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

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05984992
• Other study ID #: SRN-001-C01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 8, 2023
• Est. completion date: August 15, 2024

Study information

• Verified date: March 2024
• Source: siRNAgen Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: August 15, 2024
• Est. primary completion date: March 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• SRN-001
siRNA therapeutics, Self Assembled Micelle inhibitory RNA platform utilized
• Placebo
0.9% Sodium Chloride(Normal saline)

Locations

Country	Name	City	State
Australia	CMAX Clinical Research	Adelaide	South Australia

Sponsors (1)

Lead Sponsor	Collaborator
siRNAgen Therapeutics Inc.

Country where clinical trial is conducted

Australia, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of treatment-emergent Anti-Drug Antibody(ADA)		Up to 672 hours post-dose
Other	Change from baseline in specific biomarkers		Up to 24 hours post-dose
Primary	Number of participants with treatment-emergent adverse events(TEAEs)		Up to 4 weeks
Primary	Number of participants with serious adverse events(SAEs)		Up to 4 weeks
Secondary	Cmax	Maximum observed concentration	Up to 168 hours post-dose
Secondary	Clast	Observed concentration corresponding to Tlast	Up to 168 hours post-dose
Secondary	Tlast	Time of last measurable observed concentration	Up to 168 hours post-dose
Secondary	AUClast	Area under the drug concentration-time curve, from time zero to the last measurable concentration	Up to 168 hours post-dose
Secondary	AUCinf	Area under the drug concentration-time curve, from time zero to infinity	Up to 168 hours post-dose
Secondary	T½	Apparent terminal half-life	Up to 168 hours post-dose
Secondary	Kel	Apparent terminal elimination rate constant	Up to 168 hours post-dose
Secondary	CL	Total body clearance	Up to 168 hours post-dose
Secondary	Vz	Volume of distribution	Up to 168 hours post-dose
Secondary	MRT	Mean residence time	Up to 168 hours post-dose

External Links

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