Global Study of MK-2060 (Anti-Factor XI Monoclonal Antibody) in Participants With End Stage Renal Disease Receiving Hemodialysis (FXI Hemodialysis Study) (MK-2060-007)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of two different doses of MK-2060 (a monoclonal antibody against Factor XI) in end stage renal disease (ESRD) participants receiving hemodialysis via an arteriovenous graft (AVG). Data from this study will be used to aid dose selection of MK-2060 in future studies. The primary hypothesis is that at least one of the MK-2060 doses is superior to placebo in increasing the time to first occurrence of AVG event.

Official Title
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A Randomized Parallel-group, Placebo-controlled, Double-blind, Event-driven, Multi-center Phase 2 Clinical Outcome Trial of Prevention of Arteriovenous Graft Thrombosis and Safety of MK-2060 in Patients With End Stage Renal Disease Receiving Hemodialysis

Conditions
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End-Stage Renal Disease, End-Stage Kidney Disease, Kidney Failure, Chronic

Intervention / Treatment
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* Drug: MK-2060
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current diagnosis of ESRD. Receiving hemodialysis (including hemodiafiltration) ≥3 times per week for a minimum of 3 hours per session via a mature normally functioning, uninfected AVG with at least 75% of the sessions meeting these criteria over the 4 weeks prior to randomization. A female participant is not pregnant or breastfeeding, not a woman of child-bearing potential (WOCBP) or is a WOCBP and agrees to follow contraceptive guidance during the intervention period and for at least 90 days after the last dose of study intervention. Exclusion Criteria: Recent history of cancer (<1 year). Non-melanoma skin cancers are allowed. Mechanical/prosthetic heart valve. Recent hemorrhagic stroke or lacunar stroke (<1 month). Recent evidence (<1 month) of bleeding requiring hospitalization or unplanned medical attention, a history (≤2 years) of recurrent bleeding episodes including epistaxis, gastrointestinal (GI) bleeds or genitourinary (GU) bleeds requiring medical treatment or events requiring treatment with blood products. Recent history (<1 year) of drug or alcohol abuse or dependence. Currently receiving or planning to receive anticoagulants or antiplatelet medications (intradialytic heparin and aspirin are permitted). Planning on receiving a living donor renal transplant within 12 months (participants are permitted to be candidates for deceased donor renal transplants). Planning on receiving an arteriovenous fistula (AVF) placement within 12 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-2060 Low Dose<br>MK-2060 low dose administered via intravenous (IV) infusion as a loading dose: Every other day (QOD) during week 1 (3 administrations), then once a week (QW) after week 1 | Drug: MK-2060<br>* MK-2060 lyophilized powder diluted in normal saline and administered via IV infusion<br>|
| Experimental: MK-2060 High Dose<br>MK-2060 high dose administered via IV infusion as a loading dose: QOD during week 1 (3 administrations), then QW after week 1 | Drug: MK-2060<br>* MK-2060 lyophilized powder diluted in normal saline and administered via IV infusion<br>|
| Placebo Comparator: Placebo<br>Placebo (normal saline) administered via IV infusion as a loading dose: QOD during week 1 (3 administrations), then once a week after week 1 | Drug: Placebo<br>* Normal saline administered via IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First AVG Thrombosis Event | An AVG thrombosis event is defined as the sudden occlusion of the participant's AVG requiring thrombectomy/thrombolysis, or clinical evidence of thrombosis with surgical, radiological or pathological conformation of an AVG thrombosis. This endpoint will be adjudicated by an independent clinical adjudication committee (CAC). | From date of randomization until the date of first occurrence of an AVG thrombosis event, assessed up to approximately 34 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Each Arteriovenous Graft Thrombosis Event (First and Recurrent) | An AVG thrombosis event is defined as the sudden occlusion of the participant's AVG requiring thrombectomy/thrombolysis, or clinical evidence of thrombosis with surgical, radiological or pathological conformation of an AVG thrombosis. This endpoint will be adjudicated by an independent CAC. | Up to approximately 34 months | 
| Number of Participants who Experience One or More Adverse Events (AEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 37 months | 
| Number of Major Bleeding Events or Clinically Relevant Non-Major Bleeding Events per International Society on Thrombosis (ISTH) Criteria | Major bleeding events will be defined as having a symptomatic presentation and including one or more of the following criteria: 1) Fatal bleeding 2) Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, intramuscular with compartment syndrome, 3) Bleeding causing a decrease in hematocrit level of 20 g/L or more or leading to transfusion of 2 or more units of whole blood or red cells. Clinically relevant non-major bleeding events will be defined as having signs or symptoms of hemorrhage that do not meet the criteria for major bleeding events, but do meet at least 1 of the following criteria: 1) Requiring medical intervention by a healthcare professional 2) Leading to hospitalization or increased level of care 3) Prompting a face to face evaluation by a healthcare professional. | Up to approximately 37 months | 
| Number of Participants Who Discontinue Study Intervention Due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 34 months |