CONSORTIUM - A Double-Blind Placebo-Controlled Phase 2 Study of VE303 for Prevention of Recurrent Clostridium (Clostridioides) Difficile Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 79
- 试验地点
- 37
- 主要终点
- CDI Recurrence Week 8
研究概览
简要总结
This study evaluated the safety and efficacy of VE303 for participants with primary C. difficile infection (pCDI) at high risk for recurrence or subjects with recurrent C. difficile infections (rCDI).
详细描述
CONSORTIUM was a randomized, placebo-controlled double-blind Phase 2 study to evaluate safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy of VE303 in prevention of subsequent Clostridioides difficile infection (CDI) -associated diarrhea compared with placebo following completion of at least 1 successful course of standard-of-care (SOC) antibiotics. VE303 or placebo capsules were taken orally for 14 days after completion of a course of SOC antibiotics. The proportions of subjects experiencing a confirmed CDI recurrence within 8 weeks after the first dose of study treatment were compared across the study arms, to understand the efficacy of VE303 in preventing rCDI.
The study originally planned to enroll 146 subjects but through a protocol amendment was revised to an enrollment target of 60 to 80 subjects with a prior history of CDI diarrhea or first occurrence of CDI diarrhea with a higher risk for recurrence. Subjects must have had a positive C. difficile stool sample and have responded to SOC antibiotic treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
To reduce potential bias and increase study data integrity, study participants, care providers, site investigators, and study outcomes assessors were masked to study treatment assignment.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to provide written informed consent
- •Subjects with a qualifying CDI episode who had a prior history of CDI diarrhea (≥ 18 years of age) or first occurrence of CDI diarrhea with a higher risk for recurrence (≥ 75 years of age, or ≥ 65 years of age with one or more prespecified conditions)
- •CDI symptoms must have started within 30 days (inclusive) prior to the day of randomization
- •The diarrhea was considered unlikely to have another etiology.
- •Completed an Investigator's choice SOC antibiotic regimen of a minimum of 10 days and up to 21 days of total duration
- •Have a positive C. difficile stool
- •Recovered from any complications of severe or fulminant CDI and clinically stable by the time of randomization.
排除标准
- •History of diarrhea (defined as 3 or more loose stools per day lasting for at least 4 weeks) that was not related to C. difficile infection within the 3 months prior to randomization.
- •Known or suspected toxic megacolon and/or known small bowel ileus at the time of randomization.
- •Contraindication to oral/enteral therapy (e.g., severe reflux, severe nausea/vomiting, or ileus).
- •Prior administration of genetically modified investigational live bacterial/fungal/bacteriophage/viral isolates for CDI-associated diarrhea
- •History of administration of fecally-derived investigational live biotherapeutic products, or fecally-derived live bacterial isolates for CDI-associated diarrhea including fecal microbiota transplantation (FMT) within the last 6 months.
- •Use of drugs that alter gut motility
- •History of acute leukemia or hematopoietic stem cell transplantation or myelosuppressive chemotherapy within 2 months prior to randomization.
- •Subjects with compromised immune system
- •Major gastrointestinal surgery (e.g., significant bowel resection or diversion) within 3 months prior to randomization or any history of total colectomy or bariatric surgery that disrupts the gastrointestinal lumen.
- •History of confirmed celiac disease, inflammatory bowel disease, short gut, gastrointestinal tract fistulas, or ischemia.
研究组 & 干预措施
VE303 High Dose
Study subjects assigned the high dose VE303 arm took 10 capsules (dosage: 8.0 × 10^9 CFU daily) containing VE303 per day for 14 days.
干预措施: VE303 (Drug)
VE303 Low Dose
Study subjects assigned to the low dose VE303 arm took 2 capsules (dosage: 1.6 × 10^9 CFU daily) containing VE303 per day for 14 days.
干预措施: VE303 (Drug)
Placebo
Study subjects assigned to the placebo dose arm took placebo capsules each day for 14 days. The capsules did not contain any VE303.
干预措施: Placebo (Drug)
结局指标
主要结局
CDI Recurrence Week 8
时间窗: 8 weeks
Percentage of participants with toxin-positive, laboratory-confirmed, or clinically diagnosed and treated CDI recurrence before or at Week 8 (i.e., 8 weeks after the first dose of study treatment).
次要结局
- VE303 Strains Detected(24 weeks)
- VE303 Relative Abundance(24 weeks)