A Study to Evaluate the Safety, Immunogenicity and Efficacy of GlaxoSmithKline (GSK) Biologicals' Candidate Malaria Vaccine RTS,S/AS02A, When Administered to Children Aged 1 to 4 Years Living in a Malaria-endemic Region of Mozambique.

Summary

Malaria is an important cause of death and serious illness among Mozambican children. Although the risk of malaria can be reduced by drugs and by impregnated bed nets, it would be helpful if children could be protected against malaria by a vaccine. GSK Biologicals is developing in partnership with Malaria Vaccine Initiative at PATH a candidate malaria vaccine RTS,S/AS02 for the routine immunization of infants and children living in malaria endemic areas. The vaccine would offer protection against malaria disease due to the parasite Plasmodium falciparum and also would provide protection against infection with hepatitis B virus. Previous studies have shown the candidate malaria vaccine RTS,S/AS02 to be safe when administered in adults and children aged 1-11 years. However, to assess if this vaccine could provide protection against malaria in children, this study has been undertaken.

Timeline

Start

2003-07

Primary completion

2005-04

Completion

2005-04

Outcome

Met primary endpoint

paper During the single-blind phase, VE(8.5-21) was 28.9% (95% CI 8.4-44.8; p=0.008). PMID 16338450 ↗

Publications

• Kurtovic L, Feng G, Hysa A, Haghiri A, O'Flaherty K, Wines BD, Santano R, D'Andrea L, Drummer HE, Hogarth PM, Sacarlal J, Fowkes FJI, Simpson JA, Dobano C, Beeson JG. Antibody mechanisms of protection against malaria in RTS,S-vaccinated children: a post-hoc serological analysis of phase 2 trial. Lancet Microbe. 2024 Oct;5(10):100898. doi: 10.1016/S2666-5247(24)00130-7. Epub 2024 Aug 7.
• Jairoce C, Macia D, Torres-Yaguana JP, Mayer L, Vidal M, Santano R, Hurtado-Guerrero R, Reiter K, Narum DL, Lopez-Gutierrez B, Hamerly T, Sacarlal J, Aguilar R, Dinglasan RR, Moncunill G, Izquierdo L, Dobano C. RTS,S/AS02A Malaria Vaccine-Induced IgG Responses Equally Recognize Native-Like Fucosylated and Nonfucosylated Plasmodium falciparum Circumsporozoite Proteins. J Infect Dis. 2024 Mar 14;229(3):795-799. doi: 10.1093/infdis/jiad471.
• Feng G, Kurtovic L, Agius PA, Aitken EH, Sacarlal J, Wines BD, Hogarth PM, Rogerson SJ, Fowkes FJI, Dobano C, Beeson JG. Induction, decay, and determinants of functional antibodies following vaccination with the RTS,S malaria vaccine in young children. BMC Med. 2022 Aug 25;20(1):289. doi: 10.1186/s12916-022-02466-2.
• Cheung YB, Ma X, Lam KF, Milligan P. Estimation of the primary, secondary and composite effects of malaria vaccines using data on multiple clinical malaria episodes. Vaccine. 2020 Jul 6;38(32):4964-4969. doi: 10.1016/j.vaccine.2020.05.086. Epub 2020 Jun 12.
• Campo JJ, Dobano C, Sacarlal J, Guinovart C, Mayor A, Angov E, Dutta S, Chitnis C, Macete E, Aponte JJ, Alonso PL. Impact of the RTS,S malaria vaccine candidate on naturally acquired antibody responses to multiple asexual blood stage antigens. PLoS One. 2011;6(10):e25779. doi: 10.1371/journal.pone.0025779. Epub 2011 Oct 12.
• Aide P, Dobano C, Sacarlal J, Aponte JJ, Mandomando I, Guinovart C, Bassat Q, Renom M, Puyol L, Macete E, Herreros E, Leach A, Dubois MC, Demoitie MA, Lievens M, Vekemans J, Loucq C, Ballou WR, Cohen J, Alonso PL. Four year immunogenicity of the RTS,S/AS02(A) malaria vaccine in Mozambican children during a phase IIb trial. Vaccine. 2011 Aug 11;29(35):6059-67. doi: 10.1016/j.vaccine.2011.03.041. Epub 2011 Apr 7.
• Sacarlal J, Aide P, Aponte JJ, Renom M, Leach A, Mandomando I, Lievens M, Bassat Q, Lafuente S, Macete E, Vekemans J, Guinovart C, Sigauque B, Sillman M, Milman J, Dubois MC, Demoitie MA, Thonnard J, Menendez C, Ballou WR, Cohen J, Alonso PL. Long-term safety and efficacy of the RTS,S/AS02A malaria vaccine in Mozambican children. J Infect Dis. 2009 Aug 1;200(3):329-36. doi: 10.1086/600119.
• Guinovart C, Aponte JJ, Sacarlal J, Aide P, Leach A, Bassat Q, Macete E, Dobano C, Lievens M, Loucq C, Ballou WR, Cohen J, Alonso PL. Insights into long-lasting protection induced by RTS,S/AS02A malaria vaccine: further results from a phase IIb trial in Mozambican children. PLoS One. 2009;4(4):e5165. doi: 10.1371/journal.pone.0005165. Epub 2009 Apr 14.
• Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Aide P, Sigauque B, Milman J, Mandomando I, Bassat Q, Guinovart C, Espasa M, Corachan S, Lievens M, Navia MM, Dubois MC, Menendez C, Dubovsky F, Cohen J, Thompson R, Ballou WR. Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial. Lancet. 2005 Dec 10;366(9502):2012-8. doi: 10.1016/S0140-6736(05)67669-6.

Drugs

Indications