A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants
Study Details
Study Description
Brief Summary
The primary objective of the study is to evaluate the efficacy of REGN9933 for the prevention of venous thromboembolism (VTE) after unilateral total knee arthroplasty (TKA), compared to enoxaparin
The secondary objectives of the study are:
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To evaluate the bleeding risk (ie, major and clinically relevant non-major [CRNM] bleeding) of REGN9933 after unilateral TKA through time of venography, compared to enoxaparin
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To assess overall safety and tolerability of REGN9933 in participants undergoing TKA
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To evaluate the efficacy of REGN9933 in prevention of clinically relevant VTE, compared to enoxaparin
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To evaluate the efficacy of REGN9933 in prevention of deep venous thrombosis (DVT) detected by venography, compared to enoxaparin
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To evaluate the pharmacokinetics (PK) of REGN9933 after single intravenous (IV) administration
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To assess pharmacodynamic (PD) effects of REGN9933 on intrinsic and extrinsic coagulation pathways
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To assess immunogenicity following a single dose of REGN9933 over time
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To compare the efficacy of enoxaparin and apixaban in prevention of VTE after unilateral TKA
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: REGN9933 REGN9933 will be administered by intravenous (IV) infusion |
Drug: REGN9933
Participants will receive a single dose of REGN9933 by IV infusion
|
| Active Comparator: Enoxaparin Enoxaparin will be administered by subcutaneous (SC) administration |
Drug: Enoxaparin
Participants will receive enoxaparin by SC administration daily through the time of venography (or day 12, whichever is earlier)
Other Names:
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| Active Comparator: Apixaban Apixaban will be administered orally twice a day |
Drug: Apixiban
Participants will receive apixaban orally twice a day through the time of venography (or day 12, whichever is earlier)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of confirmed, adjudicated venous thromboembolism (VTE) [Through Day 12]
Asymptomatic deep DVT 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 (REGN9933 vs enoxaparin)
Secondary Outcome Measures
- Incidence of major bleeding [Up to approximately Day 12]
International Society on Thrombosis and Hemostasis (ISTH) criteria for Major Bleeding as described in the protocol
- Incidence of clinically relevant non-major (CRNM) bleeding [Up to approximately Day 12]
International Society on Thrombosis and Hemostasis (ISTH) criteria for Clinically Relevant Non-Major Bleeding as described in the protocol
- Incidence of treatment emergent adverse events (TEAEs) [Through end of study; approximately Day 75]
A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment
- Incidence of major VTE [Through Day 12]
Major VTE is defined as: proximal DVT; confirmed symptomatic DVT of either leg; confirmed fatal or nonfatal PE including unexplained death for which PE cannot be ruled out
- Incidence of DVT [Approximately Day 12]
DVT will be measured by venography of the operated leg
- Concentrations of REGN9933 in serum [Through end of study; approximately Day 75]
The concentrations of REGN9933 over time will be summarized by descriptive statistics by study arm for the overall population
- Change in activated partial thromboplastin time (aPTT) [Baseline to end of study; approximately Day 75]
aPTT will be used to measure the anticipated anticoagulant effect of REGN9933
- Change in prothrombin time (PT) [Baseline to end of study; approximately Day 75]
PT is a measure of extrinsic and/or common pathway function.
- Incidence of anti-drug antibodies (ADA) to REGN9933 [Through end of study; approximately Day 75]
Immunogenicity will be characterized per drug molecule by ADA status
- Titer of anti-drug antibodies to REGN9933 [Through end of study; approximately Day 75]
Immunogenicity will be characterized per drug molecule by ADA status.
- Incidence of confirmed, adjudicated VTE [Baseline through Day 12]
Asymptomatic deep DVT 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 (enoxaparin vs apixaban)
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Undergoing elective unilateral TKA
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Has a body weight ≤130 kg at screening visit
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Is judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and Electrocardiograms (ECG) performed at screening and/or prior to administration of initial dose of study drug
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Is in good health based on laboratory safety testing obtained during the screening period as described in the protocol
Key Exclusion Criteria:
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History of bleeding in the past 6 months 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.
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History of thromboembolic disease or thrombophilia
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History of major surgery, including brain, spinal, or ocular, within approximately the past 6 months.
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History of major trauma within approximately the past 6 months.
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Hospitalized (>24 hours) for any reason within 30 days of the screening visit
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Using the Modification of Diet in Renal Disease equation, has an estimated glomerular filtration rate as described in the protocol
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R9933-DVT-2230
- 2022-501470-18-00