Publication:
Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: A phase 3, randomised, observer-masked, placebo-controlled trial

Issued Date

2014-01-01

Resource Type

Article

ISSN

1474547X
01406736

DOI

10.1016/S0140-6736(14)61060-6

Other identifier(s)

2-s2.0-84908160975

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet. Vol.384, No.9951 (2014), 1358-1365

Suggested Citation

Maria Rosario Capeding, Ngoc Huu Tran, Sri Rezeki S. Hadinegoro, Hussain Imam Hj Muhammad Ismail, Tawee Chotpitayasunondh, Mary Noreen Chua, Chan Quang Luong, Kusnandi Rusmil, Dewa Nyoman Wirawan, Revathy Nallusamy, Punnee Pitisuttithum, Usa Thisyakorn, In Kyu Yoon, Diane Van Der Vliet, Edith Langevin, Thelma Laot, Yanee Hutagalung, Carina Frago, Mark Boaz, T. Anh Wartel, Nadia G. Tornieporth, Melanie Saville, Alain Bouckenooghe Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: A phase 3, randomised, observer-masked, placebo-controlled trial. The Lancet. Vol.384, No.9951 (2014), 1358-1365. doi:10.1016/S0140-6736(14)61060-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/34867

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Title

Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: A phase 3, randomised, observer-masked, placebo-controlled trial

Author(s)

Maria Rosario Capeding
 Ngoc Huu Tran
 Sri Rezeki S. Hadinegoro
 Hussain Imam Hj Muhammad Ismail
 Tawee Chotpitayasunondh
 Mary Noreen Chua
 Chan Quang Luong
 Kusnandi Rusmil
 Dewa Nyoman Wirawan
 Revathy Nallusamy
 Punnee Pitisuttithum
 Usa Thisyakorn
 In Kyu Yoon
 Diane Van Der Vliet
 Edith Langevin
 Thelma Laot
 Yanee Hutagalung
 Carina Frago
 Mark Boaz
 T. Anh Wartel
 Nadia G. Tornieporth
 Melanie Saville
 Alain Bouckenooghe

Other Contributor(s)

Gokila
 Pasteur Institute in Ho Chi Minh City
 University of Indonesia, RSUPN Dr. Cipto Mangunkusumo
 Kuala Lumpur Hospital
 Queen Sirikit National Institute of Child Health
 Chong Hua Hospital
 Universitas Padjadjaran
 Universitas Udayana
 Penang Hospital
 Mahidol University
 Armed Forces Research Institute of Medical Sciences, Thailand
 Sanofi Pasteur
 Sanofi Pasteur
 Sanofi Pasteur
 Sanofi Pasteur
 Sanofi Pasteur SA

Abstract

© © 2014 Elsevier Ltd. Background An estimated 100 million people have symptomatic dengue infection every year. This is the fi rst report of a phase 3 vaccine effi cacy trial of a candidate dengue vaccine. We aimed to assess the effi cacy of the CYD dengue vaccine against symptomatic, virologically confi rmed dengue in children.Methods We did an observer-masked, randomised controlled, multicentre, phase 3 trial in fi ve countries in the Asia- Pacifi c region. Between June 3, and Dec 1, 2011, healthy children aged 214 years were randomly assigned (2:1), by computer-generated permuted blocks of six with an interactive voice or web response system, to receive three injections of a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV), or placebo, at months 0, 6, and 12. Randomisation was stratifi ed by age and site. Participants were followed up until month 25. Trial staff responsible for the preparation and administration of injections were unmasked to group allocation, but were not included in the follow-up of the participants; allocation was concealed from the study sponsor, investigators, and parents and guardians. Our primary objective was to assess protective effi cacy against symptomatic, virologically confi rmed dengue, irrespective of disease severity or serotype, that took place more than 28 days after the third injection. The primary endpoint was for the lower bound of the 95% CI of vaccine effi cacy to be greater than 25%. Analysis was by intention to treat and per procotol. This trial is registered with ClinicalTrials.gov, number NCT01373281.Findings We randomly assigned 10 275 children to receive either vaccine (n=6851) or placebo (n=3424), of whom 6710 (98%) and 3350 (98%), respectively, were included in the primary analysis. 250 cases of virologically confi rmed dengue took place more than 28 days after the third injection (117 [47%] in the vaccine group and 133 [53%] in the control group). The primary endpoint was achieved with 565% (95% CI 438664) effi cacy. We recorded 647 serious adverse events (402 [62%] in the vaccine group and 245 [38%] in the control group). 54 (1%) children in the vaccine group and 33 (1%) of those in the control group had serious adverse events that happened within 28 days of vaccination. Serious adverse events were consistent with medical disorders in this age group and were mainly infections and injuries.Interpretation Our fi ndings show that dengue vaccine is effi cacious when given as three injections at months 0, 6, and 12 to children aged 214 years in endemic areas in Asia, and has a good safety profi le. Vaccination could reduce the incidence of symptomatic infection and hospital admission and has the potential to provide an important public health benefi t.Funding Sanofi Pasteur.

Keyword(s)

Medicine

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https://repository.li.mahidol.ac.th/handle/20.500.14594/34867

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