Back to resultsThe First-in-human Study of SRN-001 in Healthy Participants
Primary Purpose
Idiopathic Pulmonary Fibrosis
Status
Recruiting
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
SRN-001
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis
Eligibility Criteria
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
Sites / Locations
- CMAX Clinical ResearchRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
SRN-001
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Number of participants with treatment-emergent adverse events(TEAEs)
Number of participants with serious adverse events(SAEs)
Secondary Outcome Measures
Cmax
Maximum observed concentration
Clast
Observed concentration corresponding to Tlast
Tlast
Time of last measurable observed concentration
AUClast
Area under the drug concentration-time curve, from time zero to the last measurable concentration
AUCinf
Area under the drug concentration-time curve, from time zero to infinity
T½
Apparent terminal half-life
Kel
Apparent terminal elimination rate constant
CL
Total body clearance
Vz
Volume of distribution
MRT
Mean residence time
Full Information
NCT ID
NCT05984992
First Posted
July 26, 2023
Last Updated
September 15, 2023
Sponsor
siRNAgen Therapeutics Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05984992
Brief Title
The First-in-human Study of SRN-001 in Healthy Participants
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 8, 2023 (Actual)
Primary Completion Date
January 3, 2024 (Anticipated)
Study Completion Date
March 15, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
siRNAgen Therapeutics Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Pulmonary Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SRN-001
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
SRN-001
Intervention Description
siRNA therapeutics, Self Assembled Micelle inhibitory RNA platform utilized
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
0.9% Sodium Chloride(Normal saline)
Primary Outcome Measure Information:
Title
Number of participants with treatment-emergent adverse events(TEAEs)
Time Frame
Up to 4 weeks
Title
Number of participants with serious adverse events(SAEs)
Time Frame
Up to 4 weeks
Secondary Outcome Measure Information:
Title
Cmax
Description
Maximum observed concentration
Time Frame
Up to 168 hours post-dose
Title
Clast
Description
Observed concentration corresponding to Tlast
Time Frame
Up to 168 hours post-dose
Title
Tlast
Description
Time of last measurable observed concentration
Time Frame
Up to 168 hours post-dose
Title
AUClast
Description
Area under the drug concentration-time curve, from time zero to the last measurable concentration
Time Frame
Up to 168 hours post-dose
Title
AUCinf
Description
Area under the drug concentration-time curve, from time zero to infinity
Time Frame
Up to 168 hours post-dose
Title
T½
Description
Apparent terminal half-life
Time Frame
Up to 168 hours post-dose
Title
Kel
Description
Apparent terminal elimination rate constant
Time Frame
Up to 168 hours post-dose
Title
CL
Description
Total body clearance
Time Frame
Up to 168 hours post-dose
Title
Vz
Description
Volume of distribution
Time Frame
Up to 168 hours post-dose
Title
MRT
Description
Mean residence time
Time Frame
Up to 168 hours post-dose
Other Pre-specified Outcome Measures:
Title
Incidence of treatment-emergent Anti-Drug Antibody(ADA)
Time Frame
Up to 672 hours post-dose
Title
Change from baseline in specific biomarkers
Time Frame
Up to 24 hours post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dongho Kim
Phone
+82-42-930-8654
Email
dongho-kim@sirnagen.com
Facility Information:
Facility Name
CMAX Clinical Research
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victoria Lingleson
Phone
61413063547
Email
victoria.ingleson@cmax.com.au
First Name & Middle Initial & Last Name & Degree
Jessica Micarone
Phone
61416793321
Email
jessica.micarone@cmax.com.au
First Name & Middle Initial & Last Name & Degree
Nicholas Farinola
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
26817844
Citation
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.
Results Reference
background
Links:
URL
https://pubmed.ncbi.nlm.nih.gov/26817844/
Description
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The First-in-human Study of SRN-001 in Healthy Participants
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