A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SRN001 in Healthy Korean and Caucasian Adult Males

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

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

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: SRN001; Drug: 0.9% sodium chloride (normal saline)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Eunkyeong Woo; Phone Number: +82-42-930-8654; Email: wek@sirnagen.com

Study Locations

• South Korea
  • Seoul, South Korea
    • Recruiting
    • Seoul National University Hospital
    • Contact: InJin Jang; Phone Number: +82-10-7573-2458; Email: ijjang@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy Korean or Caucasian male volunteers aged 19 to 60 years at the time of screening.

2. 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/m2.

   Body mass index (BMI, kg/m2) = weight (kg) / {height (m2)} 2

3. Those whose screening results showed a serum amphiregulin concentration of 100 pg/mL or higher.
4. 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.

Exclusion Criteria:

1. 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.
2. 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.).
3. Those with a positive serum test result (hepatitis B test, hepatitis C test, human immunodeficiency virus (HIV) test, syphilis test).
4. Those with a history of drug abuse or a positive urine drug screening test for drugs of abuse.

5. 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 ℃

6. 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

7. 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
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.

17. 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]

18. 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.
19. Those whom the investigator determines to be unsuitable for clinical trial participation for reasons other than those listed above.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cohort1 Drug: SRN001 45mg	Drug: SRN001; SRN001 is an investigational drug administered at doses of 45 mg, 90 mg, or 180 mg depending on cohort.
Experimental: cohort2 Drug: SRN001 90mg	Drug: SRN001; SRN001 is an investigational drug administered at doses of 45 mg, 90 mg, or 180 mg depending on cohort.
Experimental: cohort3 Drug: SRN001 180mg	Drug: SRN001; SRN001 is an investigational drug administered at doses of 45 mg, 90 mg, or 180 mg depending on cohort.
Placebo Comparator: Placebo Comparator; Participants receive placebo (0.9% sodium chloride, normal saline)	Drug: 0.9% sodium chloride (normal saline); 0.9% sodium chloride solution administered as placebo control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (TEAEs)	Number of participants experiencing one or more TEAEs during the study period.	From first dose through end of study (up to 114 days)
Number of participants with serious adverse events (SAEs)	Number of participants with SAEs as defined in protocol.	From first dose through end of study (up to 114 days)
Number of participants with clinically significant abnormal laboratory results	Counts of clinically significant abnormal lab tests during study.	From first dose through end of study (up to 114 days)
Maximum Observed Plasma Concentration (Cmax) of SRN001	Maximum observed plasma concentration (Cmax) following IV administration of SRN001.	Pre-dose samples: Day 1, Day 15, and Day 29 (pre-dose)
Time to Maximum Plasma Concentration (Tmax) of SRN001	Time to reach maximum observed plasma concentration following IV administration.	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
Area Under the Curve from time zero to last measurable concentration (AUClast)	AUClast of SRN001 plasma concentration versus time curve.	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
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.	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
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.	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
Clearance (CL) of SRN001	Systemic clearance (CL) will be determined from non-compartmental analysis of plasma concentrations at steady state after multiple dosing.	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
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.	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
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.	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
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of SRN001	Maximum observed plasma concentration at steady state following multiple intravenous doses.	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
Minimum Observed Plasma Concentration at Steady State (Cmin,ss) of SRN001	Minimum observed plasma concentration at steady state following multiple doses.	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
Average Plasma Concentration at Steady State (Cavg,ss) of SRN001	Average plasma concentration at steady state following multiple intravenous doses.	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
Trough Plasma Concentration at Steady State (Ctrough) of SRN001	Plasma concentration just prior to the next dose at steady state following multiple dosing.	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
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.	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
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)	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) of SRN001 at Steady State	Accumulation ratio (R) comparing exposure at steady state with that after the first dose (e.g., based on Cmax or AUC).	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Serum Amphiregulin Concentration	Baseline to post-study visit (pre-dose on Days 1, 15, and 29; post-dose on Days 1 and 29 at 2 and 12 hours; and at Days 43, 57, 85, and end-of-study)	Changes from baseline in circulating amphiregulin concentrations will be evaluated using 11 blood sampling time points, including pre-dose, early post-dose, and follow-up assessments.
