A Phase 1 Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of BYN-001 in Healthy Adult Participants and Participants With Moderate to Severe Atopic Dermatitis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 56
- 主要终点
- Incidence and severity of adverse events (AEs)
研究概览
简要总结
This first-in-human study evaluates BYN-001, a humanized IgG1 monoclonal antibody targeting interleukin-25 (IL-25), a cytokine implicated in atopic dermatitis. Parts A and B are randomized, double-blind, placebo-controlled single and multiple ascending dose cohorts in healthy adults, that will assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of BYN-001. Part C will assess BYN-001 in adults with moderate to severe atopic dermatitis.
详细描述
Atopic dermatitis (AD) is a common chronic inflammatory skin disease for which current type 2 cytokine-targeted biologics leave a substantial proportion of patients with an inadequate response or residual pruritus. IL-25 acts upstream of type 2 inflammation and has been shown to drive pruritus and epidermal barrier dysfunction. BYN-001 selectively binds and neutralises IL-25 (with a long predicted terminal half-life), supporting an infrequent dosing interval.
Part A will consist of a single ascending dose (SAD) design, with administration in up to five cohorts. Part B will consist of a multiple ascending dose (MAD) design, with administration in up to three cohorts. Both parts will enroll healthy participants and will be conducted under a sentinel dosing approach, with dose escalation decisions governed by a Safety Monitoring Committee (SMC) at each escalation step.
Part C will enroll participants with moderate to severe AD.
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)
盲法说明
Double blinded study design. Site staff, participants and the Sponsor/CRO may become unblinded within 2 weeks of interim analysis completion.
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
- •Part A and B Key Inclusion Criteria:
- •Age 18-55 years of age
- •Must be in good health with no significant medical conditions
- •Willing and able to attend all study visits and comply with study requirements
- •Able and willing to provide written informed consent
- •Part A and B
排除标准
- •Evidence of clinically significant condition or disease
- •Any physical or psychosocial condition that prohibits study completion
- •Know history of illicit drug use or abuse, alcoholism and/or smoking more than -5 cigarettes a day in the prior 3 months
- •History of sever allergic reactions of hypersensitivity
- •Part C Inclusion Criteria
- •Age 18-55 years of age
- •Must be in good health with no significant medical conditions
- •Willing and able to attend all study visits and comply with study requirements
- •Able and willing to provide written informed consent
- •Documented chromic atopic dermatitis within 1 year prior to screening
- •Moderate to severe atopic dermatitis
- •Part C Key Exclusion Criteria
- •Evidence of clinically significant condition or disease
- •Any physical or psychosocial condition that prohibits study completion
- •Know history of illicit drug use or abuse, alcoholism and/or smoking more than 5 cigarettes a day in the prior 3 months
- •History of sever allergic reactions of hypersensitivity
- •Incomplete washout of prior atopic dermatitis medications
- •Other confounding skin diseases
研究组 & 干预措施
Experimental, Part A, SAD Cohorts: BYN-001 Active drug
Healthy participants will receive a single dose of BYN-001 in a dose escalation format
干预措施: BYN-001 (Biological)
Placebo Comparator Part B, MAD Cohorts: BYN-001 Placebo
Healthy participants will receive repeated doses of placebo comparator
干预措施: Placebo (Drug)
Placebo Comparator, Part C, Participants with mild to severe atopic dermatitis, Placebo
Participants with mild to severe atopic dermatitis will be randomized to receive repeat doses of placebo
干预措施: Placebo (Drug)
Placebo Comparator, Part A, SAD Cohorts Placebo
Healthy participants will receive a single dose of placebo comparator
干预措施: Placebo (Drug)
Experimental, Part B, MAD Cohorts: BYN-001 Active drug
Healthy participants will receive a repeated doses of BYN-001 in a dose escalation format
干预措施: BYN-001 (Biological)
Experimental, Part C, Participants with mild to severe atopic dermatitis, BYN-001
Participants with mild to severe atopic dermatitis will be randomized to receive repeat doses of BYN-001
干预措施: BYN-001 (Biological)
结局指标
主要结局
Incidence and severity of adverse events (AEs)
时间窗: From first dose through end of study (up to Week 48 for BYN-001 recipients; up to 2 weeks post-unblinding for placebo recipients)
Includes clinically relevant findings from clinical laboratory tests (haematology, urinalysis, blood chemistry), physical examination, vital signs, and 12-lead ECG. Assessed separately for the healthy-volunteer participants (Part A and B) and the AD participants in Part C.
次要结局
- Pharmacokinetic parameters of BYN-001(Serial PK sampling per the Schedule of Assessments, through Week 48)
- Incidence of anti-drug antibodies (ADA) to BYN-001(Baseline through Week 48)
- Titer of anti-drug antibodies (ADA) to BYN-001(Baseline through Week 48)