Early Clinical Development of a Live, Attenuated Combination Vaccine Against Shigella and ETEC Diarrhoea: Phase 1b Clinical Trial of ShigETEC Vaccine in Bangladeshi Adults and Three Paediatric Age Groups
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 196
- 试验地点
- 1
- 主要终点
- Reactogenicity
研究概览
简要总结
The goal of this clinical trial is to test ShigETEC vaccine, a combination vaccine against Shigella and ETEC diarrhoea in Bangladeshi adults (aged 18-45 years) and paediatric participants of three different age groups (aged 2-5 years, 12-23 months and 6-11 months).
The main question[s] it aims to answer are:
- Safety and clinical tolerability of the vaccine
- Immune responses generated by the vaccine In the age-descending dose-escalating study
- Adult participants will be divided into 2 escalating dose cohorts
- Each age group of paediatric participants will be divided into 3 escalating dose cohorts
- Participants in each cohort will receive three doses of vaccine/placebo two weeks apart
- Solicited and unsolicited adverse events (AE) and serious adverse events (SAE) will be monitored after each vaccination dose
- Stool samples will be collected for immunological analysis and shedding of vaccine strain
- Blood samples will be collected for immunological analysis
详细描述
A double-blind, randomized, placebo-controlled, age-descending and dose-escalating phase 1b clinical trial will be carried out in Bangladeshi adults and three paediatric age groups to evaluate the safety, clinical tolerance, and immunogenicity of ShigETEC, a live, attenuated Shigella/ETEC combination vaccine.
Objectives of the study
Primary Objectives:
To evaluate the safety and clinical tolerability of oral ShigETEC vaccine in Bangladeshi adults and different age groups of paediatric participants by monitoring the occurrence and severity of clinical signs and symptoms after administration of each of the three vaccinations.
Secondary Objectives:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Quadruple
入排标准
- 年龄范围
- 6 Months 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female adults, children, toddlers, and infants aged between 18-45 years, 2-5 years, 12-23 months, and 6-11 months, respectively at the time of vaccination.
- •Free of obvious health problems as determined by medical history and clinical examination before entering into the study.
- •Normal bowel habits.
- •Informed consent form signed.
- •Negative pregnancy tests before each vaccination for females of childbearing potential. Adult participants agree to use birth control steps or abstinence.
排除标准
- •Nursing and breast-feeding women.
- •Presence of any known significant medical or psychiatric condition / systemic disorder.
- •History of congenital abdominal disorders, intussusception, abdominal surgery, any other congenital disorder, any neurologic disorders or seizures.
- •Clinically significant abnormalities in screening hematology, serum chemistry.
- •Known or suspected HIV, hepatitis infection.
- •Clinical evidence of active gastrointestinal illness or acute disease at the time of enrolment.
- •Prior receipt of any Shigella or ETEC vaccine, blood transfusion or blood products.
- •History of febrile illness within 48 hours prior to vaccination or fever at the time of immunization.
- •History of diarrhoea within 7 days and / or acute diarrhoea due to culture confirmed Shigella or ETEC infections within one month prior to vaccination.
- •Screening stool positive for any Shigella or ETEC strain by culture.
- •Participation in research involving another investigational product within 30 days before before planned date of first vaccination concurrent participation in another clinical trial.
- •Receipt of antimicrobial drugs for any reason within 7 days before vaccination.
- •Allergy to quinolone, sulfa, and penicillin classes of antibiotics
- •Any conditions which, in the opinion of the investigator, might jeopardize the safety of study participants or interfere with the evaluation of the study objectives.
研究组 & 干预措施
ShigETEC vaccine
The vaccine will consist of a suspension of a live, attenuated Shigella bacterial strain (a clinical isolate of Shigella flexneri 2457T strain) into which the genes for nontoxic forms of the ETEC heatlabile toxin B subunit (LTB) and a mutant heat stable toxin (STm) have been inserted.
干预措施: ShigETEC live, attenuated, oral vaccine (Biological)
Placebo
A saline solution with corn starch
干预措施: Placebo (Other)
结局指标
主要结局
Reactogenicity
时间窗: 72 hours after vaccination
Solicited adverse events in participants after vaccination. ShigETEC vaccine may result in symptoms similar to infection with Shigella or ETEC including fever, decreased appetite, irritability, decreased activity, abdominal pain, nausea, vomiting, loose stool, diarrhoea, dysentery, bloating, excess flatulence and constipation.
Serious adverse event (SAE)
时间窗: From first vaccination throughout 56 days
Adverse event(s) classified as serious per definition.
Unsolicited adverse event (AE)
时间窗: From first vaccination throughout 56 days
Any untoward medical occurrence in study participants during the conduct of a clinical trial, for which there is no or less possibility that the drug caused the event.
次要结局
- Functional antibodies induced by ShigETEC- neutralization(From the day of first vaccination throughout 56 days in a 14 day interval)
- Functional antibodies induced by ShigETEC - SBA(From the day of first vaccination throughout 56 days in a 14 day interval)
- Characterization of the antibody repertoire induced by ShigETEC(From the day of first vaccination throughout 56 days in a 14 day interval)
- Antibody avidity induced by ShigETEC(From the day of first vaccination throughout 56 days in a 14 day interval)
- Shedding of vaccine in stool(From the day of first vaccination throughout 56 days)
- Functional antibodies induced by ShigETEC - adherence(From the day of first vaccination throughout 56 days in a 14 day interval)
- Antigen-specific Antibody titers induced by ShigETEC(From the day of first vaccination throughout 56 days in a 14 day interval)