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

August 25, 2014 updated by: Ionis Pharmaceuticals, Inc.

An Open-label, Randomized, Active Comparator-Controlled, Adaptive Parallel-group Phase 2 Study to Assess the Safety and Efficacy of Multiple Doses of ISIS 416858 Administered Subcutaneously to Patients Undergoing Total Knee Arthroplasty

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

315

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Plovdiv, Bulgaria, 4002
        • Isis Investigational Site
      • Rousse, Bulgaria, 7002
        • Isis Investigational Site
      • Sofia, Bulgaria, 1527
        • Isis Investigational Site
  • Canada
    • Ontario
      • Ajax, Ontario, Canada, LIS 2J4
        • Isis Investigational Site
      • Oshawa, Ontario, Canada, LIG 2B9
        • Isis Investigational Site
  • Latvia
      • Adazi, Latvia, LV 2164
        • Isis Investigational Site
      • Riga, Latvia, LV 1004
        • Isis Investigational Site
      • Valmiera, Latvia, LV4201
        • Isis Investigational Site
  • Russian Federation
      • Chelyabinsk, Russian Federation, 454026
        • Isis Investigational Site
      • Orenburg, Russian Federation, 460000
        • Isis Investigational Site
      • Saint Petersburg, Russian Federation, 193312
        • Isis Investigational Site
      • Saint Petersburg, Russian Federation, 194291
        • Isis Investigational Site
      • Saint Petersburg, Russian Federation, 194354
        • Isis Investigational Site
      • Samara, Russian Federation, 443095
        • Isis Investigational Site
      • Yaroslavl, Russian Federation, 150047
        • Isis Investigational Site
  • Ukraine
      • Cherkassy, Ukraine, 18009
        • Isis Investigational Site
      • Ivano-Frankivsk, Ukraine, 76000
        • Isis Investigational Site
      • Kharkiv, Ukraine, 61024
        • Isis Investigational Site
      • Kyiv, Ukraine, 01107
        • Isis Investigational Site
      • Odessa, Ukraine, 65025
        • Isis Investigational Site
      • Sevastopol, Ukraine, 99018
        • Isis Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ISIS-FXIRx Dose 2
Group B: ISIS-FXIRx Dose #2
Drug: ISIS-FXIRx Dose #2
Group B: ISIS-FXIRx dose #2 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.
Other Names:
  • ISIS-FXIRx
Experimental: ISIS-FXIRx Dose 3
Group C: ISIS-FXIRx Dose #3
Drug: ISIS-FXIRx Dose #3
Group C: ISIS-FXIRx dose #3 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.
Other Names:
  • ISIS-FXIRx
Active Comparator: Enoxaparin
Enoxaparin (40mg)
Drug: Enoxaparin
Enoxaparin (40mg) will be administered by subcutaneous injection the evening prior to total knee arthroplasty (optionally), 6 to 8 hours after surgery, followed by daily injections for at least 8 additional days post surgery (a total of at least 9 consecutive days). [Except for Canadian region, in which the subcutaneous injection of enoxaparin the evening prior to total knee arthroplasty is expected, resulting in a total of at least 10 consecutive days of enoxaparin.]
Other Names:
  • Clexane
  • Lovenox

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary efficacy outcome
Time Frame: 1st dose to up to Day 76
All DVTs and PEs up to 4 weeks after bilateral venography
1st dose to up to Day 76

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ionis Pharmaceuticals, Inc.

Investigators

  • Study Director: Sanjay Bhanot, MD, PhD, VP, Clinical Development, Isis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

October 4, 2012

First Submitted That Met QC Criteria

October 23, 2012

First Posted (Estimate)

October 24, 2012

Study Record Updates

Last Update Posted (Estimate)

August 27, 2014

Last Update Submitted That Met QC Criteria

August 25, 2014

Last Verified

August 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISIS 416858-CS3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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