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Clinical Trial
. 2011 Nov 17;365(20):1863-75.
doi: 10.1056/NEJMoa1102287. Epub 2011 Oct 18.

First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children

RTS,S Clinical Trials PartnershipSelidji Todagbe Agnandji  1 Bertrand LellSolange Solmeheim SoulanoudjingarJosé Francisco FernandesBéatrice Peggy AbossoloCornelia ConzelmannBarbara Gaelle Nfono Ondo MethogoYannick DouckaArnaud FlamenBenjamin MordmüllerSaadou IssifouPeter Gottfried KremsnerJahit SacarlalPedro AideMiguel LanaspaJohn J AponteArlindo NhamuaveDiana QuelhasQuique BassatSofia MandjateEusébio MacetePedro AlonsoSalim AbdullaNahya SalimOmar JumaMwanajaa ShomariKafuruki ShubisFrancisca MacheraAli Said HamadRose MinjaAli MtoroAlma SykesSaumu AhmedAlwisa Martin UrassaAli Mohammed AliGrace MwangokaMarcel TannerHalidou TintoUmberto D'AlessandroHermann SorghoInnocent ValeaMarc Christian TahitaWilliam KaboréSayouba OuédraogoYara SandrineRobert Tinga GuiguemdéJean Bosco OuédraogoMary J HamelSimon KariukiChris OderoMartina OnekoKephas OtienoNorbert AwinoJackton OmotoJohn WilliamsonVincent Muturi-KioiKayla F LasersonLaurence SlutskerWalter OtienoLucas OtienoOtsyula NekoyeStacey GondiAllan OtienoBernhards OgutuRuth WasunaVictorine OwiraDavid JonesAgnes Akoth OnyangoPatricia NjugunaRoma ChilengiPauline AkooChristine KeruboJesse GitakaCharity MaingiTrudie LangAlly OlotuBenjamin TsofaPhilip BejonNorbert PeshuKevin MarshSeth Owusu-AgyeiKwaku Poku AsanteKingsley Osei-KwakyeOwusu BoahenSamuel AyambaKingsley KayanRuth Owusu-OforiDavid DosooIsaac AsanteGeorge AdjeiGeorge AdjeiDaniel ChandramohanBrian GreenwoodJohn LusinguSamwel GesaseAnangisye MalabejaOmari AbdulHassan KilavoColine MahendeEdwin LihelukaMartha LemngeThor TheanderChris DrakeleyDaniel AnsongTsiri AgbenyegaSamuel AdjeiHarry Owusu BoatengTheresa RettigJohn BawaJustice SylverkenDavid SambianAlex AgyekumLarko OwusuFrancis MartinsonIrving HoffmanTisungane MvaloPortia KamthunziRuthendo NkomoAlbans MsikaAllan JumbeNelecy ChomeDalitso NyakuipaJoseph ChintedzaW Ripley BallouMyriam BrulsJoe CohenYolanda GuerraErik JongertDidier LapierreAmanda LeachMarc LievensOpokua Ofori-AnyinamJohan VekemansTerrell CarterDidier LeboulleuxChristian LoucqAfiya RadfordBarbara SavareseDavid SchellenbergMarla SillmanPreeti Vansadia
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Clinical Trial

First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children

RTS,S Clinical Trials Partnership et al. N Engl J Med. .
Free article

Abstract

Background: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries.

Methods: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories.

Results: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64).

Conclusions: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).

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