A Phase 1b Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of a Prime-Boost Regimen of Three Dose Levels of PHV02, a Nipah Virus Vaccine Candidate (rVSV-ΔG-EBOV GP-NiVG) in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Percentage of participants with local injection site and systemic adverse events (AEs)
研究概览
简要总结
The goal of this clinical trial is to test the safety and immunogenicity of PHV02 live, attenuated recombinant vesicular stomatitis virus vaccine expressing the Nipah Virus glycoprotein in healthy adult subjects. The main questions it aims to answer are:
- which doses of PHV02 are safe to administer to and well-tolerated by healthy adult subjects as a 2 dose regimen given 1 month apart?
- what is the immunologic response (Nipah-specific IgG ELISA antibody and neutralizing antibodies) to each dose level after a 2-dose regimen given 1 month apart? Participants will receive 2 intramuscular injections of PHV02 (2x105, 2x106, and 2x107 plaque-forming units [pfu]) or placebo on Day 1 and Day 29 and will be followed for 197 days.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy, adult, male or non-pregnant, non-lactating females
- •Given written informed consent
- •No clinically significant health problems
- •Negative test for SARS-CoV-2
- •Agree to avoid conception through Day 57
- •Agree to minimize blood and body fluid exposures to others after vaccination through Day 57
- •Agree to avoid exposure to immunocompromised persons after vaccination through Day 57
- •Agree to avoid employment in industry involved with livestock after vaccination through Day 57
排除标准
- •Prior infection with Nipah virus, related Henipaviruses or Ebola virus
- •Prior infection with vesicular stomatitis virus (VSV)
- •Received VSV-vectored vaccine or Ebola vaccine
- •BMI < 18.5 or ≥ 35
- •Healthcare worker with direct physical contact with patients
- •Childcare worker in direct contact with children 5 years old or younger
- •Household contact who is immunodeficient, or on immunosuppressive medication
- •Hands-on food preparation job
- •Primary care or treatment of cattle, horses, or swine
- •Hepatitis B, hepatitis C, HIV-1, HIV-2, diabetes, atopic dermatitis (eczema), chronic inflammatory disease, autoimmune or autoinflammatory disorder, malignancy, chronic or active neurologic disorder
- •History of severe reactions to any vaccine or history of severe allergies
- •Receipt of investigational product up to 30 days prior to, or planned receipt within 196 days after randomization, or ongoing participation in another interventional clinical trial.
- •Receipt of licensed non-live vaccines within 14 days of planned study immunization (30 days for live vaccines) or planned receipt of non-live or live vaccine within 60 days after first study immunization (30 days after the 2nd vaccination).
- •Known allergy to components of PHV02
- •Injection sites obscured by tattoos or physical condition
- •Significant psychiatric or medical condition or laboratory abnormality on screening
- •History of Guillain Barre Syndrome or any chronic or acute neurological disorder
- •Alcohol or illicit drug abuse within past 5 years
- •Pregnant or lactating female
- •Administration of blood or IgG within 120 days preceding study
- •History of blood donation within 60 days of study
- •Unwilling to undergo diagnostic evaluation of rash (skin biopsy, if indicated) or joint symptoms (arthrocentesis if indicated by joint effusion), in both cases if acceptable to subject
- •Elective surgery planned during the study period
研究组 & 干预措施
Cohort 1 (first 60 subjects) PHV02 high dose
干预措施: PHV02 (Biological)
Cohort 1 (first 60 subjects) PHV02 medium dose
干预措施: PHV02 (Biological)
Cohort 1 (first 60 subjects) PHV02 low dose
干预措施: PHV02 (Biological)
Cohort 1 (first 60 subjects) Placebo
干预措施: Lactated Ringer's (Biological)
Cohort 2 (next 60 subjects) PHV02 high dose
干预措施: PHV02 (Biological)
Cohort 2 (next 60 subjects) PHV02 medium dose
干预措施: PHV02 (Biological)
Cohort 2 (next 60 subjects) PHV02 low dose
干预措施: PHV02 (Biological)
Cohort 2 (next 60 subjects) Placebo
干预措施: Lactated Ringer's (Biological)
结局指标
主要结局
Percentage of participants with local injection site and systemic adverse events (AEs)
时间窗: 14 days after each dose
Percentage of participants with joint related symptoms, rash and unsolicited AEs
时间窗: 28 days after each dose
Percentage of participants with neurologic AEs
时间窗: Study Days 1-57
Percentage of participants with medically-attended AEs (MAAEs) and serious AEs (SAEs)
时间窗: From time of injection through final study visit (Day 197)
Proportion of participants with recombinant vesicular stomatitis virus (rVSV) RNA (Cohort 1 only) in plasma, urine and saliva
时间窗: From time of injection through Day 43
Proportion of participants who seroconvert compared to Day 1
时间窗: Day 29 and Day 57
Geometric mean titers of IgG and ELISA neutralizing antibodies
时间窗: Day 1, 29, 57
次要结局
未报告次要终点