Brief Summary
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.
Brief Title
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)
Categories
Completion Date
Completion Date Type
Actual
Conditions
End-Stage Renal Disease
End-Stage Kidney Disease
Kidney Failure, Chronic
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05027074
Org Class
Industry
Org Full Name
Merck Sharp & Dohme LLC
Org Study Id
2060-007
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
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).
Outcome Measure
Time to First AVG Thrombosis Event
Outcome Time Frame
From date of randomization until the date of first occurrence of an AVG thrombosis event, assessed up to approximately 34 months
Secondary Ids
Secondary Id
MK-2060-007
Secondary Id
2024-511055-17
Secondary Id
U1111-1303-0286
Secondary Id
2020-002397-27
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to approximately 34 months
Outcome Measure
Time to Each Arteriovenous Graft Thrombosis Event (First and Recurrent)
Outcome Description
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.
Outcome Time Frame
Up to approximately 37 months
Outcome Measure
Number of Participants who Experience One or More Adverse Events (AEs)
Outcome Description
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.
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.
Outcome Time Frame
Up to approximately 37 months
Outcome Measure
Number of Major Bleeding Events or Clinically Relevant Non-Major Bleeding Events per International Society on Thrombosis (ISTH) Criteria
Outcome Description
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.
Outcome Time Frame
Up to approximately 34 months
Outcome Measure
Number of Participants Who Discontinue Study Intervention Due to an AE
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Matthew Abramowitz
Investigator Email
matthew.abramowitz@einsteinmed.org