A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM17321 in Healthy and Obese Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (TEAEs) Following Single and Multiple Subcutaneous Doses of HM17321
研究概览
简要总结
This is a Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM17321 after single and multiple ascending doses in healthy and obese participants.
详细描述
This is a Phase 1, randomized, double-blind, placebo-controlled, single and multiple ascending dose study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of HM17321, a urocortine 2 (UCN2) analog, administered by subcutaneous (SC) injection in healthy and obese participants.
The study consists of two parts: Part A (Single Ascending Dose) and Part B (Multiple Ascending Dose), with approximately 90 participants to be enrolled in total.
In Part A, approximately 40 healthy participants with a body mass index (BMI) of ≥20 kg/m² and ≤27 kg/m² will be enrolled across 5 sequential dose cohorts. Each cohort will consist of approximately 8 participants randomized in a 6:2 ratio to receive a single SC dose of HM17321 or placebo. A sentinel dosing strategy will be applied in each cohort to ensure participant safety, with initial safety data reviewed prior to dosing the remainder of the cohort. Dose escalation decisions will be made by a Safety Review Committee (SRC) based on safety, tolerability, and available PK data. Part A will include a screening period of up to 28 days, a 5-day inpatient stay with single SC dosing, and an outpatient follow-up period through Day 29, with an overall study duration of approximately 8 weeks per participant.
In Part B, approximately 50 healthy obese participants with a BMI of ≥30 kg/m² and ≤45 kg/m² will be enrolled across 5 sequential dose cohorts. Each cohort will consist of approximately 10 participants randomized in an 8:2 ratio to receive once-weekly SC doses of HM17321 or placebo over a 12-week treatment period. Dose escalation will be guided by SRC review of safety, tolerability, and PK data at predefined time points. Part B will include a screening period of up to 45 days, a 12-week treatment period with once-weekly SC dosing, and a 4-week follow-up period through Day 113, with an overall study duration of approximately 22 weeks per participant.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The study will be conducted in a double-blind manner. Participants, investigators, and outcome assessors will remain blinded to treatment assignments. Only designated unblinded personnel (e.g., pharmacist or site staff responsible for drug preparation) will have access to treatment allocation information, and they will not be involved in any other study assessments.
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
- •Adults aged 18-65 years.
- •Part A: Healthy participants with BMI ≥20 kg/m² and ≤27 kg/m² at screening.
- •Part B: Healthy obese participants with BMI ≥30 kg/m² and ≤45 kg/m² at screening.
- •Stable body weight (<5% change) in the past 3 months.
- •Able and willing to provide written informed consent.
- •Male participants must use contraception or remain abstinent from women of childbearing potential.
- •Female participants must not be pregnant or breastfeeding and use highly effective contraception if of childbearing potential.
排除标准
- •History of any bariatric procedure.
- •Uncontrolled thyroid disease (TSH >6.0 or <0.4 mIU/L).
- •Abnormal liver function or clinically significant liver disease
- •Part A: ALT or AST ≥ ULN, or total bilirubin ≥ ULN
- •Part B: ALT or AST >2× ULN, or total bilirubin >1.5× ULN
- •Abnormal pancreatic function
- •Part A: amylase or lipase ≥ ULN
- •Part B: amylase or lipase >3× ULN
- •Clinically significant cardiovascular disorders (e.g., myocardial infarction, congestive heart failure, long QT syndrome).
- •Abnormal renal function (eGFR <60 mL/min/1.73 m²).
- •Positive test for hepatitis B, hepatitis C, or HIV at screening.
- •Women who are pregnant, planning to become pregnant, or breastfeeding.
- •History of drug or alcohol abuse within defined timeframes (e.g., alcohol >14 standard units/week in past year, or positive drug screen).
- •Use of any investigational product within 30 days or 5 half-lives (whichever is longer) prior to screening.
- •Additional Exclusion Criteria for Part B
- •HbA1c ≥6.5% or a history of diabetes mellitus (type 1 or type 2).
- •Obesity induced by other endocrine disorders (e.g., Cushing syndrome).
- •Use of weight control treatments (e.g., GLP-1 receptor agonists or other anti-obesity medications) and antihypertensive medications within 3 months prior to screening.
- •Use of any lipid-lowering medications, unless on a stable dose for at least 3 months prior to screening.
研究组 & 干预措施
HM17321
干预措施: HM17321 (Drug)
Placebo
干预措施: Placebo of HM17321 (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (TEAEs) Following Single and Multiple Subcutaneous Doses of HM17321
时间窗: Up to Day 29 (Part A); Up to Day 113 (Part B)
Number, type, and severity of treatment-emergent adverse events, including changes in vital signs, electrocardiograms, clinical laboratory tests, and immunogenicity assessments following administration of HM17321 or placebo
Incidence of Treatment-Emergent Adverse Events Following a Single Subcutaneous Dose of HM17321
时间窗: Up to Day 29
Number and type of treatment-emergent adverse events and changes in vital signs and laboratory tests up to Day 29
次要结局
- Peak Plasma Concentration (Cmax) of HM17321(Up to Day 29 (Part A); Up to Day 113 (Part B))
- Time to Maximum Plasma Concentration (Tmax) of HM17321(Up to Day 29 (Part A); Up to Day 113 (Part B))
- Area Under Plasma Concentration-Time Curve (AUC) of HM17321(Up to Day 29 (Part A); Up to Day 113 (Part B))
- Peak Plasma Concentration (Cmax) of HM17321(Up to Day 29)
- Time to Maximum Plasma Concentration (Tmax) of HM17321(Up to Day 29)
- Area Under Plasma Concentration-Time Curve (AUC) of HM17321(Up to Day 29)