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Clinical Trial
. 2012 Dec 13;367(24):2284-95.
doi: 10.1056/NEJMoa1208394. Epub 2012 Nov 9.

A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants

RTS,S Clinical Trials PartnershipSelidji Todagbe AgnandjiBertrand LellJosé Francisco FernandesBéatrice Peggy AbossoloBarbara Gaelle Nfono Ondo MethogoAnita Lumeka KabwendeAyola Akim AdegnikaBenjamin MordmüllerSaadou IssifouPeter Gottfried KremsnerJahit SacarlalPedro AideMiguel LanaspaJohn J AponteSonia MachevoSozinho AcacioHelder BuloBetuel SigauqueEusébio MacetePedro AlonsoSalim AbdullaNahya SalimRose MinjaMaxmillian MpinaSaumu AhmedAli Mohammed AliAli Takadir MtoroAli Said HamadPaul MutaniMarcel TannerHalidou TintoUmberto D'AlessandroHermann SorghoInnocent ValeaBiébo BihounIssa GuiraudBerenger KaboréOlivier SombiéRobert Tinga GuiguemdéJean Bosco OuédraogoMary J HamelSimon KariukiMartina OnekoChris OderoKephas OtienoNorbert AwinoMeredith McMorrowVincent Muturi-KioiKayla F LasersonLaurence SlutskerWalter OtienoLucas OtienoNekoye OtsyulaStacey GondiAllan OtienoVictorine OwiraEsther OgukGeorge OdongoJon Ben WoodsBernhards OgutuPatricia NjugunaRoma ChilengiPauline AkooChristine KeruboCharity MaingiTrudie LangAlly OlotuPhilip BejonKevin MarshGabriel MwambinguSeth Owusu-AgyeiKwaku Poku AsanteKingsley Osei-KwakyeOwusu BoahenDavid DosooIsaac AsanteGeorge AdjeiEvans KwaraDaniel ChandramohanBrian GreenwoodJohn LusinguSamwel GesaseAnangisye MalabejaOmari AbdulColine MahendeEdwin LihelukaLincoln MalleMartha LemngeThor G TheanderChris DrakeleyDaniel AnsongTsiri AgbenyegaSamuel AdjeiHarry Owusu BoatengTheresa RettigJohn BawaJustice SylverkenDavid SambianAnima SarfoAlex AgyekumFrancis MartinsonIrving HoffmanTisungane MvaloPortia KamthunziRutendo NkomoTapiwa TemboGerald TeghaMercy TsidyaJane KilembeChimwemwe ChawingaW Ripley BallouJoe CohenYolanda GuerraErik JongertDidier LapierreAmanda LeachMarc LievensOpokua Ofori-AnyinamAurélie OlivierJohan VekemansTerrell CarterDavid KaslowDidier LeboulleuxChristian LoucqAfiya RadfordBarbara SavareseDavid SchellenbergMarla SillmanPreeti Vansadia
Free article
Clinical Trial

A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants

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

Abstract

Background: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial.

Methods: We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed.

Results: The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222).

Conclusions: The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.).

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