A Phase 1 Study to Evaluate the Safety, Tolerability, PK/PD of SRSD107 in Healthy Participants

Thrombosis Clinical Trial

Official title:

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered SRSD107 in Healthy Participants

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06116617
• Other study ID #: SRSD107 101
• Status: Recruiting
• Phase: Phase 1
• Start date: January 23, 2024
• Est. completion date: August 2025

Study information

• Verified date: October 2023
• Source: Sirius Therapeutics Co., Ltd.
• Contact: Qiuyue Qu
• Phone: +86 21 61207756
• Email: medical[@]siriusrna.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate safety and tolerability data when SRSD107 is administered as single and multiple SC injections to healthy participants. This information, along with PK/PD data, will help establish the appropriate doses and dosing regimen for future studies in patients.

Description:

SRSD107 is a synthetic, chemically modified, double stranded, small interfering ribonucleic acid (siRNA). The antisense strand is designed to specifically recognize and cleave human factor XI (FXI) messenger ribonucleic acid (mRNA) which reduces FXI protein. FXI protein reduction may prevent thromboembolic events without increasing bleeding risk. This study will be a phase 1, randomized, double blind, placebo controlled, single and multiple ascending dose study conducted in two parts. Part A will comprise a single dose, sequential group design. A total of 40 participants will be studied in 5 groups (Groups A1 to A5), with each group comprising 8 participants. In each group, 6 participants will receive SRSD107 and 2 participants will receive placebo. Part B will comprise a multiple dose, sequential group design. A total of 24 participants will be studied in 3 groups (Groups B1 to B3), with each group comprising 8 participants. In each group, 6 participants will receive SRSD107 and 2 participants will receive placebo.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: August 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Body mass index between 18.0 and 32.0 kg/m2, inclusive.
• In good health, based on no clinically significant findings from medical history, 12 lead ECG, vital signs measurements, and clinical laboratory evaluations.
• Activated partial thromboplastin time and PT within the normal range.
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
• Able to understand and willing to sign an ICF and to abide by the study restrictions.

Exclusion Criteria:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
• History or evidence of any abnormal bleeding or coagulation disorder; or evidence of coagulopathy, prolonged or unexplained, clinically significant bleeding, or frequent unexplained bruising or thrombus formation; or a history of spontaneous bleeding.
• Evidence of an active or suspected cancer, or a history of malignancy, within 5 years prior to screening. Nonmelanoma skin cancer, curatively treated localized prostate cancer, or other carcinoma in situ are not exclusionary, providing that they did not require systemic therapy and are considered cured.
• Acute of febrile illness within 7 days prior to dose administration or evidence of active infection.
• Any major surgery within 3 months prior to screening or plan to have any surgery during the study.
• History of clinically significant hypersensitivity, intolerance, or allergy to any drug compound, oligonucleotide, GalNAc, food, or other substance, as determined by the investigator (or designee).
• Confirmed systolic blood pressure =140 mmHg or diastolic blood pressure =90 mmHg.
• QT interval corrected for heart rate using Fridericia's method (QTcF) >450 ms in males or >470 ms in females confirmed by repeat measurement.
• White blood cell count <3.5 × 109/L, platelets <100 × 109/L, or hemoglobin below the lower limit of normal.
• Alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, or total bilirubin >1.5 × the upper limit of normal (ULN).
• Estimated glomerular filtration rate <80 mL/min/1.73m2, as calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration equation.
• Positive hepatitis panel and/or positive human immunodeficiency virus test.
• Positive pregnancy test at screening or check in.
• Receipt of blood products within 2 months prior to check in.
• Loss of >500 mL whole blood or donation of blood products within 1 month prior to screening.
• History of intolerance to SC injections, or scarring (eg, from surgical procedures or burns) in areas when SC dose administration may occur.
• Participants who, in the opinion of the investigator (or designee), should not participate in this study.

Related Conditions & MeSH terms

• Thrombosis

Intervention

Drug:
• SRSD107
SRSD107 is a synthetic, chemically modified double-stranded, small interfering ribonucleic acid (siRNA).
• Placebo
Sodium chloride

Locations

Country	Name	City	State
Australia	Linear Clinical Research	Perth	Other (Non U.s.)

Sponsors (1)

Lead Sponsor	Collaborator
Sirius Therapeutics Co., Ltd.

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of adverse events (AEs)	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.	up to 168 days post last dose
Primary	Proportion of Serious Adverse Events (SAEs)	A serious AE (SAE) is defined as any untoward medical occurrence that at any dose either: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (disability is defined as a substantial disruption of a person's ability to conduct normal life functions); results in a congenital anomaly/birth defect; results in an important medical event (see below).	up to 168 days post last dose
Secondary	Cmax	Maximum observed plasma concentration	Group A, Day 1 to Day 3; Group B, Day 1 to Day 3 and Day 29 to 31
Secondary	tmax	Time to maximum plasma concentration	Group A, Day 1 to Day 3; Group B, Day 1 to Day 3 and Day 29 to 31
Secondary	t1/2	Plasma half-life	Group A, Day 1 to Day 3; Group B, Day 1 to Day 3 and Day 29 to 31
Secondary	AUC	Area under the plasma concentration-time curve from 0 to infinity	Group A, Day 1 to Day 3; Group B, Day 1 to Day 3 and Day 29 to 31
Secondary	CL/F	Apparent total clearance	Group A, Day 1 to Day 3; Group B, Day 1 to Day 3 and Day 29 to 31
Secondary	Effect of SRSD107 on circulating FXI Levels	Determination of % Lowering of FXI to Baseline FXI Level	up to 168 days post last dose
Secondary	Effect of SRSD107 on coagulation	Determination of % APTT to baseline APTT	up to 168 days post last dose