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
Phase: PHASE2
Conditions: End-Stage Renal Disease, End-Stage Kidney Disease, Kidney Failure, Chronic
Sponsor: Merck Sharp & Dohme LLC

Official Protocol Title:
NCT number:                NCT05027074
Document Date:            14-Dec-2022
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

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Title Page
THIS PROTOCOL AMENDMENT AND ALL OF THE INFORMATION RELATING 
TO IT ARE CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK 
SHARP & DOHME LLC, RAHWAY, NJ, USA (MSD).
Protocol 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 
Protocol Number: 007-04
Compound Number: MK-2060
Sponsor Name:
Merck Sharp & Dohme LLC
(hereafter called the Sponsor or MSD)
Legal Registered Address:
126 East Lincoln Avenue
P.O. Box 2000
Rahway, NJ 07065 USA
Regulatory Agency Identifying Number(s):
EudraCT
2020-002397-27
IND
142237
Approval Date: 14 December 2022
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Sponsor Signatory
Typed Name:
Title:
Date
Protocol-specific Sponsor contact information can be found in the Investigator Study
File Binder (or equivalent).
Investigator Signatory
I agree to conduct this clinical study in accordance with the design outlined in this protocol 
and to abide by all provisions of this protocol.
Typed Name:
Title:
Date
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DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
Amendment 04
14-DEC-2022
To add a test of the efficacy hypothesis at the interim analysis and to reduce the study 
power.
Amendment 03
23-JUN-2022
Canada-specific amendment created to fulfill health authority request.
Amendment 02
06-APR-2022
Germany-specific amendment created to fulfill health authority request.
Amendment 01
08-MAR-2022
To update an inclusion criterion and provide sites with additional screening time to 
identify suitable participants for this study.
Original Protocol
12-JAN-2021
Not applicable
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PROTOCOL AMENDMENT SUMMARY OF CHANGES
Amendment: 4
Overall Rationale for the Amendments:
To add a test of the efficacy hypothesis at the interim analysis and to reduce the study power.
Summary of Changes Table:
Section # and Name
Description of Change 
Brief Rationale 
1.2  Schema
1.3  Schedule of Activities
4.1  Overall Design
4.4.1  Clinical Criteria for Early Study 
Termination
9.1  Statistical Analysis Plan Summary
9.6  Statistical Methods
9.7  Interim Analyses
9.8  Multiplicity
9.9.1  Efficacy
10.1.4.2  External DMC
10.8  Appendix 8: PK Substudy
Added a test of the efficacy hypothesis at 
the interim analysis.
To permit the study to stop early for 
efficacy.
9.9  Sample Size and Power Calculations
Reduced the study power to 80%.
To allow study completion within 
reasonable timelines due to slower than 
expected efficacy event accrual.
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Section # and Name
Description of Change 
Brief Rationale 
1.1  Synopsis
3 Hypotheses, Objectives, and Endpoints
4.2.1.1  Efficacy Endpoints
9.4.1  Efficacy Endpoints
9.6.1.2  Secondary Efficacy Endpoints
Updated the secondary objective from 
‘reducing the number of AVG 
thrombosis events’ to ‘increasing the 
time to each AVG thrombosis event (first 
and recurrent)’ and the statistical 
analysis.
The Andersen-Gill model will be used to 
analyze the time to each AVG thrombosis 
event (first and recurrent). 
1.3  Schedule of Activities
Added reference to Section 6.4 Study 
Intervention Compliance.
Consultation between the investigator and 
Sponsor is required for study interruptions 
>4 consecutive doses.
Added note for vital status assessment.
A participant’s vital status should be 
assessed whenever in question.
Added note for FSH assessment.
FSH is assessed to confirm postmenopausal 
status.
2.1  Study Rationale
Updated background on clinical trials for
FXI inhibitors.
New clinical study data became available.
2.2.2 Preclinical and Clinical Studies
Updated description of Study P004.
Study P004 was completed.
2.3  Benefit/Risk Assessment
Updated section with data from the 
current Investigator’s Brochure.
Study P004 was completed and new clinical 
study data became available.
3  Hypotheses, Objectives, and Endpoints
Updated the endpoints for evaluation of 
exposure-response or dose-response of 
MK-2060 QW for AVG thrombosis 
events. 
To clarify that pharmacokinetic endpoints 
will be collected (steady state Cmax and 
Ctrough)
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Section # and Name
Description of Change 
Brief Rationale 
4.1  Overall Design
4.2.1.1  Efficacy Endpoints
9.6.2  Analysis Methods for Safety 
Analyses
10.1.4.3  Clinical Adjudication 
Committee
Death was added to the list of events 
needing adjudication.
To adjudicate all deaths, including deaths 
that are not captured within the secondary
safety endpoint (ie, major bleed) or the 
exploratory efficacy endpoint (major 
thrombotic cardiovascular event).
4.1  Overall Design 
9.6.1.1  Primary Efficacy Endpoint
9.6.2  Analysis Methods for Safety 
Analyses
Added statement regarding censoring 
kidney transplant events in the primary 
efficacy analysis and safety analyses.
To avoid including in the analysis events 
(both efficacy and safety) occurring in 
participants who underwent kidney 
transplant, which could confound the 
results.
4.3.1  Starting Dose for This Study
Removed paragraph related to ongoing 
Study P004
Study P004 was completed.
5.2  Exclusion Criteria
Exclusion criterion #7 was revised. 
To clarify that regular use of aspirin in 
doses >150 mg per day is prohibited and to 
allow the use of periprocedural heparin, 
low-dose heparin for DVT prophylaxis
while hospitalized, and topical NSAIDs.
6.5  Concomitant Therapy
Added aspirin in doses >150 mg per day 
to the list of prohibited medications.
6.1  Study Intervention(s) Administered
Updated the NIMP definition to 
NIMP/AxMP
To align with EU CTR.
6.3.2  Stratification
Added note to clarify the ‘aspirin use’
stratification criterion.
‘As needed’ aspirin use is not included in 
the stratification criterion.
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Section # and Name
Description of Change 
Brief Rationale 
6.4  Study Intervention Compliance
Revised the statement regarding the 
management of participants with study 
intervention interruptions.
To clarify which study intervention 
interruptions require consultation between 
the investigator and Sponsor. 
7.1  Discontinuation of Study 
Intervention
Added discontinuation criterion for 
participants with prolonged study 
intervention interruptions and 
clarification for participant reloading.
To provide the option to maintain 
participants in the study after a prolonged 
study intervention interruption 
(>4 consecutive doses).
8.2  Efficacy Assessments
Revised statement regarding PRO
questionnaire administration.
To clarify that the PRO questionnaires are 
administered by the interviewer
(investigator or qualified designee).
8.11.6  Premature Discontinuation Visit
Added time frame for the Safety Follow-
up Visit for discontinued participants 
who continue to be monitored in the trial.
To clarify the timing of the Safety 
Follow-up Visit.
Title Page
Section 10.1.1  Code of Conduct for 
Clinical Trials
Throughout Document
Sponsor entity name and address change.
Merck Sharp & Dohme Corp. underwent an 
entity name and address change to Merck 
Sharp & Dohme LLC, Rahway, NJ, USA. 
This conversion resulted only in an entity 
name change and update to the address.
Section 10.7 Appendix 7: Country-
specific Requirements
Country-specific amendments for 
Germany and Canada were added to this 
global amendment. Changes are outlined 
in Section 10.7 and referenced in 
Sections 1.3 Schedule of Activities, 
5.2 Exclusion Criteria, and 8.3.5.1 Serum 
Pregnancy Test.
To consolidate country-specific 
amendments 2 and 3.
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Section # and Name
Description of Change 
Brief Rationale 
10.9  Appendix 9: Hemostasis
Added information related to an in vivo 
study of reversal of MK-2060-induced 
aPTT prolongation by transfusion of FFP 
in rhesus monkeys. Change is referenced 
in Section 6.5.2 Surgery Guidance.
To include additional data that may assist 
study investigators with the management of 
bleeding events.
Throughout Document
Minor administrative, formatting, 
grammatical, and/or typographical 
changes were made throughout the 
document.
To ensure clarity and accurate interpretation 
of the intent of the protocol.
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Table of Contents
DOCUMENT HISTORY ........................................................................................................3
PROTOCOL AMENDMENT SUMMARY OF CHANGES...............................................4
1
PROTOCOL SUMMARY ............................................................................................17
1.1
Synopsis.................................................................................................................17
1.2
Schema ..................................................................................................................20
1.3
Schedule of Activities...........................................................................................21
2
INTRODUCTION..........................................................................................................24
2.1
Study Rationale....................................................................................................24
2.2
Background ..........................................................................................................25
2.2.1
Pharmaceutical and Therapeutic Background .............................................25
2.2.2
Preclinical and Clinical Studies ...................................................................25
2.3
Benefit/Risk Assessment......................................................................................27
3
HYPOTHESES, OBJECTIVES, AND ENDPOINTS................................................28
4
STUDY DESIGN............................................................................................................30
4.1
Overall Design......................................................................................................30
4.2
Scientific Rationale for Study Design.................................................................31
4.2.1
Rationale for Endpoints ...............................................................................32
4.2.1.1
Efficacy Endpoints.............................................................................32
4.2.1.2
Patient-reported Outcomes Endpoints ...............................................33
4.2.1.3
Safety Endpoints................................................................................34
4.2.1.4
Pharmacokinetic Endpoints ...............................................................35
4.2.1.5
Immunogenicity Endpoints................................................................35
4.2.1.6
Pharmacodynamic Endpoints.............................................................35
4.2.1.7
Planned Exploratory Biomarker Research.........................................36
4.2.1.7.1
Planned Genetic Analysis ........................................................36
4.2.1.8
Future Biomedical Research..............................................................36
4.2.2
Rationale for the Use of Placebo .................................................................36
4.3
Justification for Dose...........................................................................................37
4.3.1
Starting Dose for This Study........................................................................37
4.3.2
Maximum Dose/Exposure for This Study ...................................................37
4.3.3
Rationale for Dose Interval and Study Design ............................................38
4.4
Beginning and End of Study Definition .............................................................38
4.4.1
Clinical Criteria for Early Study Termination .............................................38
5
STUDY POPULATION ................................................................................................38
5.1
Inclusion Criteria.................................................................................................39
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5.2
Exclusion Criteria................................................................................................40
5.3
Lifestyle Considerations......................................................................................43
5.4
Screen Failures.....................................................................................................43
5.5
Participant Replacement Strategy......................................................................43
6
STUDY INTERVENTION............................................................................................43
6.1
Study Intervention(s) Administered...................................................................43
6.2
Preparation/Handling/Storage/Accountability .................................................45
6.2.1
Dose Preparation..........................................................................................45
6.2.2
Handling, Storage, and Accountability........................................................45
6.3
Measures to Minimize Bias: Randomization and Blinding..............................46
6.3.1
Intervention Assignment..............................................................................46
6.3.2
Stratification.................................................................................................46
6.3.3
Blinding........................................................................................................46
6.4
Study Intervention Compliance..........................................................................47
6.5
Concomitant Therapy..........................................................................................47
6.5.1
Rescue Medications and Supportive Care ...................................................49
6.5.2
Surgery Guidance.........................................................................................50
6.6
Dose Modification ................................................................................................50
6.7
Intervention After the End of the Study............................................................50
6.8
Clinical Supplies Disclosure................................................................................50
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL............................................................................................................51
7.1
Discontinuation of Study Intervention...............................................................51
7.2
Participant Withdrawal From the Study...........................................................52
7.3
Lost to Follow-up .................................................................................................52
8
STUDY ASSESSMENTS AND PROCEDURES........................................................53
8.1
Administrative and General Procedures ...........................................................53
8.1.1
Informed Consent.........................................................................................53
8.1.1.1
General Informed Consent.................................................................54
8.1.1.2
Consent and Collection of Specimens for Future Biomedical 
Research.............................................................................................54
8.1.1.3
Consent for PK Substudy...................................................................54
8.1.1.4
Consent for Quality of Life Questionnaires.......................................55
8.1.2
Inclusion/Exclusion Criteria ........................................................................55
8.1.3
Participant Identification Card.....................................................................55
8.1.4
Medical History ...........................................................................................55
8.1.5
Prior and Concomitant Medications Review...............................................55
8.1.5.1
Prior Medications...............................................................................55
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8.1.5.2
Concomitant Medications..................................................................55
8.1.6
Assignment of Screening Number...............................................................56
8.1.7
Assignment of Treatment/Randomization Number.....................................56
8.1.8
Study Intervention Administration ..............................................................56
8.1.8.1
Timing of Dose Administration.........................................................56
8.1.9
Discontinuation and Withdrawal .................................................................56
8.1.9.1
Withdrawal From Future Biomedical Research ................................57
8.1.10
Participant Blinding/Unblinding..................................................................57
8.1.11
Calibration of Equipment.............................................................................58
8.1.12
Identification of External Contact Person....................................................58
