A Randomized, Double-Blind, Placebo/Active Controlled, Multiple Ascending Dose, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Subcutaneous Injections of YH35324 in Atopic Healthy Subjects or Subjects With Allergic Diseases
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 试验地点
- 9
- 主要终点
- Occurrence and severity of adverse events (AEs)
研究概览
简要总结
This study aims to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles following multiple subcutaneous injections of YH35324 in healthy subjects or subjects with allergic diseases, who have atopy.
详细描述
YH35324 is a drug under development as a novel therapeutic agent for various IgE-mediated allergic diseases. Since YH35324 has a high binding affinity to human IgE, it prevents serum IgE from binding to receptors on mast cells and basophil, thereby inhibiting histamine release caused by degranulation when exposed to allergens. This study aims to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles following multiple subcutaneous injections of YH35324 in healthy subjects or subjects with allergic diseases, who have atopy.
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
As the YH35324 group and placebo group will be double-blinded, YH35324 and placebo will have the same appearance and packaging. Therefore, the double-blind will apply to the subjects, investigators, study coordinators, and study personnel including study pharmacists.
The active control omalizumab has a different appearance and packaging from YH35324 and placebo, and will be administered in an open-label manner.
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female adults aged ≥ 19 to ≤ 55 years(Cohort 5, Mald or female adults ≥ 19)
- •Serum total IgE level ≥ 30 IU/mL or 30 to 700 IU/mL or >700IU/mL(Not Applicable for Cohort 5)
- •Meeting the following cohort-specific disease severity criteria [Cohorts 1-4]: Healthy subjects without any pathological symptoms or findings from medical examination, or subjects with a history of mild allergic diseases (allergic rhinitis, atopic dermatitis, food allergy, urticaria, or allergic asthma) [Cohort 5]: Subject who have been diagnosed with moderate to severe atopic dermatitis
排除标准
- •History of malignancy
- •Positive drug screen result
- •transaminase (AST) or alanine transaminase (ALT) level > 2 X the upper limit of normal
- •Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
- •Allergy immunotherapy initiated or changed within 6 months prior to randomization(For Cohort 5, within 12 months prior to randomization)
- •History of participation in another clinical trial within 6 months prior to randomization
研究组 & 干预措施
YH35324
There will be 5 dose groups of YH35324, escalating from low to high doses in a stepwise manner: Cohort 1(A mg/kg) → Cohort 2(B mg/kg) → Cohorts 3(C mg/kg) and 4(C mg/kg) → Cohort 5(C mg/kg) YH35324 and placebo will be administered in a double-blinded manner.
干预措施: YH35324 (Drug)
Placebo
There will be 5 dose groups of YH35324, escalating from low to high doses in a stepwise manner: Cohort 1(A mg/kg) → Cohort 2(B mg/kg) → Cohorts 3(C mg/kg) and 4(C mg/kg) → Cohort 5(C mg/kg) YH35324 and placebo will be administered in a double-blinded manner.
干预措施: Placebo (Drug)
Omalizumab
For Cohort 3, omalizumab 300 mg will be administered in an open-label manner.
干预措施: Omalizumab (Drug)
结局指标
主要结局
Occurrence and severity of adverse events (AEs)
时间窗: Occurrence and severity of adverse events will be observed for 141 days after administration in Cohorts 1 to 5
To evaluate the safety and tolerability following multiple administrations of YH35324
次要结局
- Time to Maximum Serum Concentration (Tmax)(Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4)
- Apparent Serum Clearance (CL/F)(Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4)
- Area Under the Serum Concentration-Time Curve from Zero to the Time of the Last Quantitative Concentration (AUClast)(Serum concentrations of YH35324 will be observed for 141 days after administrationin in Cohorts 1 to 4)
- Area Under the Serum Concentration-Time Curve from Zero to Infinity (AUCinf)(Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4)
- Maximum Serum Concentration(Cmax)(Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4)
- Area Under the Serum Concentration-Time Curve during dosing interval at steady-state (AUCtau)(Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4)
- Serum concentrations of YH35324(Serum concentrations of YH35324 will be observed for 99 days after administration in Cohorts 5)
- Change in SCORing Atopic Dermatitis (SCORAD)(Change in SCORing Atopic Dermatitis (SCORAD) will be observed for 141 days after administration in Cohorts 5)
- Change in Pruritus-Numerical Rating Scale (NRS)(Change in Pruritus-Numerical Rating Scale (NRS) will be observed for 141 days after administration in Cohorts 5)
- Terminal Elimination Rate Constant, Apparent Terminal Elimination Half-life (t1/2)(Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4)
- Maximum Serum Concentration at steady-state (Cmax,ss)(Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4)
- Change in Eczema Area and Severity Index (EASI)(Change in Eczema Area and Severity Index (EASI) will be observed for 141 days after administration in Cohorts 5)
- Apparent Volume of Distribution (Vz/F)(Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4)
- Time to Maximum Serum Concentration at steady-state (Tmax,ss)(Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4)
- Change in serum total IgE level(Change in serum Total IgE will be observed for 141 days after administration in Cohorts 1 to 4)
- Accumulation ratio (Rac)(Serum concentrations of YH35324 will be observed for 141 days after administration in Cohorts 1 to 4)
- Change in serum free IgE level(Change in serum Free IgE will be observed for 141 days after administration in Cohorts 1 to 5)
- Change in Validated Investigator Global Assessment (vIGA-AD)(Change in Validated Investigator Global Assessment (vIGA-AD) will be observed for 141 days after administration in Cohorts 5)
- Change in body surface area (BSA) of atopic dermatitis involvement(Change in body surface area (BSA) of atopic dermatitis involvement will be observed for 141 days after administration in Cohorts 5)
- Number of days of rescue treatment (TCS or TCI) used(Number of days of rescue treatment (TCS or TCI) used will be observed for 141 days after administration in Cohorts 5)