Efficacy/Effectiveness, Safety, and Immunogenicity of LC16m8 Mpox Vaccine in Colombia — MPOX-COL  

Monkeypox Clinical Trial

Official title: 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 Recruiting

Clinical Trial 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.

Clinical Trial 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.

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: This section was included in the study design as a contingency plan in case the people invited do not agree to participate in the study. In this component, the subcohort of vaccinated subjects belonging to the HIV and HIV pre-exposure prophylaxis (PrEP) lists will be compared with the subcohort of subjects who were invited to participate but decided not to participate or, those participants who have signed informed consent, decided not to participate after randomization, either due to voluntary withdrawal or loss to pre-vaccination follow-up. A comparison of the cumulative incidence in the cohort of vaccinated subjects with the incidence in the cohort of non-participants will be performed. The evaluation period is 180 days. Non-participant cases and withdrawals will be obtained by passive surveillance of records in the National Institute of Health of Colombia (INS- Spanish acronym) and local health entities. These groups will be compared using the incidence ratio or relative risk (RR). Considering the low expected frequency of events (less than 1%), it could also be estimated based on the odds ratio (OR) from a multivariate model that allows adjustment for possible effect-modifying or known confounding factors (unconditional logistic regression).

• Cohort study compared to the real-world cohort: the investigators will take all the subjects in HIV and HIV Pre-exposure prophylaxis programs, in this component, the sub-cohort of vaccinated subjects belonging to the lists of subjects with HIV and the PrEP program will be compared with the sub-cohort of subjects who were not invited to participate and who did not receive the vaccine. Comparison of the cumulative incidence in the cohort of vaccinated subjects will be made with the incidence in the cohort of non-participants. Cases of non-participants and withdrawals will be obtained by passive surveillance from the records of the INS and local health entities of the selected cities. These groups will be compared using the incidence ratio or RR. Given the low expected frequency of events (less than 1%), the OR could also be estimated from a multivariate model that allows adjustment for possible known effect-modifying or confounding factors (unconditional logistic regression). ;

Related Conditions & MeSH terms

• Monkeypox

• NCT number: NCT06223919
• Study type: Interventional
• Source: Universidad Nacional de Colombia
• Contact: Carlos A Alvarez, PhD
• Phone: 3143302367
• Email: caalvarezmo@unal.edu.co
• Status: Recruiting
• Phase: Phase 3
• Start date: December 16, 2023
• Completion date: December 6, 2024