Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa

Guerra Mendoza, Yolanda; Garric, Elodie; Leach, Amanda; Lievens, Marc; Ofori-Anyinam, Opokua; Pirçon, Jean-Yves; Stegmann, Jens-Ulrich; Vandoolaeghe, Pascale; Otieno, Lucas; Otieno, Walter; Owusu-Agyei, Seth; Sacarlal, Jahit; Masoud, Nahya Salim; Sorgho, Hermann; Tanner, Marcel; Tinto, Halidou; Valea, Innocent; Mtoro, Ali Takadir; Njuguna, Patricia; Oneko, Martina; Otieno, Godfrey Allan; Otieno, Kephas; Gesase, Samwel; Hamel, Mary J.; Hoffman, Irving; Kaali, Seyram; Kamthunzi, Portia; Kremsner, Peter G.; Lanaspa, Miguel; Lell, Bertrand; Lusingu, John; Malabeja, Anangisye; Aide, Pedro Carlos Paulino; Akoo, Pauline; Ansong, Daniel; Asante, Kwaku Poku; Berkley, James A.; Adjei, Samuel; Agbenyega, Tsiri; Agnandji, Selidji Todagbe; Schuerman, Lode

Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa

A phase III, double-blind, randomized, controlled trial (NCT00866619) in sub-Saharan Africa showed RTS,S/AS01 vaccine efficacy against malaria. We now present in-depth safety results from this study. 8922 children (enrolled at 5-17\xC2\xA0months) and 6537 infants (enrolled at 6-12\xC2\xA0weeks) were...

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Autores:	Guerra Mendoza, Yolanda, Garric, Elodie, Leach, Amanda, Lievens, Marc, Ofori-Anyinam, Opokua, Pirçon, Jean-Yves, Stegmann, Jens-Ulrich, Vandoolaeghe, Pascale, Otieno, Lucas, Otieno, Walter, Owusu-Agyei, Seth, Sacarlal, Jahit, Masoud, Nahya Salim, Sorgho, Hermann, Tanner, Marcel, Tinto, Halidou, Valea, Innocent, Mtoro, Ali Takadir, Njuguna, Patricia, Oneko, Martina, Otieno, Godfrey Allan, Otieno, Kephas, Gesase, Samwel, Hamel, Mary J., Hoffman, Irving, Kaali, Seyram, Kamthunzi, Portia, Kremsner, Peter G., Lanaspa, Miguel, Lell, Bertrand, Lusingu, John, Malabeja, Anangisye, Aide, Pedro Carlos Paulino, Akoo, Pauline, Ansong, Daniel, Asante, Kwaku Poku, Berkley, James A., Adjei, Samuel, Agbenyega, Tsiri, Agnandji, Selidji Todagbe, Schuerman, Lode
Tipo de documento:	artigo
Estado:	Versão publicada
Data de publicação:	2019
País:	España
Recursos:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/135358
Acesso em linha:	https://hdl.handle.net/2445/135358
Access Level:	Acceso aberto
Palavra-chave:	Vacuna de la malària Infants Àfrica subsahariana Malaria vaccine Children Sub-Saharan Africa