8.2
Efficacy Assessments ...........................................................................................58
8.3
Safety Assessments...............................................................................................59
8.3.1
Physical Examinations.................................................................................59
8.3.1.1
Height.................................................................................................59
8.3.1.2
Weight................................................................................................59
8.3.2
Systemic Infusion Reaction Assessment .....................................................59
8.3.3
Vital Signs....................................................................................................60
8.3.3.1
Body Temperature .............................................................................60
8.3.3.2
Heart Rate and Blood Pressure ..........................................................60
8.3.4
Electrocardiograms ......................................................................................60
8.3.5
Clinical Safety Laboratory Assessments .....................................................61
8.3.5.1
Serum Pregnancy Test .......................................................................61
8.3.5.2
Serum Follicle Stimulating Hormone................................................62
8.3.6
Quality of Life Questionnaires.....................................................................62
8.3.7
Vital Status Assessment...............................................................................62
8.4
Adverse Events, Serious Adverse Events, and Other Reportable Safety 
Events....................................................................................................................62
8.4.1
Time Period and Frequency for Collecting AE, SAE, and Other 
Reportable Safety Event Information ..........................................................62
8.4.2
Method of Detecting AEs, SAEs, and Other Reportable Safety Events......64
8.4.3
Follow-up of AE, SAE, and Other Reportable Safety Event Information...64
8.4.4
Regulatory Reporting Requirements for SAE .............................................65
8.4.5
Pregnancy and Exposure During Breastfeeding ..........................................65
8.4.6
Disease-related Events and/or Disease-related Outcomes Not Qualifying 
as AEs or SAEs............................................................................................65
8.4.7
Events of Clinical Interest............................................................................66
8.5
Treatment of Overdose........................................................................................66
8.6
Pharmacokinetics.................................................................................................66
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8.6.1
Blood Collection for Plasma MK-2060 .......................................................67
8.7
Immunogenicity Assessments .............................................................................67
8.8
Pharmacodynamics..............................................................................................67
8.9
Biomarkers ...........................................................................................................67
8.9.1
Planned Genetic Analysis Sample Collection..............................................67
8.10
Future Biomedical Research Sample Collection...............................................68
8.11
Visit Requirements...............................................................................................68
8.11.1
Screening......................................................................................................68
8.11.2
Randomization.............................................................................................68
8.11.3
Treatment Period..........................................................................................69
8.11.4
Final Efficacy Visit......................................................................................69
8.11.5
Safety Follow-up Visit.................................................................................69
8.11.6
Premature Discontinuation Visit..................................................................69
8.11.7
Premature Intervention Discontinuation Safety Follow-up Visit ................70
9
STATISTICAL ANALYSIS PLAN .............................................................................70
9.1
Statistical Analysis Plan Summary.....................................................................70
9.2
Responsibility for Analyses/In-house Blinding .................................................71
9.3
Hypotheses/Estimation ........................................................................................72
9.4
Analysis Endpoints...............................................................................................72
9.4.1
Efficacy Endpoints.......................................................................................72
9.4.2
Patient-reported Outcome Endpoints...........................................................72
9.4.3
Safety Endpoints..........................................................................................72
9.4.4
Pharmacokinetic Endpoint...........................................................................72
9.4.5
Immunogenicity Endpoints..........................................................................72
9.4.6
Pharmacodynamic Endpoints.......................................................................73
9.5
Analysis Populations............................................................................................73
9.5.1
Efficacy Analysis Population.......................................................................73
9.5.2
Patient-reported Outcome Analysis Population...........................................73
9.5.3
Safety Analysis Population..........................................................................73
9.5.4
Pharmacokinetic Analysis Population .........................................................73
9.5.5
Immunogenicity Analysis Population..........................................................74
9.5.6
Pharmacodynamic Analysis Population ......................................................74
9.6
Statistical Methods...............................................................................................74
9.6.1
Statistical Methods for Efficacy Analyses...................................................74
9.6.1.1
Primary Efficacy Endpoint ................................................................75
9.6.1.2
Secondary Efficacy Endpoints...........................................................76
9.6.2
Analysis Methods for Safety Analyses........................................................76
9.7
Interim Analyses ..................................................................................................78
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9.8
Multiplicity ...........................................................................................................80
9.9
Sample Size and Power Calculations .................................................................81
9.9.1
Efficacy........................................................................................................81
9.9.2
Safety ...........................................................................................................81
9.10
Subgroup Analyses...............................................................................................82
9.11
Compliance (Medication Adherence).................................................................82
9.12
Extent of Exposure...............................................................................................82
10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.....................................................................................................83
10.1
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations........83
10.1.1
Code of Conduct for Clinical Trials.............................................................83
10.1.2
Financial Disclosure.....................................................................................85
10.1.3
Data Protection.............................................................................................86
10.1.3.1
Confidentiality of Data ......................................................................86
10.1.3.2
Confidentiality of Participant Records...............................................86
10.1.3.3
Confidentiality of IRB/IEC Information............................................86
10.1.4
Committees Structure...................................................................................87
10.1.4.1
Executive Oversight Committee........................................................87
10.1.4.2
External DMC....................................................................................87
10.1.4.3
Clinical Adjudication Committee ......................................................87
10.1.4.4
Scientific Advisory Committee..........................................................88
10.1.5
Publication Policy........................................................................................88
10.1.6
Compliance with Study Registration and Results Posting Requirements ...88
10.1.7
Compliance with Law, Audit, and Debarment ............................................88
10.1.8
Data Quality Assurance ...............................................................................89
10.1.9
Source Documents .......................................................................................90
10.1.10
Study and Site Closure.................................................................................90
10.2
Appendix 2: Clinical Laboratory Tests..............................................................91
10.3
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting...............................................................92
10.3.1
Definition of AE ..........................................................................................92
10.3.2
Definition of SAE ........................................................................................93
10.3.3
Additional Events Reported.........................................................................94
10.3.4
Recording AE and SAE ...............................................................................94
10.3.5
Reporting of AEs, SAEs, and Other Reportable Safety Events to the 
Sponsor ........................................................................................................98
10.4
Appendix 4: Device Events, Adverse Device Events, and Medical Device 
Incidents: Definitions, Collection, and Documentation..................................100
10.5
Appendix 5: Contraceptive Guidance..............................................................101
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10.5.1
Definitions..................................................................................................101
10.5.2
Contraception Requirements......................................................................103
10.6
Appendix 6: Collection and Management of Specimens for Future 
Biomedical Research..........................................................................................104
10.7
Appendix 7: Country-specific Requirements..................................................109
10.7.1
Country-specific Requirements for Germany............................................109
10.7.2
Country-specific Requirements for Canada...............................................109
10.8
Appendix 8: PK Substudy.................................................................................110
10.9
Appendix 9: Hemostasis ....................................................................................112
10.10 Appendix 10: Abbreviations .............................................................................115
11
REFERENCES.............................................................................................................118
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LIST OF TABLES
Table 1
Study Interventions..........................................................................................44
Table 2
Reporting Time Periods and Time Frames for Adverse Events and Other 
Reportable Safety Events.................................................................................63
Table 3
Analysis Strategy for Key Efficacy Endpoints................................................76
Table 4
Analysis Strategy for Safety Parameters..........................................................78
.......79
...................................80
.................80
Table 8
Examples of AE Incidences for Which The 95% CI for the Difference 
Would Exclude Zero........................................................................................82
Table 9
Protocol-required Laboratory Assessments.....................................................91
Table 10
PK Substudy Schedule of Activities (in addition to the PK Schedule of 
Activities for the main study) ........................................................................111
Table 11
Mean aPTT Parameters in Monkeys After Dosing of MK-2060 Followed 
by Plasma-Lyte or Fresh Frozen Plasma Administration ..............................114
CCI
CCI
CCI
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LIST OF FIGURES
Figure 1
Study Design....................................................................................................20
..113
CCI
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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol 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 
Short Title: MK-2060 Global Study in Patients with End Stage Renal Disease Receiving 
Hemodialysis
Acronym: FXI Hemodialysis Study
Hypotheses, Objectives, and Endpoints:
In adult patients with ESRD receiving hemodialysis via an AVG: 
Primary Objectives
Primary Endpoints
- Objective: To evaluate the efficacy of MK-
2060 compared to placebo in increasing the 
time to first arteriovenous graft thrombosis 
event.
Hypothesis: At least 1 of the MK-2060 doses 
is superior to placebo in increasing the time 
to first occurrence of arteriovenous graft 
thrombosis event
- Arteriovenous graft thrombosis events
Secondary Objectives
Secondary Endpoints
- Objective: To evaluate the efficacy of MK-
2060 compared to placebo in increasing the 
time to each arteriovenous graft thrombosis 
event (first and recurrent).
- Arteriovenous graft thrombosis events 
- Objective: To assess the safety and 
tolerability of MK-2060.
- Adverse events
- Major bleeding events or clinically 
relevant non-major bleeding events (per 
International Society on Thrombosis and 
Haemostasis criteria)
- Discontinuation of study intervention due 
to adverse event(s)
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Overall Design:
Study Phase
Phase 2
Primary Purpose
Prevention
Indication
Prevention of arteriovenous graft thrombosis
Population
Patients with ESRD receiving hemodialysis via an 
arteriovenous graft
Study Type
Interventional
Intervention Model
Parallel
This is a multi-site study.
Type of Control
Placebo
Study Blinding
Double-blind
Blinding Roles
Sponsor
Investigator
Care Provider
Outcomes Assessor
Participants or Subjects
Estimated Duration of Study
The Sponsor estimates that the study will require 
approximately 20 months from the time the first 
participant is enrolled until the last participant’s last 
study-related telephone call or visit.
Number of Participants:
Approximately 489 participants will be randomized.
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Intervention Groups and Duration:
Intervention 
Groups
Intervention
Group Name
Drug
Loading 
Dose 
Strength
Maintenance 
Dose 
Strength
Dose 
Frequency
Route of 
Adminis-
tration
Regimen/ 
Treatment 
Period
MK-2060 
High Dose
MK-2060
20 mg
20 mg
Loading dose –
1 dose, 3 times 
during Week 1
QOD. 
Maintenance 
dose – 1 dose 
QW after 
Week 1
IV
Double-
blind 
treatment 
period 
MK-2060 
Low Dose
MK-2060
6 mg
6 mg
Loading dose –
1 dose, 3 times 
during Week 1 
QOD. 
Maintenance 
dose – 1 dose 
QW after 
Week 1
IV
Double-
blind 
treatment 
period 
Placebo
Placebo
0 mg
0 mg
Loading dose –
1 dose, 3 times 
during Week 1 
QOD. 
Maintenance 
dose – 1 dose 
QW after 
Week 1
IV
Double-
blind 
treatment 
period 
IV= intravenous; QOD= every other day; QW= once a week.
Note: Study intervention to be administered during routine hemodialysis sessions.
Total 
Number of 
Intervention 
Groups/ 
Arms
3
Duration of 
Participation
This is an event-driven study expected to run for approximately 20 months 
from FPE until LPLV. After a screening period of up to 30 days, eligible
participants will be treated with study intervention until full accrual of 
events, with an expected median treatment duration of 10 months. 
Participants will be monitored for safety events from the time of providing 
documented informed consent through the final contact, 3 months after the 
last treatment dose.
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Study Governance Committees:
Executive Oversight Committee
Yes
Data Monitoring Committee
Yes
Clinical Adjudication Committee
Yes
