 10, 14, 26 and Month 9; SAEs: From Month 0 to Month 18; Unsolicited AEs: 30 days post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.

Adverse event reporting additional description

Note that 1) safety analysis for solicited symptoms and unsolicited AEs was performed only on subjects with available results; 2) The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

RTS,S Neo-10-14 Group

Reporting group description

Reporting group title

RTS,S Neo-10-26 Group

Reporting group description

Reporting group title

RTS,S 6-10-14 Group

Reporting group description

Reporting group title

RTS,S 6-10-26 Group

Reporting group description

Reporting group title

Engerix-B Neo/RTS,S 6-10-26 Group

Reporting group description

Reporting group title

RTS,S 10-14-26 Group

Reporting group description

Reporting group title

RTS,S 14-26-9M Group

Reporting group description

Reporting group title

Engerix-B Neo Group

Reporting group description

Serious adverse events	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 60 (11.67%)	5 / 59 (8.47%)	6 / 60 (10.00%)	9 / 60 (15.00%)	8 / 60 (13.33%)	12 / 60 (20.00%)	5 / 60 (8.33%)	4 / 60 (6.67%)
number of deaths (all causes)	0	0	1	1	0	1	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Head injury
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Epilepsy
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Jaundice neonatal
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Drowning
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	1 / 60 (1.67%)	0 / 60 (0.00%)	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	2 / 60 (3.33%)	3 / 59 (5.08%)	2 / 60 (3.33%)	2 / 60 (3.33%)	2 / 60 (3.33%)	1 / 60 (1.67%)	1 / 60 (1.67%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 2	0 / 2	0 / 2	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral malaria
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	1 / 60 (1.67%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	4 / 60 (6.67%)	0 / 59 (0.00%)	2 / 60 (3.33%)	2 / 60 (3.33%)	4 / 60 (6.67%)	5 / 60 (8.33%)	2 / 60 (3.33%)	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 2	0 / 2	0 / 4	0 / 5	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	0 / 60 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malaria
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis neonatal
subjects affected / exposed	1 / 60 (1.67%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis pneumococcal
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral candidiasis
subjects affected / exposed	1 / 60 (1.67%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumococcal sepsis
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	2 / 60 (3.33%)	1 / 59 (1.69%)	2 / 60 (3.33%)	1 / 60 (1.67%)	1 / 60 (1.67%)	3 / 60 (5.00%)	2 / 60 (3.33%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2	0 / 1	0 / 1	0 / 3	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis neonatal
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Malnutrition
subjects affected / exposed	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	RTS,S Neo-10-14 Group	RTS,S Neo-10-26 Group	RTS,S 6-10-14 Group	RTS,S 6-10-26 Group	Engerix-B Neo/RTS,S 6-10-26 Group	RTS,S 10-14-26 Group	RTS,S 14-26-9M Group	Engerix-B Neo Group
Total subjects affected by non serious adverse events
subjects affected / exposed	36 / 60 (60.00%)	35 / 59 (59.32%)	28 / 60 (46.67%)	29 / 60 (48.33%)	35 / 60 (58.33%)	36 / 60 (60.00%)	47 / 60 (78.33%)	31 / 60 (51.67%)
General disorders and administration site conditions
Pain
subjects affected / exposed ^[1]	4 / 60 (6.67%)	5 / 59 (8.47%)	7 / 58 (12.07%)	7 / 60 (11.67%)	4 / 60 (6.67%)	6 / 59 (10.17%)	5 / 60 (8.33%)	6 / 59 (10.17%)
occurrences all number	4	5	7	7	4	6	5	6
Redness
