A Dose-Block Randomized, Placebo Controlled (Double-blind), Active Controlled(Open-label), Dose-escalation Study to Investigate the Tolerability, and Pharmacokinetics/Pharmacodynamics of HL2351 After a Single Subcutaneous Administration in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Handok Inc.
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Pharmacokinetics of HL2351: Apparent Volume of Distribution(Vz/F)
研究概览
简要总结
The study design of this trial is a Dose-Block Randomized, Placebo controlled (Double-blind), Active Controlled(Open-label), Dose-escalation.
详细描述
- Extended in vivo half-life of HL2351 is also anticipated to provide improved therapeutic efficacy based on sustained maintenance of an effective concentration.
- A safety concern may be addressed by utilizing IL-1Ra that is being used after getting approval by the EMA and the US FDA and known to be relatively safe, and the Fc fusion technology that has been already applied to various therapeutic agents.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •A healthy adult man aged between 20 and 45 years (inclusive) at screening
- •Weight between 55 and 90 kg (inclusive) and the body mass index(BMI) between 18.0 and 27.0 (inclusive)
- •BMI(kg/m2) = Body weight (kg)/{height (m)}2
- •Voluntary consent to participation in this study and signature on the IRB-approved informed consent form after being explained about characteristics of this clinical study, prior to any screening test
排除标准
- •Current or history of a clinically significant hepatic, renal, neurological, immunological, respiratory or endocrine disease or hematological or oncological disease, cardiovascular disease or psychiatric disease (mood disorder or compulsive disorder, etc.) (in case of a hepatic disease, a hepatitis virus-infected subject may be also included)
- •Hypersensitivity to a drug (aspirin or antibiotics, etc.) or past history of clinically significant hypersensitivity
- •In sitting vital signs measured after resting for 3 min or more, systolic blood pressure of <90mmHg or >150mmHg, or diastolic blood pressure of <60mmHg or >100 mmHg
- •Past history of drug abuse or positive urine drug screening results
- •Use of any prescription medicine or oriental medicine within 2 weeks or use of any over-the-counter(OTC) medication or vitamin preparation within 1 week prior to the scheduled first dose (however, a subject may be included if other conditions are satisfied, at the discretion of the investigator)
- •Participation in another clinical study and administration of a drug within 3 months prior to the scheduled first dose (from the dosing day)
- •Whole blood donation within 2 months or apheresis within 1 month prior to the scheduled first dose, or transfusion within 1 month prior to the first dose
- •A habitual drinker (>21 units/week, 1 unit = 10 g of pure alcohol) or a person who cannot abstain from alcohol consumption during hospitalization
- •A smoker of 10 cigarettes/day on average over the past 3 months or a person who cannot abstain from smoking during hospitalization
- •A person who is planning to get pregnant during the study or who cannot practice acceptable contraception (example: surgical sterilization of a subject or a partner, intrauterine device used by a partner, barrier contraception, diaphragm or condom used in combination) even if not planning to get pregnant
- •Notable prolongation of the QT/QTcb interval at screening (e.g., repeated confirmation of QTcb interval > 450 ms)
- •Confirmed history of a risk factor for TdP (e.g., heart failure, hypokalemia, family history of a long QT syndrome)
- •Chronic, uncontrolled or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosis)
- •Pyrexia of ≥38°C within 1 week prior to administration of the investigational product
- •Past history of tuberculosis infection and/or positive Quantiferon TB-Gold test results at screening
