Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children

Abstract

The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1∶1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme.

Trial registration: ClinicalTrials.gov NCT00380393.

Figure 1. Study design overview.

BS; Blood Sample, Vacc; Vaccination, Extension; Extension of the single-blind Phase. XsecDB: cross sectional at the end of double-blind Phase (; mean follow-up: 10 months, range: min 7.1; max 12.8 months post-dose 1; SD 1.3). XsecExt: cross sectional at the end of the extension Phase; mean follow-up: 18 months (range: min 13.8; max 20.1 months post-dose 1; SD 1.5). *Clinic Visit 8 took place on the same day as clinic Visit 7 and included consent process for participation in the extension Phase (Kilifi only). **Applicable to Kilifi only.

Figure 2. The assembly and disposition of study participants.

^a Subjects were temporally out of study area but returned for Month 14 (M14) visit. ^b Investigator decided not to continue vaccination as EPI vaccination documentation was not available, this subject returned for Month 14 (M14) visit. ^c One subject died after consent withdrawal.