Randomised, Double-blind, Placebo Controlled Phase II, Dose-ranging Study of the Safety, Tolerability and Immunogenicity of Live Attenuated ChimeriVax™-JE Vaccine (Lyophilised)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 128
- 试验地点
- 2
- 主要终点
- Number of Participants Who Seroconverted to the Respective Homologous JE Vaccine Strain, 28 Days After Completion of the Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or A Placebo
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, and immunogenicity of a new formulation of lyophilised ChimeriVax™-JE, given at three dose levels, compared with placebo.
Primary Objectives:
Safety:
- To obtain safety and tolerability data for a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels, in healthy adult volunteers (18-49 years old).
Immunogenicity:
- To obtain data on the antibody response to a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels, in healthy adult volunteers without prior Japanese encephalitis immunity.
- To assess the durability of immune response up to 12 months following a single subcutaneous vaccination with ChimeriVax™-JE, at three dose levels.
详细描述
All participants will received a single dose of study vaccine, ChimeriVax™-JE or placebo on Day 0. The double-blind treatment phase will last 30 days, with follow-up visits at 6 and 12 months.
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 48 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All aspects of the protocol explained and written informed consent obtained from the participant.
- •Aged ≥18 to < 49 years.
- •In good general health, without significant medical history, physical examination findings, or clinically significant abnormal laboratory results.
- •Participant must be available for the study duration, including all planned follow-up visits.
- •Participant must agree to take the following precautions to avoid insect bites for 7 days following vaccination by using N,N-diethyl-meta-toluamide (DEET)-containing insect repellent, where appropriate.
- •For female participants: Negative pregnancy tests at Screening and Day 0, in conjunction with a menstrual and contraceptive history indicating a low probability of pregnancy in the opinion of the physician. Females of childbearing potential will be required to be correctly using an efficacious hormonal method of contraception or intrauterine device for at least 1 month before randomisation and during the on-study phase to Day
- •Barrier methods of contraception will not be considered acceptable for study entry. Female participants of child-bearing potential will sign an agreement that contraception will be correctly practised during the specified periods and will specify the method used. Female participants unable to become pregnant must have this documented (e.g., tubal ligation, hysterectomy or postmenopausal [at least one year since last menstrual period]).
排除标准
- •A history of vaccination or infection to Japanese encephalitis (JE) or yellow fever (YF) or other flaviviruses (including Japanese encephalitis, tick-borne encephalitis, St Louis encephalitis, West Nile virus, dengue fever, Murray Valley encephalitis). Previous vaccination will be determined by history (interview of subject).
- •Previous or current military service.
- •History of residence in or travel to flavivirus endemic areas in the tropics (Cape York region of Northern Queensland, India, Southeast Asia, Central America, Caribbean or South America) for periods of 4 weeks or more.
- •Known or suspected immunodeficiency (e.g., human immunodeficiency virus [HIV] infection, primary immunodeficiency disorder, leukemia, lymphoma), use of immunosuppressive or antineoplastic drugs (corticosteroids > 10 mg prednisone, or equivalent, in the last three months or during the trial (up to Day 30).
- •History of thymoma, thymic surgery (removal) or myasthenia gravis.
- •Clinically significant abnormalities on laboratory assessment (i.e., meeting the mild, moderate or severe criteria described in the toxicity gradings for laboratory values).
- •Anaphylaxis or other serious adverse reactions characterised by urticaria or angioedema to foods, hymenoptera (bee family) stings, or drugs (including vaccines).
- •Transfusion of blood or treatment with any blood product, including intramuscular or intravenous serum globulin within six months of the Screening Visit or up to Day
- •Administration of another vaccine or antiviral within 30 days preceding the screening visit or up to Day 30 (these subjects will be rescheduled for vaccination at a later date).
- •Physical examination indicating any clinically significant medical condition.
- •Body temperature > 38.1°C (100.6°F) or acute illness within 3 days prior to inoculation (participant may be rescheduled).
- •Intention to travel out of the area prior to the study visit on Day
- •Seropositive to hepatitis C virus or HIV or positive for Hepatitis B Surface Antigen.
- •Lactation or intended pregnancy in female subjects.
- •Excessive alcohol consumption, drug abuse, significant psychiatric illness.
- •A known or suspected physiological or structural condition that compromises the integrity of the blood-brain barrier (e.g., significant hypertensive cerebrovascular disease, trauma, ischaemia, infection, inflammation of the brain).
- •Intention to increase normal exercise routine, participate in contact sports or strenuous weight lifting or to initiate vigorous exercise from Screening until after Day 30.
研究组 & 干预措施
Placebo
Participants received ChimeriVax diluent, 0.5 mL on Day 0.
干预措施: ChimeriVax™ diluent (Placebo) (Biological)
ChimeriVax™-JE Dose Level 1
Participants received ChimeriVax™-JE (Japanese Encephalitis) a dose of 3.0 log10 Plaque-forming units (PFU) on Day 0.
干预措施: Live attenuated Japanese encephalitis virus (Biological)
ChimeriVax™-JE Dose Level 2
Participants received ChimeriVax™-JE a dose of 4.0 log10 PFU on Day 0.
干预措施: Live attenuated Japanese encephalitis virus (Biological)
ChimeriVax™-JE Dose Level 3
Participants received ChimeriVax™-JE a dose of 5.0 log10 PFU on Day 0.
干预措施: Live attenuated Japanese encephalitis virus (Biological)
结局指标
主要结局
Number of Participants Who Seroconverted to the Respective Homologous JE Vaccine Strain, 28 Days After Completion of the Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or A Placebo
时间窗: Day 11 and Day 30 post-vaccination
Antibodies were measured using 50% plaque reduction neutralization test (PRNT50) for measurement of neutralizing antibodies against homologous ChimeriVax™-JE and wild type JE virus strains. Seroconversion was defined as a titer ≥ 1:20 at post vaccination timepoints for subjects who were seronegative at baseline, or ≥ 4 fold rise from baseline.
Number of Participants Who Seroconverted to Wild Type JE Virus Strains After Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or a Placebo
时间窗: Day 30 post-vaccination
Antibodies were measured using 50% plaque reduction neutralization test (PRNT50) for measurement of neutralizing antibodies against homologous ChimeriVax™-JE and wild type JE virus strains. Seroconversion was defined as a titer ≥ 1:20 at post vaccination time points for subjects who were seronegative at baseline, or ≥ 4 fold rise from baseline.
Number of Participants Reporting Solicited Local Injection Site and Treatment Related Adverse Events Post Vaccination With One of 3 Doses of ChimeriVax™-JE Vaccine or Placebo
时间窗: Day 0 (post-vaccination) up to Day 30 post-vaccination
Local Injection Site Adverse Events (AEs): Pain, Erythema, Reaction, Hemorrhage, Induration, Paresthesia. Treatment Related Systemic AEs: Fever, Chills, Malaise, Fatigue, Headache, Myalgia, Arthralgia, Nausea, Vomiting, Diarrhea, Rash. Other AEs as reported spontaneously.
次要结局
- Geometric Mean Titers to Japanese Encephalitis (Homologous Virus) Following Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or a Placebo(Day 11 and Day 30 post-vaccination)
- Geometric Mean Titers to Japanese Encephalitis (Wild Type JE Virus Strains) Following Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or a Placebo(Day 30 post-vaccination)
- Participants With Japanese Encephalitis (Homologous Virus) Seropositivity Over Time Following Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or Placebo(Day 30 up to 12 months post-vaccination)