A Phase 3 Safety, Immunogenicity, and Lot-Consistency Trial of the VLP-Based Chikungunya Vaccine PXVX0317 in Healthy Adults and Adolescents
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 3,258
- 试验地点
- 83
- 主要终点
- Incidence of Solicited Adverse Events (AE)
研究概览
简要总结
The goal of this multi-center, randomized, double blind, placebo controlled study is to evaluate the safety and immunogenicity of PXVX0317 in healthy adult and adolescent subjects.
详细描述
Coprimary Objectives:
- To evaluate the safety of PXVX0317 in healthy adult and adolescent participants 12 to <65 years of age.
- To compare the anti-CHIKV serum neutralizing antibody (SNA) response to PXVX0317 and placebo at Day 22, as measured by geometric mean titer (GMT) and clinically relevant difference in seroresponse rate.
- To demonstrate the consistency of the anti-CHIKV SNA response across three lots of PXVX0317 at Day 22.
Secondary Objectives:
- To compare the anti-CHIKV SNA response to PXVX0317 and placebo at Day 15, Day 183, and Day 8 as measured by GMT and seroresponse rate.
- To compare the GMT fold increase in anti-CHIKV SNA response and number and percentage of participants with an anti-CHIKV SNA titer >=15 and 4-fold rise over baseline, both at Day 8, 15, 22, and 183.
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
- 12 Years 至 64 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Able and willing to provide informed consent (and assent, as applicable) voluntarily signed by participant (and guardian, as applicable).
- •Males or females, 12 to <65 years of age.
- •Generally healthy, in the opinion of the investigator, based on medical history, physical examination, and screening laboratory assessments.
- •Women who are either: (i) Not of childbearing potential (CBP): pre-menarche, surgically sterile (at least six weeks post bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or postmenopausal (defined as a history of ≥12 consecutive months without menses prior to randomization in the absence of other pathologic or physiologic causes, following cessation of exogenous sex-hormonal treatment) or (ii) Meeting all the below criteria: Negative serum pregnancy test at screening visit, Negative urine pregnancy test immediately prior to dosing at Day 1, Using an acceptable method of contraception (if women of CBP) for the duration of participation, such as hormonal contraceptives (eg, implants, pills, patches) initiated ≥30 days prior to dosing, intrauterine device (IUD) inserted ≥30 days prior to dosing, double barrier type of birth control (male condom with female diaphragm, male condom with cervical cap), Abstinence is acceptable only for adolescents (12 to <18 years old) who are not sexually active.
排除标准
- •Currently pregnant, breastfeeding, or planning to become pregnant during the study.
- •Body Mass Index (BMI) ≥35 kg/m
- •Positive laboratory evidence of current infection with human immunodeficiency virus (HIV-1, HIV-2), hepatitis C virus (HCV) or hepatitis B virus (HBV).
- •History of severe allergic reaction or anaphylaxis to any component of the vaccine.
- •History of any known congenital or acquired immunodeficiency that could impact response to vaccination (eg, leukemia, lymphoma, generalized malignancy, functional or anatomic asplenia, alcoholic cirrhosis).
- •Prior receipt or anticipated use of systemic immunomodulatory or immunosuppressive medications from six months prior to screening through Day
- •Note: For systemic corticosteroids, use at a dose or equivalent dose of 20 mg of prednisone daily for 14 days or more within three months of screening through Day 22 is exclusionary. The use of inhaled, intranasal, topical, ocular, or intraocular steroids is allowed.
- •Receipt or anticipated receipt of blood or blood-derived products from 90 days prior to screening through Day
- •Acute disease within the last 14 days (participants with an acute mild febrile illness can be considered for a deferral of vaccination two weeks after the illness has resolved and treatment has been completed).
- •Clinically significant cardiac, pulmonary, rheumatologic, or other chronic disease, in the opinion of the investigator. This may include chronic illness requiring hospitalization in the last 30 days prior to screening.
- •Enrollment in an interventional study and/or receipt of another investigational product from 30 days prior to screening through the duration of study participation.
- •Receipt or anticipated receipt of any vaccine from 30 days prior to Day 1 through Day
- •Evidence of substance abuse that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study.
