First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children

Selidji Todagbe Agnandji; Bertrand Lell; Solange Solmeheim Soulanoudjingar; José Francisco Fernandes; Béatrice Peggy Abossolo; Cornelia Conzelmann; Barbara Gaelle Nfono Ondo Methogo; Yannick Doucka; Arnaud Flamen; Benjamin Mordmüller; Saadou Issifou; Peter Gottfried Kremsner; Jahit Sacarlal; Pedro Aide; Miguel Lanaspa; John J Aponte; Arlindo Nhamuave; Diana Quelhas; Quique Bassat; Sofia Mandjate; Eusébio Macete; Pedro Alonso; Salim Abdulla; Nahya Salim; Omar Juma; Mwanajaa Shomari; Kafuruki Shubis; Francisca Machera; Ali Said Hamad; Rose Minja; Ali Mtoro; Alma Sykes; Saumu Ahmed; Alwisa Martin Urassa; Ali Mohammed Ali; Grace Mwangoka; Marcel Tanner; Halidou Tinto; Umberto D'Alessandro; Hermann Sorgho; Innocent Valea; Marc Christian Tahita; William Kaboré; Sayouba Ouédraogo; Yara Sandrine; Robert Tinga Guiguemdé; Jean Bosco Ouédraogo; Mary J Hamel; John Lusingu; Thor Theander; RTS,S Clinical Trials Partnership

doi:10.1056/NEJMoa1102287

First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children

Selidji Todagbe Agnandji, Bertrand Lell, Solange Solmeheim Soulanoudjingar, José Francisco Fernandes, Béatrice Peggy Abossolo, Cornelia Conzelmann, Barbara Gaelle Nfono Ondo Methogo, Yannick Doucka, Arnaud Flamen, Benjamin Mordmüller, Saadou Issifou, Peter Gottfried Kremsner, Jahit Sacarlal, Pedro Aide, Miguel Lanaspa, John J Aponte, Arlindo Nhamuave, Diana Quelhas, Quique Bassat, Sofia MandjateEusébio Macete, Pedro Alonso, Salim Abdulla, Nahya Salim, Omar Juma, Mwanajaa Shomari, Kafuruki Shubis, Francisca Machera, Ali Said Hamad, Rose Minja, Ali Mtoro, Alma Sykes, Saumu Ahmed, Alwisa Martin Urassa, Ali Mohammed Ali, Grace Mwangoka, Marcel Tanner, Halidou Tinto, Umberto D'Alessandro, Hermann Sorgho, Innocent Valea, Marc Christian Tahita, William Kaboré, Sayouba Ouédraogo, Yara Sandrine, Robert Tinga Guiguemdé, Jean Bosco Ouédraogo, Mary J Hamel, John Lusingu, Thor Theander, RTS,S Clinical Trials Partnership

Centre for Medical Parasitology

598 Citationer (Scopus)

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.)

Originalsprog	Engelsk
Tidsskrift	New England Journal of Medicine
Vol/bind	365
Udgave nummer	20
Sider (fra-til)	1863-75
Antal sider	13
ISSN	0028-4793
DOI	https://doi.org/10.1056/NEJMoa1102287
Status	Udgivet - 17 nov. 2011

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Agnandji, S. T., Lell, B., Soulanoudjingar, S. S., Fernandes, J. F., Abossolo, B. P., Conzelmann, C., Methogo, B. G. N. O., Doucka, Y., Flamen, A., Mordmüller, B., Issifou, S., Kremsner, P. G., Sacarlal, J., Aide, P., Lanaspa, M., Aponte, J. J., Nhamuave, A., Quelhas, D., Bassat, Q., ... RTS,S Clinical Trials Partnership (2011). First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. New England Journal of Medicine, 365(20), 1863-75. https://doi.org/10.1056/NEJMoa1102287

Agnandji, ST, Lell, B, Soulanoudjingar, SS, Fernandes, JF, Abossolo, BP, Conzelmann, C, Methogo, BGNO, Doucka, Y, Flamen, A, Mordmüller, B, Issifou, S, Kremsner, PG, Sacarlal, J, Aide, P, Lanaspa, M, Aponte, JJ, Nhamuave, A, Quelhas, D, Bassat, Q, Mandjate, S, Macete, E, Alonso, P, Abdulla, S, Salim, N, Juma, O, Shomari, M, Shubis, K, Machera, F, Hamad, AS, Minja, R, Mtoro, A, Sykes, A, Ahmed, S, Urassa, AM, Ali, AM, Mwangoka, G, Tanner, M, Tinto, H, D'Alessandro, U, Sorgho, H, Valea, I, Tahita, MC, Kaboré, W, Ouédraogo, S, Sandrine, Y, Guiguemdé, RT, Ouédraogo, JB, Hamel, MJ, Lusingu, J, Theander, T & RTS,S Clinical Trials Partnership 2011, 'First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children', New England Journal of Medicine, bind 365, nr. 20, s. 1863-75. https://doi.org/10.1056/NEJMoa1102287

