Three-year Efficacy and Safety of Takeda's Dengue Vaccine Candidate (TAK-003)

Authors

Luis Rivera, Hospital Maternidad Nuestra Señora de la Altagracia
Shibadas Biswal
Xavier Sáez-Llorens, Hospital del Niño Dr. José Renán Esquivel
Humberto Reynales, Centro de Atención e Investigación Médica (CAIMED)
Eduardo López-Medina, Universidad del Valle, Cali
Charissa Borja-Tabora, Gokila
Lulu Bravo, University of the Philippines Manila
Chukiat Sirivichayakul, Faculty of Tropical Medicine, Mahidol University
Pope Kosalaraksa, Faculty of Medicine, Khon Kaen University
Luis Martinez Vargas, Heart Care Dominicana
Delia Yu, De La Salle Medical and Health Sciences Institute
Veerachai Watanaveeradej, Phramongkutklao College of Medicine
Felix Espinoza, National Autonomous University of Nicaragua
Reynaldo Dietze, Federal University of Espirito Santo
Lak Kumar Fernando, Negombo General Hospital
Pujitha Wickramasinghe, University of Colombo
Edson Duarte MoreiraJr, Fundacao Oswaldo Cruz
Asvini D. Fernando, University of Kelaniya
Dulanie Gunasekera, University of Sri Jayawardenenpura
Kleber Luz, Universidade Federal do Rio Grande do Norte
Rivaldo Venâncioda Cunha, Universidade Federal de Mato Grosso do Sul
Martina Rauscher, Takeda Pharmaceuticals International AG
Olaf Zent, Takeda Pharmaceuticals International AG
Mengya Liu
Elaine Hoffman
Inge LeFevre, Takeda Pharmaceuticals International AG
Vianney Tricou, Takeda Pharmaceuticals International AG
Derek Wallace
Maria Theresa Alera, Philippines-Armed Forces Research Institute of Medical Sciences Virology Research Unit
Astrid Borkowski, Takeda Pharmaceuticals International AG

Publication Date

8-24-2022

Document Type

Article

Publication Title

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Abstract

BACKGROUND: Takeda's live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across 8 dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year postvaccination. This exploratory analysis provides an update with cumulative and third-year data. METHODS: Healthy 4-16 year olds (n = 20099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific reverse transcriptase-polymerase chain reaction. RESULTS: Cumulative efficacy after 3 years was 62.0% (95% confidence interval, 56.6-66.7) against virologically confirmed dengue (VCD) and 83.6% (76.8-88.4) against hospitalized VCD. Efficacy was 54.3% (41.9-64.1) against VCD and 77.1% (58.6-87.3) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9-70.1) against VCD and 86.0% (78.4-91.0) against hospitalized VCD in baseline seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5-54.7), whereas efficacy against hospitalized VCD was sustained at 70.8% (49.6-83.0). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (ie, second half of the 3 years following vaccination), but none were related. No important safety risks were identified. CONCLUSIONS: TAK-003 was efficacious against symptomatic dengue over 3 years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.

First Page

107

Last Page

117

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