A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants
- Conditions
- Venous Thromboembolism
- Interventions
- Registration Number
- NCT05618808
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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:
* 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
* To assess overall safety and tolerability of REGN9933 in participants undergoing TKA
* To evaluate the efficacy of REGN9933 in prevention of clinically relevant VTE, compared to enoxaparin
* To evaluate the efficacy of REGN9933 in prevention of deep venous thrombosis (DVT) detected by venography, compared to enoxaparin
* To evaluate the pharmacokinetics (PK) of REGN9933 after single intravenous (IV) administration
* To assess pharmacodynamic (PD) effects of REGN9933 on intrinsic and extrinsic coagulation pathways
* To assess immunogenicity following a single dose of REGN9933 over time
* To compare the efficacy of enoxaparin and apixaban in prevention of VTE after unilateral TKA
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 373
- Undergoing elective unilateral TKA
- Has a body weight ≤130 kg at screening visit
- 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
- Is in good health based on laboratory safety testing obtained during the screening period as described in the protocol
Key
- 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.
- History of thromboembolic disease or thrombophilia
- History of major surgery, including brain, spinal, or ocular, within approximately the past 6 months.
- History of major trauma within approximately the past 6 months.
- Hospitalized (>24 hours) for any reason within 30 days of the screening visit
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Apixaban Apixiban Apixaban will be administered orally twice a day REGN9933 REGN9933 REGN9933 will be administered by intravenous (IV) infusion Enoxaparin Enoxaparin Enoxaparin will be administered by subcutaneous (SC) administration
- Primary Outcome Measures
Name Time Method Percentage of Participants With Confirmed, Adjudicated Venous Thromboembolism (VTE) (REGN9933 vs Enoxaparin) 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 Outcome Measures
Name Time Method 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) Up to 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 DVT (REGN9933 vs Enoxaparin) Through Day 12 DVT measured by venography of the operated leg
Total REGN9933 Concentrations in Serum Days 0.0625 (post-dose), 4, 9, 29, and 74 The concentrations of REGN9933 over time were summarized by descriptive statistics by study arm for the overall population
Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) Days 1, 5, 10, 30, and 75 aPTT was used to measure the anticipated anticoagulant effect of REGN9933. Fold change is based on the follow-up value/baseline value within an arm.
Number of Participants With Anti-REGN9933 Antibodies by Status Through Day 75 Immunogenicity characterized by anti-drug antibody (ADA) status
Fold Change From Baseline in Prothrombin Time (PT) Days 1, 5, 10, 30, and 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 Treatment-Emergent or Treatment-Boosted Anti-REGN13335 Antibodies by Maximum Titer Level Through Day 75 Immunogenicity characterized per drug molecule by ADA status
Percentage of Participants With Confirmed, Adjudicated VTE (Enoxaparin vs Apixaban) 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.
Percentage of Participants With Major VTE (REGN9933 vs Enoxaparin) 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
Trial Locations
- Locations (16)
Ziekenhuis Oost-Limburg- Campus Sint-Jan
🇧🇪Genk, Limburg, Belgium
MBAL Heart and Brain Hospital
🇧🇬Pleven, Bulgaria
Durham Bone and Joint Specialists
🇨🇦Ajax, Ontario, Canada
MAV Korhaz es Rendelointezet Szolnok
🇭🇺Szolnok, Jász-Nagykun-Szolnok, Hungary
Department of Orthopedics, Somogy County Mór Kaposi Teaching Hospital
🇭🇺Kaposvar, Hungary
Liepaja Regional Hospital
🇱🇻Liepaja, Latvia
Vidzemes Hospital
🇱🇻Riga, Latvia
Riga's 2nd Hospital
🇱🇻Riga, Latvia
Hospital of Traumatology and Orthopaedics
🇱🇻Riga, Latvia
Lietuvos Sveikatos Mokslu Universiteto Ligonine Kauno Klinik
🇱🇹Kaunas, Kauno Apskritis, Lithuania
Scroll for more (6 remaining)Ziekenhuis Oost-Limburg- Campus Sint-Jan🇧🇪Genk, Limburg, Belgium