Efficacy of a Dengue Vaccine Candidate (TAK-003) in Healthy Children and Adolescents 2 Years after Vaccination

Abstract

Background: Takeda's dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we present a 2-year update.

Methods: Children (20 099, 4-16 years old) were randomized to receive 2 doses of TAK-003 or placebo 3 months apart and are under surveillance to detect dengue by serotype-specific RT-PCR.

Results: Cumulative efficacy against dengue approximately 27 months since first dose was 72.7% (95% confidence interval [CI], 67.1%-77.3%), including 67.0% (95% CI, 53.6%-76.5%) in dengue-naive and 89.2% (95% CI, 82.4%-93.3%) against hospitalized dengue. In the second year, decline in efficacy was observed (56.2%; 95% CI, 42.3%-66.8%) with the largest decline in 4-5 year olds (24.5%; 95% CI, -34.2% to 57.5%); efficacy was 60.6% (95% CI, 43.8%-72.4%) in 6-11 year and 71.2% (95% CI, 41.0%-85.9%) in 12-16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to efficacy differences in year-by-year analysis. No related serious adverse events occurred during the second year.

Conclusions: 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.Clinical Trials Registration. NCT02747927.Takeda's tetravalent dengue vaccine (TAK-003) continued to demonstrate benefit in reducing dengue independent of baseline serostatus up to 2 years after completing vaccination with some decline in efficacy during the second year in 4-16 year olds in dengue-endemic countries.

Keywords: TAK-003; dengue; efficacy; immunogenicity; persistence; safety; vaccine.

Figure 1.

Vaccine efficacy (95% CI) in prevention of VCD fever, hospitalization due to VCD, severe VCD, and DHF between first dose administration and 12 months after end of part 1 (month 27, year 2 after second dose). Forest plot shows efficacy according to serotype, baseline serostatus, age, and region (safety set data; lower bound 95% CI values < minus 50 not shown on x-axis). For serotype-specific efficacy calculations, only the first instance of VCD due to the individual serotype in question was included, regardless of previous instances of VCD due to other serotypes. Participants were classified as seronegative when testing seronegative for all dengue serotypes at baseline. Participants were classified as seropositive when demonstrating a reciprocal neutralizing antibody titer ≥ 10 against at least 1 dengue serotype at baseline. Cases of severe VCD were determined according to Dengue Case Adjudication Committee criteria. Cases of DHF were determined according to World Health Organization 1997 criteria [23]. Abbreviations: CI, confidence interval; DENV, dengue virus; DHF, dengue hemorrhagic fever; TAK-003, Takeda dengue vaccine candidate; VCD, virologically confirmed dengue.

Figure 2.

Cumulative incidence of (A) VCD cases and (B) hospitalized VCD cases (safety set data), occurring between first vaccination and 12 months after the end of part 1 (month 27, year 2 after second dose). Abbreviations: SP, seropositive; SN, seronegative; TAK-003, Takeda dengue vaccine candidate; VCD, virologically confirmed dengue.

Figure 3.

Cumulative incidence of VCD cases for each serotype (safety set data), occurring between first vaccination and 12 months after the end of part 1 (month 27, year 2 after second dose). Abbreviations: DENV, dengue virus; SP, seropositive; SN, seronegative; TAK-003, Takeda dengue vaccine candidate; VCD, virologically confirmed dengue.

Figure 4.

Serotype-specific GMTs (95% CI) in participants seronegative at baseline (per protocol set for immunogenicity data). Abbreviations: CI, confidence interval; DENV, dengue virus; GMT, geometric mean titer; TAK-003, Takeda dengue vaccine candidate.