A Multicenter, Randomized, Placebo-Controlled, Double-Blinded Pivotal Study To Evaluate Safety And Immunogenicity Of A Live-Attenuated Chikungunya Virus Vaccine Candidate In Adults Aged 18 Years And Above
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 4,128
- 试验地点
- 66
- 主要终点
- Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination
研究概览
简要总结
This was a prospective, randomized, double-blinded, multicenter, pivotal clinical study evaluating the final dose of VLA1553 (1 x10E4 TCID50 per dose) in comparison to a placebo control. The final dose of VLA1553 or control was administered as single immunization on Day 1. Overall, 4.128 male and female subjects aged 18 years and above were randomized into the study.
详细描述
This was a prospective, double-blinded, multicenter, randomized, pivotal Phase 3 study and 4.128 participants aged 18 years or above were randomized in a 3:1 ratio to the live-attenuated CHIKV vaccine candidate (VLA1553) or placebo. The final dose of lyophilized VLA1553 or placebo was administered as a single intramuscular immunization. Subjects in this study were stratified into two age strata of 18 to 64 years and 65 years of age or above. The primary objective of the study was to evaluate the immunogenicity and safety of the final dose of VLA1553 28 days following the single immunization. Immunogenicity evaluations in the immunogenicity subset included the proportion of subjects with seroprotective neutralizing CHIKV antibody titers above a surrogate threshold indicative of protection. The surrogate of protection reasonably likely to predict clinical benefit has been established in non-human primate passive transfer studies using human sera from the Phase 1 study and was supported by sero-epidemiological studies. Safety data collection and immunogenicity were assessed until Month 6.
The first enrolled and randomized 501 subjects comprised the immunogenicity subset.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 years of age or above on the Day of screening
- •able to provide informed consent
- •generally healthy as determined by the Investigator's clinical judgement based on medical history, physical examination and screening laboratory tests
- •for women of childbearing potential:
- •practiced an adequate method of contraception during 30 days before screening
- •negative serum or urine pregnancy test at screening
- •agreed to employ adequate birth control measures for the first three months post-vaccination.
排除标准
- •CHIKV infection in the past, including suspected CHIKV infection; was taking medication or other treatment for unresolved symptoms attributed to a previous CHIKV infection; or had participated in a clinical study involving an investigational CHIKV vaccine
- •acute or recent infection
- •Subject tested positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV);
- •live virus vaccine within 28 days or inactivated vaccine within 14 days prior to vaccination in this study or planned to receive a vaccine within 28 days or 14 days after vaccination, respectively
- •abnormal findings in any required study investigations (including medical history, physical examination, and clinical laboratory) considered clinically relevant by the Investigator which pose a risk for participation in the study
- •medical history of or currently had acute or progressive, unstable or uncontrolled clinical conditions that posed a risk for participation in the study
- •history of immune-mediated or clinically relevant arthritis / arthralgia
- •history of malignancy in the past 5 years other than squamous cell or basal cell skin cancer. If there had been surgical excision or treatment more than 5 years ago that was considered to have achieved a cure, the subject could be enrolled.
- •known or suspected defect of the immune system, such as subjects with congenital or acquired immunodeficiency, including infection with HIV, status post organ transplantation or immuno-suppressive therapy within 4 weeks prior to vaccination.
- •history of any vaccine related contraindicating event (e.g., anaphylaxis, allergy to components of the candidate vaccine, other known contraindications)
- •with clinical conditions representing a contraindication to intramuscular vaccination and blood draws
- •pregnant or lactating at the time of enrollment
- •Donation of blood, blood fractions or plasma within 30 days or received blood-derived products (e.g. plasma) within 90 days prior to vaccination in this study or planned to donate blood or used blood products until Day 180 of the study
- •rash, dermatological condition or tattoos that would, in the opinion of the Investigator, interfere with injection site reaction rating
- •known or suspected problem with alcohol or drug abuse as determined by the Investigator
- •any condition that, in the opinion of the Investigator, could compromise the subjects well-being, interfere with evaluation of study endpoints, or would limit the subject's ability to complete the study;
- •committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities)
- •Participation in another clinical study involving an investigational medicinal product (IMP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving an IMP, or device during the course of this study
- •member of the team conducting the study or in a dependent relationship with one of the study team members. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of the Investigator or site personnel conducting the study.
结局指标
主要结局
Number of Participants With a Seroprotective CHIKV Antibody Level for Baseline Negative Subjects 28 Days Post-vaccination
时间窗: on Day 29 after single vaccination
Seroprotection rate, based on a surrogate of protection agreed with FDA Assay used for analysis was based on µPRNT (Micro Plaque Reduction Neutralization Test). Participants at pre-selected sites were included, if they had available Day 1 and Day 29 samples and without major protocol deviations that could impact the immune response.
次要结局
- Number of Participants With Seroprotective CHIKV Antibody Level(Until Day 180)
- Number of Participants Reaching an X-fold Change in CHICKV-specific Neutralizing Antibody Titer Compared to Baseline(until Day 180)
- Unsolicited AEs(Until Day 29)
- Related Adverse Event of Special Interest(within 21 days post-vaccination)
- CHIKV-specific Neutralizing Antibody Titers(Until Day 180)
- Number of Participants With Seroconversion(Until Day 180)
- Fold "Change" of CHIKV-specific Neutralizing Antibody Titers Compared to Baseline(until Day 180)
- Solicited Injection Site AEs(within 10 days post-vaccination)
- Solicited Systemic AEs(within 10 days post-vaccination)
- Adverse Events(until Day 180)
- Serious Adverse Event(until Day 180)
- Adverse Event of Special Interest(within 21 days post-vaccination)
- Related Adverse Events(until Day 180)
- Related Serious Adverse Event(until Day 180)