A Phase 1a/1b, First-in-human, Open-label Study of Escalating Doses of VE303 in Healthy Adult Volunteers With or Without Vancomycin Pre-treatment to Evaluate Safety, Dosing, and Pharmacodynamics
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Safety of VE303 measured by incidence adverse events (AEs)
研究概览
简要总结
This study was designed to evaluate safety and tolerability of a range of doses of VE303 in healthy adult volunteers. The study also evaluated pharmacokinetics of intestinal colonization by the VE303 strains and pharmacodynamics of recovery of the gut microbiota after administration of antibiotics followed by a course of VE303.
详细描述
VE303 is a rationally-defined bacterial consortium candidate being developed for the prevention of recurrent C. difficile infection. VE303 consists of 8 types of clonal human commensal bacteria strains selected for their ability to provide colonization resistance to C. difficile and manufactured under GMP conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects who are judged to be in general good health
- •Body mass index between 18.5 and 30 kg/m2
- •Women either of non-child bearing potential or using a highly effective form of contraception
- •Men using a highly effective method of contraception
排除标准
- •Past or present clinically significant diseases that may affect the outcome of the study
- •Taking any medications, herbal preparations, or natural substances, live bacteria products, or food that impacts or alter GI flora
- •Use of proton pump inhibitors or other short or long acting antacid medications
- •Taking or has received an investigation drug or treatment within 60 days of inpatient admission
- •Known allergies to involved study drugs
- •Chronic constipation or diarrhea
- •History of or active IBD
研究组 & 干预措施
Cohort 1
Cohort 1 received oral vancomycin followed by a single dose of VE303.
干预措施: VE303 (Drug)
Cohort 1
Cohort 1 received oral vancomycin followed by a single dose of VE303.
干预措施: Oral Vancomycin (Drug)
Cohort 2
Cohort 2 received oral vancomycin followed by a single day of 5 doses of VE303.
干预措施: VE303 (Drug)
Cohort 2
Cohort 2 received oral vancomycin followed by a single day of 5 doses of VE303.
干预措施: Oral Vancomycin (Drug)
Cohort 3
Cohort 3 received oral vancomycin followed by a single day of 10 doses of VE303.
干预措施: VE303 (Drug)
Cohort 3
Cohort 3 received oral vancomycin followed by a single day of 10 doses of VE303.
干预措施: Oral Vancomycin (Drug)
Cohort 4
Cohort 4 received oral vancomycin followed by 5 days of 10 doses daily of VE303.
干预措施: VE303 (Drug)
Cohort 4
Cohort 4 received oral vancomycin followed by 5 days of 10 doses daily of VE303.
干预措施: Oral Vancomycin (Drug)
Cohort 5
Cohort 5 received oral vancomycin followed by 14 days of 10 capsules daily of VE303
干预措施: VE303 (Drug)
Cohort 5
Cohort 5 received oral vancomycin followed by 14 days of 10 capsules daily of VE303
干预措施: Oral Vancomycin (Drug)
Cohort 6
Cohort 6 received 21 days of 10 doses daily of VE303
干预措施: VE303 (Drug)
Cohort 7
Cohort 7 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
干预措施: VE303 (Drug)
Cohort 7
Cohort 7 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
干预措施: Oral Vancomycin (Drug)
Cohort 8
Cohort 8 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
干预措施: VE303 (Drug)
Cohort 8
Cohort 8 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
干预措施: Oral Vancomycin (Drug)
Cohort 9
Cohort 8 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
干预措施: VE303 (Drug)
Cohort 9
Cohort 8 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
干预措施: Oral Vancomycin (Drug)
Vancomycin only
This cohort only received oral vancomycin.
干预措施: Oral Vancomycin (Drug)
结局指标
主要结局
Safety of VE303 measured by incidence adverse events (AEs)
时间窗: 12 months post-dose
Measured in terms of incidence of AEs according to CTCAE V4.0
Tolerability of VE303 using modified PROMIS questionnaire (v1.0)
时间窗: 12 months post-dose
Characterized the highest well tolerated dose regimen of VE303 using modified PROMIS questionnaire (v1.0)
次要结局
- Evaluate the colonization of the intestinal microbiota with VE303 component bacteria(12 months post-dose)
- Evaluate the changes in the intestinal microbiota due to VE303 dosing.(12 months post-dose)
- Evaluate the metabolomic changes in stool due to VE303 dosing.(12 months post-dose)