Safety, Immunogenicity of RTS,S/AS02A, and RTS,S/AS01B Malaria Vaccines in Malaria-experienced Adults.

Study Overview
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Brief Summary
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The candidate malaria vaccine RTS,S/AS02A developed by GSK Biologicals demonstrated 30% efficacy against clinical episodes of malaria and approximately 58% efficacy against severe malaria disease. As a potential improvement to RTS,S/AS02A, another candidate vaccine RTS,S/AS01B is being developed in parallel in collaboration with the Walter Reed Army Institute of Research (WRAIR). This study will be the first administration of the RTS,S/AS01B vaccine to the African adults to establish safety and immunogenicity in this population. Preliminary indication of vaccine efficacy with this adjuvant will be established by monitoring the time to the first infection with Plasmodium falciparum.

Detailed Description
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The study comprises of 3 groups and the participating subjects will be randomly allocated to one of the three groups. The first group will receive RTS,S/AS01B, the second group will receive RTS,S/AS02A and the third group will receive rabies vaccine. Immunization will be given by IM injection on 0, 1, 2 month schedule. Infants will be followed up daily for 7 days for solicited symptoms and 30 days for unsolicited symptoms after each vaccine dose. Serious adverse events will be recorded throughout the study period. A week prior to Dose 3, subjects will be treated with a licenced anti-malarial drug. Starting from two weeks after Dose 3, the subjects will be monitored for a 14-week duration for detection of malaria infection.

Official Title
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A Phase IIb Randomized, Double-blind, Controlled Study of the Safety, Immunogenicity and Proof-of-concept of RTS,S/AS02A, and RTS,S/AS01B, Two Candidate Malaria Vaccines in Malaria-experienced Adults Living in Western Kenya.

Conditions
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Plasmodium Falciparum

Intervention / Treatment
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* Biological: RTS, S/AS01B
* Biological: RTS, S/AS02A
* Biological: Rabipur (Rabies) Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male or female volunteers aged between 18 and 35 years at the time of first vaccination who have given written consent for their participation in the study were included If the volunteer is female, she must be of non-childbearing potential, i.e. either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series Exclusion criteria: If a subject plans to take vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s) with the exception of tetanus toxoid will be excluded Volunteers with any confirmed or suspected immunosuppressive or immunodeficient conditions Family history of congenital or hereditary immunodeficiency History of allergic reactions to previous immunizations HBsAg positive subjects History of splenectomy Pregnant or lactating females will be excluded from the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VACC 1 (RTS, S/AS01B)<br>RTS, S/AS01B: 0.5mL dose; 50ug RTS, S antigen, 50ug QS21 and liposomes in phosphate-buffered saline administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months. | Biological: RTS, S/AS01B<br>* 0.5mL dose; 50ug RTS, S antigen, 50ug QS21 and liposomes in phosphate-buffered saline administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months.<br>|
| Experimental: VACC 2 (RTS, S/AS02A)<br>RTS, S/AS02A: 0.5mL dose; 50ug RTS, S antigen, 50ug QS21 and proprietary oil-water emulsion in phosphate-buffered saline administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months. | Biological: RTS, S/AS02A<br>* 0.5mL dose; 50ug RTS, S antigen, 50ug QS21 and proprietary oil-water emulsion in phosphate-buffered saline administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months.<br>|
| Active Comparator: Rabipur (Rabies) Vaccine<br>Rabipur (Rabies) Vaccine: 1.0mL dose administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months. | Biological: Rabipur (Rabies) Vaccine<br>* 1.0mL dose administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Proportion of Subjects With Grade 3 Solicited and Unsolicited General Reactions After Vaccination of RTS, S/AS02A and RTS, S/AS01B | Proportion of subjects with grade 3 solicited and unsolicited general reactions after vaccination of RTS, S/AS02A and RTS, S/AS01B during a 7 day follow-up period (day of vaccination + 6 days). | 7 day follow-up (day of vaccination + 6 days) | 
| Safety: Number of Administered Doses Eliciting Grade 3 Unsolicited Symptoms | Grade 3 unsolicited symptoms reported following any number of administered doses | 6.5 months | 
| Safety: Number of Doses Eliciting Solicited Local Symptoms Reported Over 7 Day Follow-up Period | Incidence overall solicited general and local reactions over 7 day follow-up period after dose 1, 2 and 3 (Total Cohort) | 7 day follow-up period (day of vaccination + 6 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Occurrence of SAEs | Percentage of subjects experiencing SAEs classified by MedRA System Organ Class and Preferred Term (Month 6.5-12) | months 6.5 thru 12 | 
| Safety: Occurrence of SAEs | Percentage of subjects reporting SAEs classified by MedDRA System Organ Class and Preferred Term (Month 0-12) | months 0 thru 12 | 
| Occurrence of Hematology Parameters Below Normal Range | Occurrence of hematology parameters below normal range (Total Cohort) | Days 0, 6, 66, and 90; Months 6 and 12 | 
| Occurrence of Biochemistry Parameters Above Normal Ranges | Occurrence of parameters of biochemical monitoring above normal ranges (Total Cohort) | Days 0, 6, and 90 |