Study governance considerations are outlined in Appendix 1.
Study Accepts Healthy Volunteers: No
A list of abbreviations used in this document can be found in Appendix 10.
1.2
Schema
The study design is depicted in Figure 1.
Figure 1
Study Design
AVG= arteriovenous graft; ESRD= end-stage renal disease; FP= first patient; LPLV= last 
patient last visit; QOD= every other day; QW= once a week; R= randomization; V= visit.
Note: FP randomized to LPLV will be approximately 20 months. 
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1.3
Schedule of Activities
Study Period
Screening
Treatment Period
Premature Intervention Discontinuation
Notes
Visit Number/Title
1
Screen
2 
Rand
3
4
5
6
7
8
9
Visit n
Final 
Efficacy 
Visit
Safety 
Follow-up
Visit
Premature 
Discon.
Visit
Safety 
Follow-up
Visit
Visit n
Final 
Efficacy
Visit
Scheduled 
Days/Month
Day 
-30 to 
Day 1
Day 1 Day
3
Day
5
Day
8
Day 
15
Day 
29
Day 
57
Day 
85
Every 
3 months
Based on 
Efficacy 
Cutoff
datea
3 months
after Final
Efficacy
Visit
Study 
Intervention 
Discon.
3 months
after 
Discon.
Every 
3 months
Based on 
Efficacy 
Cutoff
datea
Visit Window
±1
day
±1 
day
±1 
day
±3
days
±3
days
±5
days
±7
days
±7
days
±7
days
±7
days
±7 days
±7 days
Refer to Section 6.4.
Administrative Procedures
Informed Consent
X
Informed Consent 
for Future 
Biomedical 
Research
X
Informed Consent 
for PK Substudy
X
Informed Consent 
for QoL 
Questionnaires
X
At preselected sites
Inclusion/
Exclusion Criteria
X
X
Participant 
Identification Card
X
X
Add randomization 
number to card on Day 1
Medical History 
X
Identification of 
External Contact 
Person
X
For vital status 
assessment
Prior/Concomitant 
Medication Review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Treatment/
Randomization 
Number
X
Study intervention 
Administration
X
X
X
X
Following first 3 loading doses, study 
intervention to be administered 
weekly during regularly scheduled 
hemodialysis sessions
See Section 8.1.8 for 
details. 
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Study Period
Screening
Treatment Period
Premature Intervention Discontinuation
Notes
Visit Number/Title
1
Screen
2 
Rand
3
4
5
6
7
8
9
Visit n
Final 
Efficacy 
Visit
Safety 
Follow-up
Visit
Premature 
Discon.
Visit
Safety 
Follow-up
Visit
Visit n
Final 
Efficacy
Visit
Scheduled 
Days/Month
Day 
-30 to 
Day 1
Day 1 Day
3
Day
5
Day
8
Day 
15
Day 
29
Day 
57
Day 
85
Every 
3 months
Based on 
Efficacy 
Cutoff
datea
3 months
after Final
Efficacy
Visit
Study 
Intervention 
Discon.
3 months
after 
Discon.
Every 
3 months
Based on 
Efficacy 
Cutoff
datea
Visit Window
±1
day
±1 
day
±1 
day
±3
days
±3
days
±5
days
±7
days
±7
days
±7
days
±7
days
±7 days
±7 days
Refer to Section 6.4.
Clinical Procedures/Assessments
Full Physical 
Examination
X
X
X
X
Systemic Infusion 
Reaction
Assessment
X
X
X
Any infusion reaction 
must be reported as an 
AE
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Post-dialysis
Directed Physical 
Examination
X
X
X
X
X
Vital Signs 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pre-dialysis. BP and HR 
to be measured in 
triplicate.
12-lead ECG
X
X
X
X
Clinical Events 
Assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Collection of events for 
selected endpoints
Vital Status 
Assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Assessed whenever
participant’s vital status 
is in question.
AE/SAE Review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Participants should be 
trained to contact the site 
to report AEs as soon as 
they occur
KDQOL-SF & EQ-
5D-5L
Questionnaires
X
X
X
X
At preselected sites every 
6 months
Central Laboratory Assessments
Serum FSH –
(WOCBP only)
X
Xb
To confirm 
postmenopausal status.
Pregnancy test 
(Serum) in WOCBP
Xc
X
X
X
X
X
Germany-specific 
requirements are in 
Appendix 7
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Study Period
Screening
Treatment Period
Premature Intervention Discontinuation
Notes
Visit Number/Title
1
Screen
2 
Rand
3
4
5
6
7
8
9
Visit n
Final 
Efficacy 
Visit
Safety 
Follow-up
Visit
Premature 
Discon.
Visit
Safety 
Follow-up
Visit
Visit n
Final 
Efficacy
Visit
Scheduled 
Days/Month
Day 
-30 to 
Day 1
Day 1 Day
3
Day
5
Day
8
Day 
15
Day 
29
Day 
57
Day 
85
Every 
3 months
Based on 
Efficacy 
Cutoff
datea
3 months
after Final
Efficacy
Visit
Study 
Intervention 
Discon.
3 months
after 
Discon.
Every 
3 months
Based on 
Efficacy 
Cutoff
datea
Visit Window
±1
day
±1 
day
±1 
day
±3
days
±3
days
±5
days
±7
days
±7
days
±7
days
±7
days
±7 days
±7 days
Refer to Section 6.4.
Coagulation (INR, 
PT, aPTT)
X
To be collected separate 
from hematology
laboratory tests
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
Liver Function 
Tests
X
X
X
X
X
X
X
X
X
X
Chemistry
X
X
X
X
X
X
X
X
X
X
Pharmacokinetics/Immunogenicity/Pharmacodynamics/ Biomarkers
Blood for PK 
evaluation
Xd
Xe
Xe
Xe
Xd
Xe
Xe
Xe
Record date and time of 
collection. To be 
collected for all 
participants in main 
study.
Blood for ADA
X
X
X
X
X
X
Collect pre-dialysis
Blood for 
PT/aPTT/FXI 
Activity  
X
X
X
X
X
X
X
X
X
Collect predose (Sections
8.8 and 8.10)
Blood for Genetic 
Analysis
X
Collect predose from 
enrolled participants only
ADA= anti-drug antibodies; AE= adverse event; aPTT= activated partial thromboplastin time; BP= blood pressure; Discon= discontinuation; ECG= electrocardiogram; EQ-5D-5L= Euro quality of 
life 5-dimensional, 5-level questionnaire; FSH= follicle stimulating hormone; FXI= factor XI; KDQOL-SF= kidney disease quality of life questionnaire-short form; PK= pharmacokinetics; QoL= 
quality of life; SAE= serious adverse event; WOCBP= women of childbearing potential. 
Visit n= Starting from Visit 9 (Day 85) all subsequent visits will be scheduled every 3 months until study completion is reached. 
a. Efficacy Cutoff will be declared when the required number of events has accrued for the primary efficacy endpoint (see Section 9.7). If the study stops at IA, the Final Efficacy Visits will be 
scheduled to occur within 14 days of Sponsor’s notification to stop the study. If the study continues, the Final Efficacy Visits will be scheduled to occur in the 14 days following the Final Analysis 
efficacy cutoff date. 
b. All WOCBP will have an FSH test at Visit 1. Serum FSH at Visit 2 is only required for participants who have less than 1 year of amenorrhea.
c. A pregnancy test must be performed at Visit 1. In addition, 1 pregnancy test must be performed within 6 days before the first dose of study intervention (see Section 5.1).
d. Trough and peak sample collection. Trough sample to be collected pre-dialysis before any IV heparin is administered to the participant. Peak sample to be collected approximately 30 minutes
after infusion ends. If dosing and drawing is from the same access point, flush the access point with saline before sample collection. Record the time samples were drawn, time infusion was 
started, and time the infusion ended. 
e. Trough sample collection only. To be collected pre-dialysis (before any IV heparin is administered to the participant). Record the time the sample was drawn and the time infusion was started.
Note: For sites participating in the PK substudy, see Table 10 – PK Substudy Schedule of Activities.
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2
INTRODUCTION
2.1
Study Rationale
The purpose of this study is to evaluate the efficacy and safety of MK-2060 in ESRD 
participants receiving hemodialysis via an AVG. Data from this study will be used to aid 
dose selection of MK-2060 in future studies with the ultimate goal of proving MK-2060 
effective in preventing major thrombotic cardiovascular events in individuals with ESRD. 
ESRD patients, specifically those on hemodialysis, carry an elevated risk for thrombotic 
events with associated morbidity and mortality. The relative risk in dialysis patients 
compared to the general population is >5 fold for MI, ~6 fold for ischemic stroke, and 
~2.2-fold for VTE [Tveit, D. P., et al 2002] [Casserly, L. F. 2003] [Winkelmayer, W. C., et al 
2011] [Reinecke, H., et al 2009]. This tendency to thrombosis is particularly problematic for 
ESRD patients receiving hemodialysis via an AVG. Successful hemodialysis relies on brisk 
blood flow through the AVG. AVGs are prone to developing thrombi, which often lead to 
AVG failure, with annual rates of AVG failure from thrombosis of >50% [Miller, P. E., et al 
2000]. While ESRD patients have a substantial need to reduce the risk of thrombotic events,
doing so with anticoagulants is met with the challenges that these patients have an increased 
risk of clinically important bleeding due to uremia-related platelet dysfunction, concurrent 
use of antiplatelet agents, and the uncertainty in dose adjustment of anticoagulants in ESRD 
patients. These factors make the therapeutic window for many of these patients unfeasibly
small with conventional anticoagulants [Lau, Y. C., et al 2016]. As a result, warfarin is 
generally avoided in ESRD due to its complex management and risk of bleeding in this 
setting. DOACs such as FXa inhibitors are not included in guideline recommendations for 
ESRD due to their reliance on renal clearance and a lack of clinical data. There exists 
significant unmet need in preventing thrombotic vascular events in ESRD patients and a 
demand for novel therapies.
Targeting activity of FXI is a novel approach in anticoagulation. FXI is a key component in 
the intrinsic pathway, activated by circulating thrombin, which in turn leads to greater 
thrombin production and amplification of clot formation. Congenital loss of activity of FXI 
(hemophilia C) leads to reduction in lifetime risk of thrombosis and cardiovascular events but
is associated with only minimal disruption of hemostasis [Preis, M., et al 2017]. 
Pharmacologic efforts to suppress FXI production or activity, for example using antisense 
oligonucleotides, mAb, or small molecule inhibitors, have demonstrated successful reduction 
of clot formation with minimal bleeding effects and suggest FXI is a highly desirable 
pharmacological target [Buller, H. R., et al 2015] [Weitz, J. I., et al 2020] [Verhamme, P., et 
al 2021] [Weitz, J. I., et al 2021] [Nopp, S., et al 2022]. MK-2060 is a human anti-FXI mAb 
that inhibits FXI activation of FXIa. Targeting FXI inhibition with MK-2060 may achieve 
effective anticoagulation for ESRD patients without a prohibitive increase in bleeding events.  
The Phase 2 study aims to demonstrate MK-2060 is an effective anticoagulant in ESRD 
patients receiving hemodialysis via an AVG. Selecting only ESRD patients with AVGs and 
focusing on AVG thrombosis events allows rapid assessment of the anticoagulant properties 
of MK-2060 relative to placebo due to the high frequency of these events while at the same 
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time providing an estimate of the bleeding risk associated with FXIa inhibition from 
MK-2060. 
2.2
Background
Refer to the IB for detailed background information on MK-2060.
2.2.1
Pharmaceutical and Therapeutic Background
Factor XI is a critical component in the intrinsic pathway of the coagulation cascade. 
MK-2060 is an anti-FXI mAb being developed for the prevention of thrombotic 
complications in ESRD. MK-2060 acts by preventing activation of FXI and blocking FXIa. 
Based on preclinical and human genetic data, as well as emerging clinical data from other 
groups using either an antisense oligonucleotide or a mAb approach, inhibiting FXI activity 
leads to a clinically relevant antithrombotic effect with minimal risk of bleeding 
complications and hence is expected to have an expanded therapeutic index compared to 
inhibition of more downstream clotting factors such as FXa and thrombin [Buller, H. R., et al 
2015] [Bethune, C., et al 2017]. Therefore, FXIa inhibition is a promising therapeutic 
approach for the prevention of thromboembolic complications.  
2.2.2
Preclinical and Clinical Studies
Preclinical studies
The antithrombotic efficacy of MK-2060 was assessed in cynomolgus monkeys using an AV
shunt model of thrombosis developed and validated at MSD [Wickham, L. A., et al 2016]
with reduction in thrombus weight upon treatments with
MK-2060. 
In cardiac telemetry studies, MK-2060 was administered SC at a single dose of 60 mg/kg to 
conscious, adult, male, telemetered rhesus monkeys. There were no effects on ECG intervals 
(PR, QRS, QT, and QTci), arterial BP parameters (SBP, DBP, and mean BP), and HR at 60-
mg/kg SC dose. Based on the absence of findings from this cardiac telemetry study, the 
NOEL for cardiovascular effects after a single SC dose in rhesus monkeys was ≥60 mg/kg 
MK-2060.
MK-2060 was assessed in rhesus monkeys in a repeat-dose 2-week (3 doses per week)
toxicity study, a repeat-dose 4-week (1 dose every week in SWs 1 to 3 SC and 1 dose in 
SW 4 IV) toxicity study with an 8-week treatment-free period, and a repeat-dose 6-month 
(QW SC) toxicity study with a 3-month treatment-free period. An exploratory toxicity and
toxicokinetic study in nonpregnant rabbits was also conducted. MK-2060 effects on embryo-
fetal development were evaluated in a rabbit pEFD study. All animals survived to scheduled 
termination. There were no test article-related organ weight changes, gross observations, or
histomorphologic findings at the final (end of dosing) necropsy or recovery (end of
treatment-free period) necropsy.
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Clinical Studies
Study MK-2060-P001
Study MK-2060-P001 was a double-blind, randomized, placebo-controlled, single site, 
sequential panel study to evaluate the safety, tolerability, PK, and PD of single ascending 
dose administration of SC and IV doses of MK-2060 in healthy male participants. Forty-five
healthy male participants received single doses of MK-2060 up to 120 mg administered SC 
(27 participants) or 40 mg IV (18 participants). MK-2060 was generally well tolerated and 
there were no SAEs or discontinuations due to AEs. In healthy male participants single IV 
doses of 20 mg and 40 mg of MK-2060 resulted in increases in 
for 120 hours. Refer to the IB for a detailed overview of the study, and available PK, PD, and 
safety results.
Study MK-2060-P004 
Study MK-2060-004 was a double-blind, randomized, placebo-controlled, multiple-site, 
sequential panel study to evaluate the safety, tolerability, PK, and PD of single (Part 1) and 
multiple (Part 2) doses of IV administration of MK-2060 in older adult participants (age 
≥40 and ≤80; men and WONCBP) with ESRD on hemodialysis. The study had 2 parts: Part 1 
assessed single ascending IV doses (8 mg, 20 mg, and 40 mg). In each of the 3 panels in 
Part 1, Panels A-C, 8 participants were randomized to receive a single dose of MK-2060 or 
placebo in a treatment ratio of 3:1 (6 active and 2 placebo). Part 2 followed Part 1 and 
assessed multiple doses in older participants with ESRD on hemodialysis (n=21; 16 active 
and 5 placebo). MK-2060 was generally well tolerated. No deaths or SAEs considered 
related to MK-2060 by the investigator were reported, and no participant discontinued due to 
an AE considered related to MK-2060 by the investigator. There were no AEs suggestive of 
hypersensitivity.
Across Part 1 and Part 2 of the study, apart from mechanism-based aPTT increases, there 
were no clinically significant changes from baseline for ECGs, safety laboratory tests, and no 
changes in hematology laboratory tests suggestive of bleeding. Similarly, an exploratory 
assessment of time to vascular access site hemostasis after removal of the hemodialysis 
needles remained unchanged from baseline. 
Based on mean concentration-time profiles, MK-2060 showed a biphasic terminal phase in 
participants with ESRD, with an apparent median observed Tmax of approximately 1 hour at 
end of infusion, which was consistent across dose levels in Parts 1 and 2. After single-dose 
administration in participants with ESRD, t1/2 ranged from approximately 14 days (8 mg 
MK-2060 IV) to approximately 21 days (40 mg MK-2060 IV), compared to ≥30 days in 
healthy participants. Exposure (AUC0-inf and Cmax) after single IV administration of 8 mg 
MK-2060 in participants with ESRD was comparable to that in healthy participants while 
exposure after single IV administration of 20 mg or 40 mg MK-2060 in participants with 
ESRD was slightly lower than that in healthy participants due to higher clearance. After 
multiple dose administrations in participants with ESRD, observed CL (0.0171 L/h) was 
consistent with that observed after single doses of 20 mg and 40 mg MK-2060 and slightly 
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higher than that after single doses of 8 mg MK-2060; t1/2 was approximately 19 days, which 
was consistent with that after single doses. In participants with ESRD, observed PK 
concentration profiles after multiple IV MK-2060 doses were consistent with projected PK 
concentrations after single IV MK-2060 doses, suggesting that the PK of IV MK-2060 is not 
time-dependent in patients with ESRD.
After single-dose administration in participants with ESRD, the mean observed aPTT fold-
change (relative to baseline) at 168 hours increased with higher doses and the mean observed 
FXI activity fold-change (relative to baseline) at 168 hours showed dose-dependent 
decreases. aPTT values returned to near-baseline at Day 22 and FXI activity values returned 
to near-baseline at Day 29. After multiple dose administrations of 25 mg MK-2060 in 
participants with ESRD, the mean observed 
mean observed 
 
