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)

Merck Sharp & Dohme LLC506 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

506

Conditions

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

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (120)

Nephrology Consultants ( Site 0681)

Huntsville, Alabama, United States

AKDHC MEDICAL RESEARCH SERVICES, LLC-Maryvale ( Site 0723)

Phoenix, Arizona, United States

AKDHC Medical Research Services, LLC ( Site 0629)

Tucson, Arizona, United States

DaVita Anaheim West Dialysis-Davita Anaheim West Dialysis - Ismail ( Site 0562)

Anaheim, California, United States

DaVita Bakersfield Oak Street Dialysis-Clinical Research ( Site 0547)

Bakersfield, California, United States

Outcomes

Primary Outcomes

Time to First Arteriovenous Graft (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. A blinded independent clinical adjudication committee (CAC) adjudicated AVG thrombosis events. A time-to-event methodology was used to evaluate the results. The incidence rate is presented.

Time frame: From date of randomization until the date of first occurrence of an AVG thrombosis event, assessed up to approximately 37 months

Secondary Outcomes

Time to Each AVG 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. A blinded independent CAC adjudicated AVG thrombosis events. A time-to-event methodology was used to evaluate the results. The incidence rate is presented.

Time frame: Up to approximately 37 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. The number of participants with one or more AEs is presented.

Time frame: Up to approximately 40 months

Time to First Event of International Society on Thrombosis (ISTH) Major Bleeding Event or a Clinically Relevant Non-Major Bleeding Event

Major bleeding events were defined as a having symptomatic presentation and including ≥1 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 decrease in hematocrit level of 20 g/L or more or leading to transfusion of ≥2 units of whole blood or red cells. Clinically relevant non-major bleeding events were defined as signs or symptoms of hemorrhage that do not meet criteria for major bleeding events but meet ≥1 of the following criteria: 1) Requiring medical intervention by healthcare professional 2) Leading to hospitalization or increased level of care 3) Prompting face-to-face evaluation by healthcare professional. A time-to-event methodology was used. The incidence rate is presented.

Time frame: From date of first dose of study intervention until the first ISTH major bleeding event or a clinically relevant non-major bleeding event. assessed up to approximately 40 months

Number of Participants Who Discontinue Study Intervention Due to an AE

Time frame: Up to approximately 37 months