P-1395. Safety and Effectiveness of LC16m8 for Pre-Exposure Prophylaxis Against mpox in High-Risk Population: An Open-Label Randomized Trial

Abstract Background Since May 2022, the incidence of mpox cases has surged outside endemic regions. Although vaccination remains pivotal in mpox prevention, data on LC16m8, a third-generation smallpox vaccine, are scant. We provided LC16m8 pre-exposure prophylaxis opportunities to high-risk individuals, including those with HIV, and conducted a randomized controlled trial to assess LC16m8’s effectiveness in mpox prevention and safety. Methods Our multicenter randomized open-label trial enrolled men and women aged ≥18 years at high mpox risk who provided written consent. Participants were randomly assigned 1:1 to early or late vaccination groups, receiving vaccinations approximately 70 days apart. Primary endpoint: vaccine effectiveness (VE) against mpox development between early and late vaccinations. VE against severe mpox, symptoms, “take” incidence, and adverse events were secondary endpoints. Results A total of 1,135 participants were recruited; 570 and 565 were assigned to early and late vaccination groups, respectively; 530 and 476 were vaccinated. Median age: 41 years; 99.7% were male; 89.7% Japanese; and 34.4% HIV-infected. No mpox cases occurred during the observation period, precluding VE calculation. “Take” rates: 90.3% (HIV-infected), 94.6% (uninfected). Adverse events related to the study were observed in 96.6% and 98.0% of the HIV-infected and uninfected participants, respectively. No fatal adverse events were observed; serious adverse events (SAE): 0.6% (HIV-infected), 0.5% (uninfected). One HIV-uninfected participant reported pulmonary embolism and deep vein thrombosis as a causally undeniable SAE. Local skin reactions: 96.6% (HIV-infected), 97.9% (uninfected); systemic reactions: 63.6% (HIV-infected), 64.2% (uninfected). Conclusion LC16m8’s effectiveness in mpox prevention remains inconclusive. Yet, its use in well-controlled HIV-infected and -uninfected individuals showed no significant safety concerns, suggesting potential for targeted vaccination strategies in at-risk groups. Disclosures All Authors: No reported disclosures