EFFICACY AND SAFETY OF TAKEDA'S TETRAVALENT DENGUE VACCINE CANDIDATE (TAK-003) AFTER 4.5 YEARS OF FOLLOW-UP: RESULTS FROM PARTICIPANTS IN ASIA

Abstract

Intro: An ongoing, long-term, phase 3 trial (NCT02747927) in eight dengueendemic countries across Asia and Latin America is evaluating the efficacy, safety, and immunogenicity of Takeda's tetravalent dengue vaccine candidate, TAK-003. We present 4.5 years of follow-up data from participants in Asia. Methods: Healthy participants aged 4–16 years were randomized 2:1 to receive two doses of TAK-003 or placebo at Months 0 and 3. An active febrile illness surveillance was implemented to detect both outpatient and hospitalized symptomatic dengue using serotype-specific real-time polymerase chain reaction (RT-PCR). Safety was monitored throughout the trial. Findings: 20,071 participants received ≥1 dose of TAK-003 or placebo; 27.6% (5,547/20,063) were seronegative at baseline. 18,260 (91.0%) completed up to 4.5 years of post-vaccination follow-up. 27,684 febrile illnesses were reported, leading to detection of 1,007 RT-PCR confirmed dengue cases; of which, 188 required hospitalization (placebo group, n=142; TAK-003 group, n=46). Cumulative vaccine efficacy (VE; 95% CI) across all countries from first dose until 4.5 years post second dose was 61.2 (56.0, 65.8) against virologically-confirmed dengue (VCD) and 84.1 (77.8, 88.6) against hospitalized VCD. In Asia, 637 VCD cases were reported, with 150 requiring hospitalization (placebo group, n=112; TAK-003 group, n=38). VE (95% CI) from one month post second dose to 4.5 years of follow-up was 60.0 (52.8, 66.1) against VCD and 83.0 (74.9, 88.5) against hospitalized VCD; long-term protection against VCD and hospitalized VCD was observed irrespective of baseline serostatus (VCD: 63.3 [55.2, 69.9] in seropositive participants and 50.9 [33.5, 63.8] in seronegative participants; hospitalized VCD: 86.2 [77.0, 91.7] in seropositive participants and 75.8 [55.2, 86.9] in seronegative participants). No important safety risks were identified. Conclusion: TAK-003 was well tolerated and provided sustained protection against symptomatic dengue through 4.5 years, irrespective of baseline serostatus.