Factor XI inhibiTion for the Prevention of Venous Thromboembolism in Patients Undergoing Total Knee Arthroplasty

Study Overview
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Brief Summary
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This study was to compare the study drug KN060 to enoxaparin, for the prevention of blood clotting and safety in patients undergoing total knee arthroplasty (TKA).

Official Title
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An Open, Randomized, Active-comparator-controlled, Multicenter Study to Assess the Efficacy and Safety of Different Doses of KN060 for the Prevention of Venous Thromboembolism in Patients Undergoing Unilateral Total Knee Arthroplasty.

Conditions
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Knee Arthroplasty, Total

Intervention / Treatment
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* Drug: Enoxaparin
* Drug: KN060 Low
* Drug: KN060 Middle
* Drug: KN060 Hight


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged between 18 and 75 years old (including the cut-off value); undergoing unilateral Total Knee Arthroplasty (TKA); Voluntarily participate in the study and sign a written informed consent; Exclusion Criteria: There is a high risk of bleeding or abnormal bleeding related indicators: Evidence of venous thrombosis, such as the presence of related symptoms or auxiliary tests indicating thrombosis; Or have a history of venous embolic disease. Acute myocardial infarction or ischemic stroke occurred within 6 months before screening. Presence of malignant tumors or history of malignant tumors.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Enoxaparin<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received enoxaparin for at least 10 days post-surgery. | Drug: Enoxaparin<br>* 40 mg enoxaparin administered as subcutaneous injection once daily<br>|
| Experimental: KN060 Low (post-surgery)<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received KN060 low dose once post-surgery. | Drug: KN060 Low<br>* Single dose of KN060 administered as intravenous infusion<br>|
| Experimental: KN060 Middle (post-surgery)<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received KN060 middle dose once post-surgery. | Drug: KN060 Middle<br>* Single dose of KN060 administered as intravenous infusion<br>|
| Experimental: KN060 Hight (post-surgery)<br>Adult patients who underwent Total Knee Arthroplasty (TKA) surgery and received KN060 hight dose once post-surgery. | Drug: KN060 Hight<br>* Single dose of KN060 administered as intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of composite endpoint consisting of asymptomatic DVT as detected by mandatory bilateral venography, objectively confirmed symptomatic DVT, non-fatal PE, fatal PE, unexplained death for which PE cannot be excluded | DVT - Deep vein thrombosis / PE - Pulmonary embolism. All suspected events were reviewed and classified by the investigator | Up to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of composite endpoint of major and clinically relevant non-major bleeding | All suspected events were reviewed and classified by the investigator | Up to 14 days | 
| Incidence of composite endpoint consisting of asymptomatic DVT as detected by mandatory bilateral venography, objectively confirmed symptomatic DVT, non-fatal PE, fatal PE, unexplained death for which PE cannot be excluded | All suspected events were reviewed and classified by the investigator | Up to 35\100 days | 
| Incidence of symptomatic DVT, non-fatal PE | All suspected events were reviewed and classified by the investigator | Up to 14 \35\100 days | 
| Incidence of fatal PE | All suspected events were reviewed and classified by the investigator | Up to 14 \35\100 days | 
| Incidence of unexplained death for which PE cannot be excluded | All suspected events were reviewed and classified by the investigator | Up to 14 \35\100 days | 
| Incidence of composite endpoint of major and clinically relevant non-major bleeding | All suspected events were reviewed and classified by the investigator | Up to 35\100 days | 
| Incidence of bleeding | All suspected events were reviewed and classified by the investigator | Up to 14 \35\100 days | 
| Incidence of major bleeding | All suspected events were reviewed and classified by the investigator | Up to 14 \35\100 days | 
| Incidence of clinically relevant non-major bleeding | All suspected events were reviewed and classified by the investigator | Up to 14 \35\100 days | 
| Incidence of treatment emergent adverse event/adverse drug reaction | All suspected events were reviewed and classified by the investigator | Up to 14 \35\100 days | 
| Plasma Concentration of KN060 |  | Up to 100 days | 
| Pharmacodynamics index: Changes of plasma concentration of Free FⅪ from baseline; | Free FⅪ: Free Factor XI; Factor XI is a clotting factor. | Up to 100 days | 
| Pharmacodynamics index: Changes of FⅪ activity from baseline; | FⅪ: Factor XI; Factor XI is a clotting factor. | Up to 100 days | 
| Pharmacodynamics index: Changes of APTT from baseline; | APTT: activated partial thromboplastin time; | Up to 100 days |