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

Ionis Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Venous Thromboembolism

Treatments: Drug: ISIS-FXIRx Dose #3; Drug: ISIS-FXIRx Dose #2; Drug: Enoxaparin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01713361

ISIS 416858-CS3

Details and patient eligibility

About

The purpose of this study is:

• To assess the safety and efficacy profile of ISIS-FXIRx, including incidence of bleeding and VTE, in patients undergoing total knee arthroplasty.
• To compare the efficacy and safety profile of ISIS-FXIRx in patients who achieve less than or equal to 0.2 U/mL FXI activity levels to that of enoxaparin.

Enrollment: 315 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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315 participants in 3 patient groups

ISIS-FXIRx Dose 2

Experimental group

Description:

Group B: ISIS-FXIRx Dose #2

Treatment:

Drug: ISIS-FXIRx Dose #2

ISIS-FXIRx Dose 3

Experimental group

Description:

Group C: ISIS-FXIRx Dose #3

Treatment:

Drug: ISIS-FXIRx Dose #3

Enoxaparin

Active Comparator group

Description:

Enoxaparin (40mg)

Treatment:

Drug: Enoxaparin