Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Three years efficacy and safety of Takeda's dengue vaccine candidate (TAK-003)(Oxford University Press, 2022) Rivera, L.; Biswal, S.; Sáez-Llorens, X.; Reynales, H.; López-Medina, E.; Borja-Tabora, C.; Bravo, L.; Sirivichayakul, C.; Kosalaraksa, P.; Vargas, L.M.; Yu, D.; Watanaveeradej, V.; Espinoza, F.; Dietze, R.; Fernando, L.; Wickramasinghe, P.; Duarte Moreira, E. J.; Fernando, A. D.; Gunasekera, D.; Luz, K.; Venâncio da Cunha, R.; Rauscher, M.; Zent, O.; Liu, M.; Hoffman, E.; LeFevre, I.; Tricou, V.; Wallace, D.; Alera, M.T.; Borkowski, A.Background: Takeda's live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across eight 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 post-vaccination. This exploratory analysis provides an update with cumulative and third year data. Methods: Healthy 4-16 year-olds (n=20,099) 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 RT-PCR. Results: Cumulative efficacy after three 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 seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5%, 54.7%), while 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 (i.e. second half of the three years following vaccination), but none were related. No important safety risks were identified. Conclusions: TAK-003 was efficacious against symptomatic dengue over three years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.Item Efficacy of a dengue vaccine candidate (TAK-003) in healthy children and adolescents two years after vaccination(University of Chicago Press, 2022) López-Medina, E.; Biswal, S.; Saez-Llorens, X.; Borja-Tabora, C.; Bravo, L.; Sirivichayakul, C.; Vargas, L.M.; Alera, M.T.; Velásquez, H.; Reynales, H.; Rivera, L.; Watanaveeradej, V.; Rodriguez-Arenales, E.J.; Yu, D.; Espinoza, F.; Dietze, R.; Fernando, L.; Wickramasinghe, P.; Moreira Jr, E.D.; Fernando, A.D.; Gunasekera, D.; Luz, K.; da Cunha, R.V.; Tricou, V.; Rauscher, M.; Liu, M.; LeFevre, I.; Wallace, D.; Kosalaraksa, P.; Borkowski, A.; TIDES study group.BACKGROUND: Takeda's dengue vaccine is under evaluation in an ongoing Phase 3 efficacy study; we present an update after 2 years. METHODS: 20,099 children (4-16 years old) were randomized to receive two doses of TAK-003 or placebo three months apart and are under long-term febrile surveillance to detect dengue by serotype-specific RT-PCR. (NCT02747927). RESULTS: Cumulative efficacy against dengue over ~27 months since first dose was 72.7% (95% CI: 67.1 - 77.3), which included efficacy of 67.0% (95% CI: 53.6 - 76.5) in dengue-naïve and 89.2% (82.4 - 93.3) against hospitalized dengue. In the second year after vaccination, a decline in efficacy was observed [56.2% (42.3 - 66.8)] with the largest decline in 4 - 5 year-old children [24.5% (-34.2 - 57.5)]; efficacy was 60.6% (43.8 - 72.4) in 6 - 11 year and 71.2% (41.0 - 85.9) in 12 - 16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to the efficacy differences in year by year analysis. No related serious adverse events occurred during the second year. CONCLUSION: TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be important to see if efficacy stabilizes or declines further. KEYWORDS: Dengue; TAK-003; efficacy; immunogenicity; persistence; safety; vaccine.