Efficacy of RTS,S/AS01 Vaccine Against Episodes of Malaria Due to P. Falciparum Infection in Children.

GlaxoSmithKline894 enrolled

Overview

This phase IIb trial is being done to find out if the RTS,S/AS01 vaccine helps to prevent children from falling ill with malaria and to evaluate vaccine safety. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

894

Conditions

Malaria

Interventions

GSK malaria vaccine 257049 VaccineBIOLOGICAL

3 dose intramuscular injection

Sanofi-Pasteur's Human Diploid Cell Rabies VaccineBIOLOGICAL

3 dose intramuscular injection

Eligibility

Sex: ALLMin age: 5 MonthsMax age: 17 MonthsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * A male or female child of between 5 months and 17 months of age at the time of first vaccination. * Written or oral, signed or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child.. * Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol. Exclusion Criteria: * Acute disease at the time of enrolment. * Serious acute or chronic illness determined by clinical or physical examination and laboratory screening tests. * Laboratory screening tests for haemoglobin, total white cell count, platelets, ALT and creatinine out of acceptable limits. * Planned administration/administration of a vaccine not foreseen by the study within 30 days of the first dose of vaccine(s) with the exception of tetanus toxoid or scheduled diphtheria, pertussis or measles vaccine. * Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. * Administration of immunoglobulins, blood transfusions or other blood products within the three months preceding the first dose of study vaccine or planned administration during the study period. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose * Previous participation in any other malaria vaccine trial. * Simultaneous participation in any other clinical trial. * Same sex twin. * History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunizations. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

Locations (2)

GSK Investigational Site

Kilifi, Kenya

GSK Investigational Site

Amani, Tanga, Tanzania

Outcomes

Primary Outcomes

Frequency of First Case of Malaria Meeting the Primary Case Definition

The first case of malaria meeting the primary case definition was defined as the first or only episodes with the presence of Plasmodium falciparum asexual parasitemia above (\>) 2500 per microliter (μL) and the presence of fever greater than or equal to (≥) 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of first case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

Time frame: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Secondary Outcomes

Frequency of First Case Malaria Meeting the Secondary Case Definition

The first case of malaria meeting the secondary case definition was defined as the first or only episodes with the presence of P.falciparum asexual parasitemia \> 0 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of first case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

Time frame: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Multiple Events of Malaria Meeting the Primary Case Definition

Multiple episodes of malaria meeting the primary case definition was defined as episodes with the presence of P.falciparum asexual parasitemia \> 25000 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of primary case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

Time frame: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Multiple Events of Malaria Meeting the Secondary Case Definition

Multiple episodes of malaria meeting the secondary case definition was defined as episodes with the presence of P.falciparum asexual parasitemia \> 0 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of secondary case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

Data from ClinicalTrials.gov

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Time frame: Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Number of Subjects Positive for P. Falciparum Parasitaemia

Time frame: At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Geometric Mean Density of Asexual P. Falciparum Parasite

Estimates of asexual P. falciparum parasite density were made at the investigator's sites according to laboratory standard operating procedures. Parasite density was presented as a geometric mean (GMean), expressed in parasite per microliters (μL).

Time frame: At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Haemoglobin Values at Cross-Sectional Visit

Haemoglobin values are expressed in grams per deciliter (g/dL).

Time frame: At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Assessed solicited local symptoms were pain and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 swelling = swelling spreading beyond 20 millimeters (mm) of injection site.

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

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

Assessed solicited general symptoms were drowsiness, fever \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever higher than (\>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

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

Number of Subjects With Any Unsolicited Adverse Events (AEs)

An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

Time frame: Within the 30-day (Days 0-29) post-vaccination follow-up period

Number of Subjects With Serious Adverse Events (SAEs)

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

Time frame: Throughout the study period (Day 0 - Month 14)

Number of Subjects With Hemoglobin Values Outside Normal Ranges With Toxicity Grades

Definitions for toxicity grading for hemoglobin were: Normal Hemoglobin = equal to or above (≥) 8.0 g/dL; Grade 1 Hemoglobin = under (\<) 8.0 g/dL and above (\>) 6.0 g/dL.; Grade 2 Hemoglobin = under (\<) 6.0 g/dL.