临床试验/NCT07407543

NCT07407543招募中1 期

A Randomized, Double-blind, Placebo-controlled, Multiple Doses, Dose-escalation Phase 1 Clinical Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SRN001 in Healthy Korean and Caucasian Adult Males

siRNAgen Therapeutics Inc.1 个研究点分布在 1 个国家目标入组 30 人开始时间: 2026年1月5日最近更新: 2026年2月12日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方
入组人数: 30
试验地点: 1
主要终点: Accumulation Ratio (R) of SRN001 at Steady State

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of SRN001 in healthy adult volunteers.

详细描述

SRN001 is a novel small interfering RNA (siRNA) drug being developed to treat fibrosis using Self Assembled Micelle inhibitory ribonucleic acid (SAMiRNA™) technology. Amphiregulin (AREG) is a growth factor involved in fibroblast proliferation and myofibroblast transformation which is the hallmark of fibrosis in lung and kidney tissues. AREG is a downstream gene overexpressed by Transforming growth factor-β (TGF-β) during fibrosis, promoting fibroblast to myofibroblast transition (FMT). SRN001 is designed to downregulate generating amphiregulin by RNA interference (RNAi). The goal of this clinical trial is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of SRN001 in healthy Korean and Caucasian adult males.

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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围: 19 Years 至 60 Years（Adult）
性别: Male
接受健康志愿者: 是

入选标准

•Healthy Korean or Caucasian male volunteers aged 19 to 60 years at the time of screening.
•Those who weighed 50.0 kg or more at the time of screening and had a body mass index (BMI) between 18.5 kg/m2 and 29.9 kg/m
•Body mass index (BMI, kg/m2) = weight (kg) / {height (m2)} 2
•Those whose screening results showed a serum amphiregulin concentration of 100 pg/mL or higher.
•Those who voluntarily agreed to participate in this clinical trial after receiving a thorough explanation and fully understanding the clinical trial. Those who decided to participate and gave written consent to comply with the precautions.

排除标准

•Those with or have a history of clinically significant diseases of the hepatobiliary system (severe liver failure, viral hepatitis, etc.), kidney (severe renal failure, etc.), nervous system, immune system, respiratory system, digestive system, endocrine system, hematological/oncological system, cardiovascular system (heart failure, torsades de pointes, etc.), urinary system, psychiatric system (mood disorder, obsessive-compulsive disorder, etc.), or sexual dysfunction.
•Those with a history of hypersensitivity to RNA drugs or other drugs (aspirin, antibiotics, etc.) or a history of clinically significant hypersensitivity reactions (atopy, asthma, etc.).
•Those with a positive serum test result (hepatitis B test, hepatitis C test, human immunodeficiency virus (HIV) test, syphilis test).
•Those with a history of drug abuse or a positive urine drug screening test for drugs of abuse.
•Those who were screened in a sitting position after resting for at least 3 minutes. Those who exhibited the following values in measured vital signs:
•Systolic blood pressure < 80 mmHg or ≥ 140 mmHg
•Diastolic blood pressure < 45 mmHg or ≥ 90 mmHg
•Pulse < 45 bpm or > 100 bpm
•Body temperature < 35.5 ℃ or > 37.7 ℃
•Those who exhibited the following values or clinically significant abnormal rhythm findings on the electrocardiogram (12-lead ECG) during the screening test:
•QTcF > 450 msec
•Those who exhibited one or more of the following results in clinical laboratory tests during the screening test, including additional tests:
•AST (SGOT) or ALT (SGPT) > 60 IU/L
•Estimated glomerular filtration rate (CKD-EPI equation) < 60 mL/min/1.73 m2
•Those who have taken any prescription drugs or herbal medicines within two weeks prior to the scheduled first administration of the investigational drug, or have taken any over-the-counter drugs, health functional foods including liver function supplements, or vitamin preparations within one week (however, at the investigator's discretion, subjects may be selected as subjects if other conditions are appropriate) or are expected to take such drugs.
•Those who have taken drug-metabolizing enzyme inducers such as barbiturates or drug metabolism inhibitors such as clarithromycin within one month prior to the scheduled first administration of the investigational drug.
•Those who have participated in another clinical trial (including bioequivalence trials) and received the investigational drug within six months prior to the scheduled first administration of the investigational drug.
•Those who have donated whole blood within two months prior to the scheduled first administration of the investigational drug, or have donated blood components within one month prior to the scheduled first administration of the investigational drug, or have received a blood transfusion.
•Smokers (however, subjects may be selected as subjects if they quit smoking three months prior to the scheduled first administration of the investigational drug) or those who are unable to quit smoking until the completion of the clinical trial.
•Those who have continuously consumed alcohol (21 units/week, 1 unit = 10 g of pure alcohol) or cannot abstain from alcohol from 3 days before the scheduled first dose of the investigational drug until the end of the clinical trial.
•Those who have continuously consumed excessive caffeine (more than 5 units/day, 1 unit = 80 mg of caffeine) or cannot abstain from consuming caffeinated foods and beverages (coffee, tea (black tea, green tea, etc.), carbonated beverages, coffee drinks, coffee milk, tonic drinks, energy drinks, etc.) from 3 days before the scheduled first dose of the investigational drug until the end of the clinical trial.
•Those who cannot abstain from consuming grapefruit (grapefruit), grapefruit juice, or grapefruit-containing foods from 3 days before the scheduled first dose of the investigational drug until the end of the clinical trial.
•Those who have unusual eating habits (e.g., consuming more than 1 L of grapefruit juice per day) or cannot consume the standardized diet provided by the clinical trial center during their hospitalization.
•Those who use their own condoms from 3 days before the scheduled first dose of the investigational drug until the end of the clinical trial. Women of childbearing potential (spouse or partner) who do not consent to a contraceptive method considered highly effective.
•[Contraceptive methods considered highly effective]
•Those who do not agree to refrain from donating sperm from 3 days prior to the scheduled first dose of the investigational drug until the end of the clinical trial.
•Those whom the investigator determines to be unsuitable for clinical trial participation for reasons other than those listed above.