@article{965be7ddd2d54e1381f94146b02807fa,

title = "First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children",

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.)",

keywords = "Africa, Age Factors, Double-Blind Method, Female, Follow-Up Studies, Humans, Incidence, Infant, Intention to Treat Analysis, Malaria Vaccines, Malaria, Falciparum, Male, Meningitis, Parasite Load, Plasmodium falciparum, Seizures, Treatment Outcome",

author = "Agnandji, {Selidji Todagbe} and Bertrand Lell and Soulanoudjingar, {Solange Solmeheim} and Fernandes, {Jos{\'e} Francisco} and Abossolo, {B{\'e}atrice Peggy} and Cornelia Conzelmann and Methogo, {Barbara Gaelle Nfono Ondo} and Yannick Doucka and Arnaud Flamen 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 Arlindo Nhamuave and Diana Quelhas and Quique Bassat and Sofia Mandjate and Eus{\'e}bio Macete and Pedro Alonso and Salim Abdulla and Nahya Salim and Omar Juma and Mwanajaa Shomari and Kafuruki Shubis and Francisca Machera and Hamad, {Ali Said} and Rose Minja and Ali Mtoro and Alma Sykes and Saumu Ahmed and Urassa, {Alwisa Martin} and Ali, {Ali Mohammed} and Grace Mwangoka and Marcel Tanner and Halidou Tinto and Umberto D'Alessandro and Hermann Sorgho and Innocent Valea and Tahita, {Marc Christian} and William Kabor{\'e} and Sayouba Ou{\'e}draogo and Yara Sandrine and Guiguemd{\'e}, {Robert Tinga} and Ou{\'e}draogo, {Jean Bosco} and Hamel, {Mary J} and John Lusingu and Thor Theander and {RTS,S Clinical Trials Partnership}",

year = "2011",

month = nov,

day = "17",

doi = "10.1056/NEJMoa1102287",

language = "English",

volume = "365",

pages = "1863--75",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "20",

}

TY - JOUR

T1 - First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children

AU - Agnandji, Selidji Todagbe

AU - Lell, Bertrand

AU - Soulanoudjingar, Solange Solmeheim

AU - Fernandes, José Francisco

AU - Abossolo, Béatrice Peggy

AU - Conzelmann, Cornelia

AU - Methogo, Barbara Gaelle Nfono Ondo

AU - Doucka, Yannick

AU - Flamen, Arnaud

AU - Mordmüller, Benjamin

AU - Issifou, Saadou

AU - Kremsner, Peter Gottfried

AU - Sacarlal, Jahit

AU - Aide, Pedro

AU - Lanaspa, Miguel

AU - Aponte, John J

AU - Nhamuave, Arlindo

AU - Quelhas, Diana

AU - Bassat, Quique

AU - Mandjate, Sofia

AU - Macete, Eusébio

AU - Alonso, Pedro

AU - Abdulla, Salim

AU - Salim, Nahya

AU - Juma, Omar

AU - Shomari, Mwanajaa

AU - Shubis, Kafuruki

AU - Machera, Francisca

AU - Hamad, Ali Said

AU - Minja, Rose

AU - Mtoro, Ali

AU - Sykes, Alma

AU - Ahmed, Saumu

AU - Urassa, Alwisa Martin

AU - Ali, Ali Mohammed

AU - Mwangoka, Grace

AU - Tanner, Marcel

AU - Tinto, Halidou

AU - D'Alessandro, Umberto

AU - Sorgho, Hermann

AU - Valea, Innocent

AU - Tahita, Marc Christian

AU - Kaboré, William

AU - Ouédraogo, Sayouba

AU - Sandrine, Yara

AU - Guiguemdé, Robert Tinga

AU - Ouédraogo, Jean Bosco

AU - Hamel, Mary J

AU - Lusingu, John

AU - Theander, Thor

AU - RTS,S Clinical Trials Partnership

PY - 2011/11/17

Y1 - 2011/11/17

N2 - 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.)

AB - 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.)

KW - Africa

KW - Age Factors

KW - Double-Blind Method

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Incidence

KW - Infant

KW - Intention to Treat Analysis

KW - Malaria Vaccines

KW - Malaria, Falciparum

KW - Male

KW - Meningitis

KW - Parasite Load

KW - Plasmodium falciparum

KW - Seizures

KW - Treatment Outcome

U2 - 10.1056/NEJMoa1102287

DO - 10.1056/NEJMoa1102287

M3 - Journal article

C2 - 22007715

SN - 0028-4793

VL - 365

SP - 1863

EP - 1875

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 20

ER -

First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children

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