NCT06223919

Efficacy/Effectiveness, Safety, and Immunogenicity of LC16m8 Mpox Vaccine in Colombia

Randomized Trial to Evaluate the Efficacy/Effectiveness, Safety, and Immunogenicity of Replicative Live Attenuated Vaccinia Virus Vaccine LC16m8 for Prevention Against Mpox in High-risk Populations During Vaccination Deployment in Colombia

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 8,686 (estimated)
• Sponsor: Universidad Nacional de Colombia · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

Background: Mpox is a zoonotic disease caused by the mpox virus (MPXV). It has been endemic in West and Central African countries. However, the soaring number of those has been reported in non-endemic countries since May 2022, making World Health Organization (WHO) declare a global mpox Public Health Emergency of International Concern in July 2022. Those with mpox are primarily young men (96%, and median age of 34 \[interquartile range (IQR):29-41 years\]), and 84% are self-identified homosexual, bisexual, and men who have sex with men (MSM) . Furthermore, about half of these mpox cases with known human immunodeficiency virus 1(HIV-1, hereafter shown as HIV). WHO recommended prioritizing vaccinating those populations as high-risk populations, including those with HIV, since they will be severely ill if infected mpox virus (MPXV). The smallpox vaccine is expected to offer cross-immunity against MPXV. Under these circumstances, WHO included LC16m8 in the recommended vaccine lists for mpox as the product is expected to have cross-efficacy and immunogenicity against MPXV. Additionally, the safety profile was demonstrated in both adults and children, including infants who have low immuno-functions. Given that Colombia has the fifth highest mpox prevalence worldwide, WHO encouraged the authorities to implement vaccine programs while evaluating the safety and efficacy of LC16m8 as collaborative research. Following WHO initiative, this study is being conducted with the collaboration of various experts from Colombia and Japan on a large scale, with vaccine contributions and funding from Japan and Colombia However, the current infection situation differs from six months ago, and there have been few recent cases of MPXV infection in the country. Primary objective: To determine the efficacy of the replicating attenuated live vaccinia virus vaccine LC16m8 against laboratory-confirmed mpox and safety in a Colombian population with a high risk of being infected with MPXV(See the Inclusion Criteria), by comparing the immediate vaccination group and the delayed vaccination groups to assess safety and tolerability until 180 days after vaccination. Study design: An open randomized deployment study (1:1 Immediate and Delayed vaccination group). Study population: People at high risk of serious illness if infected with MPXV and those who engage in risk behaviors for acquiring MPXV infection.

