Prophylaxis of venous thromboembolism (VTE) in patients undergoing total knee arthroplasty (TKA) MedDRA version: 14.1 Level: LLT Classification code 10049909 Term: Venous thromboembolism prophylaxis System Organ Class: 100000004865
Conditions
Interventions
Product Name: Factor XI Antisense Oligonucleotide
Product Code: ISIS 416858
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ISIS 416858
CAS Number: 1223657-78-0
Current Sponsor code:
Sponsors
Isis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements 2. Males or Females aged 18 to 80 years old at the time of informed consent 3. Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion such as bilateral tubal ligation, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or post-menopausal (>12 months since last period). Males must be surgically sterile, abstinent or if engaged in sexual relations of child-bearing potential, the patient must be using an acceptable contraceptive method during and for at least 97 days (approximately 5 half-lives of ISIS 416858) after the last dose of Study Drug. 4. Undergoing elective, primary unilateral total knee arthroplasty Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: 1. Body weight 1.5 x ULN •Total bilirubin >ULN •Platelet count <150,000 (or history of thrombocytopenia) •Factor IX activity <LLN •Factor VIII activity, vWF antigen or Ristocetin cofactor activity <0.5 U/mL •FXI activity <0.3 U/mL 11. Uncontrolled hypertension as judged by the Investigator 12. Hypersensitivity to contrast media 13. Hypersensitivity to enoxaparin or any contraindication listed in the local labeling of enoxaparin 14. Anticipated concomitant use of anticoagulants/antiplatelet agents (e.g., dabigatran, rivaroxaban, clopidogrel) 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 416858 15. Treatment with another investigational Drug, biological agent, or device within one month of screening, or 5 half-lives of study agent, whichever is longer 16. Treatment with any non-ISIS oligonucleotide (including siRNA) at any time or prior treatment with an ISIS oligonucleotide within 9 months of screening. Patients that have previously received only a single dose of an ISIS oligonucleotide as part of a clinical study may be included as long as a duration =4 months elapsed since dosing 17. Recent history of, or current drug or alcohol abuse 18. Active infection (e.g., endocarditis, sepsis) requiring systemic antiviral or antimicrobial therapy 19. Anticipated use of indwelling intrathecal or epidural catheters 20. Anticipated use of intermittent pneumatic compression devices and electrical/mechanical muscle stimulators 21. History of or clinically significant abnormal ECG as judged by the Investigator at Screening 22. Allergy to sulfur containing drugs such as Sultrin, Bactrim (sulfonamide) and captopril, pantoprazole (non-sulfonamide). If necessary, consult with Sponsor Medical Monitor for concomitant medication review. 23. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B at Screening 24. An
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the safety and efficacy profile of ISIS 416858, including incidence of bleeding and VTE, in patients undergoing total knee arthroplasty • to compare the efficacy and safety profile of ISIS 416858 in patients who achieve </= 0.2 U/mL FXI activity levels tothat of enoxaparin;Secondary Objective: To assess a potential dose-response relationship of ISIS 416858 with respect to the reduction of VTE incidence in patients undergoing unilateral total knee arthroplasty ;Primary end point(s): A composite of asymptomatic DVT and objectively confirmed symptomatic VTE, fatal PE and unexplained death.;Timepoint(s) of evaluation of this end point: Up to 12 days in the post-surgery treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): All DVTs and non-fatal and fatal PEs;Timepoint(s) of evaluation of this end point: From first study drug administration up to 4 weeks after mandatory bilateral venography is performed. | — |
Countries
Bulgaria, Canada, Latvia, Russian Federation, Ukraine
Contacts
Public ContactMatt R. Buck
Isis Pharmaceuticals, Inc.
Outcome results
None listed