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spelling	Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan AfricaGuerra Mendoza, YolandaGarric, ElodieLeach, AmandaLievens, MarcOfori-Anyinam, OpokuaPirçon, Jean-YvesStegmann, Jens-UlrichVandoolaeghe, PascaleOtieno, LucasOtieno, WalterOwusu-Agyei, SethSacarlal, JahitMasoud, Nahya SalimSorgho, HermannTanner, MarcelTinto, HalidouValea, InnocentMtoro, Ali TakadirNjuguna, PatriciaOneko, MartinaOtieno, Godfrey AllanOtieno, KephasGesase, SamwelHamel, Mary J.Hoffman, IrvingKaali, SeyramKamthunzi, PortiaKremsner, Peter G.Lanaspa, MiguelLell, BertrandLusingu, JohnMalabeja, AnangisyeAide, Pedro Carlos PaulinoAkoo, PaulineAnsong, DanielAsante, Kwaku PokuBerkley, James A.Adjei, SamuelAgbenyega, TsiriAgnandji, Selidji TodagbeSchuerman, LodeVacuna de la malàriaInfantsÀfrica subsaharianaMalaria vaccineChildrenSub-Saharan AfricaA phase III, double-blind, randomized, controlled trial (NCT00866619) in sub-Saharan Africa showed RTS,S/AS01 vaccine efficacy against malaria. We now present in-depth safety results from this study. 8922 children (enrolled at 5-17\xC2\xA0months) and 6537 infants (enrolled at 6-12\xC2\xA0weeks) were 1:1:1-randomized to receive 4 doses of RTS,S/AS01 (R3R) or non-malaria control vaccine (C3C), or 3 RTS,S/AS01 doses plus control (R3C). Aggregate safety data were reviewed by a multi-functional team. Severe malaria with Blantyre Coma Score \xE2\x89\xA42 (cerebral malaria [CM]) and gender-specific mortality were assessed post-hoc. Serious adverse event (SAE) and fatal SAE incidences throughout the study were 24.2%-28.4% and 1.5%-2.5%, respectively across groups; 0.0%-0.3% of participants reported vaccination-related SAEs. The incidence of febrile convulsions in children was higher during the first 2-3 days post-vaccination with RTS,S/AS01 than with control vaccine, consistent with the time window of post-vaccination febrile reactions in this study (mostly the day after vaccination). A statistically significant numerical imbalance was observed for meningitis cases in children (R3R: 11, R3C: 10, C3C: 1) but not in infants. CM cases were more frequent in RTS,S/AS01-vaccinated children (R3R: 19, R3C: 24, C3C: 10) but not in infants. All-cause mortality was higher in RTS,S/AS01-vaccinated versus control girls (2.4% vs 1.3%, all ages) in our setting with low overall mortality. The observed meningitis and CM signals are considered likely chance findings, that - given their severity - warrant further evaluation in phase IV studies and WHO-led pilot implementation programs to establish the RTS,S/AS01 benefit-risk profile in real-life settings.Taylor & Francis2019201920192019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/135358Articles publicats en revistes (ISGlobal)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1080/21645515.2019.1586040Human Vaccines & Immunotherapeutics, 2019http://dx.doi.org/10.1080/21645515.2019.1586040cc by (c) GlaxoSmithKline Biologicals S. A., 2019http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1353582026-05-29T05:05:01Z
dc.title.none.fl_str_mv	Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa
title	Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa
spellingShingle	Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa Guerra Mendoza, Yolanda Vacuna de la malària Infants Àfrica subsahariana Malaria vaccine Children Sub-Saharan Africa
title_short	Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa
title_full	Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa
title_fullStr	Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa
title_full_unstemmed	Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa
title_sort	Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa
dc.creator.none.fl_str_mv	Guerra Mendoza, Yolanda Garric, Elodie Leach, Amanda Lievens, Marc Ofori-Anyinam, Opokua Pirçon, Jean-Yves Stegmann, Jens-Ulrich Vandoolaeghe, Pascale Otieno, Lucas Otieno, Walter Owusu-Agyei, Seth Sacarlal, Jahit Masoud, Nahya Salim Sorgho, Hermann Tanner, Marcel Tinto, Halidou Valea, Innocent Mtoro, Ali Takadir Njuguna, Patricia Oneko, Martina Otieno, Godfrey Allan Otieno, Kephas Gesase, Samwel Hamel, Mary J. Hoffman, Irving Kaali, Seyram Kamthunzi, Portia Kremsner, Peter G. Lanaspa, Miguel Lell, Bertrand Lusingu, John Malabeja, Anangisye Aide, Pedro Carlos Paulino Akoo, Pauline Ansong, Daniel Asante, Kwaku Poku Berkley, James A. Adjei, Samuel Agbenyega, Tsiri Agnandji, Selidji Todagbe Schuerman, Lode
author	Guerra Mendoza, Yolanda
