A Phase 1 Dose-Escalating Study of dscCfaE, Co-Administered With and Without LTR192G, by Transcutaneous Immunization (TCI) in Healthy Adult U.S. Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Number of adverse events
研究概览
简要总结
The purpose of the study is to determine if immunization with a recombinant E. coli protein, dscCfaE, is safe and immunogenic when administered through the skin using a patch.
详细描述
The purpose of the study is to determine if immunization with dscCfaE with or without a modified E. coli heat labile enterotoxin, LTR192G, is safe and immunogenic when administered transcutaneously using a skin wet-patch. If the vaccine is found safe and adequately immunogenic in humans, a phase 2b vaccination/challenge study would be undertaken to further evaluate vaccine safety and allow a preliminary assessment of efficacy. 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 such as, chronic medical conditions such as psychiatric conditions, diabetes mellitus, hypertension or any other conditions that might place the volunteer at increased risk of adverse events. Study clinicians, in consultation with the principal investigator (PI), will use clinical judgment on a case-by-case basis to assess safety risks under this criterion. The PI will consult with the Medical Monitor as appropriate.
- •Clinically significant abnormalities on physical examination.
- •Immunosuppressive drugs (use of systemic corticosteroids or chemotherapeutics that may influence antibody development) or illness (including IgA deficiency).
- •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.
- •Immunosuppressive illness or IgA deficiency (below the normal limits).
- •Exclusionary skin history/findings that would confound assessment or prevent appropriate local monitoring of adverse events (AEs), or possibly increase the risk of an AE.
- •History of chronic skin disease (clinician judgment).
- •History of atopy.
- •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.
- •History of microbiologically confirmed Enterotoxigenic E. coli (ETEC) or V. cholerae infection.
- •Travel to countries where ETEC or V. cholerae 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. cholerae vaccine or live ETEC or V. cholerae challenge.
- •Occupation involving handling of ETEC or V. cholerae currently, or in the past 3 years.
结局指标
主要结局
Number of adverse events
时间窗: Days 0 - 180
Adverse event monitoring will survey and specifically inquire about fever (oral temperature \> 100.4 o F), malaise, headache, rash, pain, diarrhea, abdominal pain, extremity pain or swelling. Clinical definitions will be used to grade severity of symptoms in accordance to the severity scale below: Grade 0 = None Grade 1= Barely noticeable Grade 2= Noticeable, does not interfere with daily activities Grade 3=Interferes with daily activities Grade 4=Prevents daily activities
次要结局
- Number of Mucosal responses (fecal IgA); defined as a > 4-fold increase in endpoint titer after adjusting for total IgA.(Study Days 0 - 180)
- Number of Seroconversion to LT and dscCfaE; defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples.(Study Days 0 - 180)
- Number of positive IgA-ASC responses; defined as a > 2-fold increase over th e baseline value of the ASC per 10 6 PBMC, when the number of ASC is > 0.5 per 10 6 in the baseline sample(Study Days 0 - 180)