- •A person who had participated in this study and received the investigational product
- •A person who is otherwise determined as not eligible for clinical study participation by the investigator due to other reasons including clinical laboratory test results
研究组 & 干预措施
Kineret(Anakinra)
100 mg (SC) / Single-Dose
干预措施: Kineret(Anakinra) (Biological)
Placebo
1, 2, 4, 8, 12 mg/kg (SC) / Single-Dose
干预措施: HL2351 (Biological)
HL2351
1, 2, 4, 8, 12 mg/kg (SC) / Single-Dose
干预措施: HL2351 (Biological)
结局指标
主要结局
Pharmacokinetics of HL2351: Apparent Volume of Distribution(Vz/F)
时间窗: 29 days
To assess pharmacokinetics after single subcutaneous injection of HL2351
Tolerability as measured by Cytokine Laboratory Test
时间窗: 4 days
Cytokine Laboratory Test after single subcutaneous dose of HL2351 : check Day 1, 2, 4
Pharmacodynamics of HL2351: IL-6 inhibition assay
时间窗: 7 days
To assess the pharmacodynamic dose-response relationship after single subcutaneous injection of HL2351 IL-6 inhibition assay: AUEClast, Emax
Pharmacokinetics of HL2351: Maximum plasma concentration(Cmax)
时间窗: 29 days
To assess pharmacokinetics after single subcutaneous injection of HL2351
Tolerability as measured by Physical Examination, Vital Signs and Safety Laboratory Tests
时间窗: 29 days
Changes from baseline in physical examination, vital signs, ECG, clinical laboratory tests (routine hematology, routine chemistry, blood coagulation and urinalysis) after single subcutaneous dose of HL2351
Pharmacokinetics of HL2351: Area under plasma drug concentration-time curve [AUC(0-last), AUCinf]
时间窗: 29 days
To assess pharmacokinetics after single subcutaneous injection of HL2351
Tolerability as measured by the occurrence of Adverse Events
时间窗: 29 days
Adverse Events after single subcutaneous dose of HL2351 : check Day -1, 1, 2, 3, 4, 5, 7, 11, 15, 22, 29
Tolerability as measured by the occurrence of Local Toxicity
时间窗: 4 days
Local Toxicity after single subcutaneous dose of HL2351 : check Day 1, 2, 4
Pharmacokinetics of HL2351: Apparent Clearance(CL/F)
时间窗: 29 days
To assess pharmacokinetics after single subcutaneous injection of HL2351
Pharmacokinetics of HL2351: Time of maximum concentration(Tmax)
时间窗: 29 days
To assess pharmacokinetics after single subcutaneous injection of HL2351
Pharmacokinetics of HL2351: Elimination half-life(T1/2)
时间窗: 29 days
To assess pharmacokinetics after single subcutaneous injection of HL2351
Pharmacokinetics of HL2351: Mean Residence Time (MRT)
时间窗: 29 days
To assess pharmacokinetics after single subcutaneous injection of HL2351
次要结局
- Tolerability in comparison with Kineret(Anakinra): measured by the occurrence of Adverse Events(3 days)
- Pharmacokinetics in comparison with Kineret(Anakinra): Time of maximum concentration(Tmax)(3 days)
- Immunogenicity of HL2351: Anti-drug Antibody(Day 1, Day 29)
- Tolerability in comparison with Kineret(Anakinra): measured by Physical Examination, Vital Signs and Safety Laboratory Tests(3 days)
- Pharmacokinetics in comparison with Kineret(Anakinra): Mean Residence Time (MRT)(3 days)
- Pharmacodynamics in comparison with Kineret(Anakinra): IL-6 inhibition assay(1 day)
- Tolerability in comparison with Kineret(Anakinra): measured by the occurrence of Local Toxicity(3 days)
- Pharmacokinetics in comparison with Kineret(Anakinra): Elimination half-life(T1/2)(3 days)
- Pharmacokinetics in comparison with Kineret(Anakinra): Apparent Volume of Distribution(Vz/F)(3 days)
- Tolerability in comparison with Kineret(Anakinra): measured by Cytokine Laboratory Test(3 days)
- Pharmacokinetics in comparison with Kineret(Anakinra): Maximum plasma concentration(3 days)
- Pharmacokinetics in comparison with Kineret(Anakinra): Area under plasma drug concentration-time curve [AUC(0-last), AUCinf](3 days)
- Pharmacokinetics in comparison with Kineret(Anakinra): Apparent Clearance(CL/F)(3 days)