A Phase 1b, Double-Blind, Randomized, Placebo-Controlled, Antigen Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of LEP-F1 + GLA-SE in Healthy Adult Participants in Areas Endemic for Leprosy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 54
- 试验地点
- 2
- 主要终点
- Phase 1b_The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection.
研究概览
简要总结
This is a phase 1b, double-blind, randomized, placebo-controlled clinical trial to evaluate the safety, tolerability, and immunogenicity of LEP-F1 + GLA-SE compared to placebo administered as three intramuscular (IM) injections in adult participants aged 18 to 55.
详细描述
The LepVax Clinical Development Plan includes two indications for use. The first would be the prophylactic indication, where individuals at greater risk, such as contacts of patients affected by leprosy and who may be subclinically infected with M. leprae, would be vaccinated. This concept is not unique and many countries, such as Brazil, re-immunize leprosy patients and their close contacts with BCG (5, 12, 13). The proposed clinical trial, however, is to establish an initial safety profile in a leprosy endemic region where healthy adults will be included. The second use indication is for therapeutic indication of the vaccine that would be an adjuvant to the current treatment for leprosy. After vaccine safety is established, phase 2 protocols in leprosy patients will be proposed to assess vaccine dose and safety in this population, and then move on to phase 3, where vaccine efficacy will be evaluated.
This phase 1b, double-blind, randomized, placebo-controlled clinical trial will evaluate the safety, tolerability, and immunogenicity of LEP-F1 + GLA-SE in healthy adults. Two dose levels of LEP-F1 will be tested (2 and 10 µg of LEP-F1) and a fixed dose of 5 µg of GLA-SE in adults. These doses were selected because they demonstrated an acceptable safety and immunogenicity profile in the LEPVPX-118 study, the first clinical trial in humans. This study will establish a safety and immunogenicity profile in an endemic population that will allow the vaccine to advance in clinical development.
Participants will be randomized within each Group to receive three doses of vaccine or placebo administered IM on Days 0, 28, and 56. Participants will be monitored for one year following the last study injection, including safety laboratory analyses 7 days following each study injection. Blood samples will be obtained for immunological assays at Days 0, 35, 63, and 168.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind study. Participants, investigators, study personnel performing any study-related assessments following study injection, and laboratory personnel performing immunology assays will be blinded to treatment assignment.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women between 18 and 55 years old.
- •They should be in good general health, confirmed by a medical history and physical examination, with negative clinical evaluation for leprosy.
- •Female subjects of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on study vaccination days (D0, D28, and D56). They must not be breastfeeding and must use at least one method of contraception from the time of study enrollment (Day 0) through 30 days after the last injection if they have sex with men.
- •Screening laboratory tests with normal, within laboratory reference limits for: sodium, potassium, AST, ALT, total bilirubin, alkaline phosphatase, creatinine, glucose, total WBC count, hemoglobin and platelet count. Abnormal results may be repeated at the discretion of the Principal Investigator and/or sub-investigators, who may share doubts with the sponsor's Scientific Leader and if necessary, with the DSMB.
- •Negative serological tests for: HIV 1/2 antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody.
- •Normal or not clinically significant urinalysis as determined by the study doctor or designee. Abnormal results may be repeated at the discretion of the Principal Investigator.
- •Must be able to complete the study adverse events diary.
- •Must consent to participate in the study, be able and willing to make all evaluation visits, be accessible by telephone or home visits, and live in the region until study follow-up completion.
- •Having completed the primary vaccination course for Covid 19, at least 14 days before inclusion in the study. If 14 days have not been completed, the participant may be rescheduled for a new eligibility assessment
排除标准
- •History of infection with Mycobacterium leprae.
- •History of exposure to experimental products containing GLA-SE.
- •History of active tuberculosis or documented recurrence.
- •History of previous infection with other non-tuberculous mycobacteria.
- •Participation in another trial protocol and/or receipt of any trial products in the last 3 months prior to screening.
- •Treatment with immunosuppressive drugs (eg, oral or injectable steroids such as prednisone; high-dose inhaled steroids) or cytotoxic therapies (eg, chemotherapy or radiotherapy) within six months prior to screening.
- •Have received blood transfusion within the last 3 months prior to screening.
- •Donated blood products (platelets, whole blood, plasma, etc.) within the last month prior to screening.
- •Received any vaccine 1 month prior to screening or planned immunizations during the follow-up from D0 to D63 and D154 to D
- •History of autoimmune disease or other immunosuppressive causes.
- •History of any other uncompensated acute or chronic disease (including cardiovascular, pulmonary, neurological, hepatic, rheumatic, hematological, metabolic or renal disease, uncontrolled hypertension) or use of medications that, in the opinion of the Principal Investigator, may interfere with safety or immunogenicity of the vaccine.
- •Rash, tattoos, or any other dermatological condition that may adversely affect the injection site of the vaccine or interfere with its evaluation.
- •Body mass index (BMI) ≥
- •Systemic arterial hypertension (systolic > 150 or diastolic > 95).
- •History of psychiatric illness with current medication use.
- •Alcohol or drug abuse in the last 6 months prior to screening.
- •Chronic smoker (1 pack or more per day).
- •History of previous anaphylaxis or severe allergic reaction to unknown vaccines or allergens.
- •Individuals who do not wish to cooperate with all procedures recommended in the study protocol.
结局指标
主要结局
Phase 1b_The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection.
时间窗: 7 days following each injection
The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection.
Phase 1b_Number of participants experiencing unsolicited AEs
时间窗: Day 0 to Day 84 following each injection
The number of participants spontaneously reporting adverse events from Day 0 to Day 84.
Phase 1b_The number of physician-attended adverse events
时间窗: Through study completion, an average of 1 year
The number of physician-attended adverse events considered to be related to any of the study injections reported at any time during the study period.
次要结局
- Phase 1b_IgG antibody responses to LEP-F1 by ELISA on Days 0, 35, 63,and 168.(Days 0, 35, 63 and 168)
- Phase 1b_ The T cell responses measured by LEP-F1-specific cytokine production in PBMC assay by ELISA or multiplex assay on Days 0, 35, 63,and 168.whole blood assay(Days 0, 35, 63 and 168)