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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
450
SRSD107 is an investigational siRNA product for anticoagulants.
Enoxaparin is a low molecular weight heparin \[LMWH\] indicated for Prophylaxis of deep vein thrombosis (DVT) in abdominal surgery, hip replacement surgery, knee replacement surgery, or medical patients with severely restricted mobility during acute illness.
Hospital Nové Město na Moravě
Nové Město na Moravě, Czechia
RECRUITINGIncidence of total venous thromboembolism (VTE) events
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.
Time frame: From the date of surgery through 12±2 days after surgery.
Incidence of major VTE
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.
Time frame: From the date of surgery through 12±2 days after surgery and Day 64, respectively.
Incidence of total VTE events
Defined as symptomatic DVT, asymptomatic DVT (confirmed by venogram), non-fatal and fatal PE, unexplained death for which PE cannot be excluded.
Time frame: From the date of surgery through Day 64.
Incidence of total VTE events for each individual dosing cohort of SRSD107 compared to enoxaparin
Defined as symptomatic DVT, asymptomatic DVT (confirmed by venogram), non-fatal and fatal PE, unexplained death for which PE cannot be excluded.
Time frame: From the date of surgery through 12±2 days after surgery.
Incidence of composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB)
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).
Time frame: From the Pre-surgical Period through 12±2 days after surgery.
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Incidence of composite of MB, CRNMB, and any bleeding
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).
Time frame: From the Pre-surgical Period through 12±2 days after surgery, Day 64, and Day 169, respectively.
Incidence of MB
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).
Time frame: From the Pre-surgical Period through 12±2 days after surgery.
Incidence of CRNMB
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).
Time frame: From the Pre-surgical Period through 12±2 days after surgery.
Incidence of adverse events (AEs)
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.
Time frame: From Day 1 through Day 169.