Changes in PBMC LPS-Stimulated Amphiregulin Levels	PBMCs collected will be stimulated ex vivo with LPS, and increases in amphiregulin concentrations relative to baseline will be measured across 7 sampling time points.	Baseline to Day 29 (pre-dose on Days 1, 15, and 29; post-dose at 2 and 24 hours on Days 1 and 29)
Changes in Urine Albumin-to-Creatinine Ratio (uACR)	Changes from baseline in urine ACR (albumin/creatinine ratio) will be assessed.	Day 1 to 48 hours post-dose on Day 29 (pre-dose and 0-3, 3-6, 6-12, 12-24, and 24-48 hours post-dose)
Changes in Serum Inflammatory Cytokines (IFN-γ, IL-6, IL-1β, TNFα)	Changes from baseline in serum concentrations of IFN-γ, IL-6, IL-1β, and TNFα will be assessed at 12 time points, including pre-dose and multiple post-dose intervals.	Baseline to Day 29 (pre-dose on Days 1, 15, and 29; post-dose 1, 6, and 12 hours on Days 1, 15, and 29)
Incidence of Anti-SRN001 Antibody Formation	Presence of anti-SRN001 antibodies will be evaluated. If antibody positivity is detected, antibody titers will be quantified across five serum sampling time points.	Baseline to end-of-study visit (pre-dose on Days 1, 15, and 29; and follow-up on Day 57 and post-study visit)
Maximum Observed SRN001 Concentration in PBMCs (Cmax)	Cmax is the maximum observed SRN001 concentration in peripheral blood mononuclear cells following drug administration.	30 Minutes Post-Dose on Day 1
Area Under PBMC Concentration-Time Curve (AUCtau)	AUCtau is the area under the plasma concentration versus time curve over the dosing interval for SRN001 in PBMCs.	Sampling up to 12 Hours Post-Dose on Day 1
Area Under PBMC Concentration-Time Curve from Time Zero to Last Measurement (AUClast)	AUClast is the area under the PBMC concentration versus time curve from predose until the last quantifiable concentration.	Sampling up to 12 Hours Post-Dose on Day 1
Maximum Observed SRN001 Concentration in PBMCs at Steady State (Cmax,ss)	Cmax,ss is the maximum SRN001 concentration observed in PBMCs at steady state after multiple doses.	30 Minutes Post-Dose on Day 29
Area Under PBMC Concentration-Time Curve at Steady State (AUCtau,ss)	AUCtau,ss is the area under the PBMC concentration versus time curve over one dosing interval at steady state.	Sampling up to 12 Hours Post-Dose on Day 29
Accumulation Ratio of SRN001 in PBMCs (R)	Accumulation ratio is the ratio of exposure at steady state (AUCtau,ss) relative to single dose exposure (AUCtau).	From Predose on Day 1 and Predose on Day 29
PBMC-to-Plasma Concentration Ratio of SRN001 at Steady State	Ratio of SRN001 concentration in PBMCs versus plasma at steady state.	Sampling at 30 Minutes Post-Dose on Day 29
Change in Serum Amphiregulin Concentration from Baseline to 2 Hours Post-Dose on Day 1	Change from baseline in circulating amphiregulin concentration through 2 hours after dosing on Day 1, as measured in blood samples.	Baseline and 2 Hours Post-Dose on Day 1
Change in Serum Amphiregulin Concentration from Baseline to 12 Hours Post-Dose on Day 1	Change from baseline in circulating amphiregulin concentration through 12 hours after dosing on Day 1.	Baseline and 12 Hours Post-Dose on Day 1
Change in Serum Amphiregulin Concentration from Baseline to Predose on Day 15	Change from baseline in circulating amphiregulin concentration measured prior to dosing on Day 15.	Baseline and Predose on Day 15
Change in Serum Amphiregulin Concentration from Baseline to Predose on Day 29	Change from baseline in circulating amphiregulin concentration measured prior to dosing on Day 29.	Baseline and Predose on Day 29.
Change in Serum Amphiregulin Concentration from Baseline to Predose on Day 43	Change from baseline in circulating amphiregulin concentration measured at predose (0 hour) on Day 43.	Baseline and Predose on Day 43
Change in Serum Amphiregulin Concentration from Baseline to Predose on Day 57	Change from baseline in circulating amphiregulin concentration measured at predose (0 hour) on Day 57.	Baseline and Predose on Day 57
Change in Serum Amphiregulin Concentration from Baseline to Predose on Day 85	Change from baseline in circulating amphiregulin concentration measured at predose (0 hour) on Day 85.	Baseline and Predose on Day 85
Change in Serum Amphiregulin Concentration from Baseline to End-of-Study Visit (Post-Study Visit)	Change from baseline in circulating amphiregulin concentration measured at the post-study visit conducted between Day 111 and Day 114.	Baseline and Day 111-114

Collaborators and Investigators

• Sponsor: siRNAgen Therapeutics Inc.

Publications and helpful links

General Publications

• Yoon PO, Park JW, Lee CM, Kim SH, Kim HN, Ko Y, Bae SJ, Yun S, Park JH, Kwon T, Kim WS, Lee J, Lu Q, Kang HR, Cho WK, Elias JA, Yang JS, Park HO, Lee K, Lee CG. Self-assembled Micelle Interfering RNA for Effective and Safe Targeting of Dysregulated Genes in Pulmonary Fibrosis. J Biol Chem. 2016 Mar 18;291(12):6433-46. doi: 10.1074/jbc.M115.693671. Epub 2016 Jan 27.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: January 5, 2026
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Pharmaceutical Preparations; Inorganic Chemicals; Chlorine Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Sodium Compounds; Chlorides; Hydrochloric Acid; Saline Solution; Sodium Chloride
• Other Study ID Numbers: SRN001-CA-25001A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No