2.3
Benefit/Risk Assessment
It cannot be guaranteed that participants in clinical studies will directly benefit from 
treatment during participation, as clinical studies are designed to provide information about 
the safety and effectiveness of an investigational medicine.
In clinical studies to date, FXI inhibitors have generally been demonstrated to be well 
tolerated, with a low bleeding risk [Piccini, J. P., et al 2022] [Shoamanesh, A., et al 2022] 
[European Society of Cardiology 2022] (see Section 2.1).
In 2 completed Phase 1 studies, 80 participants received MK-2060. No deaths or SAEs 
considered related to MK-2060 by the investigator have been reported, and no participant has 
discontinued from the studies due to an AE considered related to MK-2060 by the 
investigator. No dose-dependent patterns of drug-related AEs, or clinically meaningful trends 
in laboratory values (chemistry, hematology, urinalysis) apart from mechanism-based aPTT 
increases, physical examination, VS, or ECG safety parameter values have been observed as 
a function of treatment. There were no AEs suggestive of hypersensitivity. Safety-related 
study stopping rules have not been triggered.
The high dose of MK-2060 (20 mg) selected for Phase 2 is predicted to provide effective 
anticoagulation in ESRD participants. In general, anticoagulants have been associated with 
increased rates of bleeding events though the degree of anticoagulation provided by a 
specific class of anticoagulant is not related to its bleeding risk. Completed preclinical and 
clinical studies have not identified an increase in bleeding events with MK-2060, though
preclinical and Phase 1 studies have demonstrated a dose-dependent prolongation of aPTT 
with MK-2060 treatment. With a prolonged aPTT there is a theoretical increase in risk of 
bleeding events, however there is little empirical evidence for a direct correlation between 
pharmacological prolongation of aPTT and bleeding risk [Thachil, J. 2014]. Hemophilia C 
patients (FXI deficiency) also have a prolonged aPTT with minimal disruption in hemostasis 
outside major surgeries. 
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Medical monitoring by the Sponsor including blinded assessment for safety signals will 
occur throughout the study to ensure appropriate safety reporting and identification of early 
safety signals. Unblinded safety monitoring during the study will be performed by an 
external DMC at routine intervals, in addition to an efficacy and futility assessment at the IA. 
This will allow for ongoing benefit/risk assessment throughout the study (Section 9.7, and
Section 10.1.4). 
Additional details regarding specific benefits and risks for participants in this clinical study 
may be found in the accompanying IB and informed consent documents.
3
HYPOTHESES, OBJECTIVES, AND ENDPOINTS
In adult patients with ESRD receiving hemodialysis via an AVG: 
Objectives
Endpoints
Primary

