A Phase III, Randomized, Comparator-Controlled, Double-Blind, Multicenter Study to Evaluate the Immunogenicity, Safety and Lot to Lot Consistency of Three Lots of a PIKA Rabies Vaccine（Vero Cell）for Human Use,Freeze-dried in Healthy Adults Using a Post-Exposure Prophylaxis Schedule
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 4,500
- 试验地点
- 8
- 主要终点
- Co-primary Safety(solicited AEs)
研究概览
简要总结
This is a phase III, randomized, comparator-controlled, double-blind, multicenter study to evaluate lot-to-lot consistency of three lots of a PIKA Rabies Vaccine, immunogenicity and safety in healthy adults using a post-exposure prophylaxis schedule. It is also the aim of this study to evaluate non-inferiority and superiority of the PIKA Rabies Vaccine compared to the rabies vaccine comparator ChiroRab.
详细描述
This is a phase III, randomized, comparator-controlled, double-blind, multicenter study to evaluate lot-to-lot consistency of three lots of a PIKA Rabies Vaccine, immunogenicity and safety in healthy adults using a post-exposure prophylaxis schedule. It is also the aim of this study to evaluate non-inferiority and superiority of the PIKA Rabies Vaccine compared to the rabies vaccine comparator ChiroRab.
A total of 4,500 subjects will be enrolled in the study randomized into 2:1 with 3000 subjects allocated to PIKA rabies vaccine and 1,500 allocated to receive the comparator rabies vaccine ChiroRab . There will be two study Groups: Group 1 (20%) and Group 2 (80%).
Within each study group, subjects will be randomly allocated in a 2:2:2:3 ratios to receive 1 of the 3 lots of PIKA rabies vaccine or ChiroRab. The ChiroRab group will receive the classic Essen 5 dose regimen (1-1-1-1-1 schedule on Days 0, 3, 7, 14 and 28), whilst the PIKA rabies vaccine group will receive an accelerated regimen (2-2-1 schedule with a double-dose injection on Days 0 and 3 and a single-dose injection on Day 7). For blinding purposes, normal saline will be injected on Days 14 and 28 for PIKA rabies group and Days 0 and 3 for ChiroRab group.
Group 1 will enrol a total of 900 subjects, approximately 20% of the total sample population. Subjects will be randomized at 2:2:2:3 ratio (PIKA lot #1: 200 subjects, PIKA lot #2: 200 subjects, PIKA lot #3: 200 and 300 will be randomized to receive ChiroRab). Blood will be collected pre-vaccination (Day 0) and post-vaccination on Days 7, 14, 28, 90, 180 and 365 to evaluate the primary immunogenicity, safety and secondary immunogenicity endpoints. Subjects will be followed up for the whole study period through clinic visits or phone calls.
The first 50 participants randomized in each of the 3 PIKA lots and that for the ChiroRab in Goup 1 (200 in total) will form the safety subset and will have additional blood draw for safety laboratory parameters for CBC platelet, urinalysis, serum chemistry and coagulation on Day 0 (prior to vaccination), Day 7 and Day 28.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Has completed the written informed consent process.
- •For Singapore sites: age ≥21 and ≤ 65 years on Study Day 0; for other country sites: age ≥18 and ≤ 65 years on Screening.
- •Healthy males and females.
- •No history of rabies exposure, administration of rabies vaccination or rabies immunoglobulin.
- •Agree to refrain from blood donation during the course of the study.
- •Be able to commit to the vaccine schedule strictly.
- •Has the ability and commitment to comply with requirements of the study, such as completion of diary cards, return for follow-up visits, accessible by phone and reside within the study area for the duration of study.
- •For female subjects: agree to avoid pregnancy from Study Day 0 to Study Day 90 during the course of the study. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the combination of a condom or diaphragm with spermicide.
排除标准
- •Pregnant and nursing female volunteers will be excluded from the study.
- •Previous exposure to a suspect rabid animal within the last 12 months.
- •Any subject who needs post-exposure prophylaxis against rabies.
- •History of rabies infection or treatment (immunoglobulin or vaccine).
- •History of previous rabies vaccination.
- •History of hypersensitivity reaction to human immunoglobulin.
- •Received any vaccine in the past 30 days before randomization except for COVID 19 and flu vaccination.
- •Received immunoglobulin or blood products within 90 days before randomization or plans to receive such products at any time during active period of the study (through Day 90).
- •Received any investigational therapy (including vaccine) within 90 days before randomization, or planned participation in any other investigational study during the active study period (through Day 90).
- •Used immunosuppressant medications in the past 180 days (defined as more than 14 continuous days before randomization or plans to receive any products during the active vaccination period (through Day 28). An immunosuppressant dose of a glucocorticoid will be defined as a systemic dose of ≥10mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted).
- •At high risk for rabies infection during the trial: (such as veterinarians and their staff, animal handlers, rabies researchers, and certain laboratory workers, persons whose activities bring them into frequent contact with rabies virus or potentially rabid bats, raccoons, skunks, cats, dogs, or other species at risk for having rabies, people travelling where rabies is enzootic, previous bite by a rabid animal with no post-exposure treatment administered).
- •History of HBV or HCV infection.
- •History of any past, present, or future possible immunodeficiency state including but not limited to any laboratory indication of HIV-1 infection.
- •History of treatment for depression or mental illness in the past 5 years; history of any attempt of suicide.
- •Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating IM vaccination based on Investigator's judgment.
- •Donation of blood within the last 2 months or who have donated plasma within the last 14 days before Study Day
- •Clinical signs of encephalitis.
- •History or evidence on physical examination of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
- •History of neurological disorder, either congenital or acquired (e.g. seizures, meningitis, encephalitis, Guillain-Barre syndrome, dementia, vasculitis, hereditary CNS disorders).
- •History of cancer (malignancy) in the past 10 years (exception is non-melanomatous skin CA).
- •A history of alcohol or drug addiction in the past 2 years.
- •History of hypersensitivity or serious reactions (eg. anaphylaxis, urticarial, other significant reaction) to previous vaccinations.
- •Plans to permanently move from the catchment area during trial conduct.
- •Concerns of compliance with protocol or social condition that makes the subject a poor candidate for the trial as determined by the PI.
结局指标
主要结局
Co-primary Safety(solicited AEs)
时间窗: 7 days after each vaccination.
Incidence of solicited local and systemic reactions on the day of each study vaccination
Co-primary Safety(unsolicited AEs)
时间窗: From day of first vaccination through 14 days after the last vaccination
Incidence of unsolicited adverse events
Co-primary Safety(SAEs)
时间窗: through study completion, an average of 1 year
Incidence of serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), adverse events of special interest (AESIs) and AEs leading to withdrawal
Co-primary Safety
时间窗: through study completion, an average of 1 year
Incidence of significant changes in the clinical laboratory test results, vital signs and physical examination by study visits.
Primary Immunogenicity
时间窗: 14 days post-vaccination
GMTs of rabies virus neutralizing antibodies (RVNA) at Day 14 to demonstrate lot-to-lot consistency in all subjects enrolled in Group 1
次要结局
- Secondary Immunogenicity(Day 90 and 180 for Group 1 only and Day 365 for all subjects (Group 1 and Group 2))