A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Food Effect of UA026 Tablets in Healthy Adult Subjects and Adult Subjects With Moderate to Severe Plaque Psoriasis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Number of Participants Experiencing Adverse Events (AEs)
研究概览
简要总结
This study is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetic profile, and food effect of UA026 tablets.
The study consists of four parts: Part A is a single ascending dose (SAD) study, Part B is a multiple ascending dose (MAD) study, Part C is a food effect (FE) study, and Part D is a multi-dose parallel control study. Part A, B, and C will be conducted in healthy subject, and Part D will be conducted in subjects with moderate to severe plaque psoriasis.
详细描述
Interleukin (IL)-17A is a proinflammatory cytokine that when dysregulated can lead to inflammatory disorders. Inhibiting IL-17A has shown remarkable clinical efficacy in psoriasis.UA026 is a high potency small molecule IL-17A inhibitor. This first-in-human study assessed the safety, tolerability, pharmacokinetics (PKs), and biomarkers including circulating IL-17A target engagement profile of single or multiple oral doses of the UA026 in healthy subject and subjects with moderate to severe plaque psoriasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
UA026
Part A: SAD in healthy subjects
Part B: MAD in healthy subjects
Part C: FE in healthy subjects
Part D: Multiple dose study in psoriasis patients
干预措施: UA026 (Drug)
Placebo
Part A: SAD in healthy subjects
Part B: MAD in healthy subjects
Part D: Multiple dose study in psoriasis patients
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants Experiencing Adverse Events (AEs)
时间窗: up to 56 days
Number of participants with clinically significant changes from baseline in vital signs
时间窗: up to 56 days
Number of participants with clinically significant changes from baseline in clinical laboratory values
时间窗: up to 56 days
Safety and tolerability outcome measures include, but are not limited to vital signs, physical examination, 12-lead ECGs, clinical laboratory tests, and adverse events.
Number of participants with clinically significant changes from baseline in physical examination
时间窗: up to 56 days
Number of participants with clinically significant changes from baseline in 12-lead electrocardiograms(ECGs)
时间窗: up to 56 days
次要结局
- Area under the plasma concentration-time curve from time zero to end of dosing interval (AUCtau) for Parts A, B, C and D(up to 72 hours after the last dose)
- Area under the plasma concentration-time curve from time zero to infinity (AUCinf) for Parts A, B, C, and D(up to 72 hours after the last dose)
- Maximum observed plasma concentration (Cmax) for Parts A, B, C and D(up to 72 hours after the last dose)
- Time to maximum plasma concentration (Tmax) for Parts A, B, C and D(up to 72 hours after the last dose)
- Apparent terminal elimination half-life (t½) for Parts A, B, C and D(up to 72 hours after the last dose)
- Apparent systemic clearance (CL/F) for Parts A, B, and C(up to 72 hours after the last dose)
- Apparent volume of distribution (Vz/F) for Parts A, B, and C(up to 72 hours after the last dose)
- MRT（Mean Residence Time）for Parts A, B, C and D(up to 72 hours after the last dose)
- Accumulation ratios (Rac) for Parts B and D(up to 72 hours after the last dose)
- degree of fluctuation（DF）for Parts B and D(up to 72 hours after the last dose)
- the change in serum IL-17A level from the baseline for Parts A, B and D(up to 72 hours after the last dose)
- the changes in serum beta-defensin 2(BD-2) from the baseline for Part D(up to 72 hours after the last dose)
- the changes in serum IL-19 level from the baseline for Part D(up to 72 hours after the last dose)
- The percentage change in psoriasis area and severity index (PASI) score from the baseline for Part D(up to 56 days)
- Number of Participants Achieving 50% Improvement from Baseline in PASI (PASI-50) Score for Part D(up to 56 days)
- Number of Participants Achieving 75% Improvement from Baseline in PASI (PASI-75) Score(up to 56 days)
- Number of Participants Achieving 90% Improvement from Baseline in PASI (PASI-90) Score(up to 56 days)
- Number of Participants Achieving a Static Physician's Global Assessment (sPGA) of Clear (0) or Almost Clear (1) for Part D(up to 56 days)
- The change in sPGA score from the baseline for Part D(up to 56 days)
- The change in body surface area(BSA) from the baseline for Part D(up to 56 days)