Phase 1 Two Stage Randomized, Double-blind, Placebo Controlled Dose- and Schedule Ranging Trial to Assess the Acute Safety, Tolerability, and Immunogenicity of a Live, Attenuated Shigella/ETEC Combination Vaccine Delivered Orally to Healthy Adults Age 18 to 45 Years Old
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Number and percentage of participants with treatment related acute adverse events post vaccination
研究概览
简要总结
This is a Phase 1 dose escalating study to assess the safety, tolerability, and immunogenicity of ShigETEC, a live, attenuated Shigella/ETEC combination vaccine given orally to healthy European adults 18 to 45 years of age.
The major aim is the development of an efficacious and safe vaccine that prevents diarrhea caused by Shigella and ETEC in travelers, military personal visiting endemic countries and children of the developing world.
This Phase 1 safety and immunogenicity study used a double-blind, placebo-control design and was conducted in two stages, a single ascending and a multiple ascending stage.
详细描述
ShigETEC vaccine is intended to stimulate an immune response in which protective antibodies are generated that prevent infection if a vaccinee is subsequently exposed to Shigella and ETEC.
Main objective of the study:
In Stage 1 is to determine Maximum Tolerated Single Dose of ShigETEC vaccine. Determine optimal immunogenicity of single dose in dose escalation.
In Stage 2 is to determine safety of multiple dose regimens of ShigETEC Determine number of doses for maximum immune response to Shigella and ETEC.
In both stages to determine the duration of shedding.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Generally healthy male and non-pregnant, non-nursing female adults aged 18 to 45 years
- •Who are determined by medical history, physical examination and clinical judgment to be eligible for this study;
- •Who provide written informed consent after the nature of the study had been explained;
- •Who are available for the two to three months duration of follow-up (from enrolment to study completion);
- •Who are available to be interviewed by study staff for the 2-month post-immunization follow-up;
排除标准
- •Subjects who are perceived to be unavailable or difficult to contact for evaluation or study visits during the study period;
- •Who have a known or suspected disease of cancer (excluding healed skin lesions), the immune system, or those who are receiving immunosuppressive therapy, including systemic corticosteroids or cytotoxic agents;
- •Who have received any blood products, including immunoglobulin, in the period from six months prior to vaccination or are anticipated to receive such products through to the conclusion of the study;
- •Who have ever received a cholera vaccine;
- •Who are receiving antibiotics or completed antibiotic therapy in previous 7 days;
- •Who have or are participating in or have concluded participation in a clinical research study in the last 30 days or have not cleared the experimental product or the biological effects of such experimental products prior to vaccination or received a licensed vaccine in the 30 days prior to vaccination;
- •Who have a chronic non-gastrointestinal medical condition (e.g. hypertension, hyperlipidemia) that is not well controlled with medication;
- •Who have a significant history of or current diagnosis of diseases of the gastrointestinal tract (i.e. liver, gallbladder, bowel, or stomach), are on medication for such disease, or have had significant bowel surgery (with the exclusion of hernia repair or appendectomy);
- •Who have significant abnormality of blood chemistry, hematology, or screening tests (including tests for hepatitis B, HIV, HCV);
- •Who have a history of reactive arthritis following GI infection;
- •Who expect to work in the subsequent 2 weeks as a food handler or in direct patient, child day care, or elder care;
- •Who have immunocompromised household member;
- •Who have ever had a diagnosed Shigella or ETEC infection;
- •Who have developed symptoms of Shigella or ETEC infections after having travelled to Shigella or ETEC endemic areas in the past 12 months;
- •Who have any condition which in the opinion of the investigator puts the subject at risk of non-compliance with the protocol;
- •Who have known allergy to quinolone or azithromycin that will be used in the study;
- •Who are HLA-B27 positive (a possible risk factor for reactive arthritis following naturally acquired bacterial gastrointestinal infection).
- •Who are dependent of the Sponsor, of the investigational team or his/her immediate family, or are medical students at the Clinical Trial Study Site in Debrecen.
- •Who are living in community (i.e. students living in a dormitory).
- •Who are positive for CoVID19 infection by PCR testing prior to randomization.
研究组 & 干预措施
ShigETEC vaccine
In Stage 1 subjects will be allocated randomly to one of four study cohorts to receive a single oral dose of one of four escalating dose levels of ShigETEC vaccine (ShigETEC 1x10^9 CFU, ShigETEC 1x10^10 CFU, ShigETEC 5x10^10 CFU, ShigETEC 2x10^11 CFU). 8 subjects per dose group will be administered.
Subjects in Stage 2 will be enrolled sequentially by group and allocated randomly to one of three study cohorts determined from Stage 1 to receive either two, three or four doses of the 5x10^10 ShigETEC vaccine at 3-day interval. 8 subjects per dose group will be administered.
干预措施: ShigETEC live, attenuated, oral vaccine (Biological)
Placebo
In Stage 1: 4 subjects in each dose group will receive a single oral dose of placebo
In Stage 2: 4 subjects in each cohort will either receive 2, 3 or 4 doses of placebo at 3-day intervals.
干预措施: Placebo (Drug)
结局指标
主要结局
Number and percentage of participants with treatment related acute adverse events post vaccination
时间窗: Day 1-6 following each vaccination
Acute gastrointestinal and systemic illness symptoms following immunization(s)- treatment related Adverse events according to CTCAE v4.0 including nausea, vomiting, diarrhoea, abdominal pain, fever, joint ache, muscle/joint aches, fatigue/malaise, headache, loss of appetite.
Number and percentage of participants with any adverse event.
时间窗: until 60 days after the last vaccination (max 110 days in stage 2)
Number and percentage of participants with adverse event according to CTCAE v4.0 occuring during the entire study period
Number and percentage of participants with serious adverse event.
时间窗: until 60 days after the last vaccination (max 110 days in stage 2)
Number and percentage of participants with serious adverse event occurring during the entire study period in stage 2
Number and percentage of participants with Vaccine Shedding
时间窗: 14 days after last immunization
Fecal shedding of vaccine - duration of detectable presence of ShigETEC in stool by polymerase chain reaction (PCR) and/or culture.
Reactogenicity
时间窗: Days 0 to 6
Reactogenicity events accumulated through day 6 for acute safety and tolerability in acute changes in reactogenicity events at a scale (none or mild or moderate or severe) or an absolute value: * Temperature: degrees Celsius (°C) * Nausea: none/mild/moderate/severe * Vomiting: none/mild/moderate/severe * Diarrhea: none/mild/moderate/severe * Number of stools: discrete value * Abdominal pain: none/mild/moderate/severe * Muscle/joint aches: none/mild/moderate/severe * Tiredness/fatigue/malaise: none/mild/moderate/severe * Headache: none/mild/moderate/severe * Loss of appetite: none/mild/moderate/severe * Chills: none/mild/moderate/severe * Difficulty sleeping: none/mild/moderate/severe * Dizziness: none/mild/moderate/severe * Difficulty swallowing: none/mild/moderate/severe
次要结局
- Immunogenicity assessment - serum(Day 0 and days 6, 10, 28, 60 after the last vaccination)
- Immunogenicity assessment - ALS(Day 0 and days 6, 10 after the last vaccination)
- Immunogenicity assessment - stool extract(Day 0 and days 10, 28 after the last vaccination)