- •Prior receipt of an investigational CHIKV vaccine/product.
- •Any other medical condition that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study.
结局指标
主要结局
Incidence of Solicited Adverse Events (AE)
时间窗: 7 days post-vaccination
Incidence of solicited AEs through Day 8 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).
Incidence of Adverse Events of Special Interest (AESI)
时间窗: 182 days post-vaccination
Incidence of AESIs, through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).
Incidence of Serious Adverse Event (SAE)
时间窗: 182 days post-vaccination
Incidence of SAEs through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (Data Reported Per Arm - Adults 18 to <46)
时间窗: 21 days post-vaccination
Anti-CHIKV SNA GMTs and associated 95% CIs for PXVX0317 (CHIKV VLP vaccine) and placebo in adults 18 to \<46 years of age in the IEP at Day 22.
Incidence of Unsolicited AEs
时间窗: 28 days post-vaccination
Incidence of unsolicited AEs through Day 29 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).
Incidence of Medically Attended Adverse Event (MAAE)
时间窗: 182 days post-vaccination
Incidence of MAAEs through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).
Anti-CHIKV Serum Neutralizing Antibody (SNA) Seroresponse Rates at Day 22
时间窗: 21 days post-vaccination
Anti-CHIKV SNA seroresponse rates for PXVX0317 (CHIKV VLP vaccine) and placebo, difference (PXVX0317 minus placebo), and associated 95% confidence interval (CI) at Day 22 for the immunogenicity evaluable population (IEP), all age strata combined.
Anti-CHIKV Serum Neutralizing Antibody (SNA) Seroresponse Rates at Day 22 (Data Reported Per Arm)
时间窗: 21 days post-vaccination
Anti-CHIKV SNA seroresponse rates and associated 95% confidence interval for PXVX0317 (CHIKV VLP vaccine) and placebo at Day 22 for the immunogenicity evaluable population (IEP), all age strata combined.
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22
时间窗: 21 days post-vaccination
Anti-CHIKV SNA GMTs and associated 95% CIs at Day 22 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined.
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (Data Reported Per Arm - All Age Strata)
时间窗: 21 days post-vaccination
Anti-CHIKV SNA GMTs and associated 95% CIs at Day 22 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined.
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (for Lot Comparison)
时间窗: 21 days post-vaccination
Anti-CHIKV SNA GMTs and associated 95% CIs between all three pairs of PXVX0317 (CHIKV VLP vaccine) lots (104:105, 104:106, 105:106) in adults 18 to \<46 years of age in the IEP at Day 22. Placebo group 4 is not relevant for this lot-to-lot consistency analysis. Reported GMT estimates and 95% CIs are derived from an ANOVA model that includes site and product lot as fixed effects assuming normality of log titers.
次要结局
- Anti-CHIKV SNA Seroresponse Rates at Days 15, 183, and 8(Day 15, 183, and 8 (14, 182, and 7 days post-vaccination, respectively))
- Anti-CHIKV SNA Seroresponse Rates at Days 15, 183, and 8 (Data Reported Per Arm)(Day 15, 183, and 8 (14, 182, and 7 days post-vaccination, respectively))
- Anti-CHIKV SNA Geometric Mean Titers (GMTs) at Days 8, 15, and 183(Day 8, 15, and 183 (7, 14, and 182 days post-vaccination, respectively))
- Anti-CHIKV SNA Geometric Mean Titers (GMTs) at Days 8, 15, and 183 (Data Reported Per Arm)(Day 8, 15, and 183 (7, 14, and 182 days post-vaccination, respectively))
- Geometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titers From Day 1 to Days 8, 15, 22, and 183(Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively))
- Geometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titers From Day 1 to Days 8, 15, 22, and 183 (Data Reported Per Arm)(Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively))
- Number and Percentage of Participants With Anti-CHIKV SNA Titer ≥15 and 4-fold Rise Over Baseline at Days 8, 15, 22, and 183(Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively))
- Number and Percentage of Participants With Anti-CHIKV SNA Titer ≥15 and 4-fold Rise Over Baseline at Days 8, 15, 22, and 183 (Data Reported Per Arm)(Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively))