Venous Thromboembolism
Conditions
Keywords
venous thromboembolism, adhesion molecule, P-selectin glycoprotein ligand 1, P-selectin, venous thrombosis
Brief summary
The main purpose of this study is to determine if an investigational medication called SelK2 works in preventing a condition called venous thromboembolism (VTE) in patients having a total knee replacement. SelK2 has been designed to attach to a protein found on blood cells and blood vessels. By attaching to this protein, SelK2 is designed to decrease the inflammatory process in the blood vessel wall that leads to the formation of blood clots in the vessel (called thrombosis). By decreasing the inflammatory process, SelK2 may reduce the risk of VTE following joint replacement surgery. In addition, because SelK2 is not a blood thinner, it is expected that the risk for bleeding will also be reduced.
Interventions
DRUGSelK2
I.V., single-dose
BIOLOGICALEnoxaparin
SC, QD for up to 10 ± 2 days
Sponsors
Tetherex Pharmaceuticals Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
This was an adaptive design study. The first two arms of the study enrolled patients in a 1:1 ratio to receive either SelK2 or an active comparator. The adaptive arm (SelK2 plus active comparator) was initiated at the discretion of the Steering and Safety Committee. The study then enrolled patients in a 2:1 ratio to receive either SelK2 with an active comparator or an active comparator only.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Males or females, 18-80 years of age (inclusive) * Planned to undergo elective, primary total unilateral Total Knee Arthroplasty under general anesthesia Key
Exclusion criteria
* Previous deep vein thrombosis (DVT) of the leg or pulmonary embolism (PE) within the past year * Any underlying condition (e.g., atrial fibrillation, mechanical heart valve, or recent pulmonary embolism) that may lead to the required concomitant use of anticoagulants/antiplatelet agents (e.g., warfarin, dabigatran, rivaroxaban, apixaban, clopidogrel) that may affect study outcome or any other drug influencing coagulation (except low dose aspirin (100 mg or less)) * Anticipated use of intermittent pneumatic compression devices and/or electrical/mechanical muscle stimulators post Total Knee Arthroplasty procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Total Venous Thromboembolism | 10 ± 2 Days After Total Knee Replacement | The primary efficacy endpoint was incidence of total VTE (reported as a percentage of patients) during the Treatment Phase up to venography day (10 ± 2 days after total knee replacement). All efficacy endpoint data was adjudicated by the blinded Central Independent Adjudication Committee (CIAC). |
| Percentage of Participants With Major or Clinically Relevant Non-major Bleeding Events | 10 ± 2 Days After Total Knee Replacement | All suspected bleeding events were reviewed by the Central Independent Adjudication Committee (CIAC) in a blinded fashion and were adjudicated for categorization as Major Bleeding (MB), Clinically Relevant Non-Major Bleeding (CRNMB), Minor Bleeding, or combination of MB and CRNMB. The outcome measure assessed the incidence of MB or CRNMB. |
Countries
Bulgaria, Latvia, Lithuania, Poland, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SelK2 I.V., single-dose | 55 |
| SelK2 and Enoxaparin I.V., single-dose (SelK2) and SC, QD for up to 10 ± 2 days (Enoxaparin)
SelK2: I.V., single-dose
Enoxaparin: SC, QD for up to 10 ± 2 days | 63 |
| Enoxaparin SC, QD for up to 10 ± 2 days
Enoxaparin: SC, QD for up to 10 ± 2 days | 89 |
| Total | 207 |
Baseline characteristics
| Characteristic | SelK2 | SelK2 and Enoxaparin | Enoxaparin | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 35 Participants | 38 Participants | 56 Participants | 129 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 25 Participants | 33 Participants | 78 Participants |
| Age, Continuous | 66.3 years STANDARD_DEVIATION 6.35 | 66.3 years STANDARD_DEVIATION 7.54 | 65.6 years STANDARD_DEVIATION 7.3 | 66.0 years STANDARD_DEVIATION 7.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants | 63 Participants | 88 Participants | 205 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 55 Participants | 63 Participants | 89 Participants | 207 Participants |
| Region of Enrollment Bulgaria | 0 participants | 4 participants | 4 participants | 8 participants |
| Region of Enrollment Latvia | 15 participants | 27 participants | 30 participants | 72 participants |
| Region of Enrollment Lithuania | 11 participants | 15 participants | 18 participants | 44 participants |
| Region of Enrollment Poland | 11 participants | 1 participants | 10 participants | 22 participants |
| Region of Enrollment Ukraine | 18 participants | 16 participants | 27 participants | 61 participants |
| Sex: Female, Male Female | 42 Participants | 52 Participants | 68 Participants | 162 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 21 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 63 | 0 / 88 |
| other Total, other adverse events | 9 / 55 | 6 / 63 | 10 / 88 |
| serious Total, serious adverse events | 2 / 55 | 3 / 63 | 2 / 88 |
Outcome results
Primary
Percentage of Participants With Major or Clinically Relevant Non-major Bleeding Events
All suspected bleeding events were reviewed by the Central Independent Adjudication Committee (CIAC) in a blinded fashion and were adjudicated for categorization as Major Bleeding (MB), Clinically Relevant Non-Major Bleeding (CRNMB), Minor Bleeding, or combination of MB and CRNMB. The outcome measure assessed the incidence of MB or CRNMB.
Time frame: 10 ± 2 Days After Total Knee Replacement
Population: Analysis was performed on the safety population consisting of all patients who received at least 1 dose of study drug, analyzed by actual treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SelK2 | Percentage of Participants With Major or Clinically Relevant Non-major Bleeding Events | 2 Participants |
| SelK2 and Enoxaparin | Percentage of Participants With Major or Clinically Relevant Non-major Bleeding Events | 1 Participants |
| Enoxaparin | Percentage of Participants With Major or Clinically Relevant Non-major Bleeding Events | 0 Participants |
Primary
Percentage of Participants With Total Venous Thromboembolism
The primary efficacy endpoint was incidence of total VTE (reported as a percentage of patients) during the Treatment Phase up to venography day (10 ± 2 days after total knee replacement). All efficacy endpoint data was adjudicated by the blinded Central Independent Adjudication Committee (CIAC).
Time frame: 10 ± 2 Days After Total Knee Replacement
Population: Analysis was performed on the modified intent-to-treat (mITT) population consisting of all randomized patients who also had a successful venogram or symptomatic VTE event, which allowed for assessment of the primary efficacy outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SelK2 | Percentage of Participants With Total Venous Thromboembolism | 19 Participants |
| SelK2 and Enoxaparin | Percentage of Participants With Total Venous Thromboembolism | 29 Participants |
| Enoxaparin | Percentage of Participants With Total Venous Thromboembolism | 17 Participants |