Evaluation of REGN7508 Versus Enoxaparin Sodium for Venous Thromboembolism Prevention in Patients Undergoing Elective Unilateral Total Knee Arthroplasty

The primary objective of this study is to evaluate the **efficacy** of REGN7508, a Factor XI monoclonal antibody, in the prevention of **venous thromboembolism (VTE)** following unilateral total knee arthroplasty (TKA), compared to enoxaparin. This is clinically relevant as VTE is a significant complication post-surgery, and effective prevention can reduce morbidity and improve patient outcomes.

Secondary objectives include:

• Evaluating the bleeding risk, including major and clinically relevant non-major bleeding, of REGN7508 after unilateral TKA compared to enoxaparin.
• Assessing the overall safety and tolerability of REGN7508 in participants undergoing TKA.
• Evaluating the efficacy of REGN7508 in the prevention of clinically relevant VTE and deep venous thrombosis (DVT) detected by venography, compared to enoxaparin.
• Evaluating the pharmacokinetics of REGN7508 after a single intravenous administration.
• Assessing the pharmacodynamic effects of REGN7508 on intrinsic and extrinsic coagulation pathways, specifically activated partial thromboplastin time (aPTT) and prothrombin time (PT).
• Assessing immunogenicity following a single dose of REGN7508 over time.

The clinical trial focuses on evaluating the efficacy of REGN7508 for the prevention of **venous thromboembolism** (VTE) following unilateral total knee arthroplasty (TKA). The study population includes both male and female participants, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants are required to be in good health, as determined by medical history, physical examination, vital sign measurements, and electrocardiograms (ECGs) conducted during the screening process. Additionally, laboratory safety tests are performed to ensure participants' health status. The trial does not include a vulnerable population. Participants must be undergoing a primary elective unilateral TKA and have a body weight of 130 kg or less at the screening visit. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed as a **randomized**, open-label, active-controlled study to evaluate the efficacy of **REGN7508**, a Factor XI monoclonal antibody, in preventing venous thromboembolism (VTE) in participants undergoing elective unilateral total knee arthroplasty. The trial will compare REGN7508 with **enoxaparin sodium**, a commonly used anticoagulant. The study is expected to last approximately 12 months, with recruitment starting on June 21, 2024, and the estimated end date being July 14, 2025.

Participants will undergo a series of study visits, beginning with a screening visit to assess eligibility based on criteria such as undergoing a primary elective unilateral total knee arthroplasty, having a body weight of 130 kg or less, and being in good health as determined by medical history, physical examination, and laboratory tests. Following the screening, eligible participants will be randomized to receive either REGN7508 or enoxaparin sodium. The primary endpoint is the incidence of confirmed, adjudicated VTE through day 12, with secondary endpoints including the incidence of major bleeding, clinically relevant non-major bleeding, and treatment-emergent adverse events through approximately day 75.

Study visits will include follow-up assessments to monitor the safety and efficacy of the treatment, with the final visit occurring at the end of the study period. The expected length of participant involvement is approximately 75 days, with conditions for early termination including the occurrence of significant adverse events or withdrawal of consent. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of **REGN7508**, a monoclonal antibody targeting Factor XI, for the prevention of venous thromboembolism in participants undergoing elective unilateral total knee arthroplasty. **REGN7508** is provided as a **solution for injection** and is administered via **intravenous use**. The dosing schedule for **REGN7508** is set for a maximum treatment period of 1 day, with the specific dosage amount not specified in the available data. Participant compliance with the administration of **REGN7508** will be monitored throughout the trial.

In addition to the experimental treatment, the study includes the use of **Inhixa**, a comparator treatment. **Inhixa** is a **solution for injection** containing **enoxaparin sodium** at a concentration of 4,000 IU (40 mg) per 0.4 mL, provided in a pre-filled syringe. The administration route for **Inhixa** is via **subcutaneous injection**. The maximum daily dose and total dose for **Inhixa** are both 40 mg, with a treatment period extending up to 12 days. Compliance with the administration of **Inhixa** will be monitored to ensure adherence to the dosing schedule.

Another comparator treatment used in the study is **CLEXANE**, which also contains **enoxaparin sodium** at a concentration of 4,000 IU (40 mg) per 0.4 mL, provided in a pre-filled syringe. Similar to **Inhixa**, **CLEXANE** is administered via **subcutaneous injection**. The maximum daily dose and total dose for **CLEXANE** are 40 mg, with a treatment period of up to 12 days. Participant compliance with **CLEXANE** administration will be monitored to ensure adherence to the prescribed dosing regimen.

The efficacy of the investigational product, REGN7508, in the prevention of **venous thromboembolism (VTE)** following unilateral total knee arthroplasty will be assessed through a series of predefined endpoints. The primary endpoint is the incidence of confirmed, adjudicated VTE through day 12. Secondary endpoints include the incidence of major bleeding and clinically relevant non-major bleeding up to approximately day 12, the incidence of treatment-emergent adverse events through the end of the study (approximately day 75), and the incidence of major VTE through day 12. Additional secondary endpoints involve the incidence of deep venous thrombosis at approximately day 12, concentrations of REGN7508 in serum through the end of the study, changes in activated partial thromboplastin time and prothrombin time from baseline to the end of the study, and the incidence and titer of anti-drug antibodies to REGN7508 through the end of the study.