A Multi-part, FiH Study in Healthy Participants and Participants With Atopic Dermatitis (AD) to Assess the Safety, Tolerability, Pharmacokinetics (PK) of Single & Multiple Ascending Doses and Selected Dose of SYX-5219 (AD Participants).
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 149
- 试验地点
- 14
- 主要终点
- The Proportion of Participants With Treatment-Emergent Adverse Events
研究概览
简要总结
The purpose of this study is to evaluate the study drug, SYX-5219, in a multi-part First-in-Human (FiH) study to be conducted in healthy volunteers and participants with Atopic Dermatitis (AD). The objectives of this study are to determine the safety, tolerability and levels of SYX-5219 in the blood and urine when SYX-5219 is given in each part of the study (SAD, MAD, Food Effect and Participants with AD).
The study will be split into up to 3 parts as follows:
- Part 1 - Single Ascending Dose (SAD) and Food Effect in healthy volunteers
- Part 2 - Multiple Ascending Dose (MAD) in healthy volunteers
- Part 3 - Multiple Dose in Participants with AD - enrolling up to 45 males and females with a confirmed diagnosis of AD of at least 6 months, evaluating multiple dose administrations of SYX-5219 or placebo daily over a period of 42 days.
详细描述
This is a multi-part, adaptive, Phase 1, double-blind, first-in-human study to evaluate the safety, tolerability, and pharmacokinetics of SYX-5219 following single ascending doses (SAD), multiple ascending doses (MAD), and selected dosing in participants with atopic dermatitis (AD).
Parts 1 and 2 will be conducted at a single site in the UK. Part 3 will be conducted globally at multiple sites.
Part 1 (Single Ascending Dose & Food Effect) Part 1 (SAD) will enrol up to 48 healthy participants in cohorts (3:1, active:placebo). Participants will receive single doses of SYX-5219, with a food effect evaluation including a second dosing period following washout.
Part 2 (Multiple Ascending Dose) Part 2 (MAD) will enrol up to 24 healthy participants in cohorts (3:1, active:placebo). Participants will receive multiple doses of SYX-5219 over a defined treatment period.
Part 3 (AD Participants) Part 3 will enrol up to 45 participants with AD across multiple global sites. Participants will be randomised (2:1) to receive SYX-5219 or placebo for up to 42 days. Prior exposure to targeted systemic therapy will be limited. Study assessments will include safety and exploratory efficacy evaluations during treatment and follow-up.
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
- Double (Participant, Investigator)
盲法说明
Double-Blind
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Parts 1 & 2
- •Healthy male and female participant, between ≥ 18 to ≤ 65 years of age, inclusive, with a BMI of body mass index (BMI) of 18-32 kg/m
- •Female participant of non-childbearing potential or female of childbearing potential that is sexually abstinent.
- •No clinically significant abnormalities in laboratory, vital signs or ECG measurements.
- •Male and female participants with clinically confirmed diagnosis of active AD, between ≥ 18 to ≤ 65 years of age, inclusive, with a BMI of body mass index (BMI) of ≤40 kg/m
- •Meet minimum AD entry criteria;
- •AD covering ≥10% of the body surface area (BSA) at screening and baseline.
- •Eczema Area and Severity Index (EASI) score ≥16 at screening and baseline.
- •Validated Investigator's Global Assessment (vIGA) score of ≥ 3 (moderate) at screening and baseline.
- •Peak Pruritus NRS score of ≥ 4 at screening and baseline.
排除标准
- •Parts 1 & 2
- •Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 35 days or 5 half-lives (whichever is longer) prior to the first dose of IMP.
- •Any clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the Investigator, put the participant at undue risk.
- •Has medical history as stated in the main study exclusion criteria.
- •Received treatment(s) as stated in the main study exclusion criteria.
研究组 & 干预措施
Part 1 Single Ascending Dose (SAD)
Single dose of SYX-5219 (active or matching placebo) administered on Day 1 for all cohorts and Day 1 of each treatment period for food effect cohorts (in fasted and fed conditions).
干预措施: SYX-5219 Oral Capsule (Drug)
Part 2 Multiple Ascending Dose (MAD)
Multiple doses of SYX-5219 (active or matching placebo) administered once or twice daily for all cohorts.
干预措施: SYX-5219 Oral Capsule (Drug)
Part 3 AD Participants Multiple Doses
Multiple doses of SYX-5219 (active or matching placebo) administered twice daily for multiple dose administration
干预措施: SYX-5219 Oral Capsule (Drug)
结局指标
主要结局
The Proportion of Participants With Treatment-Emergent Adverse Events
时间窗: Adverse events are collected from the date of consent until up to 10 days after the dose in Part 1 (Day 11), 14 days after the last dose in Part 2 (Day 28) and up to Day 56 in Part 3.
The number of participants who reported a treatment-emergent adverse event (TEAE) will be summarised.
次要结局
- Concentrations of SYX5219 in Plasma(For Part 1: 14 timepoints from pre-dose Day 1 up to 120 h post-dose Day 6. For Part 2: 28 timepoints from pre-dose Day 1 up to Day 19. For Part 3: 8 timepoints from pre-dose Day 1 up to Day 56.)
- Concentrations of SYX5219 in Urine(For Part 1: continuous urine collection from Day 1 up to 48 hr post-dose on Day 2. For Part 2: continuous urine collection from Day 1 up to 48 hr post-dose on Day 2 and Day 14 up to 48 hr post-dose on Day 16.)