A Phase 1b, Placebo-controlled, Study of the Safety and Efficacy of MET-2 in Patients With Ulcerative Colitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Gut Microbiome restoration
研究概览
简要总结
To define the parameters for dose-dependent engraftment of MET-2 commensal bacteria for the treatment of mild to moderate ulcerative colitis
详细描述
This study will deliver MET-2 at two different doses via an oral capsule in patients with active mucosal inflammation and observe its safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy as compared to placebo. The goal is to define the parameters for dose-dependent engraftment of MET-2 commensal bacteria for the treatment of mild to moderate ulcerative colitis not fully responsive to conventional therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The assessor will be blinded as to which dosing arm the subjects are assigned.
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
- •Mild to Moderate UC.
- •≥ 18 years old.
- •Able to provide informed consent, or have a caregiver able to provide consent.
- •Subjects must have a documented diagnosis (radiologic or endoscopic with histology) of UC for >3 months before screening. The following must be available in each subject's source documentation:
- •A biopsy report to confirm the histological diagnosis
- •A report documenting disease duration and medication history prior to study colonoscopy
- •Subjects receiving any treatment(s) forUC are eligible provided they are anticipated to be on a stable dose for the duration of the study period and have been on therapy prior to the randomization visit for the following amount of time:
- •Prednisone - 4 weeks; Budesonide - 4 weeks; 5-aminosalicylic acid (5-ASA) containing products - 4 weeks; Thiopurine analogs (azathioprine, 6-mercaptopurine) - 12 weeks; Biologic therapy (infliximab, adalimumab, vedolizumab) - 12 weeks; Tofacitinib - 8 weeks.
- •No change in dose is permitted for the following time period prior to the randomization visit:
- •Prednisone - 2 weeks; Budesonide - 4 weeks; 5-ASA containing products - 4 weeks; Thiopurine analogs (azathioprine, 6-mercaptopurine) - 6 weeks; Biologic therapy (infliximab, adalimumab, vedolizumab) - 6 weeks; Tofacitinib - 4 weeks.
- •Subjects are males or nonpregnant, nonlactating females who, if sexually active, agree to comply with the contraceptive requirements of the protocol, or females of nonchildbearing potential. Males and females of reproductive potential who are sexually active must agree to use acceptable contraception for the duration of the study.
- •Willing to participate in follow up as part of the study.
排除标准
- •Ulcerative colitis with disease limited to only the distal rectum (<5cm from dentate line).
- •Subjects with indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical/histologic findings suggestive of Crohn's disease will be excluded.
- •Subjects with colonic dysplasia or neoplasia. (Subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed).
- •Subjects with toxic megacolon or hospitalized for ulcerative colitis.
- •Subjects with colonic stricture, past medical history of colonic resection, a history of bowel surgery within 6 months before screening, or who are likely to require surgery for UC during the treatment period.
- •Use of antibiotics within 6 weeks of randomization visit.
- •Allergy to vancomycin.
- •Elective surgery that will require preoperative antibiotics planned within 3 months of enrolment.
- •Pregnant or planning to get pregnant in the next 6 months.
- •Any condition for which, in the opinion of the investigator, the subject should be excluded from the study.
研究组 & 干预措施
MET-2 20 g
Subjects will be given a once-daily loading dose of 5 grams (g) of MET-2 in the form of 10 MET-2 capsules orally for the first 4 days. For the following 10 days, patients will take 1.5 g MET-2 in the form of three MET-2 capsules taken once-daily
干预措施: MET-2 (Biological)
MET-2 40 g
Subjects will be given a once-daily loading dose of 10 g of MET-2 in the form of 20 MET-2 capsules orally for the first 4 days. For the following 10 days, subjects will take 1.5 g MET-2 in the form of three MET-2 capsules taken once daily
干预措施: MET-2 (Biological)
Placebo oral capsule
Subjects receive 10 placebo capsules that are identical in appearance to the MET-2 capsules
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Gut Microbiome restoration
时间窗: Baseline vs. day 42
Microbiologic assessment of fecal deoxyribonucleic acid (DNA) samples will be obtained before, during and after treatment to quantify the change in microbial alpha diversity using statistical methods such as Shannon Diversity Index and Microbiome Health Index
次要结局
- Assessment of mucosal healing(Baseline vs. Day 42)
- Inflammatory Bowel Disease Questionnaire(Baseline vs. Day 42)