The First-in-human Study of SRN-001 in Healthy Participants
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SRN-001
|
Drug: SRN-001
siRNA therapeutics, Self Assembled Micelle inhibitory RNA platform utilized
|
| Placebo Comparator: Placebo
|
Drug: Placebo
0.9% Sodium Chloride(Normal saline)
|
Outcome Measures
Primary Outcome Measures
- 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
- Cmax [Up to 168 hours post-dose]
Maximum observed concentration
- Clast [Up to 168 hours post-dose]
Observed concentration corresponding to Tlast
- Tlast [Up to 168 hours post-dose]
Time of last measurable observed concentration
- AUClast [Up to 168 hours post-dose]
Area under the drug concentration-time curve, from time zero to the last measurable concentration
- AUCinf [Up to 168 hours post-dose]
Area under the drug concentration-time curve, from time zero to infinity
- T½ [Up to 168 hours post-dose]
Apparent terminal half-life
- Kel [Up to 168 hours post-dose]
Apparent terminal elimination rate constant
- CL [Up to 168 hours post-dose]
Total body clearance
- Vz [Up to 168 hours post-dose]
Volume of distribution
- MRT [Up to 168 hours post-dose]
Mean residence time
Other Outcome Measures
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 18-60
-
BMI ≥18.0 kg/m2 and ≤32 kg/m2
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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
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Compliance to contraception restriction
-
Participants who are able and willing to give written informed consent
Exclusion Criteria:
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Who has clinically significant history
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Who is with history of multiple drug allergies or history of allergic reaction to an oligonucleotide or common medicine or clinically significant hypersensitivity
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No tolerance to IV injections or significant potential of intolerance
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Clinically significant surgical history within 1 year
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History of drug abuse or alcoholism within 2 years
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Pregnant or lactating females
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Liver function test is 1.5 times greater than upper limit of normal (ULN)
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Albumin ≥ 35 g/L and ≤ 50 g/L
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Hb < 115 g/L (female), < 125 g/L (male)
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estimated glomerular filtration rate (eGFR) < 60 mL/min (CKD-EPI), 90 mL/min (MDRD)
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Glucose < 3 mmol/L
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Positive screen for alcohol or drugs of abuse
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HBsAg, Hepatitis B virus (HBV), Hepatitis C virus (HCV), or HIV infection
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QTcF > 450 msec for male, > 470 msec for female
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Inappropriate lab result by physician's discretion
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Who have donated > 500 mL of blood within 3 months
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Who have received an investigational agent within 3 months, or 5 half-lives
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Who have used prescription medication within 4 weeks including vaccines
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Who have used OTC medication within 7 days
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With clinically relevant wounds, following a clinically relevant surgery or have recently completed any invasive procedures within 1 week
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Who have a significant infection or known inflammatory process ongoing
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Any conditions that, in physician's opinion,, would make the participant unsuitable for enrollment or could interfere with the participant's participation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CMAX Clinical Research | Adelaide | South Australia | Australia | 5000 |
Sponsors and Collaborators
- siRNAgen Therapeutics Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- SRN-001-C01