A Study to Compare the Efficacy and Safety of SRSD107 and Enoxaparin in Adult Subjects Undergoing TKA

Not Applicable

Not yet recruiting

• Conditions: Venous Thromboembolism
• Interventions: Drug: SRSD107; Drug: enoxaparin

• Registration Number: NCT07140523
• Lead Sponsor: Sirius Therapeutics Co., Ltd.

Brief Summary

This is a Phase 2, multicenter, randomized, open-label, parallel group, blinded endpoint evaluation, active-controlled, dose-finding study.This study is designed to compare the efficacy and safety of 3 dose levels of SRSD107 and enoxaparin 40 mg daily in subjects undergoing elective primary unilateral TKA.

Detailed Description

This study is designed to compare the efficacy and safety of 3 dose levels of SRSD107 and enoxaparin 40 mg daily in subjects undergoing elective primary unilateral TKA. While the identity of the study drug will be unblinded, the specific dose of SRSD107 will be blinded. Up to approximately 450 subjects will be randomized.

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-11
• Study Start: 2025-08-15
• Study First Submitted QC: 2025-08-18
• Last Update Submitted: 2025-08-18
• Study First Posted: 2025-08-24
• Last Update Posted: 2025-08-24
• Primary Completion: 2026-06-30
• Study Completion: 2026-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

1. Able to provide written informed consent before any study assessment is performed.
2. Male and female subjects, of any race, between 60 and 80 years of age, inclusive.
3. Body mass index between 18.0 and 35.0 kg/m2, inclusive.
4. Eligible to undergo elective primary unilateral TKA under general anesthesia.
5. Willing to comply with study requirements including taking study drug at least 28 days prior to TKA, clinic visits, and venography at 10-14 days post TKA.
6. aPTT, PT, and INR within the normal reference range at screening.

Exclusion Criteria

1. Active bleeding requiring medical or surgical intervention within 4 weeks prior to screening.
2. Known bleeding disorder; history of increased bleeding tendency or any other condition that in the opinion of the investigator contraindicates prophylactic anticoagulation.
3. History of intracranial, intraspinal, or intraocular bleeding.
4. Evidence of active cancer, or a history of malignancy, within 2 years prior to screening.
5. Myocardial infarction, DVT, PE, stroke , transient ischemic attack, systemic embolism, valvular thrombosis, or splanchnic thrombosis in the 6 months prior to screening.
6. Uncontrolled blood pressure at the time of screening.
7. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2.
8. Liver dysfunction, liver cirrhosis, history of hepatic encephalopathy, esophageal varices, or portocaval shunt.
9. Clinically significant anemia at screening.
10. Platelet counts <100,000/m3 at screening or a history of heparin-induced thrombocytopenia.
11. Positive test for human immunodeficiency virus (HIV) , positive hepatitis B surface antigen, and/or active hepatitis C at screening.
12. Ongoing or anticipated need for anticoagulation or antiplatelet therapy from 7 days prior to surgery through the EoS visit.
13. Participation in an interventional clinical study within 5 half-lives of the investigational drug or 30 days prior to screening, whichever is longer.
14. Use of any ASO or siRNA products within 1 year prior to screening. Diet and Lifestyle.
15. Recent or current history of alcoholism or recreational drug abuse.
16. History of hypersensitivity to any of the study drugs or its excipients, to drugs of similar chemical classes or drugs issued from the same biologic origin or any contraindication listed in the label for enoxaparin.
17. Unable to undergo venography due to a known allergy to the contrast agent, anticipated poor venous access, impaired renal function, or any other reason identified and specified by the investigator.
18. Anticipated elective surgery during the study period.
19. Any other condition or circumstance that would affect the subject's ability to be compliant with study drug administration or study procedures, in the opinion of the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SRSD107 low dose	SRSD107	Cohort 1: SRSD107, low dose level, subcutaneous (s.c.), single dose
SRSD107 medium dose	SRSD107	Cohort 2: SRSD107, medium dose level, subcutaneous (s.c.), single dose
SRSD107 high dose	SRSD107	Cohort 3: SRSD107, high dose level, subcutaneous (s.c.), single dose
Enoxaparin	enoxaparin	Cohort 4: Enoxaparin 40 mg s.c., once a day (q.d.), 12 ±2 days post-surgery

Primary Outcome Measures

Name	Time	Method
Incidence of total venous thromboembolism (VTE) events	From the date of surgery through 12±2 days after surgery.	Defined as deep vein thrombosis (DVT) (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), non-fatal and fatal PE, and unexplained death for which PE cannot be excluded.

Secondary Outcome Measures

Name	Time	Method
Incidence of major VTE	From the date of surgery through 12±2 days after surgery and Day 64, respectively.	Defined as objectively confirmed symptomatic DVT and PE, asymptomatic proximal DVT (confirmed by venogram), fatal PE, and unexplained death for which PE cannot be excluded.
Incidence of total VTE events	From the date of surgery through Day 64.	Defined as symptomatic DVT, asymptomatic DVT (confirmed by venogram), non-fatal and fatal PE, unexplained death for which PE cannot be excluded.
Incidence of total VTE events for each individual dosing cohort of SRSD107 compared to enoxaparin	From the date of surgery through 12±2 days after surgery.	Defined as symptomatic DVT, asymptomatic DVT (confirmed by venogram), non-fatal and fatal PE, unexplained death for which PE cannot be excluded.
Incidence of composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB)	From the Pre-surgical Period through 12±2 days after surgery.	Based on the 2013 Guideline on clinical investigation of medicinal products for prevention of venous thromboembolism (VTE) in patients undergoing high VTE-risk surgery (EMA/CHMP/325170/2012), as well as updated guidance from the International Society of Thrombosis and Haemostasis (ISTH; Schulman 2010).
Incidence of composite of MB, CRNMB, and any bleeding	From the Pre-surgical Period through 12±2 days after surgery, Day 64, and Day 169, respectively.	Based on the 2013 Guideline on clinical investigation of medicinal products for prevention of venous thromboembolism (VTE) in patients undergoing high VTE-risk surgery (EMA/CHMP/325170/2012), as well as updated guidance from the International Society of Thrombosis and Haemostasis (ISTH; Schulman 2010).
Incidence of MB	From the Pre-surgical Period through 12±2 days after surgery.	Based on the 2013 Guideline on clinical investigation of medicinal products for prevention of venous thromboembolism (VTE) in patients undergoing high VTE-risk surgery (EMA/CHMP/325170/2012), as well as updated guidance from the International Society of Thrombosis and Haemostasis (ISTH; Schulman 2010).
Incidence of CRNMB	From the Pre-surgical Period through 12±2 days after surgery.	Based on the 2013 Guideline on clinical investigation of medicinal products for prevention of venous thromboembolism (VTE) in patients undergoing high VTE-risk surgery (EMA/CHMP/325170/2012), as well as updated guidance from the International Society of Thrombosis and Haemostasis (ISTH; Schulman 2010).
Incidence of adverse events (AEs)	From Day 1 through Day 169.	An adverse event (AE) is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.