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Efficacy of GSK Biologicals' candidate malaria vaccine 257049 against malaria disease in infants and children in Africa

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GSK study ID

110021

See study documents

Clinicaltrials.gov ID

NCT00866619

See results summary

EudraCT ID

2012-005716-26

EU CT Number

Not applicable

Trial status

Study complete

Overview

Eligibility

Locations

Study documents

Results summary

Plain language summaries

Additional information

Trial overview

Official title: Efficacy of GSK Biologicals’ candidate malaria vaccine (257049) against malaria disease caused by P. falciparum infection in infants and children in Africa

Trial description: The purpose of this observer-blind study is to gather key efficacy, safety, and immunogenicity information on GSK’s candidate malaria vaccine in infants and children.

Primary purpose:

Prevention

Trial design:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Allocation:

Randomized

Primary outcomes:

Time to first or only clinical episode of Plasmodium falciparum (P. falciparum) malaria infection (CPFMI), or clinical malaria episode of Primary Case Definition (CPFMI-PCD)

Timeframe: From Month 2.5 to Month 14

Time to first or only clinical episode of P. falciparum malaria infection (CPFMI), or clinical malaria episode of Primary Case Definition (CPFMI-PCD)

Timeframe: From Month 2.5 to Month 14

Secondary outcomes:

Time to all episodes of P. falciparum clinical malaria infection (CPFMI) of PCD and of secondary case definitions (SCD) 1, SCD 2 and SCD 3

Timeframe: From Month 2.5 to Month 14

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of PCD, overall and by center

Timeframe: From Month 2.5 to Month 20

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of SCD1, SCD2 and SCD3 (overall)

Timeframe: From Month 2.5 to Month 20

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of primary case definition (PCD), by centers and across centers

Timeframe: From Month 2.5 up to study End (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of Secondary Case Definition 1 (SCD1), across centers

Timeframe: From Month 2.5 up to study end (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of Primary Case Definition (PCD) and Secondary Case Definition 1 (SCD1), across centers

Timeframe: From Booster at Month 20 up to study end (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of PCD and SCD1, across centers

Timeframe: From Month 33 up to study end (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of PCD, by center and across centers

Timeframe: From Month 2.5 to Month 32

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of Secondary Case Definition 1 (SCD1)

Timeframe: From Month 2.5 to Month 32

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of Primary Case Definition (PCD) and Secondary Case Definition 1 (SCD1)

Timeframe: From Booster at Month 20 up to Month 32

Percentage of subjects with severe PFMI (SPFMI) of PCD, SCD1, SCD2 and SCD3, across centers

Timeframe: From Month 2.5 up to the time when 250 subjects were diagnosed with severe malaria of PCD, SCD1, SCD2 and SCD3 (up to the Month 14 time point for each age category or date of booster dose, whichever occurred first)

Percentage of subjects with severe PFMI (SPFMI) of PCD and SCD1

Timeframe: From Month 2.5 to Month 14

Percentage of subjects with severe PFMI (SPFMI) of PCD and SCD1

Timeframe: From Month 2.5 to Month 20 at Booster

Percentage of subjects with severe PFMI (SPFMI) of PCD and SCD1

Timeframe: From Month 2.5, from Month 20(booster), from Month 33 up to study end (median follow-up time of 48 months post-Dose 1 for 5-17M age category and of 38 months post-Dose 1 for 6-12W age category) and from Month 2.5 to Month 32 and from Month 20 to Month 32

Percentage of subjects with incident severe anaemia (ISA) and malaria hospitalization (MH) for case definitions (CD) considered

Timeframe: From Month 2.5 to Month 20

Percentage of subjects with incident severe anaemia (ISA), malaria hospitalization (MH) and fatal malaria (FM) for case definitions (CD) considered

Timeframe: From Month 2.5 to up to study end (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Percentage of subjects with incident severe anaemia (ISA), malaria hospitalization (MH) and fatal malaria (FM) for case definitions (CD) considered

Timeframe: From Month 2.5 to Month 32

Percentage of subjects with prevalent parasitemia, prevalent gametocytemia and prevalent severe and moderate anemia

Timeframe: At Month 20 (Booster)

Percentage of subjects with prevalent parasitemia and prevalent severe and moderate anemia

Timeframe: At Months 32, 44, at study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category) (early and late)

Percentage of subjects with pneumonia, all-cause hospitalization and sepsis, as per case definitions assessed

Timeframe: From Month 2.5 to Month 20

Percentage of subjects with fatal malaria (FM) and all-cause mortality (ACM) as per case definitions assessed

Timeframe: From Month 2.5 to Month 20

Percentage of subjects with pneumonia, all-cause hospitalization/mortality and sepsis, as per case definitions assessed

Timeframe: From Month 2.5 up to study end (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Percentage of subjects with blood transfusion, as per case definition assessed

Timeframe: From Month 2.5 up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of primary case definition (PCD), by gender and overall

Timeframe: From Month 2.5 to Month 32

Height, weight and mid upper arm circumference for age z-score (HAZ, WAZ and MUACZ)

