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

Phase 2

Completed

• Conditions: Venous Thromboembolism
• Interventions: Drug: ISIS-FXIRx Dose #3; Drug: ISIS-FXIRx Dose #2; Drug: Enoxaparin

• Registration Number: NCT01713361
• Lead Sponsor: Ionis Pharmaceuticals, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10
• Study First Submitted: 2012-10-04
• Study First Submitted QC: 2012-10-23
• Study First Posted: 2012-10-24
• Primary Completion: 2014-05
• Status Verified: 2014-08
• Study Completion: 2014-08
• Last Update Submitted: 2014-08-25
• Last Update Posted: 2014-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 315

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ISIS-FXIRx Dose 3	ISIS-FXIRx Dose #3	Group C: ISIS-FXIRx Dose #3
ISIS-FXIRx Dose 2	ISIS-FXIRx Dose #2	Group B: ISIS-FXIRx Dose #2
Enoxaparin	Enoxaparin	Enoxaparin (40mg)

Primary Outcome Measures

Name	Time	Method
Primary efficacy outcome	up to 12 days post-surgery	Composite of asymptomatic DVT (via bilateral venography), and symptomatic VTE, fatal PE, and unexplained death.

Secondary Outcome Measures

Name	Time	Method
Secondary efficacy outcome	1st dose to up to Day 76	All DVTs and PEs up to 4 weeks after bilateral venography

Trial Locations

Locations (1)

Isis Investigational Site; 🇺🇦 Sevastopol, Ukraine