研究组 & 干预措施

cohort1 Drug: SRN001 45mg

Experimental

cohort1 Drug: SRN001 45mg

干预措施: SRN001 (Drug)

cohort2 Drug: SRN001 90mg

Experimental

cohort2 Drug: SRN001 90mg

干预措施: SRN001 (Drug)

cohort3 Drug: SRN001 180mg

Experimental

cohort3 Drug: SRN001 180mg

干预措施: SRN001 (Drug)

Placebo Comparator

Participants receive placebo (0.9% sodium chloride, normal saline)

干预措施: 0.9% sodium chloride (normal saline) (Drug)

结局指标

主要结局

Accumulation Ratio (R) of SRN001 at Steady State

时间窗: Pre-dose samples: Day 1, Day 15, and Day 29 (pre-dose) Post-dose samples (Day 1 and Day 29): 0 (end of infusion), 10, 20, 30, and 45 minutes, and 1, 1.5, 2, 3, 6, 12, 24, and 48 hours after dosing

Accumulation ratio (R) comparing exposure at steady state with that after the first dose (e.g., based on Cmax or AUC).

Incidence of Treatment-Emergent Adverse Events (TEAEs)

时间窗: From first dose through end of study (up to 114 days)

Number of participants experiencing one or more TEAEs during the study period.

Number of participants with serious adverse events (SAEs)

时间窗: From first dose through end of study (up to 114 days)

Number of participants with SAEs as defined in protocol.

Number of participants with clinically significant abnormal laboratory results

时间窗: From first dose through end of study (up to 114 days)

Counts of clinically significant abnormal lab tests during study.

Maximum Observed Plasma Concentration (Cmax) of SRN001

时间窗: Pre-dose samples: Day 1, Day 15, and Day 29 (pre-dose)

Maximum observed plasma concentration (Cmax) following IV administration of SRN001.

Time to Maximum Plasma Concentration (Tmax) of SRN001

Time to reach maximum observed plasma concentration following IV administration.

Area Under the Curve from time zero to last measurable concentration (AUClast)

AUClast of SRN001 plasma concentration versus time curve.

Area Under the Plasma Concentration-Time Curve over the Dosing Interval (AUCtau) of SRN001

AUCtau will be calculated as the area under the plasma concentration versus time curve over one complete dosing interval following multiple escalating intravenous doses of SRN001.

Terminal Half-Life (t½) of SRN001

Terminal elimination half-life (t½) will be calculated from the plasma concentration-time profile at steady state following multiple doses.

Clearance (CL) of SRN001

Systemic clearance (CL) will be determined from non-compartmental analysis of plasma concentrations at steady state after multiple dosing.

Apparent Volume of Distribution (Vz) of SRN001

Apparent volume of distribution (Vz) will be calculated from plasma concentration data at steady state following multiple doses.

Time to Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of SRN001

Time to reach maximum observed plasma concentration at steady state following multiple intravenous doses.

Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of SRN001

Maximum observed plasma concentration at steady state following multiple intravenous doses.

Minimum Observed Plasma Concentration at Steady State (Cmin,ss) of SRN001

Minimum observed plasma concentration at steady state following multiple doses.

Average Plasma Concentration at Steady State (Cavg,ss) of SRN001

Average plasma concentration at steady state following multiple intravenous doses.

Trough Plasma Concentration at Steady State (Ctrough) of SRN001

Plasma concentration just prior to the next dose at steady state following multiple dosing.

Area Under the Plasma Concentration-Time Curve over the Dosing Interval at Steady State (AUCtau,ss) of SRN001

AUCtau,ss will be calculated over one dosing interval at steady state following multiple intravenous doses.

Peak-to-Trough Fluctuation (PTF) of SRN001 at Steady State Description: Peak-to-trough fluctuation in plasma concentration at steady state, defined as (Cmax,ss - Cmin,ss)/Cavg,ss.

Pre-dose samples: Day 1, Day 15, and Day 29 (pre-dose)

次要结局

未报告次要终点

研究者

发起方

siRNAgen Therapeutics Inc.

申办方类型

Industry

责任方

Sponsor

研究点 (1)

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