Timeframe: At Month 20 (Booster)

Height, weight and mid upper arm circumference for age z-score (HAZ, WAZ and MUACZ)

Timeframe: At Months 32, 44, at study end (early and late) (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Antibody concentrations against Plasmodium falciparum circumsporozoite (anti-CS)

Timeframe: At Day 0 and at Month 3

Antibody concentrations against P. falciparum circumsporozoite (anti-CS)

Timeframe: At Day 0 and at Month 3

Antibody concentrations against P. falciparum circumsporozoite (anti-CS)

Timeframe: At Months 20, 21 and 32

Antibody concentrations against P. falciparum circumsporozoite (anti-CS)

Timeframe: At Month 44 and at study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Antibody concentrations against P. falciparum circumsporozoite (anti-CS), by tertile

Timeframe: At Month 3

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of primary case definition (PCD), by tertile

Timeframe: From Month 2.5 to Month 32

Antibody concentrations against P. falciparum circumsporozoite (anti-CS), by tertile

Timeframe: At Month 21

Time to all episodes of clinical P. falciparum malaria infection (CPFMI) of primary case definition (PCD), by tertile

Timeframe: From Booster at Month 20 to Month 32

Antibody concentrations against Hepatitis B surface antigen (anti-HBs)

Timeframe: At Day 0 and at Month 3

Antibody concentrations against Hepatitis B surface antigen

Timeframe: At Day 0 and at Month 3

Antibody concentrations against Hepatitis B surface antigen (anti-HBs)

Timeframe: At Months 20 and 21

Antibody titers against poliomyelitis (anti-polio) type 1, 2 and 3

Timeframe: At Day 0 and at Month 3

Number of subjects with any and grade 3 solicited local symptoms

Timeframe: During the 7-day (Days 0-6) post-primary vaccination period following each dose and across doses

Number of subjects with any, grade 3 and related solicited general symptoms

Timeframe: During the 7-day (Days 0-6) post-primary vaccination period following each dose and across doses

Number of subjects with any and grade 3 solicited local symptoms

Timeframe: During the 7-day (Days 0-6) post-booster vaccination period

Number of subjects with any, grade 3 and related solicited general symptoms

Timeframe: During the 7-day (Days 0-6) post-booster vaccination period

Number of doses with seizures by diagnostic certainty level

Timeframe: During the 7-day (Days 0-6) post-booster vaccination period

Number of subjects reporting mucocutaneous changes (all levels)

Timeframe: During the 30-day (Days 0-29) post-booster vaccination

Number of subjects reporting any meningitis and encephalitis serious adverse events (SAEs)

Timeframe: At Month 0 until study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Number of subjects reporting any meningitis and encephalitis SAEs

Timeframe: From Booster up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Number of subjects reporting any potential immune-mediated disorders (pIMDs)

Timeframe: From Month 0 up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Number of subjects with any unsolicited adverse events (AEs)

Timeframe: Within the 30-day (Days 0-29) post-primary vaccination period

Number of subjects with unsolicited AEs related to or leading to vaccination withdrawal

Timeframe: Within the 30-day (Days 0-29) post-primary vaccination period

Number of subjects with any unsolicited AEs

Timeframe: Within the 30-day (days 0-29) post-booster vaccination period

Number of subjects with unsolicited AEs related to or leading to vaccination withdrawal

Timeframe: Within the 30-day (Days 0-29) post-primary and post-booster vaccination period in HIV-infected children

Number of subjects with unsolicited AEs related to or leading to vaccination withdrawal in the low-weight (LW) and very low-weight (VLW) category

Timeframe: Within the 30-day (Days 0-29) post-primary vaccination period in HIV-infected children

Number of subjects with unsolicited AEs related to vaccination in the low-weight (LW) and very low-weight (VLW) category

Timeframe: Within the 30-day (Days 0-29) post-booster vaccination period

Number of subjects with serious adverse events (SAEs)

Timeframe: From Month 0 up to Month 14

Number of subjects with serious adverse events (SAEs)

Timeframe: During the 30-day (Days 0-29) post-primary vaccination period

Number of subjects with serious adversee events (SAEs)

Timeframe: From Month 0 up to Month 20

Number of subjects with serious adverse events (SAEs)

Timeframe: From Booster (at Month 20) up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Number of subjects with serious adverse events (SAEs)

Timeframe: From Month 0 up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Number of subjects with serious adverse events (SAEs)

Timeframe: Within the 30-day (Days 0-29) post-booster vaccination period

Number of subjects with serious adverse events (SAEs)

Timeframe: From Month 0 up to Booster (Month 20), from Month 0 up to study end and from Month 20 up to study end

Number of low-weight (LW) subjects with serious adverse events (SAEs)

Timeframe: From Month 0 up to Month 20

Number of low-weight (LW) subjects with serious adverse events (SAEs)

Timeframe: From Booster (Month 20) up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Number of very low-weight (VLW) subjects with serious adverse events (SAEs)

Timeframe: From Month 0 up to Month 20

Number of very low-weight subjects with serious adverse events (SAEs)

Timeframe: From Booster (Month 20) up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)]

Number of subjects with fatal outcomes, by gender

Timeframe: From Month 0 up to study end (SE - median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Interventions:

Biological/vaccine: Malaria Vaccine 257049

Biological/vaccine: Meningococcal C Conjugate Vaccine

Biological/vaccine: Cell-culture rabies vaccine

Biological/vaccine: TritanrixHepB/Hib

Biological/vaccine: Polio Sabin Oral Polio Vaccine (GSK)

Enrollment:

15459

Primary completion date:

2011-01-03

Observational study model:

Not applicable

Time perspective:

Not applicable

Clinical publications:

Agnandji ST et al (2012) A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med. 367(24):2284-2295.

