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

NCT06223919 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: PI-UN-1760
• Study Type: interventional
• Target: 8,686
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Monkeypox

Keywords

Vaccines; monkeypox; Mpox; Mpox virus

Outcome Measures

Primary Outcomes (3)

• Incidence rate of mpox infection between the immediate versus delayed vaccination groups from day 15 to day 56 post-vaccination of the immediate group.

  The incidence rate of new cases of mpox (laboratory-confirmed) will be calculated with a 95% confidence interval (CI) based on the Poisson distribution for each vaccination group. The time to the onset of the first occurrence of a confirmed mpox case in the subject will be summarized graphically using the Kaplan-Meier method.

  For immediate vaccination group: from days 15th to 56th post vaccination. For delayed vaccination group: from enrollment to the day of vaccination (42 days later)

• Incidence of adverse events between the vaccination groups

  Proportion of adverse events (serious and non-serious) presented in participants included in the two vaccination groups (immediate and delayed)

  up to 6 months post vaccination

• Incidence rate of mpox infection between the vaccinated cohort versus the unvaccinated cohort

  The incidence rate of new cases of mpox (laboratory-confirmed) will be calculated with a 95% confidence interval (CI) based on the Poisson distribution for each cohort. The time to the onset of the first occurrence of a confirmed mpox case in the subject will be summarized graphically using the Kaplan-Meier method.

  6 months post vaccination

Secondary Outcomes (6)

• Frequency of laboratory-confirmed severe cases of MPOX in the immediate and delayed vaccination groups.

  6 months post-vaccination

• Incidence rate of mpox suspected cases without laboratory confirmation between the immediate versus delayed vaccination groups from day 15 to day 56 post-vaccination of the immediate group.

  - For immediate vaccination group: from days 15th to 56th post vaccination. For delayed vaccination group: from enrollment to the day of vaccination (42 days later

• Proportion of patients with seroconversion of geometric mean neutralizing titer (GMT) of LC16m8.

  up to 6 months post vaccination

• Geometric mean of LC16m8 neutralizing titer by vaccination group.

  up to 6 months post vaccination

• Geometric mean of LC16m8 neutralizing titer by helper T lymphocytes (CD4) count in each vaccination group

  up to 6 months post vaccination

Study Arms (2)

Immediate vaccination

EXPERIMENTAL

This vaccin is a yellowish-yellow dry preparation containing live vaccinia virus (strain LC16m8). When the accompanying solvent is added, it dissolves rapidly to form a clear or slightly cloudy yellowish-red or reddish liquid. The ingredients of this vaccin are contained in 0.5 mL of a solution of this product dissolved in 0.5 mL of the accompanying solvent (20 vol% glycerin-added water for injection). Just one dose of vaccine will be administered according to standardized operating procedure (SOP). Briefly, the vaccine is dissolved with 0.5 mL of a diluent provided. The reconstituted vaccine is usually administered percutaneously at a dose of approximately 0.025 mL by the multiple puncture technique using a bifurcated needle. The number of punctures will be 15 times. Procedures for vaccine administration are described in detail in the SOP. The participant must be observed at the vaccination site for 30 minutes after vaccine administration to observe possible immediate reactions.

Biological: LC16m8

Delayed vaccination

ACTIVE COMPARATOR

The use of placebo as a control group is essential to scientifically assess the efficacy of vaccines in clinical trials and to obtain reliable evidence in preventing the onset of disease. However, the use of a placebo is unethical. Subjects are at high risk of mpox and must not be given a placebo. Therefore, a design was applied in which the immediate treatment group was evaluated with the delayed group as a control group. A period of six weeks was set aside between the immediate and delayed treatment groups to be used for logistics, such as preparations and delivery of the vaccine in the delayed treatment group. It is ethical, for the same reason, because it prevents inequities based on the abovementioned reasons.

Biological: LC16m8

Interventions

LC16m8 BIOLOGICAL

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

Delayed vaccination; Immediate vaccination

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Sex: Males and females
• Age: ≥18 and ≤ 50 years old
• Persons must be willing and sign the Informed Consent (I.C.).
• Any of the following conditions including clinical conditions /manifestation:
• People living with the HIV, with stable infection determined by participant´s being on antiretroviral therapy with a blood CD4+ cell count, ≥ 200 cells/mm3 in the last six months before study enrolment
• Persons that use PrEP (HIV Pre-exposure prophylaxis).
• Homosexual, Bisexual, or other men who have sex with men (MSM) with multiple sexual partners. Commercial sex workers (CSW) and partners CSW
• The participant has non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least one year or surgically sterile. OR
• The participant has a childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks before the vaccine administration until at least 2 months after the administration and have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 10 days before vaccination.

You may not qualify if:

• Subjects with an unstable medical condition as determined by their initial medical history, physical examination, or laboratory results
• Subjects with a terminal disease.
• Subjects with a medical record of anaphylaxis caused by any of the vaccine's excipients or with previous undesired reactions to other vaccines such us (Allergic reactions, Guillain barre syndrome, Varicella zoster, or shingles).
• Previous medical record of Mpox.
• Subjects living with HIV with a CD4+ T cell count of fewer than 200 cells/mm3.
• Pregnant or breastfeeding woman.
• Active or medical record of atopic dermatitis or eczema, or with close contact with someone with an active or medical record of atopic dermatitis or eczema.
• The presence of a skin condition with extensive breaks in the skin, such as burns, impetigo, contact dermatitis, or zoster (shingles), is not likely to heal by the day of vaccination.
• Using immunosuppressive medications, in eye drops, by mouth, or topically (nasal sprays and inhaled corticosteroids are permissible).
• Active or past malignancy except for cutaneous basal or squamous cell carcinomas.
• An Autoimmune disease.
• History of heart failure with decreased left ventricular ejection fraction (\<40%).
• Medical record of splenectomy.
• Medical record of solid organ or bone marrow transplantation.
• Medical record of keloid scar development

Sponsors & Collaborators

• Universidad Nacional de Colombia: lead
• Ministerio de Salud y Protección Social de Colombia: collaborator
• Ministry of Health, Labour and Welfare, Japan: collaborator
• Japan Agency for Medical Research and Development: collaborator
• National Center for Global Health and Medicine, Japan: collaborator
• National Institute of Infectious Disease, Japan: collaborator
• Instituto Nacional de Salud: collaborator

Study Sites (3)

Clinica Universitaria Colombia - Centro Medico Teusaquillo

Bogotá, Bogota D.C., Colombia

Location

Hospital Universitario San Ignacio

Bogotá, Bogota D.C., Colombia

Location

Infecto Clinicos

Bogotá, Bogota D.C., Colombia

Location

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MeSH Terms

Conditions

Mpox, Monkeypox

Interventions

smallpox vaccine LC16m8

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Primate Diseases; Animal Diseases; Rodent Diseases

Study Officials

• Carlos A Álvarez

  Universidad Nacional de Colombia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Vaccinate LC16m8 randomly assigned to two groups consisting of two groups of Immediate and Delayed vaccination 1:1 with a follow-up period of 180 days to evaluate newly MPXV-infected cases as well as immuno-responses including neutralizing antibody titers.

Study Record Dates

• First Submitted: December 28, 2023
• First Posted: January 25, 2024
• Study Start: December 16, 2023
• Primary Completion: August 20, 2024
• Study Completion: December 1, 2025
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CO (3)