A Trial to Learn How Well REGN7508 Works for Preventing Blood Clots After a Knee Replacement in Adult Participants

Regeneron Pharmaceuticals179 enrolled

Overview

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

179

Conditions

Venous Thromboembolism

Interventions

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

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/ Exclusion Criteria apply

Locations (14)

Multi-profile Hospital for Active Treatment Hearth and Brain EAD

Pleven, Bulgaria

Multiprofile Hospital For Active Treatment Park Hospital Ltd.

Plovdiv, Bulgaria

Budai Irgalmasrendi Korhaz

Budapest, Hungary

Szolnoki MAV Hospital

Szolnok, Hungary

Vidzemes Hospital

Valmiera, Valmieras Aprinkis, Latvia

Liepaja Regional Hospital

Liepāja, Latvia

Riga's 2nd Hospital

Riga, Latvia

Hospital of Traumatology and Orthopaedics

Riga, Latvia

Orto Klinika

Riga, Latvia

Lietuvos sveikatos mokslu universiteto ligonine Kauno klinik

Kaunas, Kaunas County, Lithuania

...and 4 more locations

Outcomes

Primary Outcomes

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

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: Through day 75

Percentage of Participants With Major VTE

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 Deep Venous Thrombosis (DVT)

DVT measured by venography of the operated leg

Time frame: Through day 12

Concentrations of Total REGN7508 in Serum

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

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

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.

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

Number of Participants With Anti-REGN7508 Antibodies by Status

Immunogenicity characterized by anti-drug antibody (ADA) status

Time frame: Through end of study; approximately Day 75

Number of Participants With Treatment-Emergent or Treatment-Boosted Anti-REGN7508 Antibodies by Maximum Titer

Immunogenicity characterized per by ADA status

Time frame: Through end of study; approximately Day 75