BACKGROUND:Dengue viruses (DENV1-4) cause dengue fever and dengue hemorrhagic fever. Developing a live attenuated tetravalent dengue vaccine (LATDV) faces challenges in overcoming viral interference to induce a balanced immune response. KD-382 is an LATDV candidate being developed by KM Biologics Co., Ltd. for dengue prevention.
METHODS:This first-in-human Phase I study of KD-382 is a randomized, placebo-controlled, double-blind, ascending-dose study in 60 flavivirus antibody-naïve healthy subjects aged 18-65 years. The study was conducted in two parts evaluating low dose (Part 1) and standard dose (Part 2). In each part, subjects were randomized in a 3:2:1 ratio to receive either KD-382 as a single dose, two doses, or placebo. Subjects received subcutaneous injections on Days 1 and 29 and were followed up for 1 year.
RESULTS:Eight (Part 1: 3; Part 2: 5) of 60 vaccinated subjects were withdrawn from the study. Both low and standard doses of KD-382, regardless of the dosing regimen, showed a 100 % seroconversion rate for all four serotypes (DENV1-4) at Day 57 and retained 100 % seropositivity for DENV1, 2, and 4 through the 12-month follow-up. For DENV3, a single dose in the low dose group of KD-382 retained a 100 % seroconversion rate at Months 3 and 12, while in the standard dose group, it was 91.7 % at Month 12. The most frequently reported solicited local treatment-emergent adverse events (TEAEs) were erythema, followed by pain and injection site pruritus; solicited systemic TEAEs were fatigue, followed by headache and myalgia. No serious or severe solicited TEAEs, or TEAEs leading to study vaccine withdrawal or death were reported.
CONCLUSIONS:KD-382 was safe and well-tolerated in flavivirus antibody-naïve healthy subjects. It elicited a long-lasting neutralizing antibody response for all four DENV serotypes during the 1-year follow-up, even with single-dose administration. Australia New Zealand Clinical Trial Registry: ACTRN12618001027202.