GRADE 3 SOLICITED AND UNSOLICITED ADVERSE EVENTS (AES) FOLLOWING VACCINATION WITH TAKEDA'S TETRAVALENT DENGUE VACCINE CANDIDATE (TAK-003)

Abstract

Intro: An ongoing, long-term phase 3 trial (NCT02747927) in eight dengue- endemic countries is evaluating Takeda's dengue vaccine candidate, TAK-003. We report Grade 3 (i.e., severe) solicited and unsolicited safety data through Part 3 of the trial. Methods: Participants aged 4–16 years received two doses of TAK-003 or placebo (2:1) 3 months apart. Solicited local AEs (injection-site pain/erythema/swelling) and systemic AEs (participants aged <6 years: drowsiness, fever, irritability/fussiness, and loss of appetite; participants aged ≥6 years: asthenia, fever, headache, malaise, and myalgia) were collected for 7 and 14 days post vaccination, respectively. Unsolicited AEs were collected for 28 days post vaccination. Solicited/unsolicited AEs were recorded for a subset of randomized participants; serious AEs (SAEs) were recorded for all participants throughout the trial. Findings: 20,071 participants received ≥1 dose of placebo or TAK-003, including 3,993 participants in the safety subset. Solicited local AEs were reported for 25.7% (338/1317) of placebo recipients and 36.7% (967/2633) of TAK-003 recipients. Few participants reported severe events (∼1% for both groups). Injection-site pain was the only severe event reported for participants receiving placebo (0.6%) and TAK-003 (≤1.2%). Solicited systemic AEs were reported for 38.0% (501/1317) of placebo recipients and 42.0% (1107/2635) of TAK-003 recipients. Few participants reported severe AEs (<6 years, 1.6%; ≥6 years, 3.8%). In participants aged <6 years, loss of appetite was the most frequently reported severe AE (placebo recipients, 1.2%; TAK-003 recipients, 0.9%), while headache was the most frequently reported severe AE for participants aged ≥6 years (placebo recipients, 2.5%; TAK-003 recipients, 2.9%). Participants in the placebo group (18.7% [249/1329]) and TAK-003 group (18.3% [487/2663]) reported unsolicited AEs; AEs were severe for 0.4% of TAK-003 recipients and no placebo recipients. Five participants experienced vaccine-related SAEs (placebo group, n=4; TAK-003 group, n=1). Conclusion: TAK-003 had a favorable safety profile, with few severe solicited and unsolicited AEs reported.