The First-in-human Study of SRN-001 in Healthy Participants

Study Overview
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Brief Summary
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SRN-001 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). SRN-001 is designed to downregulate generating amphiregulin by RNA interference (RNAi). The goal of this clinical trial is to evaluate safety, tolerability, and pharmacokinetics in healthy participants. This trial is first-in-human clinical trial to develop SAMiRNA™ to utilize as therapeutic use.

Detailed Description
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Participants with part in consent will be enrolled in a phase 1a study of SRN-001. Prior to initiation of treatment, participants will undergo several screening test for checking their condition of health. There is no specific test comparing with the general other clinical trial in healthy volunteers. They will be randomized into two groups, active drug and inactive placebo(normal saline) as ratio 2:1. Starting dose is planned 15mg. For confirming maximal tolerable dose, dose will be escalated when no dose-limiting toxicity (DLT) confirmed. Each cohort will take single dose and for 4 weeks, safety observation will be taken. If safety abnormality will be retained in 4 weeks, the participant's safety observation will be prolonged by the end of the adverse event once 2 weeks.

Official Title
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A Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of SRN-001 in Healthy Participants

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: SRN-001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-60 BMI ≥18.0 kg/m2 and ≤32 kg/m2 12-lead triplicate electrocardiogram (ECG) readings within normal limits or with no clinically significant abnormalities systolic blood pressure ≥ 90 mmHg and ≤160 mmHg; a diastolic blood pressure ≥ 50 mmHg and ≤95 mmHg; pulse ≥ 45 bpm and ≤100bpm; tympanic temperature ≥ 35.5°C and ≤37.7°C and respiratory rate 12rpm to 22rpm non-smokers Compliance to contraception restriction Participants who are able and willing to give written informed consent Exclusion Criteria: Who has clinically significant history Who is with history of multiple drug allergies or history of allergic reaction to an oligonucleotide or common medicine or clinically significant hypersensitivity No tolerance to IV injections or significant potential of intolerance Clinically significant surgical history within 1 year History of drug abuse or alcoholism within 2 years Pregnant or lactating females Liver function test is 1.5 times greater than upper limit of normal (ULN) Albumin ≥ 35 g/L and ≤ 50 g/L Hb < 115 g/L (female), < 125 g/L (male) estimated glomerular filtration rate (eGFR) < 60 mL/min (CKD-EPI), 90 mL/min (MDRD) Glucose < 3 mmol/L Positive screen for alcohol or drugs of abuse HBsAg, Hepatitis B virus (HBV), Hepatitis C virus (HCV), or HIV infection QTcF > 450 msec for male, > 470 msec for female Inappropriate lab result by physician's discretion Who have donated > 500 mL of blood within 3 months Who have received an investigational agent within 3 months, or 5 half-lives Who have used prescription medication within 4 weeks including vaccines Who have used OTC medication within 7 days With clinically relevant wounds, following a clinically relevant surgery or have recently completed any invasive procedures within 1 week Who have a significant infection or known inflammatory process ongoing Any conditions that, in physician's opinion,, would make the participant unsuitable for enrollment or could interfere with the participant's participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SRN-001<br> | Drug: SRN-001<br>* siRNA therapeutics, Self Assembled Micelle inhibitory RNA platform utilized<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 0.9% Sodium Chloride(Normal saline)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events(TEAEs) |  | Up to 4 weeks | 
| Number of participants with serious adverse events(SAEs) |  | Up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum observed concentration | Up to 168 hours post-dose | 
| Clast | Observed concentration corresponding to Tlast | Up to 168 hours post-dose | 
| Tlast | Time of last measurable observed concentration | Up to 168 hours post-dose | 
| AUClast | Area under the drug concentration-time curve, from time zero to the last measurable concentration | Up to 168 hours post-dose | 
| AUCinf | Area under the drug concentration-time curve, from time zero to infinity | Up to 168 hours post-dose | 
| T½ | Apparent terminal half-life | Up to 168 hours post-dose | 
| Kel | Apparent terminal elimination rate constant | Up to 168 hours post-dose | 
| CL | Total body clearance | Up to 168 hours post-dose | 
| Vz | Volume of distribution | Up to 168 hours post-dose | 
| MRT | Mean residence time | Up to 168 hours post-dose |