Safety and Efficacy Study of a Vaccine Against Enterotoxigenic Escherichia Coli (ETEC) to Prevent Moderate to Severe Diarrhea
2011年3月4日 更新者:TD Vaccines A/S
Development of a Polyvalent Vaccine Against Enterotoxigenic Escherichia Coli (ETEC)Protective Efficacy of the Deletion-Attenuated, Multi-valent ACE527 Against Challenge With a Prototype Strain of Enterotoxigenic E.Coli Expressing LT and ST Enterotoxins and CFA/I (Strain H10407) in Human Challenge Model.
This is a research study about an experimental (investigational) vaccine called ACE527.
ACE527 is a vaccine that is being made to prevent disease from a germ called enterotoxigenic Escherichia coli (ETEC).
This germ causes diarrhea, largely in children living in developing countries and in travelers to those countries.
One purpose of this study is to see if the vaccine is safe and develops an immune response.
Another purpose is to see if it prevents people from getting sick when exposed to the ETEC germ.
This ETEC germ is also experimental (investigational).
研究概览
详细说明
This is a single-center, double-blind, placebo-controlled, Phase II vaccination and challenge study designed to assess the protective efficacy of the ACE 527 vaccine, as well as collect expanded safety and immunogenicity data.
The study will be carried out in two phases.
In the initial vaccination phase, up to 72 subjects will be randomized 1:1 to receive either ACE527 or placebo on an outpatient basis.
Vaccine and placebo preparations will be given orally.
Following vaccination, subjects will be followed as out-patients for safety using diary card surveillance, for vaccine shedding by qualitative stool culture (i.e.
presence or absence) and for the development of local and systemic antibody responses to the ACE527 vaccine strains.
In the subsequent inpatient challenge phase, up to 56 vaccinated subjects will be admitted as inpatients and challenged with the ETEC strain, H10407.
The challenge dose will be administered orally.After challenge, subjects will be monitored for diarrhea and other signs/symptoms of enteric illness by daily medical checks, vital sign determinations, grading and weighing of all stools.
Monitoring for fecal shedding of the challenge ETEC strain H10407 will occur daily, after challenge, while in-patient.
Local and systemic antibody responses to the challenge ETEC strain H10407 will also be assessed.
All subjects will be treated with Abx.
研究类型
介入性
注册 (实际的)
70
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
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Maryland
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Baltimore、Maryland、美国、21205
- Center for Immunization Research (CIR)
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 50年 (成人)
接受健康志愿者
是的
有资格学习的性别
全部
描述
Inclusion criteria:
- Male or female age ≥18 and ≤ 50 years.
- General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
- Negative serum pregnancy test before first (visit V0) and before challenge (visit C0) for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female subjects unable to bear children must have this documented (e.g. tubal ligation or hysterectomy) or must have negative pregnancy tests.
- Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
- Completion of a training session and demonstrated comprehension of the protocol procedures, knowledge of ETEC-associated illness, and by passing a written examination.
- Availability for the study duration, including all planned follow-up visits.
Exclusion criteria:
- Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study. Some medical conditions which are adequately treated and stable would not preclude entry into the study. These conditions might include stable asthma controlled with inhalers or mild hypertension stably controlled with a single agent.
- Significant abnormalities in screening hematology, serum chemistry or urinalysis as determined by PI or PI in consultation with the MM and sponsor.
- Presence in the serum of HIV antibody, HBsAg, or HCV antibody.
- Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay).
- Evidence of current excessive alcohol consumption or drug dependence.
- Evidence of impaired immune function.
- BMI <19, >34
- Recent vaccination or receipt of an investigational product (within 30 days before vaccination).
- Intention to donate blood or blood products for one month following the completion of study participation (note: The Red Cross will not allow blood donations for 1 year following participation in an investigational research study).
- Any other criteria which, in the investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study
- Working as a food handler, in child-care or as a healthcare worker with direct patient contact.
- Have household contacts who are <2 years old or >80 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).
- Abnormal stool pattern (fewer than 3 per week or more than 3 per day).
- Regular use of laxatives, antacids, or other agents to lower stomach acidity.
- Use of any medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.
- Known allergy to two of the following antibiotics: quinolones, trimethoprim-sulfamethoxazole, and penicillin.
- Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within two years prior to dosing, OR planned travel to endemic countries during the length of the study.
- Vaccination for or ingestion of ETEC, cholera, or LT toxin within 3 years prior to dosing.
- Use of antibiotics during the 7 days before dosing or proton pump inhibitors, H2 blockers or antacids within 48 hours prior to dosing.
- History of diarrhea in the 7 days prior to vaccination (outpatient diarrhea is defined as ≥ 3 unformed loose stools in 24 hours).
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:预防
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:ACE527
First cohort: ACE527 vaccine doses of 9 x 10E10 cfu on study day 0 and 21 on an outpatient basis. Second cohort: ACE527 vaccine dose of 9 x 10E10 cfu on study day 0 and 21 on an outpatient basis. |
ACE527 comprises a mixture of three live, attenuated ETEC strains; ACAM2025 (CFA/I+ and LTB+), ACAM2022 (CS5+, CS6+ and LTB+), and ACAM2027 (CS1+, CS2+, CS3+ and LTB+).
The vaccine is administered orally as a two-dose regimen, at 9x1010 cfu, on Days 0 and 21, in 200 ml CeraVacx buffer.
The required volume of each vaccine strain, supplied as a frozen suspension, is mixed into the buffer solution prior to dosing.
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安慰剂比较:Placebo vaccine
First cohort: Placebo vaccine on study day 0 and 21 on an outpatient basis. Second cohort: Placebo vaccine on study day 0 and 21 on an outpatient basis. |
安慰剂
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Severe diarrhea: ≥6 grade 3-5 stools in 24 hrs, or >800g of grade 3-5 stools in 24 hrs and moderate diarrhea: 4-5 grade 3-5 stools in 24 hrs or 401-800g of grade 3-5 stools in 24 hrs
大体时间:Study Day 49 to 57
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Study Day 49 to 57
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次要结果测量
结果测量 |
大体时间 |
|---|---|
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Number of subjects with severe diarrhea (if any)
大体时间:Study Day 49 to 57
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Study Day 49 to 57
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Number of subjects with diarrhea of any severity
大体时间:Study Day 49 to 57
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Study Day 49 to 57
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Mean total weight of grade 3-5 stools passed per subject
大体时间:Study Day 49 to 57
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Study Day 49 to 57
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Mean number of grade 3-5 stools per subject
大体时间:Study day 49 to 57
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Study day 49 to 57
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Number of subjects with nausea, vomiting, anorexia, or abdominal pain/cramps rated as moderate to severe.
大体时间:Study Day 0 to 77
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Study Day 0 to 77
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Number of subjects who indicate they would have reduced their daily activity if they had been vacationing or traveling for business because of their ETEC illness.
大体时间:Last visit
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Last visit
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Mean time to onset of diarrhea.
大体时间:Study Day 49 to 57
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Study Day 49 to 57
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Number of subjects with moderate to severe ETEC illness
大体时间:Study Day 49 to 57
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Study Day 49 to 57
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Number of colony forming unite (cfu) of the challenge strain per gram of stool
大体时间:Study day 49 to 57
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Study day 49 to 57
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Number of subjects requiring early antibiotic treatment
大体时间:Study Day 49 to 57
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Study Day 49 to 57
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Number of subjects requiring IV fluids
大体时间:Study Day 49 to 57
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Study Day 49 to 57
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Systemic immune responses to the constituent strains of the vaccine
大体时间:Selected Time Points
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Selected Time Points
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Mucosal immune responses to the constituent strains of the vaccine
大体时间:Selected Time Points
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Selected Time Points
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The intestinal colonization by the three individual vaccine strains and challenge strain post-vaccination
大体时间:Selected Time Points
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Selected Time Points
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员:Clayton Harro, MD、CIR, Johns Hopkins School of Public Health
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2010年3月1日
初级完成 (实际的)
2010年10月1日
研究完成 (实际的)
2010年10月1日
研究注册日期
首次提交
2010年1月28日
首先提交符合 QC 标准的
2010年2月1日
首次发布 (估计)
2010年2月2日
研究记录更新
最后更新发布 (估计)
2011年3月7日
上次提交的符合 QC 标准的更新
2011年3月4日
最后验证
2011年3月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.