Agnandji ST et al. (2011) First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 365(20):1863-1875.

Leach A et al. (2011) Design of a phase III multicentre trial to evaluate the efficacy of the RTS,S/AS01E malaria vaccine in children across diverse transmission settings in Africa. Malar J. doi:10.1186/1475-2875-10-224.

Lievens M et al. (2011) Statistical methodology for the evaluation of vaccine efficacy in a phase III multi-center trial of the RTS,S/AS01 malaria vaccine in African children. Malar J.10:222.

Neafsey DE et al. (2015) Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine. N Engl J Med. 373(21); 2025-2037.

RTS,S Clinical Trials Partnership (2014) Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med. 11(7):e1001685.

RTS,S Clinical Trials Partnership. (2015) Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet. doi: 10.1016/S0140-6736(15)60721-8.

Swysen C et al. (2011) Development of standardized laboratory methods and quality processes for a phase III study of the RTS,S/AS01 candidate malaria vaccine. Malar J.10(1):223.

Vandoolaeghe P et al. (2016) The RTS,S/AS01 malaria vaccine in children 5 to 17 months of age at first vaccination. Expert Rev Vaccines. 15(12):1481-1493.

Vekemans J et al. (2011) Assessment of severe malaria in a multicenter, phase III, RTS,S/AS01 malaria candidate vaccine trial: case definition, standardization of data collection and patient care. Malar J.10(1):221.

Medical condition

Malaria

Product

SB257049

Collaborators

PATH Malaria Vaccine Initiative

Study date(s)

March 2009 to January 2014

Type

Interventional

Phase

Participation criteria

Sex

Female & Male

Age

6 weeks - 17 months

Accepts healthy volunteers

Yes

All subjects must satisfy the following criteria at study entry:
A male or female child of:5-17 months (inclusive) of age at time of first vaccination,or between 6-12 weeks of age at time of first vaccination

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:
Acute disease at the time of enrollment.

Inclusion and exclusion criteria

Inclusion criteria:

All subjects must satisfy the following criteria at study entry:
A male or female child of:5-17 months (inclusive) of age at time of first vaccination,or between 6-12 weeks of age at time of first vaccination and NOT have already received a dose of vaccine against diphtheria, tetanus or pertussis or Hemophilus influenzae type B and must be > 28 days of age at screening.
Signed informed consent or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child.
Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol. All subjects must satisfy the following criteria at the start of the extension phase:
Subjects who were enrolled and who received at least one vaccine dose in the primary trial phase.
Subjects who were present for Visit 35 on or before 30 September 2013.
Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) should be enrolled in the study.

Exclusion criteria:

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:
Acute disease at the time of enrollment.
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality.
Anemia associated with clinical signs or symptoms of decompensation or hemoglobin ≥ 5.0 g/dL.
Major congenital defects.
History of allergic reactions, significant IgE-mediated events or anaphylaxis to previous immunizations.
Children with a past history of a neurological disorder or atypical febrile seizure.
Children with malnutrition requiring hospital admission.
Children currently meeting the criteria for HIV disease of Stage III or Stage IV severity as defined by the World Health Organization.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to a drug or vaccine that is not licensed for that indication with the exception of studies with the objective of improving the drug treatment or clinical management of severe malaria disease.
Use of a drug or vaccine that is not approved for that indication other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Previous participation in any other malaria vaccine trial.
Receipt of a vaccine within the preceding 7 days.
Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.
Any other findings that the investigator feels would result in data collected being incomplete or of poor quality

Trial location(s)

Location

Status

Location

GSK Investigational Site

Dar-es-Salaam, Tanzania

Status

Study Complete

Location

GSK Investigational Site

Kilifi, Kenya, 80108

Status

Study Complete

Location

GSK Investigational Site

Kintampo, Ghana

Status

Study Complete

Location

GSK Investigational Site

Kisumu, Kenya

Status

Study Complete

Location

GSK Investigational Site

Kumasi, Ghana

Status

Study Complete

Location

GSK Investigational Site

Lambaréné, Gabon

Status

Study Complete

Showing 1 - 6 of 10 Results

Study documents

Clinical study report

Available language(s): English

Download document(s)

Scientific result summary

Available language(s): English

Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status

Study complete

Actual primary completion date

2011-01-03

Actual study completion date

2014-31-01

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

Additional information about the trial

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