A Multicenter, Randomized, Placebo-Controlled, Multiple-Ascending-Dose Investigation of the Oral Anti-Inflammatory Agent BT051 in Subjects With Moderately to Severely Active Ulcerative Colitis (UC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 6
- 主要终点
- Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects observed with a change from baseline in physical examinations, clinical laboratory tests, vital signs, and electrocardiograms (ECG)
研究概览
简要总结
This is a randomised, double-blind, placebo-controlled study to assess the safety and tolerability of multiple ascending doses of BT051 in subjects with moderately to severely active ulcerative colitis. Subjects will be randomised using a 3 active:1 placebo ratio to 3 ascending dose cohorts of 8 subjects and will be dosed daily for 28 days. The 3 initial dose levels will be 200 mg, 800 mg and 3200 mg per day. Progression to the next cohort will be based on the safety and tolerability of the previous cohort.
详细描述
This is a randomized, placebo-controlled, multiple-ascending-dose (MAD) study enrolling subjects with moderately to severely active UC. Subjects with prior exposure to biologic or JAK inhibitors will be limited to 30% of the total subject population; those who have failed 2 or more biologic therapies (i.e., biologic and JAK inhibitor, 2 biologics in the same class, or 2 biologics from different classes) will be limited to 20% of the total subject population. Subjects will be randomized to one of 3 doses of oral BT051 (200 mg, 800 mg, or 3200 mg) or placebo, in ascending dose groups based on the safety and tolerability of the previous cohort. Safety and tolerability will be assessed by a Safety Review Committee (SRC) after all subjects in each cohort have completed at least 14 days of treatment, before proceeding to the next higher dose cohort. The SRC may recommend that the next cohort proceed with a higher dose as planned, or the SRC may recommend additional subjects be dosed at the current, previous, or lower dose of study drug.
Each planned dose escalation cohort (Cohorts 1-3) will include 8 subjects randomized 3:1 to receive active drug or placebo. Starting with the lowest dose, each cohort of subjects will receive once daily oral BT051 or placebo for a period of 28 days. Follow-up visits will be performed at 7 and 30 days after the last dose.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BT051 200 mg
Participants will receive oral BT051 200 mg once daily for 28 days.
干预措施: BT051 200 mg (Drug)
BT051 800 mg
Participants will receive oral BT051 800 mg once daily for 28 days.
干预措施: BT051 800 mg (Drug)
BT051 3200 mg
Participants will receive oral BT051 3200 mg once daily for 28 days.
干预措施: BT051 3200 mg (Drug)
Placebo
Participants will receive oral Placebo to match BT051 once daily for 28 days.
干预措施: Matching Placebo (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects observed with a change from baseline in physical examinations, clinical laboratory tests, vital signs, and electrocardiograms (ECG)
时间窗: Baseline to Day 58
Proportion of subjects with a change from baseline from normal to abnormal in physical examinations, clinical laboratory tests, vital signs, and ECGs will be summarized
Evaluate the safety and tolerability of BT051 based on the difference of proportions between treatment groups of subjects experiencing treatment-emergent adverse events (TEAEs)
时间窗: Baseline to Day 58
Proportion of subjects experiencing a TEAE will be summarized using the MedDRA system organ class and preferred term
次要结局
- Clinical response defined as a decrease in complete Mayo Score ≥2 points and ≥30% from baseline with a concomitant decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding subscore ≤1(Baseline to Day 28)
- Histologic remission defined as Geboes Score ≤2B.0 or Nancy Index = 0(Day 28)
- Change in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score(Baseline to Day 28)
- Remission defined as a complete Mayo Score ≤2 points with no subscore >1 point at Day 28(Baseline to Day 28)
- Remission defined as a partial Mayo Score ≤2 points with no subscore >1 point at Days 14 and 28(Baseline to Days 14 and 28)
- Endoscopic remission defined as an Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score of 0(Day 28)
- Change in Mayo endoscopic, stool frequency, and rectal bleeding subscores.(Baseline to Day 28)
- Endoscopic response defined as a decrease in UCEIS ≥2 points(Day 28)
- Change in Robarts histopathology index (RHI) score(Baseline to Day 28)
- Change in UC-100 score(Baseline to Day 28)
- Clinical response defined as a decrease in complete Mayo Score ≥3 points and ≥30% from baseline with a concomitant decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding subscore ≤1 point(Baseline to Day 28)
- Remission according to the adapted Mayo Score without the physician's global assessment, defined as a stool frequency subscore ≤1 point, rectal bleeding subscore of 0, and endoscopic subscore ≤1 point(Baseline to Day 28)
- Change in stool frequency and rectal bleeding Mayo subscores(Baseline to Day 14)