Efficacy and Safety of MK-2060 in Preventing Arteriovenous Graft Thrombosis in End-Stage Renal Disease Patients Undergoing Hemodialysis

The primary objective of this clinical trial is to evaluate the **efficacy** of MK-2060 compared to placebo in increasing the time to the first arteriovenous graft thrombosis event in patients with end-stage renal disease receiving hemodialysis. This is clinically relevant as arteriovenous graft thrombosis is a common complication in hemodialysis patients, leading to increased morbidity and healthcare costs. By potentially delaying the onset of thrombosis, MK-2060 could improve patient outcomes and reduce the need for surgical interventions.

Secondary objectives include:

• Evaluating the efficacy of MK-2060 compared to placebo in increasing the time to each arteriovenous graft thrombosis event, both first and recurrent.
• Assessing the safety and tolerability of MK-2060.

The clinical trial involves a total of **452 participants** who are being studied for the **prevention of arteriovenous graft thrombosis**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants are required to have a current diagnosis of **end-stage renal disease (ESRD)** and must be receiving hemodialysis at least three times per week for a minimum of three hours per session via a mature, normally functioning, uninfected arteriovenous graft. The trial does not include a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified, but female participants must adhere to contraceptive guidance if they are of child-bearing potential. The selection of participants was based on specific inclusion criteria, ensuring that the study population is representative of individuals who are at risk of arteriovenous graft thrombosis while undergoing hemodialysis.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of MK-2060 in preventing arteriovenous graft thrombosis in patients with end-stage renal disease receiving hemodialysis. The trial is a Phase II, multi-center, event-driven study with an estimated duration from September 2021 to October 2024. Participants will be randomly assigned to receive either MK-2060 or a placebo, both administered as a **solution for infusion** via **intravenous infusion**. The primary endpoint is the time to the first arteriovenous graft thrombosis event, while secondary endpoints include the time to each thrombosis event, the number of adverse events, and the number of major or clinically relevant non-major bleeding events as per the International Society on Thrombosis and Haemostasis criteria.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will confirm eligibility based on criteria such as a current diagnosis of end-stage renal disease and regular hemodialysis sessions. Follow-up visits will occur at regular intervals to assess the occurrence of thrombosis events, monitor safety, and evaluate any adverse events. The end-of-study visit will conclude the participant's involvement, summarizing the outcomes and any adverse events experienced. The expected length of participant involvement is up to 58 weeks, with conditions for early termination including the occurrence of significant adverse events or withdrawal of consent.

The clinical trial involves the administration of **MK-2060**, an investigational medication developed by Merck & Co. Inc. **MK-2060** is formulated as a **solution for infusion** and is classified as a biological product. The active substance, also named **MK-2060**, is derived from a protein of unspecified origin. The medication is administered via **intravenous infusion**. The dosing regimen allows for a maximum daily dose of 20 mg, with a cumulative maximum dose of 1200 mg over a treatment period not exceeding 58 days. The trial aims to assess the efficacy of **MK-2060** in preventing arteriovenous graft thrombosis in patients with end-stage renal disease undergoing hemodialysis.

The study also includes a **placebo** group to serve as a comparator for evaluating the efficacy of **MK-2060**. The placebo is designed to mimic the investigational product in appearance and administration route, ensuring the study remains double-blind. The placebo does not contain any active pharmaceutical ingredients and is administered in the same manner as the investigational drug, via **intravenous infusion**. This design allows for a controlled comparison to determine the true effect of **MK-2060** on the prevention of arteriovenous graft thrombosis.

The efficacy of MK-2060 in the clinical trial will be assessed by evaluating its impact on the prevention of **arteriovenous graft thrombosis** in patients with end-stage renal disease receiving hemodialysis. The primary endpoint for efficacy is the "Time to First AVG Thrombosis Event," which will be measured to determine the effectiveness of MK-2060 compared to placebo. Secondary endpoints include "Time to Each Arteriovenous Graft Thrombosis Event (First and Recurrent)," "Number of Participants who Experience One or More Adverse Events (AEs)," "Number of Major Bleeding Events or Clinically Relevant Non-Major Bleeding Events per International Society on Thrombosis (ISTH) Criteria," and "Number of Participants Who Discontinue Study Intervention Due to an AE."

The trial is designed as a randomized, parallel-group, placebo-controlled, double-blind, event-driven, multi-center Phase 2 clinical outcome trial. The efficacy parameters will be collected and analyzed throughout the study duration, with specific timepoints for assessment not explicitly detailed. The trial aims to increase the time to the first arteriovenous graft thrombosis event, thereby demonstrating the potential benefit of MK-2060 in this patient population. The study will adhere to rigorous clinical trial standards to ensure the reliability and validity of the efficacy assessments.