subjects affected / exposed ^[2]	4 / 60 (6.67%)	5 / 59 (8.47%)	6 / 58 (10.34%)	6 / 60 (10.00%)	7 / 60 (11.67%)	5 / 59 (8.47%)	11 / 60 (18.33%)	6 / 59 (10.17%)
occurrences all number	4	5	6	6	7	5	11	6
Swelling
subjects affected / exposed ^[3]	7 / 60 (11.67%)	5 / 59 (8.47%)	6 / 58 (10.34%)	8 / 60 (13.33%)	6 / 60 (10.00%)	6 / 59 (10.17%)	8 / 60 (13.33%)	6 / 59 (10.17%)
occurrences all number	7	5	6	8	6	6	8	6
Irritability
alternative assessment type: Non-systematic
subjects affected / exposed ^[4]	4 / 60 (6.67%)	2 / 59 (3.39%)	6 / 58 (10.34%)	1 / 60 (1.67%)	3 / 60 (5.00%)	3 / 59 (5.08%)	2 / 60 (3.33%)	2 / 59 (3.39%)
occurrences all number	4	2	6	1	3	3	2	2
Fever (axillary temperature >= 37.5°C)
subjects affected / exposed ^[5]	11 / 60 (18.33%)	9 / 59 (15.25%)	10 / 58 (17.24%)	7 / 60 (11.67%)	10 / 60 (16.67%)	10 / 59 (16.95%)	10 / 60 (16.67%)	9 / 59 (15.25%)
occurrences all number	11	9	10	7	10	10	10	9
Pyrexia
subjects affected / exposed ^[6]	3 / 60 (5.00%)	2 / 59 (3.39%)	5 / 54 (9.26%)	1 / 57 (1.75%)	5 / 57 (8.77%)	2 / 52 (3.85%)	3 / 57 (5.26%)	1 / 52 (1.92%)
occurrences all number	3	2	5	1	5	2	3	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed ^[7]	1 / 60 (1.67%)	2 / 59 (3.39%)	3 / 54 (5.56%)	2 / 57 (3.51%)	3 / 57 (5.26%)	1 / 52 (1.92%)	2 / 57 (3.51%)	2 / 52 (3.85%)
occurrences all number	1	2	3	2	3	1	2	2
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed ^[8]	2 / 60 (3.33%)	2 / 59 (3.39%)	3 / 54 (5.56%)	0 / 57 (0.00%)	5 / 57 (8.77%)	2 / 52 (3.85%)	4 / 57 (7.02%)	3 / 52 (5.77%)
occurrences all number	2	2	3	0	5	2	4	3
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed ^[9]	4 / 60 (6.67%)	2 / 59 (3.39%)	0 / 54 (0.00%)	2 / 57 (3.51%)	3 / 57 (5.26%)	5 / 52 (9.62%)	2 / 57 (3.51%)	2 / 52 (3.85%)
occurrences all number	4	2	0	2	3	5	2	2
Infections and infestations
Bronchiolitis
subjects affected / exposed ^[10]	0 / 60 (0.00%)	0 / 59 (0.00%)	1 / 54 (1.85%)	3 / 57 (5.26%)	2 / 57 (3.51%)	0 / 52 (0.00%)	0 / 57 (0.00%)	0 / 52 (0.00%)
occurrences all number	0	0	1	3	2	0	0	0
Conjunctivitis
subjects affected / exposed ^[11]	4 / 60 (6.67%)	5 / 59 (8.47%)	1 / 54 (1.85%)	2 / 57 (3.51%)	2 / 57 (3.51%)	6 / 52 (11.54%)	5 / 57 (8.77%)	2 / 52 (3.85%)
occurrences all number	4	5	1	2	2	6	5	2
Gastroenteritis
subjects affected / exposed ^[12]	3 / 60 (5.00%)	5 / 59 (8.47%)	0 / 54 (0.00%)	3 / 57 (5.26%)	2 / 57 (3.51%)	9 / 52 (17.31%)	8 / 57 (14.04%)	2 / 52 (3.85%)
occurrences all number	3	5	0	3	2	9	8	2
Malaria
subjects affected / exposed ^[13]	5 / 60 (8.33%)	3 / 59 (5.08%)	2 / 54 (3.70%)	0 / 57 (0.00%)	4 / 57 (7.02%)	5 / 52 (9.62%)	9 / 57 (15.79%)	0 / 52 (0.00%)
occurrences all number	5	3	2	0	4	5	9	0
Nasopharyngitis
subjects affected / exposed ^[14]	6 / 60 (10.00%)	3 / 59 (5.08%)	6 / 54 (11.11%)	6 / 57 (10.53%)	3 / 57 (5.26%)	3 / 52 (5.77%)	7 / 57 (12.28%)	7 / 52 (13.46%)
occurrences all number	6	3	6	6	3	3	7	7
Oral candidiasis
subjects affected / exposed ^[15]	1 / 60 (1.67%)	3 / 59 (5.08%)	0 / 54 (0.00%)	0 / 57 (0.00%)	1 / 57 (1.75%)	1 / 52 (1.92%)	1 / 57 (1.75%)	0 / 52 (0.00%)
occurrences all number	1	3	0	0	1	1	1	0
Pneumonia
subjects affected / exposed ^[16]	8 / 60 (13.33%)	6 / 59 (10.17%)	3 / 54 (5.56%)	7 / 57 (12.28%)	6 / 57 (10.53%)	5 / 52 (9.62%)	9 / 57 (15.79%)	6 / 52 (11.54%)
occurrences all number	8	6	3	7	6	5	9	6
Respiratory tract infection
subjects affected / exposed ^[17]	1 / 60 (1.67%)	2 / 59 (3.39%)	0 / 54 (0.00%)	3 / 57 (5.26%)	1 / 57 (1.75%)	0 / 52 (0.00%)	1 / 57 (1.75%)	0 / 52 (0.00%)
occurrences all number	1	2	0	3	1	0	1	0
Upper respiratory tract infection
subjects affected / exposed ^[18]	11 / 60 (18.33%)	15 / 59 (25.42%)	10 / 54 (18.52%)	6 / 57 (10.53%)	11 / 57 (19.30%)	13 / 52 (25.00%)	15 / 57 (26.32%)	13 / 52 (25.00%)
occurrences all number	11	15	10	6	11	13	15	13

