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

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

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: SRN-001; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18-70
• BMI ≥18.0 kg/㎡ and ≤35 kg/㎡
• 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 ≤100 bpm; tympanic temperature ≥ 35.5°C and ≤37.7°C and respiratory rate 12rpm to 22rpm
• Negative urinary cotinine
• Compliance to contraception and sperm donation restriction
• Participants who are able and willing to give written informed consent
• Fully vaccinated against SARS-CoV-2

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 (eg, aspirin, antibiotics, etc) 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, and a restriction of consuming alcohol during study period
• 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 (ie, Endoscopy) within 1 week, or who are scheduled for an elective surgical procedure
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent Anti-Drug Antibody(ADA)	Up to 672 hours post-dose
Change from baseline in specific biomarkers	Up to 24 hours post-dose

Collaborators and Investigators

• Sponsor: siRNAgen Therapeutics Inc.

Publications and helpful links

General Publications

• Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol. 1974 Jan;111(1):58-64. doi: 10.1016/s0022-5347(17)59889-4. No abstract available.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2023
• Primary Completion (Actual): March 15, 2024
• Study Completion (Actual): September 25, 2024

Study Registration Dates

• First Submitted: July 26, 2023
• First Submitted That Met QC Criteria: August 2, 2023
• First Posted (Actual): August 9, 2023

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: SRN-001-C01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No