A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants

Selidji Todagbe Agnandji; Bertrand Lell; José Francisco Fernandes; Béatrice Peggy Abossolo; Barbara Gaelle Nfono Ondo Methogo; Anita Lumeka Kabwende; Ayola Akim Adegnika; Benjamin Mordmüller; Saadou Issifou; Peter Gottfried Kremsner; Jahit Sacarlal; Pedro Aide; Miguel Lanaspa; John J Aponte; Sonia Machevo; Sozinho Acacio; Helder Bulo; Betuel Sigauque; Eusébio Macete; Pedro Alonso; Salim Abdulla; Nahya Salim; Rose Minja; Maxmillian Mpina; Saumu Ahmed; Ali Mohammed Ali; Ali Takadir Mtoro; Ali Said Hamad; Paul Mutani; Marcel Tanner; Halidou Tinto; Umberto D'Alessandro; Hermann Sorgho; Innocent Valea; Biébo Bihoun; Issa Guiraud; Berenger Kaboré; Olivier Sombié; Robert Tinga Guiguemdé; Jean Bosco Ouédraogo; Mary J Hamel; Simon Kariuki; Martina Oneko; Chris Odero; Kephas Otieno; Norbert Awino; Meredith McMorrow; Vincent Muturi-Kioi; John Lusingu; Thor G Theander; RTS,S Clinical Trials Partnership

doi:10.1056/NEJMoa1208394

A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants

Selidji Todagbe Agnandji, Bertrand Lell, José Francisco Fernandes, Béatrice Peggy Abossolo, Barbara Gaelle Nfono Ondo Methogo, Anita Lumeka Kabwende, Ayola Akim Adegnika, Benjamin Mordmüller, Saadou Issifou, Peter Gottfried Kremsner, Jahit Sacarlal, Pedro Aide, Miguel Lanaspa, John J Aponte, Sonia Machevo, Sozinho Acacio, Helder Bulo, Betuel Sigauque, Eusébio Macete, Pedro AlonsoSalim Abdulla, Nahya Salim, Rose Minja, Maxmillian Mpina, Saumu Ahmed, Ali Mohammed Ali, Ali Takadir Mtoro, Ali Said Hamad, Paul Mutani, Marcel Tanner, Halidou Tinto, Umberto D'Alessandro, Hermann Sorgho, Innocent Valea, Biébo Bihoun, Issa Guiraud, Berenger Kaboré, Olivier Sombié, Robert Tinga Guiguemdé, Jean Bosco Ouédraogo, Mary J Hamel, Simon Kariuki, Martina Oneko, Chris Odero, Kephas Otieno, Norbert Awino, Meredith McMorrow, Vincent Muturi-Kioi, John Lusingu, Thor G Theander, RTS,S Clinical Trials Partnership

Centre for Medical Parasitology

480 Citations (Scopus)

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 personyear 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.)

Original language	English
Journal	New England Journal of Medicine
Volume	367
Issue number	24
Pages (from-to)	2284-95
Number of pages	12
ISSN	0028-4793
DOIs	https://doi.org/10.1056/NEJMoa1208394
Publication status	Published - 13 Dec 2012

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10.1056/NEJMoa1208394

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Agnandji, S. T., Lell, B., Fernandes, J. F., Abossolo, B. P., Methogo, B. G. N. O., Kabwende, A. L., Adegnika, A. A., Mordmüller, B., Issifou, S., Kremsner, P. G., Sacarlal, J., Aide, P., Lanaspa, M., Aponte, J. J., Machevo, S., Acacio, S., Bulo, H., Sigauque, B., Macete, E., ... RTS,S Clinical Trials Partnership (2012). A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. New England Journal of Medicine, 367(24), 2284-95. https://doi.org/10.1056/NEJMoa1208394

Agnandji, ST, Lell, B, Fernandes, JF, Abossolo, BP, Methogo, BGNO, Kabwende, AL, Adegnika, AA, Mordmüller, B, Issifou, S, Kremsner, PG, Sacarlal, J, Aide, P, Lanaspa, M, Aponte, JJ, Machevo, S, Acacio, S, Bulo, H, Sigauque, B, Macete, E, Alonso, P, Abdulla, S, Salim, N, Minja, R, Mpina, M, Ahmed, S, Ali, AM, Mtoro, AT, Hamad, AS, Mutani, P, Tanner, M, Tinto, H, D'Alessandro, U, Sorgho, H, Valea, I, Bihoun, B, Guiraud, I, Kaboré, B, Sombié, O, Guiguemdé, RT, Ouédraogo, JB, Hamel, MJ, Kariuki, S, Oneko, M, Odero, C, Otieno, K, Awino, N, McMorrow, M, Muturi-Kioi, V, Lusingu, J, Theander, TG & RTS,S Clinical Trials Partnership 2012, 'A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants', New England Journal of Medicine, vol. 367, no. 24, pp. 2284-95. https://doi.org/10.1056/NEJMoa1208394