Objective: To evaluate the efficacy of 
MK-2060 compared to placebo in 
increasing the time to first arteriovenous 
graft thrombosis event.
Hypothesis: At least 1 of the MK-2060
doses is superior to placebo in increasing 
the time to first occurrence of
arteriovenous graft thrombosis event

Arteriovenous graft thrombosis events
Secondary

Objective: To evaluate the efficacy of 
MK-2060 compared to placebo in 
increasing the time to each arteriovenous
graft thrombosis event (first and 
recurrent).

Arteriovenous graft thrombosis events

Objective: To assess the safety and 
tolerability of MK-2060.

Adverse events

Major bleeding events or clinically 
relevant non-major bleeding events (per 
International Society on Thrombosis 
and Haemostasis criteria)

Discontinuation of study intervention 
due to adverse event(s)
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Objectives
Endpoints
Tertiary/Exploratory

Objective: To evaluate the 
pharmacokinetics and pharmacokinetic-
pharmacodynamic relationship of 
MK-2060.

Pharmacokinetics
o
Steady state Cmax and Ctrough

Pharmacodynamics
o
aPTT  

Objective: To evaluate anti-drug 
antibodies to MK-2060 during treatment 
with study intervention

Anti-drug antibodies to MK-2060

Objective: To evaluate exposure-
response or dose-response of MK-2060 
QW for arteriovenous graft thrombosis
events.

Pharmacokinetics
o
Steady state Cmax and Ctrough

Arteriovenous graft thrombosis events

Objective: To evaluate the effect of 
MK-2060 versus placebo on patient-
reported health-related quality of life 
using the Kidney Disease Quality of Life 
Questionnaire-Short Form 

Scale scores as measured by the Kidney 
Disease Quality of Life Questionnaire-
Short Form 

Objective: To evaluate changes in the
Visual Analog Scale and characterize 
health utilities using the EuroQoL 
5-Dimensional, 5-level questionnaire 

Visual Analog Scale scores as 
measured by the EuroQoL 5-
Dimensional, 5-level questionnaire

Health utilities as measured by the 
EuroQoL 5-Dimensional, 5-level 
questionnaire 

Objective: To explore the relationship 
between genetic variation and response 
to the treatment(s) administered, and 
mechanisms of disease. Variation across 
the human genome may be analyzed for 
association with clinical data collected in
the study.

