A Trial to Learn How Well REGN9933 Works for Preventing Blood Clots After Knee Replacement Surgery in Adult Participants

Regeneron Pharmaceuticals373 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

373

Conditions

Venous Thromboembolism

Interventions

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Undergoing 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) performed at screening and/or prior to administration of initial dose of study drug 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 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. 5. Hospitalized (\>24 hours) for any reason within 30 days of the screening visit 6. 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

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

Kaposvár, Hungary

Liepaja Regional Hospital

Liepāja, 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, Kaunas County, Lithuania

...and 6 more locations

Outcomes

Primary Outcomes

Percentage of Participants With Confirmed, Adjudicated Venous Thromboembolism (VTE) (REGN9933 vs Enoxaparin)

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

Time frame: Through Day 12

Secondary Outcomes

Number of Participants With Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding

International Society on Thrombosis and Hemostasis (ISTH) criteria for Major Bleeding and CRNM Bleeding as described in the protocol

Time frame: Through Day 12

Percentage of Participants With at Least One Treatment Emergent Adverse Event (TEAE)

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.

Time frame: Up to Day 75

Percentage of Participants With Major VTE (REGN9933 vs Enoxaparin)

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

Time frame: Through Day 12

Percentage of Participants With DVT (REGN9933 vs Enoxaparin)

DVT measured by venography of the operated leg

Time frame: Through Day 12

Total REGN9933 Concentrations in Serum

The concentrations of REGN9933 over time were summarized by descriptive statistics by study arm for the overall population

Time frame: Days 0.0625 (post-dose), 4, 9, 29, and 74

Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT)

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.

Time frame: Days 1, 5, 10, 30, and 75

Fold Change From Baseline in Prothrombin Time (PT)

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.

Time frame: Days 1, 5, 10, 30, and 75

Number of Participants With Anti-REGN9933 Antibodies by Status

Immunogenicity characterized by anti-drug antibody (ADA) status

Time frame: Through Day 75

Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN13335 Antibodies by Maximum Titer Level

Immunogenicity characterized per drug molecule by ADA status

Time frame: Through Day 75

Percentage of Participants With Confirmed, Adjudicated VTE (Enoxaparin vs Apixaban)

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.

Time frame: Through Day 12