Active Comparator-Controlled Study to Assess Safety and Efficacy of ISIS-FXIRx in Total Knee Arthroplasty
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
1 other identifier
interventional
315
5 countries
21
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2012
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2012
CompletedFirst Submitted
Initial submission to the registry
October 4, 2012
CompletedFirst Posted
Study publicly available on registry
October 24, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2014
CompletedAugust 27, 2014
August 1, 2014
1.6 years
October 4, 2012
August 25, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Primary efficacy outcome
Composite of asymptomatic DVT (via bilateral venography), and symptomatic VTE, fatal PE, and unexplained death.
up to 12 days post-surgery
Secondary Outcomes (1)
Secondary efficacy outcome
1st dose to up to Day 76
Study Arms (3)
ISIS-FXIRx Dose 2
EXPERIMENTALGroup B: ISIS-FXIRx Dose #2
ISIS-FXIRx Dose 3
EXPERIMENTALGroup C: ISIS-FXIRx Dose #3
Enoxaparin
ACTIVE COMPARATOREnoxaparin (40mg)
Interventions
Group B: ISIS-FXIRx dose #2 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.
Group C: ISIS-FXIRx dose #3 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.
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). \[Except for Canadian region, in which the subcutaneous injection of enoxaparin the evening prior to total knee arthroplasty is expected, resulting in a total of at least 10 consecutive days of enoxaparin.\]
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
Isis Investigational Site
Plovdiv, 4002, Bulgaria
Isis Investigational Site
Rousse, 7002, Bulgaria
Isis Investigational Site
Sofia, 1527, Bulgaria
Isis Investigational Site
Ajax, Ontario, LIS 2J4, Canada
Isis Investigational Site
Oshawa, Ontario, LIG 2B9, Canada
Isis Investigational Site
Ādaži, LV 2164, Latvia
Isis Investigational Site
Riga, LV 1004, Latvia
Isis Investigational Site
Valmiera, LV4201, Latvia
Isis Investigational Site
Chelyabinsk, 454026, Russia
Isis Investigational Site
Orenburg, 460000, Russia
Isis Investigational Site
Saint Petersburg, 193312, Russia
Isis Investigational Site
Saint Petersburg, 194291, Russia
Isis Investigational Site
Saint Petersburg, 194354, Russia
Isis Investigational Site
Samara, 443095, Russia
Isis Investigational Site
Yaroslavl, 150047, Russia
Isis Investigational Site
Cherkassy, 18009, Ukraine
Isis Investigational Site
Ivano-Frankivsk, 76000, Ukraine
Isis Investigational Site
Kharkiv, 61024, Ukraine
Isis Investigational Site
Kyiv, 01107, Ukraine
Isis Investigational Site
Odesa, 65025, Ukraine
Isis Investigational Site
Sevastopol, 99018, Ukraine
Related Publications (1)
Buller HR, Bethune C, Bhanot S, Gailani D, Monia BP, Raskob GE, Segers A, Verhamme P, Weitz JI; FXI-ASO TKA Investigators. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med. 2015 Jan 15;372(3):232-40. doi: 10.1056/NEJMoa1405760. Epub 2014 Dec 7.
PMID: 25482425DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Sanjay Bhanot, MD, PhD
VP, Clinical Development, Isis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 4, 2012
First Posted
October 24, 2012
Study Start
October 1, 2012
Primary Completion
May 1, 2014
Study Completion
August 1, 2014
Last Updated
August 27, 2014
Record last verified: 2014-08