Detailed description

Hypothesis: LC16m8 is a safe and effective vaccine for high-risk immunocompromised populations, including those living with HIV. Intervention evaluation plan: Vaccinate with LC16m8 those people randomly assigned to two groups: immediate and deferred vaccination 1:1 with a follow-up period of 180 days to evaluate new cases infected by MPXV. General design: This research is being carried out within the framework of the mpox vaccination implementation program in Colombia. It comprises the following three complementary components: * Study section 1: Parallel open sequential randomized controlled trial to evaluate the efficacy of LC16m8 vaccine in preventing MPXV infection. * Study section 2: Cohort study based on the same population base * Study section 3: Cohort study compared to real world cohort STUDY SECTION 1: Participants will receive LC16m8 vaccine within 6 weeks (immediate vaccination) or 6 weeks later (delayed vaccination) after randomization. Both groups will be followed up at 14, 30 and 180 days after vaccination, mainly through phone calls. The study will compare the incidence of new MPXV infections in the early vaccination group from day 14 to day 42 after vaccination with the incidence of rate at which new MPXV infections occur in the delayed vaccination group from 42 days before to 14 days after vaccination; this comparison will be made from the hazard ratio or proportional hazard model. Additionally, the immune response, including neutralizing antibody titers, will be evaluated from the day of vaccination (Day 1) to 180 days post-vaccination in 60 participants, who will be selected from a single research center and only belonging to the immediate vaccination group. Two 5 mL blood samples (converted to serum) will be collected from the participants for immunogenicity assessments at the following time points: Days 0, 14 (+/-2), 30 (+/-2), and 180 (+/-7) post-vaccination. Another blood sample for immunogenicity assessment will be collected before the vaccine is administered on Day 0. Safety events will be intensively sought, especially in the first 14 days after vaccine administration and all those arising within 180 days post-vaccination. Participants will also self-report symptoms through a mobile application designed for this purpose. STUDY SECTION 2 AND 3 (NESTED STUDIES) \- Study of cohorts supported on the same population base: A total of 1,000 vaccinated individuals, including participants in section 1 of the study, will make up the exposed group. The unexposed group will consist of 4,000 unvaccinated individuals from the same population base (a list of HIV patients with a CD4 count greater than 200 cells/ml and PrEP users). who are patients with HIV and CD4 greater than 200 cells/mm3, and PrEP users. The group of unvaccinated individuals are people who meet the study's criteria but did not agree to be vaccinated or withdrew their consent. We will compare the cumulative incidence of these two groups over a 180-day period. We will obtain information about non-participants and withdrawals from the records at the INS and local health entities. We will use the hazard ratio (HR) to compare these groups, and we will also conduct a propensity score analysis.The objective is to demonstrate the effectiveness and safety of the LC16m8 replicating vaccine against laboratory-confirmed MPXV in a Colombian population at high risk of MPXV infection (see inclusion criteria). Assumptions: * A relative risk reduction (RRR) of 75% is assumed to calculate the sample size. * Confidence level: 95% * Ratio of vaccinated:unvaccinated: 1:4 * RRR: Risk (Rx) in the unvaccinated group - Rx in the vaccinated group/(Rx) in the unvaccinated group. The incidence of the event (Mpox case) is considered to be 0.4% per period in the exposed group (I Exp (+)) and 1.6% per period in the unexposed group (I exp (-)), in accordance with the current situation of Mpox infection in Colombia. Incidence in vaccinated 4/1000 = 0.004 Incidence in unvaccinated 64/4000 = 0.016 RR\*\* = 0.2756 (95% CI: 0.1057 ; 0.7185) \*\*Relative risk (RR): Risk (Rx) in unvaccinated/Rx in vaccinated RAR\*\*\*: -1.2888 (95% CI: -2.247; - 0.3306) RRR= 0.7244 (95% CI: 0.2815; 0.8943) Power: 0.92 where RR is relative risk, RAR is absolute risk reduction and RRR is relative risk reduction. The Ho could be rejected. \- Cohort study compared to the real-world cohort: There will be no sample size because all the information from the databases will be used in the cohort, so a sample is not necessary since we will take all the subjects in HIV and PrEP programs.

Conditions

• Monkeypox

Interventions

Type	Name	Description
BIOLOGICAL	LC16m8	LC16m8 should be stored at temperatures between -35°C and -20°C. The product should not be stored at temperatures below -35°C, because deterioration or damage of the rubber stopper could occur. The virus in this product is sensitive to sunlight and is quickly inactivated, so care should be taken to avoid exposure to light, both before or after reconstitution. Carefully examine the content at the time of reconstitution. Do not use if precipitation, contamination of foreign substances, or other abnormalities are observed. This product should be dissolving the drug immediately before inoculation. Once dissolved, it should be used immediately. Since this product does not contain thimerosal, once the stopper is removed, any solution remained in the vial must be disposed of. Do not restore or reuse the remaining solution. Shelf Life: 10 years from the date of passing the national test for lot-release Bottle containing about 250 doses

Timeline

• Start date: 2023-12-16
• Primary completion: 2024-08-20
• Completion: 2025-12-01
• First posted: 2024-01-25
• Last updated: 2025-09-04

Locations

3 sites across 1 country: Colombia