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.

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.

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.