Efficacy of GSK Biologicals' Candidate Malaria Vaccine 257049 Against Malaria Disease in Infants and Children in Africa

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00866619
• Date of registration: 19/03/2009
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Efficacy of GSK Biologicals' Candidate Malaria Vaccine 257049 Against Malaria Disease in Infants and Children in Africa
• Scientific title: Efficacy of GSK Biologicals' Candidate Malaria Vaccine (257049) Against Malaria Disease Caused by P. Falciparum Infection in Infants and Children in Africa
• Date of first enrolment: March 27, 2009
• Target sample size: 15459
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00866619
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Prevention. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, Tanzania

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & 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



Age minimum: 6 Weeks
Age maximum: 17 Months
Gender: All

Health Condition(s) or Problem(s) studied

Malaria

Intervention(s)

Biological: Malaria Vaccine 257049

Biological: Meningococcal C Conjugate Vaccine

Biological: Cell-culture rabies vaccine

Biological: Polio Sabin Oral Polio Vaccine (GSK)

Biological: TritanrixHepB/Hib

Primary Outcome(s)

Rate of First or Only Clinical Episode of P. Falciparum Malaria Infection (CPFMI), or Clinical Malaria Episode of Primary Case Definition (CPFMI-PCD) [Time Frame: From Month 2.5 to Month 14]

Rate of First or Only Clinical Episode of Plasmodium Falciparum (P. Falciparum) Malaria Infection (CPFMI), or Clinical Malaria Episode of Primary Case Definition (CPFMI-PCD) [Time Frame: From Month 2.5 to Month 14]

Secondary Outcome(s)

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS), by Tertile [Time Frame: At Month 21]

Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal in the Low-weight (LW) and Very Low-weight (VLW) Category [Time Frame: Within the 30-day (Days 0-29) post-primary vaccination period in HIV-infected children]

Percentage of Subjects With Blood Transfusion, as Per Case Definition Assessed [Time Frame: 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)]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD and SCD1, Across Centers [Time Frame: 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)]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD, Overall and by Center [Time Frame: From Month 2.5 to Month 20]

Antibody Concentrations Against Hepatitis B Surface Antigen [Time Frame: At Day 0 and at Month 3]

Height, Weight and Mid Upper Arm Circumference for Age Z-score (HAZ, WAZ and MUACZ) [Time Frame: At Month 20 (Booster)]

Number of Subjects Reporting Any Potential Immune-mediated Disorders (pIMDs) [Time Frame: 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)]

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS) [Time Frame: At Months 20, 21 and 32]

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS), by Tertile [Time Frame: At Month 3]

Number of Subjects With Serious Adverse Events (SAEs) [Time Frame: From Month 0 up to Booster (Month 20), from Month 0 up to study end and from Month 20 up to study end]

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS) [Time Frame: 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)]

Number of Subjects With Serious Adverse Events (SAEs) [Time Frame: From Month 0 up to Month 14]

Number of Very Low-weight (VLW) Subjects With Serious Adverse Events (SAEs) [Time Frame: From Month 0 up to Month 20]

Number of Subjects With Any Unsolicited AEs [Time Frame: Within the 30-day (days 0-29) post-booster vaccination period]

Antibody Concentrations Against Plasmodium Falciparum Circumsporozoite (Anti-CS) [Time Frame: At Day 0 and at Month 3]

Number of Doses With Seizures by Diagnostic Certainty Level [Time Frame: During the 7-day (Days 0-6) post-booster vaccination period, at Month 20 + 7 Day (Days 0-6)]

Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) [Time Frame: At Day 0 and at Month 3]

Antibody Titers Against Poliomyelitis (Anti-polio) Type 1, 2 and 3 [Time Frame: At Day 0 and at Month 3]

Number of Low-weight (LW) Subjects With Serious Adverse Events (SAEs) [Time Frame: From Month 0 up to Month 20]

Number of Subjects Reporting Any Meningitis and Encephalitis SAEs [Time Frame: 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 With Unsolicited AEs Related to or Leading to Vaccination Withdrawal [Time Frame: Within the 30-day (Days 0-29) post-primary vaccination period]

Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) [Time Frame: At Months 20 and 21]

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS) [Time Frame: At Day 0 and at Month 3]

Percentage of Subjects With Incident Severe Anaemia (ISA), Malaria Hospitalization (MH) and Fatal Malaria (FM) for Case Definitions (CD) Considered [Time Frame: 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 Prevalent Parasitemia, Prevalent Gametocytemia and Prevalent Severe and Moderate Anemia [Time Frame: At Month 20 (Booster)]

Percentage of Subjects With Incident Severe Anaemia (ISA) and Malaria Hospitalization (MH) for Case Definitions (CD) Considered [Time Frame: From Month 2.5 to Month 20]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Tertile [Time Frame: From Booster at Month 20 to Month 32]

