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

Pujitha Wickramasinghe, Astrid Borkowski, MariaTheresa Alera, Derek Wallace, Vianney Tricou, Inge LeFevre, Elaine Hoffman, Mengya Liu, Olaf Zent, Martina Rauscher, Rivaldo Venâncioda Cunha, Kleber Luz, Dulanie Gunasekera, Asvini D Fernando, Edson Duarte MoreiraJr, Charissa Borja-Tabora, LakKumar Fernando, Reynaldo Dietze, Veerachai Watanaveeradej, Luis Martinez Vargas, Chukiat Sirivichayakul, Humberto Reynales, Xavier Sáez-Llorens, Shibadas Biswal, Luis Rivera, Lulu Bravo, Eduardo López-Medina, Felix Espinoza, Pope Kosalaraksa, Delia Yu

Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2022;75(1):107-117

PMID: 34606595

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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.

Address: Hospital Maternidad Nuestra Senora de Altagracia, Santo Domingo, Dominican Republic.; Takeda Vaccines, Inc., Boston, Massachusetts, USA.; Hospital del Niño Dr. José Renán Esquivel, Sistema Nacional de Investigación at SENACYT, Centro de Vacunación Internacional (Cevaxin), Panama City, Panama.; Centro de Atención e Investigación Médica, CAIMED, Bogotá, Colombia.; Centro de Estudios en Infectología Pediátrica, Universidad del Valle and Centro Medico Imbanaco, Cali, Colombia.; Research Institute For Tropical Medicine, Muntinlupa, Philippines.; University of the Philippines Manila, Ermita, Philippines.; Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.; CAIMED, Dominicana, Santo Domingo, Dominican Republic.; De La Salle Medical and Health Sciences Institute, Dasmariñas, Philippines.; Phramongkutklao Hospital, Bangkok, Thailand.; National Autonomous University of Nicaragua, León, Nicaragua.; Núcleo de Doenças Infecciosas, Centro de Ciencias da Saude-UFES, Vitória, Brazil.; Centre for Clinical Management of Dengue & Dengue Haemorrhagic Fever, Negombo General Hospital, Negombo, Sri Lanka.; University of Colombo, Colombo, Sri Lanka.; Associação Obras Sociais Irmã Dulce Hospital Santo Antônio and Oswaldo Cruz Foundation, Bahia, Brazil.; Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka.; Faculty of Medical Sciences, University of Sri Jayawardenenpura, Colombo, Sri Lanka.; Instituto de Medicina Tropical da Universidade Federal do Rio Grande do Norte, Natal, Brazil.; Universidade Federal de Mato Grosso do Sul, Campo Grande, Brazil.; Takeda Pharmaceuticals International AG, Zurich, Switzerland.; Philippines-Armed Forces Research Institute of Medical Sciences Virology Research Unit, Cebu City, Philippines.

DOI: 10.1093/cid/ciab864

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MeSH Terms: Antibodies, Viral, Dengue, Dengue Vaccines, Dengue Virus, Humans, Serogroup, Treatment Outcome, Vaccines, Attenuated, Vaccines, Combined