Active Comparator-Controlled Study to Assess Safety and Efficacy of ISIS-FXIRx in Total Knee Arthroplasty

Inclusion Criteria: * Give written informed consent * Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal. Males must be surgically sterile, abstinent, or if engaged in sexual relations of child-bearing potential, must use contraception * Undergoing elective, primary unilateral total knee arthroplasty Exclusion Criteria: * Body weight \<50 kg * Patients at increased risk of bleeding. History of intracranial or intraocular bleeding. History of gastrointestinal and/or endoscopically verified ulcer disease within the past year. * History of excessive intra- or direct post operative bleeding or a traumatic spinal or epidural anesthesia * Brain, spinal, or ophthalmologic surgery within the past 3 months * History of clinically significant liver disease in the past year * Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values * aPTT or PT or INR \>ULN * Factor IX activity \<LLN * Factor VIII activity, vWF antigen or Ristocetin cofactor activity \<0.5 U/mL * FXI activity \<0.3 U/mL * Urine protein or blood persistently positive by dipstick. In the event of positive test results, eligibility may be confirmed with urine microscopy or 24 hour urine protein measurement as applicable * ALT or AST \>1.5 x ULN * Total bilirubin \>ULN * Platelet count \<150,000 (or history of thrombocytopenia) * Hypersensitivity to enoxaparin * Anticipated concomitant use of anticoagulants/antiplatelet agents or the NSAID nimesulide that may affect study outcome or any other drug influencing coagulation (except low dose aspirin and short acting NSAIDs with a half-life \<20 hours) at least 7 days before surgery or during treatment with ISIS Rx. * Anticipated use of indwelling intrathecal or epidural catheters * Anemia at Screening * Have any other conditions which could interfere with the patient participating in or completing the study