A Phase 2 Multicenter, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Safety and Efficacy of TLL018 for Induction Therapy in Subjects With Moderate to Severe Ulcerative Colitis
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Percentage of subjects who achieved clinical remission per adapted Mayo score at Week 8
研究概览
简要总结
A study to investigate the safety and efficacy of TLL018 compared with placebo in subjects with moderate to severe ulcerative colitis.
详细描述
This is a phase 2, multicenter, randomized, double-blind, parallel dose groups, placebo-controlled dose ranging study to evaluate the safety and efficacy of 3 doses of TLL018 as an induction therapy in subjects with moderate to severe UC.
Eligible subjects will be randomized to receive one of the following treatments: TLL018 low dose, TLL018 middle dose, TLL018 high dose, or placebo. All subjects may remain on a stable dose of conventional therapy used prior to enrollment. Subjects will be assessed for safety, tolerability, and response to treatment. Samples for pharmacokinetics (PK) and pharmacodynamics (PD) biomarker analyses will be collected throughout the study according to the Schedule of Assessments (SoA) for potential correlation to clinical outcomes.
Further participation may continue beyond the initial 8 weeks for another 5-week Extension Period of 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
- Triple (Participant, Care Provider, Investigator)
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
- •Male and female subjects ≥ 18 and ≤ 75 years of age at baseline.
- •Capable of giving informed consent and complying with study procedures.
- •Normal renal function or mild renal impairment as determined by the Investigator following review of clinical laboratory test results.
- •Laboratory and medical history parameters within the protocol-defined ranges.
- •Diagnosis of UC for 90 days or greater prior to baseline, confirmed by colonoscopy during the screening period, with exclusion of current infection, colonic dysplasia, and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of UC, in the assessment of the Investigator, must be available.
- •Active UC with a full Mayo score of 6 to 12 points and endoscopic subscore of 2 or higher confirmed by central reader.
- •Subject must have received COVID-19 vaccine >2 months before first dose of study drug.
排除标准
- •Pregnant or nursing women.
- •Clinically significant history of cardiovascular, hematologic, renal, hepatic, bronchopulmonary, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator.
- •Current and/or recent history of a clinically significant infection.
- •Any history of malignancies, except for non-melanoma skin cancers (unless it is metastatic).
- •Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody.
- •Any condition or finding that in the Investigator's opinion would put the subjects or study conduct at risk if the subjects were to participate in the study.
- •Current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC).
- •Current diagnosis of fulminant colitis and/or toxic megacolon, or active Clostridium difficile colitis.
- •Subject with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy.
- •Subject with previous exposure to JAK inhibitor (eg, tofacitinib, baricitinib, filgotinib, upadacitinib).
研究组 & 干预措施
Low dose TLL018,BID
Drug: TLL018 all subjects will receive TLL018 for 8 weeks
干预措施: TLL018 (Drug)
Middle dose TLL018,BID
Drug: TLL018 all subjects will receive TLL018 for 8 weeks
干预措施: TLL018 (Drug)
High dose TLL018,BID
Drug: TLL018 all subjects will receive TLL018 for 8 weeks
干预措施: TLL018 (Drug)
Placebo
Placebo twice daily for 8 weeks.
干预措施: Placebo (Other)
结局指标
主要结局
Percentage of subjects who achieved clinical remission per adapted Mayo score at Week 8
时间窗: Baseline to Week 8
Number of treatment-emergent adverse events (TEAEs)
时间窗: Up to 8 weeks
TEAE defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.
Incidence of Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
时间窗: Up to 8 weeks
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
时间窗: Up to 8 weeks
Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings
时间窗: Up to 8 weeks
Clinically significant ECG criteria included QT interval corrected using the Fridericia's formula (QTCF) value 450 msec and 30\<=change\<60.
Number of Participants With Clinically Significant Changes in clinical laboratory data
时间窗: Up to 8 weeks
Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.
次要结局
- Percentage of subjects with endoscopic improvement at Week 8(Week 8)
- Percentage of subjects with endoscopic remission at Week 8(Week 8)
- Percentage of subjects achieving clinical response per adapted Mayo score at Week 8(Week 8)
- Percentage of subjects achieving clinical response per partial adapted Mayo score at Week 2(Week 2)
- Percentage of subjects who achieved histologic-endoscopic mucosal improvement (as defined by endoscopic subscore and Geboes score) at Week 8(Week 8)
- Percentage of subjects with mucosal healing (as defined by the endoscopic and histologic variables) at Week 8(Week 8)
- Percentage of subjects who achieved histologic improvement (as defined by Geboes score) at Week 8(Week 8)
- Percentage of subjects who reported no bowel urgency (as monitored electronically via a handheld device) at Week 8(Week 8)
- Change From Baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) Score(Baseline to Week 8)
- Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Questionnaire Score(Baseline to Week 8)
- Time to improvement as measured by rectal bleeding via handheld device(Baseline to Week 8)