A Phase 1 Dose Escalating Study of Two Enterotoxigenic Escherichia Coli Prototype Adhesin-based Vaccines With or Without Modified Heat-labile Enterotoxin by Intradermal or Transcutaneous Immunization
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 57
- 试验地点
- 2
- 主要终点
- Safety - Occurrence of Adverse Events
研究概览
简要总结
The purpose of the study is to determine if immunization with a chimeric E. coli protein, dsc14CfaE-sCT2/LTB5, is safe and immunogenic when administered by vaccination under the skin.
详细描述
The purpose of the study is to evaluate the safety and immunogenicity of dsc14cfaEsCTA2/LTB5 (Chimera) and dscCfaE administered with and without LTR192G by intradermal (ID) immunization and to gather additional data on the administration of dsCfaE and LTR192G via transcutaneous immunization (TCI) route. If vaccines are found to be safe and adequately immunogenic in humans, a down-selection would occur and a phase 2b vaccination/challenge study would be undertaken to further evaluate vaccine safety and allow a preliminary assessment of efficacy of one of these candidates by the ID or TCI route. With favorable evidence for safety, immunogenicity, efficacy, complemented by advances in standard methodology to combine multiple adhesins with an appropriate LT enterotoxoid form, a multivalent vaccine would be constructed and evaluated for further clinical development.
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
- None
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
- •Healthy, adult, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
- •Completion and review of comprehension test (achieved > 70% accuracy).
- •Signed informed consent document.
- •Available for the required follow-up period and scheduled clinic visits.
- •Women: Negative pregnancy test with understanding (through informed consent process) to not become pregnant during the study or within three (3) months following study completion.
排除标准
- •Health problems (for example, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension or any other conditions that might place the subjects at increased risk of adverse events. Study clinicians, in consultation with the PI, will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the Research Monitor as appropriate.
- •Clinically significant abnormalities on physical examination.
- •Use of immunosuppressive medications (systemic corticosteroids or chemotherapeutics that may influence antibody development), or immunosuppressive illness, including IgA deficiency (defined by serum IgA below the detectable limit).
- •Women who are pregnant or planning to become pregnant during the study period plus 3 months beyond the last study safety visit and currently nursing women.
- •Participation in research involving another investigational product (defined as receipt of investigational product or exposure to invasive investigational device) 30 days before planned date of first vaccination or anytime through the last study safety visit.
- •Positive blood test for HBsAg, HCV, HIV-
- •Clinically significant abnormalities on basic laboratory screening.
- •Exclusionary skin history/findings that would confound assessment or prevent appropriate local monitoring of AEs, or possibly increase the risk of an AE.
- •History of chronic skin disease (clinician judgment).
- •History of atopy such as active eczema.
- •Acute skin infection/eruptions on the upper arms including fungal infections, severe acne or active contact dermatitis.
- •Allergies that may increase the risk of AEs.
- •Regular use (weekly or more often) of antidiarrheal, anti-constipation, or antacid therapy.
- •Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on a regular basis; loose or liquid stools on other than an occasional basis.
- •Prior exposure to ETEC or Vibrio cholera.
- •History of microbiologically confirmed ETEC or cholera infection.
- •Travel to countries where ETEC or V. cholera or other enteric infections are endemic (most of the developing world) within two years prior to dosing clinician judgment).
- •Received previous experimental ETEC or V. cholera vaccine or live ETEC or V. cholera challenge.
- •Occupation involving handling of ETEC or V. cholera currently, or in the past 3 years.
结局指标
主要结局
Safety - Occurrence of Adverse Events
时间窗: 1 year
Occurrence of related and unrelated to vaccine AE's
次要结局
- Antigen-Specific IgA Geometric Mean Titers(Day 0, 21,42, 56, 70)
- Number of Participants With Immune Responses to Vaccine Antigens(baseline and post dose)