Venous ThromboembolismPhase 2NCT01713361
Active Comparator-Controlled Study to Assess Safety and Efficacy of ISIS-FXIRx in Total Knee Arthroplasty
A Phase 2 study testing ISIS-FXIRx Dose #2, ISIS-FXIRx Dose #3 and Enoxaparin in people with Venous Thromboembolism, run by Ionis Pharmaceuticals, Inc. at 21 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- ISIS-FXIRx Dose #2, ISIS-FXIRx Dose #3 and Enoxaparin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 315 participants
- Where
- 21 sitesin 5 countries
- Study dates
- Oct 2012to Aug 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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 locations and contacts
21 sites in 5 countries.
21 sites in 5 countries
Russia7 sites
Isis Investigational Site
Chelyabinsk, 454026
Isis Investigational Site
Orenburg, 460000
Isis Investigational Site
Saint Petersburg, 193312
Isis Investigational Site
Saint Petersburg, 194291
Isis Investigational Site
Saint Petersburg, 194354
Isis Investigational Site
Samara, 443095
Isis Investigational Site
Yaroslavl, 150047
Ukraine6 sites
Isis Investigational Site
Cherkassy, 18009
Isis Investigational Site
Ivano-Frankivsk, 76000
Isis Investigational Site
Kharkiv, 61024
Isis Investigational Site
Kyiv, 01107
Isis Investigational Site
Odesa, 65025
Isis Investigational Site
Sevastopol, 99018
Bulgaria3 sites
Isis Investigational Site
Plovdiv, 4002
Isis Investigational Site
Rousse, 7002
Isis Investigational Site
Sofia, 1527
Latvia3 sites
Isis Investigational Site
Adazi, LV 2164
Isis Investigational Site
Riga, LV 1004
Isis Investigational Site
Valmiera, LV4201
Canada2 sites
Isis Investigational Site
Ajax, Ontario, LIS 2J4
Isis Investigational Site
Oshawa, Ontario, LIG 2B9
About this study
Official title: 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.
- Conditions
- Venous Thromboembolism
- Being tested
- ISIS-FXIRx Dose #2, ISIS-FXIRx Dose #3, Enoxaparin
- Keywords
- total knee arthroplasty, Prophylaxis
- Medical subject headings
- Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISIS-FXIRx Dose #2Drug
Also called ISIS-FXIRx
Group B: ISIS-FXIRx dose #2 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.
ISIS-FXIRx Dose #3Drug
Also called ISIS-FXIRx
Group C: ISIS-FXIRx dose #3 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery.
EnoxaparinDrug
Also called Lovenox, Clexane
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.]
| Study group | Role | What they receive |
|---|---|---|
| ISIS-FXIRx Dose 2 | Experimental | Group B: ISIS-FXIRx Dose #2 Receives: Drug: ISIS-FXIRx Dose #2 |
| ISIS-FXIRx Dose 3 | Experimental | Group C: ISIS-FXIRx Dose #3 Receives: Drug: ISIS-FXIRx Dose #3 |
| Enoxaparin | Active comparator | Enoxaparin (40mg) Receives: Drug: Enoxaparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary efficacy outcome
Composite of asymptomatic DVT (via bilateral venography), and symptomatic VTE, fatal PE, and unexplained death.
Measured: up to 12 days post-surgery
Secondary outcomes (1)
Secondary efficacy outcome
All DVTs and PEs up to 4 weeks after bilateral venography
Measured: 1st dose to up to Day 76
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2012 (estimated)
- Study startOct 2012
- Primary completionMay 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 315 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sanjay Bhanot, MD, PhD, Study director, VP, Clinical Development, Isis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01713361
- Sponsor's protocol ID
- ISIS 416858-CS3
- Status last verified
- Aug 2014
- First submitted
- 4 Oct 2012
- Last updated
- 27 Aug 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25482425
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01713361
- Acronym / sponsor ID
- ISIS 416858-CS3
- Conditions
- Venous Thromboembolism
- Keywords
- total knee arthroplasty, Prophylaxis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 315 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- May 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 24 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ISIS-FXIRx Dose 2 | Experimental | Drug: ISIS-FXIRx Dose #2Group B: ISIS-FXIRx Dose #2 |
| ISIS-FXIRx Dose 3 | Experimental | Drug: ISIS-FXIRx Dose #3Group C: ISIS-FXIRx Dose #3 |
| Enoxaparin | Active comparator | Drug: EnoxaparinEnoxaparin (40mg) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISIS-FXIRx Dose #2Also: ISIS-FXIRxGroup B: ISIS-FXIRx dose #2 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery. | Drug | ISIS-FXIRx Dose 2 |
| ISIS-FXIRx Dose #3Also: ISIS-FXIRxGroup C: ISIS-FXIRx dose #3 subcutaneously administered 7 times prior to total knee arthroplasty, and 2 times after surgery. | Drug | ISIS-FXIRx Dose 3 |
| EnoxaparinAlso: Lovenox, ClexaneEnoxaparin (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.] | Drug | Enoxaparin |
Primary outcome
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.
1 secondary outcome
Secondary efficacy outcome
Time frame: 1st dose to up to Day 76
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2014.
- Derived from this study: PubMed 25482425Buller 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sanjay Bhanot, MD, PhD study director
VP, Clinical Development, Isis Pharmaceuticals
21 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ISIS-FXIRx Dose #2, ISIS-FXIRx Dose #3 and Enoxaparin in people with Venous Thromboembolism, run by Ionis Pharmaceuticals, Inc. at 21 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Russia, Ukraine, Bulgaria, Latvia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary efficacy outcome (time frame: up to 12 days post-surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01713361, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2014.