author_facet	Guerra Mendoza, Yolanda Garric, Elodie Leach, Amanda Lievens, Marc Ofori-Anyinam, Opokua Pirçon, Jean-Yves Stegmann, Jens-Ulrich Vandoolaeghe, Pascale Otieno, Lucas Otieno, Walter Owusu-Agyei, Seth Sacarlal, Jahit Masoud, Nahya Salim Sorgho, Hermann Tanner, Marcel Tinto, Halidou Valea, Innocent Mtoro, Ali Takadir Njuguna, Patricia Oneko, Martina Otieno, Godfrey Allan Otieno, Kephas Gesase, Samwel Hamel, Mary J. Hoffman, Irving Kaali, Seyram Kamthunzi, Portia Kremsner, Peter G. Lanaspa, Miguel Lell, Bertrand Lusingu, John Malabeja, Anangisye Aide, Pedro Carlos Paulino Akoo, Pauline Ansong, Daniel Asante, Kwaku Poku Berkley, James A. Adjei, Samuel Agbenyega, Tsiri Agnandji, Selidji Todagbe Schuerman, Lode
author_role	author
author2	Garric, Elodie Leach, Amanda Lievens, Marc Ofori-Anyinam, Opokua Pirçon, Jean-Yves Stegmann, Jens-Ulrich Vandoolaeghe, Pascale Otieno, Lucas Otieno, Walter Owusu-Agyei, Seth Sacarlal, Jahit Masoud, Nahya Salim Sorgho, Hermann Tanner, Marcel Tinto, Halidou Valea, Innocent Mtoro, Ali Takadir Njuguna, Patricia Oneko, Martina Otieno, Godfrey Allan Otieno, Kephas Gesase, Samwel Hamel, Mary J. Hoffman, Irving Kaali, Seyram Kamthunzi, Portia Kremsner, Peter G. Lanaspa, Miguel Lell, Bertrand Lusingu, John Malabeja, Anangisye Aide, Pedro Carlos Paulino Akoo, Pauline Ansong, Daniel Asante, Kwaku Poku Berkley, James A. Adjei, Samuel Agbenyega, Tsiri Agnandji, Selidji Todagbe Schuerman, Lode
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Vacuna de la malària Infants Àfrica subsahariana Malaria vaccine Children Sub-Saharan Africa
topic	Vacuna de la malària Infants Àfrica subsahariana Malaria vaccine Children Sub-Saharan Africa
description	A phase III, double-blind, randomized, controlled trial (NCT00866619) in sub-Saharan Africa showed RTS,S/AS01 vaccine efficacy against malaria. We now present in-depth safety results from this study. 8922 children (enrolled at 5-17\xC2\xA0months) and 6537 infants (enrolled at 6-12\xC2\xA0weeks) were 1:1:1-randomized to receive 4 doses of RTS,S/AS01 (R3R) or non-malaria control vaccine (C3C), or 3 RTS,S/AS01 doses plus control (R3C). Aggregate safety data were reviewed by a multi-functional team. Severe malaria with Blantyre Coma Score \xE2\x89\xA42 (cerebral malaria [CM]) and gender-specific mortality were assessed post-hoc. Serious adverse event (SAE) and fatal SAE incidences throughout the study were 24.2%-28.4% and 1.5%-2.5%, respectively across groups; 0.0%-0.3% of participants reported vaccination-related SAEs. The incidence of febrile convulsions in children was higher during the first 2-3 days post-vaccination with RTS,S/AS01 than with control vaccine, consistent with the time window of post-vaccination febrile reactions in this study (mostly the day after vaccination). A statistically significant numerical imbalance was observed for meningitis cases in children (R3R: 11, R3C: 10, C3C: 1) but not in infants. CM cases were more frequent in RTS,S/AS01-vaccinated children (R3R: 19, R3C: 24, C3C: 10) but not in infants. All-cause mortality was higher in RTS,S/AS01-vaccinated versus control girls (2.4% vs 1.3%, all ages) in our setting with low overall mortality. The observed meningitis and CM signals are considered likely chance findings, that - given their severity - warrant further evaluation in phase IV studies and WHO-led pilot implementation programs to establish the RTS,S/AS01 benefit-risk profile in real-life settings.
publishDate	2019
dc.date.none.fl_str_mv	2019 2019 2019 2019
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/135358
url	https://hdl.handle.net/2445/135358
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: http://dx.doi.org/10.1080/21645515.2019.1586040 Human Vaccines & Immunotherapeutics, 2019 http://dx.doi.org/10.1080/21645515.2019.1586040
dc.rights.none.fl_str_mv	cc by (c) GlaxoSmithKline Biologicals S. A., 2019 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc by (c) GlaxoSmithKline Biologicals S. A., 2019 http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	15 p. application/pdf application/pdf
dc.publisher.none.fl_str_mv	Taylor & Francis
publisher.none.fl_str_mv	Taylor & Francis
dc.source.none.fl_str_mv	Articles publicats en revistes (ISGlobal) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Safety profile of the RTS,S/AS01 malaria vaccine in infants and children: additional data from a phase III randomized controlled trial in sub-Saharan Africa

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