Number of Subjects Reporting Any Meningitis and Encephalitis Serious Adverse Events (SAEs) [Time Frame: 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 With Any and Grade 3 Solicited Local Symptoms [Time Frame: During the 7-day (Days 0-6) post-booster vaccination period]

Number of Subjects With Any and Grade 3 Solicited Local Symptoms [Time Frame: During the 7-day (Days 0-6) post-primary vaccination period following each dose and across doses]

Number of Subjects With Serious Adverse Events (SAEs) [Time Frame: Within the 30-day (Days 0-29) post-booster vaccination period]

Rate of All Episodes of P. Falciparum Clinical Malaria Infection (CPFMI) of PCD and of Secondary Case Definitions (SCD) 1, SCD 2 and SCD 3 [Time Frame: From Month 2.5 to Month 14]

Percentage of Subjects With Prevalent Parasitemia and Prevalent Severe and Moderate Anemia [Time Frame: 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)]

Number of Low-weight (LW) Subjects With Serious Adverse Events (SAEs) [Time Frame: 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 Reporting Mucocutaneous Changes (All Levels) [Time Frame: During the 30-day (Days 0-29) post-booster vaccination]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Centers and Across Centers [Time Frame: 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 Pneumonia, All-cause Hospitalization/Mortality and Sepsis, as Per Case Definitions Assessed [Time Frame: 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 Severe PFMI (SPFMI) of PCD and SCD1 [Time Frame: From Month 2.5 to Month 14]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Secondary Case Definition 1 (SCD1), Across Centers [Time Frame: 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)]

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [Time Frame: During the 7-day (Days 0-6) post-booster vaccination period]

Percentage of Subjects With Severe PFMI (SPFMI) of PCD and SCD1 [Time Frame: From Month 2.5 to Month 20 at Booster]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of SCD1, SCD2 and SCD3 (Overall) [Time Frame: From Month 2.5 to Month 20]

Number of Subjects With Serious Adverse Events (SAEs) [Time Frame: During the 30-day (Days 0-29) post-primary vaccination period]

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [Time Frame: During the 7-day (Days 0-6) post-primary vaccination period following each dose and across doses]

Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal [Time Frame: Within the 30-day (Days 0-29) post-primary and post-booster vaccination period in HIV-infected children]

Percentage of Subjects With Incident Severe Anaemia (ISA), Malaria Hospitalization (MH) and Fatal Malaria (FM) for Case Definitions (CD) Considered [Time Frame: From Month 2.5 to Month 32]

Number of Subjects With Fatal Outcomes, by Gender [Time Frame: 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)]

Percentage of Subjects With Pneumonia, All-cause Hospitalization and Sepsis, as Per Case Definitions Assessed [Time Frame: From Month 2.5 to Month 20]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD) and Secondary Case Definition 1 (SCD1) [Time Frame: From Booster at Month 20 up to Month 32]

Percentage of Subjects With Fatal Malaria (FM) and All-cause Mortality (ACM) as Per Case Definitions Assessed [Time Frame: From Month 2.5 to Month 20]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Tertile [Time Frame: From Month 2.5 to Month 32]

Percentage of Subjects With Severe PFMI (SPFMI) of PCD and SCD1 [Time Frame: 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]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Secondary Case Definition 1 (SCD1) [Time Frame: From Month 2.5 to Month 32]

Percentage of Subjects With Severe PFMI (SPFMI) of PCD, SCD1, SCD2 and SCD3, Across Centers [Time Frame: 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)]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD, by Center and Across Centers [Time Frame: From Month 2.5 to Month 32]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD) and Secondary Case Definition 1 (SCD1), Across Centers [Time Frame: 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)]

Height, Weight and Mid Upper Arm Circumference for Age Z-score (HAZ, WAZ and MUACZ) [Time Frame: 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)]

Number of Subjects With Any Unsolicited Adverse Events (AEs) [Time Frame: Within the 30-day (Days 0-29) post-primary vaccination period]

Number of Subjects With Serious Adverse Events (SAEs) [Time Frame: 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) [Time Frame: 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 Adversee Events (SAEs) [Time Frame: From Month 0 up to Month 20]

Number of Subjects With Unsolicited AEs Related to Vaccination in the Low-weight (LW) and Very Low-weight (VLW) Category [Time Frame: Within the 30-day (Days 0-29) post-booster vaccination period]

Number of Very Low-weight Subjects With Serious Adverse Events (SAEs) [Time Frame: 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)]]

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Gender and Overall [Time Frame: From Month 2.5 to Month 32]

Secondary ID(s)

2012-005716-26

110021

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

The PATH Malaria Vaccine Initiative (MVI)

Results

• Results available: Yes
• Date Posted: 09/10/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00866619