Partially-blind (Observer-blind) Study of Safety and Immunogenicity of Two Malaria Vaccines in Ghanaian Children

Study Overview
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Brief Summary
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This study will investigate the safety and immunogenicity of 2 candidate malaria vaccines administered according to 3 different vaccination schedules in 5 to 17 months old Ghanaian children. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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This study will be conducted in a partially blind fashion: it will be observer-blind as to which vaccine was administered, and open as to the vaccination schedule. One group of children on the 0, 1, 2-schedule will receive a Rabies vaccine as a control. One group on the same schedule will receive the RTS,S/AS02D experimental vaccine as an active comparator.

Official Title
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A Partially-blind (Observer-blind) Study to Evaluate the Safety and Immunogenicity of 3 Different Vaccination Schedules With 2 GSK Biologicals' Candidate Plasmodium Falciparum Vaccines in Children Aged 5 to 17 Months Living in Ghana

Conditions
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Malaria

Intervention / Treatment
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* Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049
* Biological: Rabipur


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female child 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. Proof that child has received a full 3-dose regimen of licensed Hepatitis B vaccine in infancy. 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 in the scope of the study) within 30 days of the first dose of vaccine(s) with the exception of tetanus toxoid or scheduled Yellow fever or Measles vaccine. Use of any investigational or non-registered drug or vaccine other than the study vaccines within 30 days preceding the first dose of the 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 of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Simultaneous participation in any other clinical trial; Previous participation in any other malaria vaccine trial; Any twins 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.

Ages Eligible for Study
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Minimum Age: 5 Months
Maximum Age: 17 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SB257049 F2 0-1 M Group<br>Healthy infants between 5 and 17 months of age at the time of first vaccination received 2 doses of SB257049 formulation 2 (F2) vaccine according to a 0, 1-month schedule administered intramuscularly (IM) in the left deltoid muscle. | Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049<br>* 2 different formulations are tested. For each formulation, 3 different dosing schedules are tested<br>* Other names: S vaccine;|
| Experimental: SB257049 F1 0-1 M Group<br>Healthy infants between 5 and 17 months of age at the time of first vaccination received 2 doses of SB257049 formulation 1 (F1) vaccine according to a 0, 1-month schedule administered intramuscularly (IM) in the left deltoid muscle. | Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049<br>* 2 different formulations are tested. For each formulation, 3 different dosing schedules are tested<br>* Other names: S vaccine;|
| Experimental: SB257049 F2 0-1-2 M Group<br>Healthy infants between 5 and 17 months of age at the time of first vaccination received 3 doses of SB257049 formulation 2 (F2) vaccine according to a 0, 1, 2-month schedule administered intramuscularly (IM) in the left deltoid muscle. | Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049<br>* 2 different formulations are tested. For each formulation, 3 different dosing schedules are tested<br>* Other names: S vaccine;|
| Experimental: SB257049 F1 0-1-2 M Group<br>Healthy infants between 5 and 17 months of age at the time of first vaccination received 3 doses of SB257049 formulation 1 (F1) vaccine according to a 0, 1, 2-month schedule administered intramuscularly (IM) in the left deltoid muscle. | Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049<br>* 2 different formulations are tested. For each formulation, 3 different dosing schedules are tested<br>* Other names: S vaccine;|
| Experimental: SB257049 F2 0-1-7 M Group<br>Healthy infants between 5 and 17 months of age at the time of first vaccination received 3 doses of SB257049 formulation 2 (F2) vaccine according to a 0, 1, 7-month schedule administered intramuscularly (IM) in the left deltoid muscle. | Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049<br>* 2 different formulations are tested. For each formulation, 3 different dosing schedules are tested<br>* Other names: S vaccine;|
| Active Comparator: SB257049 F1 0-1-7 M Group<br>Healthy infants between 5 and 17 months of age at the time of first vaccination received 3 doses of SB257049 formulation 1 (F1) vaccine according to a 0, 1, 7-month schedule administered intramuscularly (IM) in the left deltoid muscle. | Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049<br>* 2 different formulations are tested. For each formulation, 3 different dosing schedules are tested<br>* Other names: S vaccine;|
| Active Comparator: Rabipur 0-1-2 M Group<br>Healthy infants between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine according to a 0, 1, 2-month schedule administered intramuscularly (IM) in the left deltoid muscle. | Biological: Rabipur<br>* 3-dose intramuscular injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From Day 0 to Month 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | During the 30-day (Days 0 - 29) post-vaccination period following each dose and across doses | 
| Titers for Anti-Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS) | Titers are presented as geometric mean titers (GMTs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | At Day 0, at Month 2, at Month 7 and at Month 10 | 
| Titers for Anti-Hepatitis B (Anti-HBs) | Titers are presented as geometric mean titers (GMTs) and expressed in milli-international units per milliliter (mIU/mL). | At Day 0 and at Month 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Prophylaxis Plasmodium falciparum malaria, Plasmodium falciparum, Malaria