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results were only collected in subjects having results available for the 7-day (Days 0-6) periods post vaccination with the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E or the Tritanrix™HepB/Hib vaccine(s) at Weeks 0, 6, 10, 14, 26 and/or Month 9.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results were only collected in subjects having results available for the 7-day (Days 0-6) periods post vaccination with the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E or the Tritanrix™HepB/Hib vaccine(s) at Weeks 0, 6, 10, 14, 26 and/or Month 9.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results were only collected in subjects having results available for the 7-day (Days 0-6) periods post vaccination with the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E or the Tritanrix™HepB/Hib vaccine(s) at Weeks 0, 6, 10, 14, 26 and/or Month 9.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results were only collected in subjects having results available for the 7-day (Days 0-6) periods post vaccination with the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E or the Tritanrix™HepB/Hib vaccine(s) at Weeks 0, 6, 10, 14, 26 and/or Month 9.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Solicited symptoms results were only collected in subjects having results available for the 7-day (Days 0-6) periods post vaccination with the Bacille Calmette Guerin tuberculosis vaccine, Engerix™-B, Rouvax™, RTS,S/AS01E or the Tritanrix™HepB/Hib vaccine(s) at Weeks 0, 6, 10, 14, 26 and/or Month 9.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.
[18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Unsolicited AEs results were only collected in subjects having results available for the 30-day (Days 0-29) period post vaccination with 3 doses of RTS,S/AS01E versus Tritanrix™HepB/Hib for the Engerix-B Neo Group.

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Were there any global substantial amendments to the protocol? Yes

25 Nov 2008

The study design was modified for the inclusion of an additional study group with a 14, 26-week and 9 month RTS,S/AS01E schedule. This schedule explores a possible schedule outside the EPI DTPw-HepB/Hib vaccination schedule, but still co-administers 2 of the doses at existing EPI visits. A number of changes were made to the protocol as a consequence. The administration of a measles vaccine (Rouvax) was described. The study was revised from including three sites to one study site.

02 Apr 2009

GSK no longer makes the Zilbrix Hib DTPwHepB/Hib vaccine. This study therefore used a similar DTPHepB/Hib vaccine manufactured by GSK, Tritanrix HepB/Hib. The primary difference is that Zilbrix Hib a lower quantity of PRP antigen per dose than Tritanrix HepB/Hib (5 fold difference).

20 Apr 2010

Exclusion and elimination criteria on investigational or non-registered product were reworded. The blood volume specified for the collection of hematology and biochemistry safety bloods was increased to provide sufficient sample volume for analysis. In order to be able to obtain cord blood and where possible, to allow parent(s)/guardian(s) (LARs) extra time to understand the information provided to them BEFORE the child birth, an ICF was developed to provide the full information. Since this information sheet and consent could have been provided up to 3 months prior to the child birth, it was felt necessary to obtain confirmation of continued consent PRIOR to any study procedure being carried out on the infant. Using this process it was also possible for parent(s)/LARs to consent to take part in the study up to 7 days after birth if they were unable to provide consent prior to birth. The informed consent procedure was modified to avoid having to obtain consent at a sensitive time (around the birth). Based on concern that the use of new adjuvanted vaccines could promote a rupture of immunological self-tolerance, regulatory authorities required the optimization of data collection on auto-immune diseases. As a result, it was decided to define pIMDs as an adverse event of interest and to optimize auto-immunity data collection processes in studies of adjuvanted candidate vaccines, with reporting of these events being added for the entire study period. A pooled analysis of safety data performed on all controlled Phase II pediatric RTS,S/AS vaccine trials revealed an imbalance in the reporting of rashes and diaper rashes as AEs occurring in infants less than 5 months of age. As a result, the safety reporting included adverse events of specific interest, namely rashes and mucocutaneous lesions. Rashes and mucocutaneous lesions that occurred within 30 days of vaccination were to be documented and analyzed according to the Brighton Collaboration Guidelines.

