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

Monkeypox Clinical Trial

— MPOX-COL  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06223919
• Other study ID #: PI-UN-1760
• Status: Recruiting
• Phase: Phase 3
• Start date: December 16, 2023
• Est. completion date: December 6, 2024

Study information

• Verified date: January 2024
• Source: Universidad Nacional de Colombia
• Contact: Carlos A Alvarez, PhD
• Phone: 3143302367
• Email: caalvarezmo[@]unal.edu.co
• Is FDA regulated: No
• Study type: Interventional

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 8686
• Est. completion date: December 6, 2024
• Est. primary completion date: August 22, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

1. Inclusion Criteria:

1. Sex: Males and females

2. Age: =18 and = 50 years old

3. Persons must be willing and sign the Informed Consent (I.C.).

4. 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

5. Persons that use PrEP (HIV Pre-exposure prophylaxis).

6. Homosexual, Bisexual, or other men who have sex with men (MSM) with multiple sexual partners. Commercial sex workers (CSW) and partners CSW

7. A female participant is eligible to participate if the participant meets one of the inclusion criteria numbered -1, -2 or -3 above. The participant cannot be pregnant or lactating. Additionally, the female participant must meet one of the

following conditions:

• 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.

2. Exclusion Criteria:

1. Subjects with an acute and/or severe disease.

2. Subjects with a terminal disease.

3. 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).

4. Previous medical record of Mpox.

5. Subjects living with HIV with a CD4+ T cell count of fewer than 200 cells/mm3.

6. Pregnant or breastfeeding woman.

7. 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.

8. 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.

9. Using immunosuppressive medications, in eye drops, by mouth, or topically (nasal sprays and inhaled corticosteroids are permissible).

10. Active or past malignancy except for cutaneous basal or squamous cell carcinomas.

11. An Autoimmune disease.

12. Medical record of heart condition under the care of a physician.

13. Medical record of splenectomy.

14. Medical record of solid organ or bone marrow transplantation.

15. Medical record of keloid scar development

16. Evidence of immunosuppression, cardiac disease, renal disease, or unstable medical condition as determined by baseline medical history, physical assessment, and laboratory assessment.

17. Psychiatric condition that precludes compliance with the protocol.

18. People who received or plan to receive licensed live vaccines 30 days before or after study vaccination.

19. People who received or planned to receive immunoglobulin or other blood products 60 days before HIV screening.

20. People who received or plan to receive experimental drugs/vaccines 30 days before study vaccination or before study completion.

21. People who received or planned to receive systemic immunosuppressive therapy and radiation therapy 30 days before or after the study vaccination.

22. Use of systemic chemotherapy within five years before the study vaccination.

23. Medical record of smallpox vaccination and/or evidence of scarring at the vaccination site.

24. Allergies to streptomycin sulfate and/or erythromycin lactobionate.

Related Conditions & MeSH terms

• Monkeypox

Intervention

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

Locations

Country	Name	City	State
Colombia	Clinica Universitaria Colombia - Centro Medico Teusaquillo	Bogotá
Colombia	Hospital Universitario San Ignacio	Bogotá
Colombia	Infecto Clinicos	Bogotá
Colombia	SUB RED NORTE - Hospital Engativa	Bogotá

Sponsors (5)

Lead Sponsor	Collaborator
Universidad Nacional de Colombia	Instituto Nacional de Salud, Ministerio de Salud y Protección Social de Colombia, Ministry of Health, Labour and Welfare, Japan, National Center for Global Health and Medicine, Japan

Country where clinical trial is conducted

Colombia, 

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* Note: There are 65 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence rate of mpox infection between the immediate versus delayed vaccination groups from day 14 to day 42 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.	6 months post vaccination
Primary	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
Secondary	Frequency of laboratory-confirmed severe cases of MPOX in the immediate and delayed vaccination groups.	Proportion of participants with confirmed MPOX that presented severe symptoms requiring hospitalization, emergency department care, or death associated with MPOX.	6 months post-vaccination
Secondary	Incidence rate of mpox suspected cases without laboratory confirmation between the immediate versus delayed vaccination groups from day 14 to day 42 post-vaccination of the immediate group.	Mpox suspected cases correspond to participants that present with skin lesions to the emergency room or treating patient.	up to 6 months post vaccination
Secondary	Proportion of patients with seroconversion of geometric mean neutralizing titer (GMT) of LC16m8.	Seroconversion is considered in cases where the titer on day 30 is 4 times higher than on day 0.	up to 6 months post vaccination
Secondary	Geometric mean of LC16m8 neutralizing titer by vaccination group.	overall geometric mean of each group (immediate and delayed vaccination)	up to 6 months post vaccination
Secondary	Geometric mean of LC16m8 neutralizing titer by helper T lymphocytes (CD4) count in each vaccination group	Subgroups of patients with a CD4 count of 350 or less and those with a CD4 count greater than 350 will be compared for each vaccination group.	up to 6 months post vaccination
Secondary	Maximum lesion area (MLA) in mm² after scarification with vaccination LC16m8	take area measured 14 days post vaccination	up to 6 months post vaccination