Shibadas Biswal1, Humberto Reynales1, Xavier Saez-Llorens1, Pio Lopez1, Charissa Borja-Tabora1, Pope Kosalaraksa1, Chukiat Sirivichayakul1, Veerachai Watanaveeradej1, Luis Rivera1, Felix Espinoza1, LakKumar Fernando1, Reynaldo Dietze1, Kleber Luz1, Rivaldo Venâncio da Cunha1, José Jimeno1, Eduardo López-Medina1, Astrid Borkowski1, Manja Brose1, Martina Rauscher1, Inge LeFevre1, Svetlana Bizjajeva1, Lulu Bravo1, Derek Wallace1. 1. From Takeda Vaccines, Singapore (S. Biswal); Centro de Atención e Investigación Médica, Bogota (H.R.), and Centro de Estudios en Infectología Pediatrica, Centro Médico Imbanaco and Department of Pediatrics, Universidad del Valle, Cali (P.L., E.L.-M.) - both in Colombia; the Department of Infectious Diseases at Hospital del Niño Dr. José Renán Esquivel, Sistema Nacional de Investigación at Secretaria Nacional de Ciencia y Tecnologia (SENACYT), Centro de Vacunación Internacional (Cevaxin), Panama City, Panama (X.S.-L., J.J.); the Research Institute for Tropical Medicine, Muntinlupa (C.B.-T.), and the University of the Philippines Manila, Ermita (L.B.) - both in the Philippines; Srinagarind Hospital, Khon Kaen University, Khon Kaen (P.K.), and the Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University (C.S.), and Phramongkutklao Hospital (V.W.), Bangkok - all in Thailand; Hospital Maternidad Nuestra Senora de Altagracia, Santo Domingo, Dominican Republic (L.R.); National Autonomous University of Nicaragua, Leon (F.E.); Center for Clinical Management of Dengue and Dengue Haemorrhagic Fever, Negombo General Hospital, Negombo, Sri Lanka (L.K.F.); Universidade Federal Do Espirito Santo, Hospital Universitário Cassiano Antônio de Moraes, Vitória (R.D.), Instituto de Medicina Tropical da Universidade Federal do Rio Grande do Norte, Natal (K.L.), and Universidade Federal de Mato Grosso do Sul, Campo Grande (R.V.C.) - all in Brazil; Takeda Pharmaceuticals International, Zurich, Switzerland (A.B., M.B., M.R., I.L., S. Bizjajeva); and Takeda Vaccines, Boston (D.W.).
Abstract
BACKGROUND: Dengue, a mosquito-borne viral disease, was designated a World Health Organization top 10 threat to global health in 2019. METHODS: We present primary efficacy data from part 1 of an ongoing phase 3 randomized trial of a tetravalent dengue vaccine candidate (TAK-003) in regions of Asia and Latin America in which the disease is endemic. Healthy children and adolescents 4 to 16 years of age were randomly assigned in a 2:1 ratio (stratified according to age category and region) to receive two doses of vaccine or placebo 3 months apart. Participants presenting with febrile illness were tested for virologically confirmed dengue by serotype-specific reverse-transcriptase polymerase chain reaction. The primary end point was overall vaccine efficacy in preventing virologically confirmed dengue caused by any dengue virus serotype. RESULTS: Of the 20,071 participants who were given at least one dose ofvaccine or placebo (safety population), 19,021 (94.8%) received both injections and were included in the per-protocol analysis. The overall vaccine efficacy in the safety population was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group). In the per-protocol analyses, vaccine efficacy was 80.2% (95% CI, 73.3 to 85.3; 61 cases of virologically confirmed dengue in the vaccine group vs. 149 cases in the placebo group), with 95.4% efficacy against dengue leading to hospitalization (95% CI, 88.4 to 98.2; 5 hospitalizations in the vaccine group vs. 53 hospitalizations in the placebo group). Planned exploratory analyses involving the 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (95% CI, 57.0 to 85.4; 20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group). Efficacy trends varied according to serotype. The incidence of serious adverse events was similar in the vaccine group and placebo group (3.1% and 3.8%, respectively). CONCLUSIONS:TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. (Funded by Takeda Vaccines; TIDES ClinicalTrials.gov number, NCT02747927.).
RCT Entities:
BACKGROUND: Dengue, a mosquito-borne viral disease, was designated a World Health Organization top 10 threat to global health in 2019. METHODS: We present primary efficacy data from part 1 of an ongoing phase 3 randomized trial of a tetravalent dengue vaccine candidate (TAK-003) in regions of Asia and Latin America in which the disease is endemic. Healthy children and adolescents 4 to 16 years of age were randomly assigned in a 2:1 ratio (stratified according to age category and region) to receive two doses of vaccine or placebo 3 months apart. Participants presenting with febrile illness were tested for virologically confirmed dengue by serotype-specific reverse-transcriptase polymerase chain reaction. The primary end point was overall vaccine efficacy in preventing virologically confirmed dengue caused by any dengue virus serotype. RESULTS: Of the 20,071 participants who were given at least one dose of vaccine or placebo (safety population), 19,021 (94.8%) received both injections and were included in the per-protocol analysis. The overall vaccine efficacy in the safety population was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group). In the per-protocol analyses, vaccine efficacy was 80.2% (95% CI, 73.3 to 85.3; 61 cases of virologically confirmed dengue in the vaccine group vs. 149 cases in the placebo group), with 95.4% efficacy against dengue leading to hospitalization (95% CI, 88.4 to 98.2; 5 hospitalizations in the vaccine group vs. 53 hospitalizations in the placebo group). Planned exploratory analyses involving the 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (95% CI, 57.0 to 85.4; 20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group). Efficacy trends varied according to serotype. The incidence of serious adverse events was similar in the vaccine group and placebo group (3.1% and 3.8%, respectively). CONCLUSIONS: TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. (Funded by Takeda Vaccines; TIDES ClinicalTrials.gov number, NCT02747927.).
Authors: Ellen Young; Robert H Carnahan; Daniela V Andrade; Nurgun Kose; Rachel S Nargi; Ethan J Fritch; Jennifer E Munt; Michael P Doyle; Laura White; Thomas J Baric; Mark Stoops; Aravinda DeSilva; Longping V Tse; David R Martinez; Deanna Zhu; Stefan Metz; Marcus P Wong; Diego A Espinosa; Magelda Montoya; Scott B Biering; Soila Sukulpolvi-Petty; Guillermina Kuan; Angel Balmaseda; Michael S Diamond; Eva Harris; James E Crowe; Ralph S Baric Journal: Cell Host Microbe Date: 2020-05-13 Impact factor: 21.023
Authors: Panpimon Luangtrakool; Sasijit Vejbaesya; Komon Luangtrakool; Somporn Ngamhawornwong; Kusuma Apisawes; Siripen Kalayanarooj; Louis R Macareo; Stefan Fernandez; Richard G Jarman; Robert W M Collins; Steven T Cox; Anon Srikiatkhachorn; Alan L Rothman; Henry A F Stephens Journal: J Infect Dis Date: 2020-08-04 Impact factor: 5.226