28 Jun 2011

The rationale for this amendment was to ensure better safety assessment of enrolled subjects, enhance community confidence and acceptability of the study and also improve subject enrolment by: 1) Allowing for repeat safety blood samples to be drawn at any of the follow-up safety assessment time points in the event that the initial safety blood sample drawn was unsuitable for analysis; 2) Removal of the enrolment pause during Safety Report 4 (i.e. when 60 neonates have received neonatal RTS,S/AS01E doses). 3) Allowing for a repeat blood sample to be taken from a neonate at enrolment for: a) safety re-screening in the event that the initial screening blood sample failed the eligibility criteria, b) safety screening in the event that the initial screening blood sample was unsuitable for analysis, c) re-screening for both safety and immunogenicity in the event that the 24 hour maximum interval between blood sampling and enrolment is exceeded; 4) Extending the study from a single-center to a multi-center study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A phase 2, open, randomized, controlled, multi-center study to evaluate the safety and immunogenicity of 7 infant immunization schedules of the RTS,S/AS01E candidate vaccine against P. falciparum.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

Primary: Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

Primary: Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

Secondary: Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

Secondary: Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

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

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

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

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

Secondary: Number of subjects reported with biochemical abnormalities, for the alanine aminotransferase (ALT) parameter

Secondary: Number of subjects reported with biochemical abnormalities, for the alanine aminotransferase (ALT) parameter

Secondary: Number of subjects reported with biochemical abnormalities, for the creatinine (CREA) parameter

Secondary: Number of subjects reported with biochemical abnormalities, for the creatinine (CREA) parameter

Secondary: Number of subjects reported with haematological abnormalities, for the haemoglobin (HAE) parameter

Secondary: Number of subjects reported with haematological abnormalities, for the haemoglobin (HAE) parameter

Secondary: Number of subjects reported with haematological abnormalities, for the platelets (PLA) parameter

Secondary: Number of subjects reported with haematological abnormalities, for the platelets (PLA) parameter

Secondary: Number of subjects reported with haematological abnormalities, for the white blood cells (WBC) parameter

Secondary: Number of subjects reported with haematological abnormalities, for the white blood cells (WBC) parameter

Secondary: Anti-Hepatitis B surface antibody (anti-HBs) concentrations

Secondary: Anti-Hepatitis B surface antibody (anti-HBs) concentrations

Secondary: Anti-diphtheria (Anti-D) and anti-tetanus toxoids (anti-TT) antibody concentrations

Secondary: Anti-diphtheria (Anti-D) and anti-tetanus toxoids (anti-TT) antibody concentrations

Secondary: Anti-polyribosyl ribitol phosphate (anti-PRP) antibody concentrations

Secondary: Anti-polyribosyl ribitol phosphate (anti-PRP) antibody concentrations

Secondary: Anti-polio type 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody concentrations

Secondary: Anti-polio type 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody concentrations

Secondary: Concentrations of antibodies against acellular B-pertussis (BPT)

Secondary: Concentrations of antibodies against acellular B-pertussis (BPT)

Secondary: Concentrations of antibodies against measles antigens

Secondary: Concentrations of antibodies against measles antigens

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

Other pre-specified: Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

Other pre-specified: Concentrations of antibodies against circumsporozoite protein of Plasmodium falciparum (anti-CS antibodies)

Other pre-specified: Anti-Hepatitis B surface antibody (anti-HBs) concentrations

Other pre-specified: Anti-Hepatitis B surface antibody (anti-HBs) concentrations

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A phase 2, open, randomized, controlled, multi-center study to evaluate the safety and immunogenicity of 7 infant immunization schedules of the RTS,S/AS01E candidate vaccine against P. falciparum.