Germline genetic variation and 
association to clinical data collected in 
this study
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4
STUDY DESIGN
4.1
Overall Design
This is an event-driven, randomized, placebo-controlled, parallel-group, multi-site, double-
blind study of MK-2060 in participants with ESRD receiving hemodialysis via an AVG. This 
study is designed to evaluate the efficacy and safety of MK-2060 20 mg QW and MK-2060 
6 mg QW. 
During the screening period, participants will be assessed against the inclusion and exclusion 
criteria to select a suitable population of individuals receiving hemodialysis via a functioning 
AVG. Individuals using daily aspirin or heparin during dialysis are eligible; however, those 
using P2Y12 inhibitors or systemic anticoagulants are not eligible (Section 6.5). Individuals 
with recent major bleeding events or at risk for future major bleeding events are excluded
from participation (Section 5.2).
After a screening period of up to 30 days, approximately 489 eligible participants will be 
randomized in a 1:1:1 ratio and treated with MK-2060 20 mg, MK-2060 6 mg, or placebo 
(Section 6.1). During the loading phase on Week 1, participants will receive 1 loading dose 
of study intervention during 3 consecutive dialysis sessions. Starting on Week 2, participants 
will receive study intervention as a weekly dose of MK-2060 20 mg, MK-2060 6 mg, or 
placebo during their regularly scheduled dialysis session, maintaining this schedule until the 
required number of AVG thrombosis events is observed in the study (see Section 9.9.1). A 
clinical adjudication committee, whose members are blinded to the study-group assignments, 
will adjudicate clinical events of AVG thrombosis, bleeding, major thrombotic 
cardiovascular events, and death (see Section 10.1.4.3, Appendix 1). After the last treatment 
dose, each participant will be followed for 3 months to monitor for AEs. PROs will be 
completed in a subset of study sites to assess the impact of treatment intervention from the 
participant’s perspective. Participants who undergo kidney transplant will be censored from 
the analysis on the date of the kidney transplant for all efficacy analyses (Section 9.6.1.1) or 
3 months after the date of the kidney transplant for all safety analyses (Section 9.6.2), to 
avoid post-transplant events that could confound the results.
Safety monitoring will occur throughout the study. Acute infusion reactions will be assessed 
during the initial 3 infusions of study intervention in each participant. Participants will be 
assessed frequently for AEs and laboratory abnormalities at study visits throughout the study
(Section 1.3). The Sponsor will provide continuous blinded medical monitoring of AEs, 
laboratory results, and adherence to the study protocol during the study. An external DMC 
will provide unblinded assessment of the safety events at regular intervals during the study
(Section 10.1.4).
An IA will be conducted when approximately 60% of the primary endpoint events are
available to assess efficacy and futility (non-binding) (Section 9.7). At the IA, the eDMC will 
assess safety and efficacy endpoint events as described in Section 9.7 and Section 10.1.4. The 
study may stop at the IA if the criterion for efficacy is met. If the efficacy criterion is met at 
IA, the eDMC may nonetheless recommend study continuation after considering safety 
factors, including the type and quality of bleeding events (Section 4.2.1.3). If the study is not 
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stopped at the IA, the study will continue until all 171 primary endpoint events have 
occurred.  
PK and PD sampling will occur in all participants during the study. A PK substudy will 
conduct sparse sampling in a subset of participants (approximately 100) to provide additional 
PK values to allow more comprehensive PK-PD modeling of MK-2060 (Appendix 8).
Specific procedures to be performed during the study, as well as their prescribed times and 
associated visit windows, are outlined in the SoA in Section 1.3. Details of each procedure 
are provided in Section 8.
4.2
Scientific Rationale for Study Design
The overall clinical strategy for the FXI inhibitor MK-2060 is focused on developing an 
efficacious and well tolerated anticoagulant to prevent major thrombotic cardiovascular 
events in patients with ESRD. Within this strategy, the Phase 2 and Phase 3 studies will build 
the evidence of MK-2060’s efficacy, first as a well-tolerated anticoagulant in ESRD patients 
and second as an anticoagulant that prevents major thrombotic cardiovascular events in 
ESRD patients. The primary efficacy endpoints selected for Phase 2 and Phase 3 are 
therefore different reflecting the separate though related objectives.
The purpose of this Phase 2 event-driven study is to evaluate the efficacy and safety of dose-
ranging MK-2060 in ESRD participants receiving hemodialysis via an AVG. Up to 
approximately 489 adult participants with ESRD on hemodialysis who meet study eligibility 
criteria may be enrolled in this study.
Primary endpoint
Thrombosis of an AVG represents a clinically significant thrombotic event occurring in a 
large arterialized vessel in patients with ESRD and is predictive of CV events [Girerd, S., et 
al 2020]. The study design will assess the efficacy of MK-2060 at a low dose (6 mg) and a 
high dose (20 mg) in reducing AVG thrombosis. The results will provide evidence to support 
selection of a single dose of MK-2060 for larger studies investigating the efficacy of 
MK-2060 in the prevention of major thrombotic cardiovascular events in patients with 
ESRD.  
Participant population
The population studied in Phase 2 is restricted to ESRD patients receiving hemodialysis via 
an AVG. Patients receiving both traditional hemodialysis and hemodiafiltration are allowed 
to participate in the study. This population was selected based on data from the USRDS 
registry data (MSD CORE Chronic Disease Research Group ESRD Epidemiology Study 
2020, unpublished data on file) indicating that patients with AVGs have a higher rate of 
vascular access failure due to thrombosis (69.4 events per 100 patient years) compared to 
those with AVF (13.1 events per 100 patient years). Therefore, selecting AVG thrombosis as 
the primary endpoint in this population will result in rapid accrual of endpoints and 
assessment of MK-2060’s anticoagulant properties. Successful use of the AVG for 4 weeks 
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prior to study enrollment is used to establish a degree of stability in AVG function at the time 
of recruitment. This will help avoid recruitment of individuals with immature AVGs, which 
have not proven to be reliably cannulated for dialysis or with AVGs in the process of failing
or on the verge of requiring an intervention. 
Dose selection
The planned doses for this study are a high dose (20 mg loading dose on alternating days 
during the first week for a total of 3 doses followed by 20 mg weekly doses) and a low dose
(6 mg loading dose on alternating days during the first week for a total of 3 doses followed 
by 6 mg weekly doses). These doses have been chosen based on the Phase 1 PK-PD data 
from MK-2060-P004 studying single and multiple ascending doses in ESRD participants. 
The high dose arm (20 mg) is expected to result in ~90% of participants having 
 
