Safety and Effectiveness of LC16m8 for Pre-Exposure Prophylaxis against mpox in a High-Risk Population: An Open-Label Randomized Trial

BackgroundThe incidence of mpox cases has surged outside endemic regions since May 2022. However, data regarding the safety and efficacy of the LC16m8 vaccine are limited. This study provided opportunities for LC16m8 pre-exposure prophylaxis to high-risk individuals and conducted a randomized controlled trial to assess the effectiveness of LC16m8 in mpox prevention. MethodsThis multicenter, randomized, open-label trial enrolled men and women aged [≥]18 with high mpox risk. Participants were randomly assigned 1:1 to early or late vaccination groups, receiving vaccinations approximately 70 days apart. Vaccine effectiveness (VE) against mpox development between early and late vaccinations was the primary endpoint. VE against severe mpox, symptoms, "take" incidence, and adverse events were secondary endpoints. ResultsA total of 570 and 565 patients were assigned to the early and late vaccination groups, respectively, and 530 and 476 were vaccinated. The median age was 41 years; 99.7% were male, 89.7% were Japanese, and 34.4% had human immunodeficiency virus (HIV). No mpox cases occurred, precluding VE calculations. The take rate was 90.3% (HIV-infected) and 94.6% (uninfected). Adverse events were observed in 97.2% and 98.2% of patients with and without HIV, respectively. No fatal adverse events were observed. Serious adverse events (SAE) were observed in 0.6% (HIV-infected) and 0.5% (uninfected) of patients. One participant without HIV reported pulmonary embolism and deep vein thrombosis as causally undeniable SAE. Local skin reactions: 96.6% (HIV-infected) and 97.9% (uninfected); systemic reactions: 63.6% (HIV-infected) and 64.2% (uninfected). ConclusionsThe effectiveness of LC16m8 in mpox remains inconclusive. However, its use in well-controlled HIV-infected and -uninfected individuals showed no significant safety concerns, suggesting the potential for targeted vaccination strategies in at-risk groups. (Japan Registry of Clinical Trials number, jRCT1031230137.)