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

Phase 2

Completed

Interventions: Biological: RTS, S/AS02A
Biological: RTS, S/AS01B
Biological: Rabipur (Rabies) Vaccine

Brief Summary: 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: 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
VACC 2 (RTS, S/AS02A)	RTS, S/AS02A	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.
VACC 1 (RTS, S/AS01B)	RTS, S/AS01B	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.
Rabipur (Rabies) Vaccine	Rabipur (Rabies) Vaccine	Rabipur (Rabies) Vaccine: 1.0mL dose administered intramuscular deltoid of non-dominant arm at 0, 1 and 2 months.

Primary Outcome Measures

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

Secondary Outcome Measures

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