 at MK-2060 trough, while the low dose arm (6 mg) is expected to result in 
~40% of participants having an 
 at MK-2060 trough. 
Internal preclinical studies have demonstrated that an increase in 
baseline with 
MK-2060 is required to achieve equivalent anticoagulation effect as apixaban in a preclinical 
AV shunt thrombosis model. In addition, clinical data from other factor XI compounds 
suggest that 
from baseline is needed for clinical efficacy [Buller, H. R., 
et al 2015] [Weitz, J. I., et al 2020]. Finally, genetic data from hemophilia C (FXI deficiency) 
supports ~30% to 50% FXI deficiency as being sufficient to decrease the risk of MACE and 
thromboembolic events, 
[Preis, M., et al 2017].
4.2.1
Rationale for Endpoints
4.2.1.1
Efficacy Endpoints
The overarching purpose of the Phase 2 study is to identify a dose of MK-2060 that provides 
safe and effective anticoagulation to prevent thrombotic events in medium to large 
arterialized vessels in ESRD patients. The Phase 2 endpoint of AVG thrombosis event in 
ESRD patients receiving hemodialysis via an AVG will assess the anti-thrombotic properties 
of MK-2060 in ESRD participants. Vascular access thrombosis has been associated with 
future CV events in multiple studies with evidence suggesting therapies effective in 
preventing CV events may also reduce vascular access thrombosis [Girerd, S., et al 2020] 
[Kuo, T. H., et al 2015] [Kim, H. J., et al 2016] [Tanner, N. C. 2015]. AVG thrombosis will
act as a surrogate for major thrombotic cardiovascular events, which include fatal and non-
fatal MI, ischemic stroke, PE and acute limb ischemia, and VTE and will be the focus of the 
Phase 3 study.
The primary endpoint is defined as the time to first occurrence of an 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 CAC (Section 10.1.4.3, Appendix 1). The detailed definition 
of AVG thrombosis event will be provided in the CAC Charter. The CAC’s determination 
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will be based on review of the clinical history of the event along with associated radiological, 
surgical or pathological reports from the event to establish the occurrence of a thrombotic 
occlusion of the AVG. 
Selection of this endpoint will allow assessment of MK-2060’s efficacy as an anticoagulant 
in preventing thrombotic events in medium to large arterialized vessels in ESRD patients.
The secondary efficacy endpoint is the time to each AVG thrombosis event (first and 
recurrent) from randomization until the efficacy cutoff date. 
A CAC, whose members are blinded to the study-group assignments, will adjudicate all 
reported clinical events of AVG thrombosis (primary and secondary endpoint), major 
thrombotic CV events (tertiary/exploratory endpoint), and death (see Section 10.1.4.3, 
Appendix 1).
4.2.1.2
Patient-reported Outcomes Endpoints
Patient-reported outcomes can provide unique information on the impact of treatment
intervention from the participant’s perspective as some domains are difficult to observe or 
are subjective and are best when collected directly from the participant. This study will 
include 2 PRO interviewer-administered questionnaires, the KDQOL-SF and the EQ-5D-5L, 
administered in a subset of study sites. 
The KDQOL-SF questionnaire was developed for patients with kidney disease and those on 
dialysis to measure the effect of the disease on activities of daily living, work status, sexual 
function, sleep, and social interaction. It also captures symptoms and patient satisfaction with 
treatment and incorporates the SF-36 generic health-related QoL measure [Maruish, M. E. 
2011], which was developed by the RAND Corporation in 1997, includes 80 items, and can 
be completed in approximately 16 minutes [Hays, R. D., et al 1997]. It has demonstrated 
good internal consistency and reliability [Barotfi, S., et al 2006]. In a review article of PRO
measures in chronic kidney disease, Aiyegbusi et al. evaluated 25 measures from 66 
published studies. They found strong evidence of internal and structural validity, moderate 
evidence of test-retest validity, and limited evidence for content validity for the KDQOL-SF, 
recommending this instrument for research use in patients on dialysis [Aiyegbusi, O. L., et al 
2017]. 
The EQ-5D-5L is a generic questionnaire used to assess current health status as reported by 
patients and will provide data to develop health utilities for use in health economic analyses
[Rabin, R. and de Charro, F. 2001]. It consists of 5 domain questions and 1 VAS response. 
The domain questions assess mobility, self-care, usual activities, pain/discomfort, 
anxiety/depression, with 5-level response options (no problems, slight problems, moderate 
problems, severe problems, and extreme problems). Summary scores will be calculated from 
the 5 domain scores according to scoring instructions from the EuroQol group and the EQ-
5D-5L value sets for the US and for Europe. Scores range from 1.00 for perfect health to 0.00 
for death. The EQ-5D VAS included in the EQ-5D-5L records patient self-rated health on a 
20 cm vertical VAS with endpoints labeled ‘the best health you can imagine’ and ‘the worst 
health you can imagine’ and is scored on a 0 to 100 scale. The EQ-5D-5L is available in over 
60 translations with established validity, reliability, and responsiveness
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[Pickard, A. S., et al 2007] and is appropriate for a wide range of health conditions and 
treatments [EuroQol Research Foundation 2019]. It has been used in patients with ESRD and 
is a valid and sensitive health utility measure in this population [Lee, A. J., et al 2005] 
[Manns, B. J., et al 2002] [Gerard, K., et al 2004]. Minimally important difference estimates 
for the EQ-5D utility score range between 0.03 and 0.05 [McClure, N. S., et al 2018]. In 
cases when a validated translation is needed and not available for a specific language, 
participants who speak that language will be exempt from the requirement to complete the 
questionnaire. 
The KDQOL-SF and EQ-5D-5L PROs are not pure efficacy or safety endpoints because they 
are affected by both disease progression and treatment tolerability.
4.2.1.3
Safety Endpoints
General safety and tolerability will be evaluated by clinical review of all relevant parameters, 
including AEs, vital signs, laboratory safety tests (ie, blood chemistry, hematology, 
pregnancy testing), and systemic infusion reaction assessment. 12-lead ECGs will be 
performed, and vital status assessment will be collected. 
A CAC, whose members are blinded to the study-group assignments, will adjudicate all site 
reported bleeding AEs (See Section 10.1.4.3, Appendix 1). The secondary endpoint of time
to first occurrence of ISTH major bleeds plus clinically relevant non-major bleeding events
will also be evaluated.
Bleeding Endpoints
Events meeting the ISTH criteria [Schulman, S. 2005] for major bleeding or clinically
relevant non-major bleeding will be reported as bleeding endpoints. 
Major bleeding events have a symptomatic presentation and include the following criteria:
1. Fatal bleeding, and/or
2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, 
intraocular, retroperitoneal, intra-articular, pericardial, intramuscular with 
compartment syndrome, and/or
3. Bleeding causing a decrease in hemoglobin level of 20 g/L or more or leading to 
transfusion of 2 or more units of whole blood or red cells.
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Clinically relevant non-major bleeding events have 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. Prompt a face-to-face evaluation by a healthcare professional
4.2.1.4
Pharmacokinetic Endpoints
The PK data from this study may be combined with data from other Phase 1 and Phase 2 
studies for population PK analysis using nonlinear mixed effects modeling. The key 
exploratory endpoints for MK-2060 are Cmax and Ctrough. If data permit, estimates of 
population PK parameters such as CL, Vc, as well as estimates of inter-individual and 
residual variability will be determined. In addition, effects of demographic or laboratory 
factors (eg, age, race, weight, gender, renal function) on PK parameters will be assessed if 
possible. The results of this population PK analysis will be summarized in a separate report.
4.2.1.5
Immunogenicity Endpoints
Immunogenicity to MK-2060 will be described as the results of the ADA assay from samples 
taken during the double-blind treatment period.
ADA samples will be collected before the administration of study intervention at selected 
visits and from all participants. The incidence and magnitude (titer) of ADA positive 
participants and potential effects of ADA on PK, PD, and safety will be reported, as 
appropriate.
4.2.1.6
Pharmacodynamic Endpoints
PD endpoints that will be assessed include changes from baseline through the end of the 
study in FXI activity and aPTT with assays being performed at a central laboratory. 
FXI activity is the most direct measure of MK-2060’s efficacy in binding to FXI and FXIa 
and inhibiting FXIa activity. 
aPTT prolongation level (relative to baseline) is an immediate measure of the antithrombotic
effect of FXIa inhibition from MK-2060 and an important measure to allow comparison of 
MK-2060 with other FXIa inhibitors. Baseline is defined as the individual’s predose aPTT 
value.
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4.2.1.7
Planned Exploratory Biomarker Research
4.2.1.7.1
Planned Genetic Analysis
Genetic variation may impact a participant’s response to therapy, susceptibility to, severity, 
and progression of disease. Variable response to therapy may be due to genetic determinants 
that impact drug absorption, distribution, metabolism, and excretion; mechanism of action of 
the drug; disease etiology; and/or molecular subtype of the disease being treated. Therefore, 
where local regulations and IRB/IEC allow, a sample will be collected for DNA analysis 
from consenting participants.
DNA samples may be used for research related to the study intervention(s), the disease under 
study, or related diseases. They may also be used to develop tests/assays including diagnostic 
tests related to the disease under study, related diseases, and study intervention(s). Genetic 
research may consist of the analysis of 1 or more candidate genes, the analysis of genetic 
markers throughout the genome, or analysis of the entire genome. Analysis may be 
conducted if it is hypothesized that this may help further understand the clinical data.
The samples may be analyzed as part of a multi-study assessment of genetic factors involved 
in the response to understand study disease or related conditions.
Variation across the human genome may be analyzed for association with clinical data 
collected in the study. 
4.2.1.8
Future Biomedical Research
The Sponsor will conduct FBR on specimens for which consent was provided during this 
study. This research may include genetic analyses (DNA), gene expression profiling (RNA), 
proteomics, metabolomics (serum, plasma), and/or the measurement of other analytes, 
depending on which specimens are consented for FBR.
Such research is for biomarker testing to address emergent questions not described elsewhere 
in the protocol and will only be conducted on specimens from appropriately consented 
participants. The objective of collecting/retaining specimens for FBR is to explore and 
identify biomarkers that inform the scientific understanding of diseases and/or their 
therapeutic treatments. The overarching goal is to use such information to develop safer, 
more effective drugs/vaccines, and/or to ensure that participants receive the correct dose of 
the correct drug/vaccine at the correct time. The details of FBR research are presented in
Appendix 6.
4.2.2
Rationale for the Use of Placebo
The purpose of this study is to evaluate the efficacy and safety of dose-ranging MK-2060 in 
adult participants with ESRD on hemodialysis via an AVG. A placebo-controlled study will 
allow for a blinded and unbiased assessment of efficacy (AVG thrombosis), safety, and 
tolerability. Secondary outcomes are also supported using placebo, including evaluation of 
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the effect of MK-2060 on bleeding risk and on time to first major thrombotic cardiovascular 
event.
The efficacy and safety profile of any drug is best characterized versus placebo, especially 
when it is being studied in a population with subjective event reporting (eg, ESRD patients 
receiving hemodialysis via an AVG). 
4.3
Justification for Dose
4.3.1
Starting Dose for This Study
Intravenous administration of MK-2060 in participants on hemodialysis allows a simple 
infusion of the study intervention during hemodialysis by the treating provider with minimal 
disturbance to the participant. Participants will be randomized into 1 of 3 parallel treatment 
groups and will be treated with a fixed dose throughout the study.
The 2 IV doses of MK-2060 will be administered in parallel treatment arms, a low dose 
(6 mg), and a high dose (20 mg) arm, with an additional control arm (placebo). See 
Section 4.3.2 and Section 4.3.3 for the criteria used to select the high dose and low dose to be 
studied. 
4.3.2
Maximum Dose/Exposure for This Study
The maximum dose used for the study is equivalent to the dose administered in the high dose 
arm (20 mg). Participants randomized to the high dose arm will receive this fixed dose 
throughout the study duration which starts with a loading phase (1 dose at dialysis on 
alternating days during the first week for a total of 3 doses) and is followed by a maintenance 
phase (1 dose each week). This high dose is projected to result in ~90% of participants with 
an 
 at Cmin during steady state. This projection is based on a 
PK-PD model developed from the results of single ascending dose and multiple studies
completed in ESRD patients receiving hemodialysis (MK-2060-P004). 
The high dose (20 mg) selected for the study is below the maximum IV dose (40 mg IV x 1) 
tested in single-dose Phase 1 studies in normal healthy volunteers and participants with 
ESRD on hemodialysis. The 40 mg IV dose was well tolerated in those participants. 
Steady-state exposures in the high dose arm with 20 mg dosed on Day 1, Day 3, and Day 5 
followed by weekly dosing are projected to have a median AUC0-168h 9065 nM*hr in ESRD 
patients at steady state. This predicted AUC0-168h is significantly below (<1%) the chronic 
toxicology NOAEL (AUC0-168h = 1.28 x 106 nM*hr from the 4-week rhesus monkey toxicity 
study at 60 mg/kg/week). 
Since this is an event-driven study, the overall duration will depend upon the rate of 
recruitment and endpoint accrual. Based on the estimated recruitment and endpoint rate in the 
placebo arm, the median treatment duration is expected to be approximately 10 months. 
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4.3.3
Rationale for Dose Interval and Study Design
During Phase 1 single and multiple ascending dose testing, MK-2060 demonstrated good 
safety and tolerability, a steady state PK profile compatible with weekly IV dosing, and 
biomarker confirmation (FXI activity and aPTT) of on-target pharmacology. In this study, 
the dosing interval will vary between the loading phase and the maintenance phase. 
Employing a loading phase, with dosing on Day 1, Day 3, and Day 5 during Week 1, will 
achieve steady state in PK and PD within the first week as opposed to over 6 weeks with no 
loading phase. During the maintenance phase, study intervention will be administered once 
weekly on the same day each week. 
The MK-2060 doses for the low (6 mg) and high dose (20 mg) arms in Phase 2 were chosen 
to provide a range that covers the dynamic range of PD seen with MK-2060 in the Phase 1 
dose-ranging studies. The reason for choosing the MK-2060 high dose arm (20 mg) is
described in Section 4.3.2. The MK-2060 low dose (6 mg) was chosen to allow for separation 
in the predicted PD and PK response to 6 mg dose MK-2060 relative to the responses 
predicted for the 20 mg MK-2060 dose. The 6 mg dose MK-2060 is projected to result in 
~40% of participants with an 
 at Cmin during steady state.
4.4
Beginning and End of Study Definition
The overall study begins when the first participant (or their legally acceptable representative) 
provides documented informed consent. The overall study ends when the required number of 
AVG thrombosis are observed (unless the study stops for futility) and the last participant 
completes the last study-related contact, withdraws consent, or is lost to follow-up (ie, the 
participant is unable to be contacted by the investigator).
4.4.1
Clinical Criteria for Early Study Termination
The clinical study may be terminated early if the extent (incidence and/or severity) of 
emerging effects/clinical endpoints is such that the risk/benefit ratio to the study population 
as a whole is unacceptable. In addition, further recruitment in the study or at (a) particular 
study site(s) may be stopped due to insufficient compliance with the protocol, GCP, and/or 
other applicable regulatory requirements, procedure-related problems or the number of 
discontinuations for administrative reasons is too high.
Early study termination may also be considered after assessing efficacy and futility at the IA 
(Section 9.7).
5
STUDY POPULATION
Male/female participants of at least 18 years of age with ESRD receiving hemodialysis via an 
AVG will be enrolled in this study. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
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5.1
Inclusion Criteria
An individual is eligible for inclusion in the study if the individual meets all of the following 
criteria:
Type of Participant and Disease Characteristics
1. Has a current diagnosis of ESRD.
2. Has been receiving hemodialysis (including hemodiafiltration) prescribed ≥3 times per 
week for a minimum of 3 hours per session via mature normally functioning (spKt/V 
≥1.2), uninfected AVG. Criterion must be met for at least 75% of the sessions over the 
4 weeks prior to randomization.
Demographics
3. Is male or female, ≥18 years of age inclusive, at the time of providing documented
informed consent.
Female Participants
4.
A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies: (Section 10.5.1) 

