Clinical trial NCT05984992: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: siRNAgen Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-09
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events(TEAEs)
timeFrame: Up to 4 weeks
measure: Number of participants with serious adverse events(SAEs)
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: Cmax
timeFrame: Up to 168 hours post-dose
measure: Clast
timeFrame: Up to 168 hours post-dose
measure: Tlast
timeFrame: Up to 168 hours post-dose
measure: AUClast
timeFrame: Up to 168 hours post-dose
measure: AUCinf
timeFrame: Up to 168 hours post-dose
measure: T½
timeFrame: Up to 168 hours post-dose
measure: Kel
timeFrame: Up to 168 hours post-dose
measure: CL
timeFrame: Up to 168 hours post-dose
measure: Vz
timeFrame: Up to 168 hours post-dose
measure: MRT
timeFrame: Up to 168 hours post-dose
Other outcomes:
measure: Incidence of treatment-emergent Anti-Drug Antibody(ADA)
timeFrame: Up to 672 hours post-dose
measure: Change from baseline in specific biomarkers
timeFrame: Up to 24 hours post-dose
Locations:
city: Adelaide
country: Australia
facility: CMAX Clinical Research
state: South Australia
Study officials:
References:
citation: 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.