@article{ced6252208024056b4748dd23a9a47c9,

title = "A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants",

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 personyear 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.)",

author = "Agnandji, {Selidji Todagbe} and Bertrand Lell and Fernandes, {Jos{\'e} Francisco} and Abossolo, {B{\'e}atrice Peggy} and Methogo, {Barbara Gaelle Nfono Ondo} and Kabwende, {Anita Lumeka} and Adegnika, {Ayola Akim} and Benjamin Mordm{\"u}ller and Saadou Issifou and Kremsner, {Peter Gottfried} and Jahit Sacarlal and Pedro Aide and Miguel Lanaspa and Aponte, {John J} and Sonia Machevo and Sozinho Acacio and Helder Bulo and Betuel Sigauque and Eus{\'e}bio Macete and Pedro Alonso and Salim Abdulla and Nahya Salim and Rose Minja and Maxmillian Mpina and Saumu Ahmed and Ali, {Ali Mohammed} and Mtoro, {Ali Takadir} and Hamad, {Ali Said} and Paul Mutani and Marcel Tanner and Halidou Tinto and Umberto D'Alessandro and Hermann Sorgho and Innocent Valea and Bi{\'e}bo Bihoun and Issa Guiraud and Berenger Kabor{\'e} and Olivier Sombi{\'e} and Guiguemd{\'e}, {Robert Tinga} and Ou{\'e}draogo, {Jean Bosco} and Hamel, {Mary J} and Simon Kariuki and Martina Oneko and Chris Odero and Kephas Otieno and Norbert Awino and Meredith McMorrow and Vincent Muturi-Kioi and John Lusingu and Theander, {Thor G} and {RTS,S Clinical Trials Partnership}",

year = "2012",

month = dec,

day = "13",

doi = "10.1056/NEJMoa1208394",

language = "English",

volume = "367",

pages = "2284--95",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

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TY - JOUR

T1 - A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants

AU - Agnandji, Selidji Todagbe

AU - Lell, Bertrand

AU - Fernandes, José Francisco

AU - Abossolo, Béatrice Peggy

AU - Methogo, Barbara Gaelle Nfono Ondo

AU - Kabwende, Anita Lumeka

AU - Adegnika, Ayola Akim

AU - Mordmüller, Benjamin

AU - Issifou, Saadou

AU - Kremsner, Peter Gottfried

AU - Sacarlal, Jahit

AU - Aide, Pedro

AU - Lanaspa, Miguel

AU - Aponte, John J

AU - Machevo, Sonia

AU - Acacio, Sozinho

AU - Bulo, Helder

AU - Sigauque, Betuel

AU - Macete, Eusébio

AU - Alonso, Pedro

AU - Abdulla, Salim

AU - Salim, Nahya

AU - Minja, Rose

AU - Mpina, Maxmillian

AU - Ahmed, Saumu

AU - Ali, Ali Mohammed

AU - Mtoro, Ali Takadir

AU - Hamad, Ali Said

AU - Mutani, Paul

AU - Tanner, Marcel

AU - Tinto, Halidou

AU - D'Alessandro, Umberto

AU - Sorgho, Hermann

AU - Valea, Innocent

AU - Bihoun, Biébo

AU - Guiraud, Issa

AU - Kaboré, Berenger

AU - Sombié, Olivier

AU - Guiguemdé, Robert Tinga

AU - Ouédraogo, Jean Bosco

AU - Hamel, Mary J

AU - Kariuki, Simon

AU - Oneko, Martina

AU - Odero, Chris

AU - Otieno, Kephas

AU - Awino, Norbert

AU - McMorrow, Meredith

AU - Muturi-Kioi, Vincent

AU - Lusingu, John

AU - Theander, Thor G

AU - RTS,S Clinical Trials Partnership

PY - 2012/12/13

Y1 - 2012/12/13

N2 - 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 personyear 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.)

AB - 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 personyear 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.)

U2 - 10.1056/NEJMoa1208394

DO - 10.1056/NEJMoa1208394

M3 - Journal article

C2 - 23136909

SN - 0028-4793

VL - 367

SP - 2284

EP - 2295

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 24

ER -

A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants

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