Safety and immunogenicity of the LC16m8 vaccine against mpox during outbreak deployment in Colombia: a hybrid, multicentre, open-label, randomised controlled trial and observational cohort study

Background LC16m8 is a live-attenuated, replication-competent vaccinia vaccine, but clinical evidence on its efficacy against mpox remains limited. We assessed its efficacy and safety in adults at increased risk of mpox in Colombia. Methods We conducted a hybrid study comprising a multicentre, open-label, randomised delayed-vaccination trial and an observational cohort at three centres in Bogotá. Adults aged 18–50 years were randomised 1:1 using stratified permuted blocks to receive one percutaneous dose of LC16m8 at enrolment (Day 0) or on Day 42. The primary outcome was PCR-confirmed mpox during the arm-specific efficacy-assessment windows, analysed in the per-protocol efficacy population; no efficacy outcomes were imputed. Safety outcomes were assessed through Day 180. ClinicalTrials.gov NCT06223919; retrospectively registered; trial closed to recruitment. Findings Between December 16, 2023, and January 6, 2024, 208 participants were enrolled and 204 randomised (104 immediate; 100 delayed); 203 were male and one female. The trial randomised 204 of 8686 planned participants. No PCR-confirmed mpox cases occurred in the primary per-protocol efficacy analysis (0/97 immediate vs 0/69 delayed); therefore, the prespecified hazard ratio, 95% CI, p value, and vaccine efficacy were not estimable. Through Day 180, at least one adverse event was reported by 96/98 (98·0%) participants in the immediate-vaccination group and 68/69 (98·6%) in the delayed-vaccination group. One serious adverse event occurred in each group; both were unrelated to vaccination and resolved. No deaths or adverse-event-related study discontinuations occurred. Interpretation Substantial under-recruitment and the absence of primary outcome events precluded estimation of LC16m8 efficacy. The randomised safety findings were limited by the small sample size.