Is not a WOCBP
OR

Is a WOCBP and using an acceptable contraceptive method, or be abstinent from 
heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long 
term and persistent basis), as described in Appendix 5 during the intervention period 
and for at least 90 days, corresponding to the time needed to eliminate any study 
intervention (eg, 5 terminal half-lives) after the last dose of study intervention. The 
investigator should evaluate the potential for contraceptive method failure (ie, 
noncompliance, recently initiated) in relationship to the first dose of study 
intervention.

A WOCBP must have a negative highly sensitive pregnancy test (serum) within 
6 days before the first dose of study intervention.

The participant must be excluded from participation if the serum pregnancy result is 
positive.

Additional requirements for pregnancy testing during and after study intervention are 
located in Section 8.3.5.
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
The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy.

Contraceptive use by women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.
Informed Consent
5.
The participant (or legally acceptable representative) has provided documented
informed consent/assent for the study. The participant may also provide 
consent/assent for future biomedical research. However, the participant may 
participate in the main study without participating in future biomedical research.
5.2
Exclusion Criteria
The participant must be excluded from the study if the participant meets any of the following 
criteria:
Medical Conditions
1. Has a recent history of cancer (<1 year). Non-melanoma skin cancers are allowed. 
2. Has a mechanical/prosthetic heart valve. 
3. Had a recent hemorrhagic stroke or lacunar stroke (<1 month). 
4. Had recent evidence of bleeding requiring hospitalization or unplanned medical attention 
(<1 month), a history (≤2 years) of recurrent bleeding episodes including epistaxis, GI 
bleeds or GU bleeds requiring medical treatment or events requiring treatment with blood 
products.
5. Has a recent history of drug or alcohol abuse or dependence (<1 year).
6. Life expectancy <12 months.
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Prior/Concomitant Therapy
7. Is currently receiving or planning to receive anticoagulants or antiplatelet medications
(Individuals who plan to be on low-dose aspirin (up to 150 mg per day) during the study 
or require intradialytic heparin are permitted in the study).
Prohibited Medications (Section 6.5)
Oral Anticoagulants:

Warfarin

Apixaban

Dabigatran

Rivaroxaban

Edoxaban

Betrixaban
IV/SC Anticoagulants:

IV/SC Heparin and LMWH

IV Warfarin

IV Argatroban

IV Bivalirudin

IV Lepirudin

SC fondaparinux

IV antithrombin III
Note: Participants on medically indicated anticoagulants (other than intradialytic heparin, 
periprocedural heparin, or low-dose heparin for DVT prophylaxis while hospitalized) are 
excluded from the study (ie, participants may not discontinue prescribed anticoagulant 
therapy to meet study eligibility criteria in order to enroll in the study). If a participant 
has prior anticoagulant use, they must have discontinued the anticoagulant for 7 days 
prior to randomization.
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Antiplatelet Medications (P2Y12 inhibitor use is excluded)

Aspirin in doses >150 mg per day (regular use)

Clopidogrel

Prasugrel

Ticagrelor

Ticlopidine
Note: Participants taking any antiplatelet agent (except for aspirin in doses ≤150 mg per 
day) will undergo a 7-day washout period prior to randomization. Individuals may not 
discontinue prescribed antiplatelet therapy to meet study eligibility criteria.
NSAIDs (eg, ibuprofen)
Note: topical NSAIDs are permitted.
Prior/Concurrent Clinical Study Experience
8. Has participated in another investigational study within 4 weeks (or 5 half-lives of the 
investigational drug), whichever is greater, prior to the Screening Visit. The window will 
be derived from the date of the last use of study treatment in the previous study. 
Diagnostic Assessments
9. Has abnormal coagulation laboratory results including INR >2.0 and/or PT or aPTT 
>20% above the normal range. 
10. Has thrombocytopenia (platelet count <50,000/µL).
11. Has documented severe hypertension (SBP >200 mmHg or DBP >110 mmHg, pre-
dialysis) at screening or randomization. 
Other Exclusions
12. Is planning on receiving a living donor renal transplant within 12 months (participants are 
permitted to be candidates for deceased donor renal transplants)
13. Is planning on receiving an AVF placement within 12 months.
14. Is planning non-urgent invasive dental surgeries that are liable for significant blood loss 
within 12 months.
15. Has had a hypersensitivity reaction to any component of MK-2060 drug product.
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16. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or 
child) who is investigational site or Sponsor staff directly involved with this study.
17. Canada-specific criterion, see Appendix 7. 
5.3
Lifestyle Considerations
There are no lifestyle restrictions (see Section 5.2 for drug or alcohol abuse exclusion). 
5.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study, but 
are not subsequently randomized in the study. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the CONSORT 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any AEs or 
SAEs meeting reporting requirements as outlined in the data entry guidelines.
Rescreening is allowed once per participant (Section 8.1.6).
5.5
Participant Replacement Strategy
A participant who discontinues from study intervention OR withdraws consent will not be 
replaced.
6
STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
Clinical supplies of blinded study interventions provided by the Sponsor will be packaged to 
support enrollment in the study. Clinical supplies will be affixed with a clinical label in 
accordance with regulatory requirements. 
6.1
Study Intervention(s) Administered
The study intervention(s) to be used in this study are outlined in Table 1.
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Table 1
Study Interventions
Arm Name
Arm Type
Intervention 
Name
Type Dose 
Formulation
Unit 
Dose 
Strength
Dosage 
Level(s)
Route of 
Admin
Treatment 
Period
Use
IMP or 
NIMP/AxMP
Sourcing
MK-2060 
Low Dose
Experimental
MK-2060 
Low Dose
Drug Lyophilized 
Powder
6 mg
6 mg
IV 
Infusion
V2 to Vn
Test 
Product
IMP
Sponsor
MK-2060 
High Dose
Experimental
MK-2060 
High Dose
Drug Lyophilized 
Powder
20 mg
20 mg
IV 
Infusion
V2 to Vn
Test 
Product
IMP
Sponsor
Placebo
Placebo 
Comparator
Placebo
Drug Sterile
Solution
0 mg
0 mg
IV 
Infusion
V2 to Vn
Placebo
IMP
Local
EEA =European Economic Area; IMP=investigational medicinal product; NIMP/AxMP=noninvestigational/auxiliary medicinal product
The classification of IMP and NIMP/AxMP in this table is based on guidance issued by the European Commission and applies to countries in the EEA. Country differences
with respect to the definition/classification of IMP and NIMP/AxMP may exist. In these circumstances, local legislation is followed.
In this protocol, placebo for (placebo comparator arm) is diluent alone (normal saline); diluent is used for blinding purposes and does not contain active ingredients.
Vn= Patients final dose of study medication (the timing of Vn will be determined by the rate of primary endpoint accrual)
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All supplies indicated in Table 1 will be provided per the "Sourcing" column depending upon 
local country operational requirements. If local sourcing, every attempt should be made to 
source these supplies from a single lot/batch number where possible (eg, not applicable in the 
case where multiple lots or batches may be required due to the length of the study, etc.).
Refer to Section 8.1.8 for details regarding administration of the study intervention.
6.2
Preparation/Handling/Storage/Accountability
6.2.1
Dose Preparation
Specific calculations or evaluations required to be performed to administer the proper dose to 
each participant are outlined in the Pharmacy Manual provided by the Sponsor. 
6.2.2
Handling, Storage, and Accountability
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received, and any discrepancies are 
reported and resolved before use of the study intervention.
Only participants enrolled in the study may receive study intervention, and only authorized 
site staff may supply or administer study intervention. All study interventions must be stored 
in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff.
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records).
For all study sites, the local country Sponsor personnel or designee will provide appropriate 
documentation that must be completed for drug accountability and return, or local discard 
and destruction if appropriate. Where local discard and destruction is appropriate, the 
investigator is responsible for ensuring that a local discard/destruction procedure is 
documented.
The study site is responsible for recording the lot number, manufacturer, and expiry date for 
any locally purchased product (if applicable) as per local guidelines unless otherwise 
instructed by the Sponsor.
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution, and usage of study 
interventions in accordance with the protocol and any applicable laws and regulations.
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6.3
Measures to Minimize Bias: Randomization and Blinding
6.3.1
Intervention Assignment
Intervention randomization will occur centrally using an IRT system. There are 3 study 
intervention arms. Participants will be assigned randomly in a 1:1:1 ratio among 3 arms.
6.3.2
Stratification
Intervention randomization will be stratified according to the following strata:
1. Region (US, non-US)
2. Previous thrombosis of active AVG (yes/no)
3. