Venous Thromboembolism
Conditions
Keywords
Anti-factor XI (FXI) monoclonal antibody, Venous thromboembolism (VTE), Unilateral total knee arthroplasty (TKA)
Brief summary
This study is researching an experimental drug called REGN7508 (called "study drug"). The study is focused on adults undergoing elective, unilateral (one side) total knee replacement (TKR) surgery. The aim of the study is to see how effective the study drug is at preventing venous thromboembolism (VTE) and other related diseases after unilateral total knee replacement surgery. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
Interventions
DRUGREGN7508
Administered by single intravenous (IV) dose
DRUGEnoxaparin
Administered by subcutaneous (SC) dose daily through the time of venography (or day 12, whichever is earlier)
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Undergoing a primary elective unilateral TKA 2. Has a body weight ≤130 kg at screening visit 3. Is judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and electrocardiograms (ECG's) performed at screening and/or prior to administration of initial dose of study drug as described in the protocol 4. Is in good health based on laboratory safety testing obtained during the screening period as described in the protocol Key
Exclusion criteria
1. History of bleeding in the past 6 months prior to dosing requiring hospitalization or transfusion; history of intracranial or intraocular bleeding, excessive operative or post-operative bleeding, and traumatic spinal or epidural anesthesia; history of bleeding diathesis 2. History of thromboembolic disease or thrombophilia 3. History of major surgery, including brain, spinal, or ocular, within approximately the past 6 months 4. History of major trauma within approximately the past 6 months prior to dosing 5. Hospitalized (\>24 hours) for any reason within 30 days of the screening visit 6. Has an estimated glomerular filtration rate (GFR) of \<45 mL/min/1.73m\^2 at the screening visit using one of the following formulas: the Modification of Diet in Renal Disease (MDRD) equation, the Chronic Kidney Disease Epidemiology Collaboration equation, or equivalent equation Note: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Confirmed, Adjudicated Venous Thromboembolism (VTE) | Through day 12 | Composite endpoint that includes asymptomatic deep DVT (deep venous thrombosis) detected by unilateral venography of the operated leg; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal pulmonary embolism (PE) including unexplained death for which PE cannot be ruled out. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding | Through day 12 | International Society on Thrombosis and Hemostasis (ISTH) criteria for Major Bleeding and CRNM Bleeding as described in the protocol |
| Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE) | Through day 75 | A TEAE is any untoward medical occurrence in a participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. |
| Percentage of Participants With Major VTE | Through day 12 | Major VTE is a composite endpoint that includes: proximal DVT; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal PE including unexplained death for which PE cannot be ruled out. |
| Percentage of Participants With Deep Venous Thrombosis (DVT) | Through day 12 | DVT measured by venography of the operated leg |
| Concentrations of Total REGN7508 in Serum | Days 1, 5, 10, 30 and 75 | — |
| Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) | Days 1, 5, 10, 30, 75 | aPTT was used to measure the anticipated anticoagulant effect of REGN7508. Fold change is based on the follow-up value/baseline value within an arm. |
| Fold Change From Baseline in Prothrombin Time (PT) | Days 1, 5, 10, 30, 75 | PT is a measure of extrinsic and/or common pathway function. Fold change is based on the follow-up value/baseline value within an arm. |
| Number of Participants With Anti-REGN7508 Antibodies by Status | Through end of study; approximately Day 75 | Immunogenicity characterized by anti-drug antibody (ADA) status |
| Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN7508 Antibodies by Maximum Titer | Through end of study; approximately Day 75 | Immunogenicity characterized per by ADA status |
Countries
Bulgaria, Hungary, Latvia, Lithuania, Poland
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Participant flow
Pre-assignment details
Of 201 participants screened, 179 participants met eligibility criteria and were randomized. All 179 randomized participants received study intervention.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 66.3 years STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 179 Participants |
| Sex: Female, Male Female | 136 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 120 | 0 / 59 |
| other Total, other adverse events | 8 / 120 | 6 / 59 |
| serious Total, serious adverse events | 2 / 120 | 0 / 59 |
Outcome results
None listed