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
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 8,686
- 试验地点
- 3
- 主要终点
- Incidence rate of mpox infection between the immediate versus delayed vaccination groups from day 15 to day 56 post-vaccination of the immediate group.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
- •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.
排除标准
- •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/mm
- •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
- •Psychiatric condition that precludes compliance with the protocol.
- •People who received or plan to receive licensed live vaccines 30 days before or after study vaccination.
- •People who received or planned to receive immunoglobulin or other blood products 60 days before HIV screening.
- •People who received or plan to receive experimental drugs/vaccines 30 days before study vaccination or before study completion.
- •People who received or planned to receive systemic immunosuppressive therapy and radiation therapy 30 days before or after the study vaccination.
- •Use of systemic chemotherapy within five years before the study vaccination.
- •Medical record of smallpox vaccination and/or evidence of scarring at the vaccination site.
- •Allergies to streptomycin sulfate and/or erythromycin lactobionate.
研究组 & 干预措施
Immediate vaccination
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.
干预措施: LC16m8 (Biological)
Delayed vaccination
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.
干预措施: LC16m8 (Biological)
结局指标
主要结局
Incidence rate of mpox infection between the immediate versus delayed vaccination groups from day 15 to day 56 post-vaccination of the immediate group.
时间窗: 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)
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.
Incidence of adverse events between the vaccination groups
时间窗: up to 6 months post vaccination
Proportion of adverse events (serious and non-serious) presented in participants included in the two vaccination groups (immediate and delayed)
Incidence rate of mpox infection between the vaccinated cohort versus the unvaccinated cohort
时间窗: 6 months post vaccination
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.
次要结局
- 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)
- Maximum lesion area (MLA) in mm² after scarification with vaccination LC16m8(up to 6 months post vaccination)