A Phase 1b Multi-Center, Randomized, Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Plasma Exposure of TD-1473 in Subjects With Moderately-to-Severely Active Ulcerative Colitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Ctrough in plasma
研究概览
简要总结
This study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TD-1473 in subjects with moderately-to-severely active UC over 28 days. This exploratory study will also serve as a signal seeking endeavor to demonstrate biologic effect associated with TD-1473 through biomarker analysis and clinical, endoscopic, and histologic assessments.
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
- •Has a history of ulcerative colitis diagnosis at least 3 months prior to screening
- •Is intolerant, refractory, or only partially responsive to aminosalicylates, corticosteroids, immunomodulators, or biologics. If subject is currently receiving an oral aminosalicylate, he or she is eligible and can stay on that dose of aminosalicylate provided the dose has been stable for at least 2 weeks prior to screening. If the subject is currently receiving an oral corticosteroid, he or she is eligible if the dose is equivalent to or less than prednisone 20 mg/day or budesonide 9 mg/day and stable for at least 2 weeks prior to screening sigmoidoscopy if the subject has been on corticosteroids for more than 2 weeks.
- •Has a rectal bleeding score ≥ 1 and a bowel frequency score ≥ 1 on the patient-reported outcome 2 (PRO2) on screening sigmoidoscopy day and on Day 1 in addition to a modified Mayo endoscopic subscore of ≥ 2 during screening
- •Women of childbearing potential must have a negative pregnancy test and either abstain from sexual intercourse or use a highly effective method of birth control
- •Willing and able to give informed consent
- •Additional inclusion criteria apply
排除标准
- •Has fulminant colitis, toxic megacolon, primary sclerosing cholangitis, Crohn's disease, history of colitis-associated colonic dysplasia, active peptic ulcer disease
- •Medications of exclusion: a) azathioprine, 6-mercaptopurine, or methotrexate within the 28 days prior to Day 1, b) adalimumab, infliximab, golimumab, etanercept, or certolizumab within the 60 days prior to Day 1, c) intravenous corticosteroids within the 14 days prior to Day 1, d) topical mesalamine or steroid (i.e., enemas or suppositories) within the 14 days prior to Day 1, e) any prior exposure to mycophenolic acid, tacrolimus, sirolimus, cyclosporine, natalizumab, rituximab, efalizumab, ustekinumab, fingolimod, or thalidomide, f) NSAIDs on a daily basis, g) tofacitinib within the 60 days prior to Day 1; h) vedolizumab within 120 days prior to Day 1
- •Has a current bacterial, parasitic, fungal, or viral infection
- •Is positive for hepatitis A, B or C, HIV or tuberculosis
- •Has clinically significant abnormalities in laboratory evaluations
- •Participated in another clinical trial of an investigational drug (or medical device) within 30 days prior to screening (or within 60 days prior to screening if investigational drug was a biologic or another Janus kinase (JAK) inhibitor, or is currently participating in another trial of an investigational drug (or medical device)
- •Use of prescription medications started or with a dose adjustment within 4 weeks prior to study enrollment, or over-the-counter medications or supplements started or with a dose adjustment within 2 weeks prior study enrollment. Anti-diarrheal medications are allowed only if dose has been stable at least 2 weeks prior to study enrollment
- •Additional exclusion criteria apply
研究组 & 干预措施
TD-1473 low dose
10 subjects will be randomized to receive low-dose TD-1473 orally daily for 28 days
干预措施: TD-1473 (Drug)
TD-1473 mid dose
10 subjects will be randomized to receive mid-dose TD-1473 orally daily for 28 days
干预措施: TD-1473 (Drug)
TD-1473 high dose
10 subjects will be randomized to receive high-dose TD-1473 orally daily for 28 days
干预措施: TD-1473 (Drug)
Placebo
10 subjects will be randomized to receive placebo orally daily for 28 days
干预措施: Placebo (Drug)
结局指标
主要结局
Ctrough in plasma
时间窗: Day 14 (Pre-dose)
Trough Concentration of TD-1473
Electrocardiogram
时间窗: Baseline to Day 14
Number of participants who experienced a Clinically Significant Electrocardiogram (ECG) Result
Cmax in plasma
时间窗: Day 1 and Day 14
Maximum Observed Plasma Concentration of TD-1473
Tmax in plasma
时间窗: Day 1 and Day 14
Time to Reach Maximum Observed Plasma Concentration (Cmax) of TD-1473
Tlast in plasma
时间窗: Day 1 and Day 14
Time to Last Quantifiable Concentration of TD-1473
AUC0-4 in plasma
时间窗: Day 1 and Day 14
Area Under the Concentration-time Curve from Time Zero to 4 hours Post-Dose of TD-1473
Ctissue in plasma
时间窗: Day 28
Tissue Concentration of TD-1473
Treatment-emergent Adverse Events (TEAE)
时间窗: Baseline to end of follow-up (a maximum of 42 days)
Number of participants who experience one or more treatment-emergent Adverse Events (TEAE)
Moderate or Severe Treatment-emergent Adverse Events (TEAE)
时间窗: Baseline to end of follow-up (a maximum of 42 days)
Number of participants who experience one or more moderate or severe treatment-emergent Adverse Events (TEAE)
Serious Treatment-emergent Adverse Events (TEAE)
时间窗: Baseline to end of follow-up (a maximum of 42 days)
Number of participants who experience one or more serious treatment-emergent Adverse Events (TEAE)
Clinical Laboratory Measurements
时间窗: Baseline to end of follow-up (a maximum of 42 days)
Number of participants who experienced a Clinically Significant Clinical Laboratory Measurements
Vital Signs
时间窗: Baseline to end of follow-up (a maximum of 42 days)
Number of participants who experienced a Clinically Significant Vital Sign Measurement
次要结局
- C-reactive protein (CRP)(Baseline, Day 14 and Day 28)
- Fecal Calprotectin(Baseline and Day 28)
- Partial Mayo score(Baseline, Day 14 and Day 28)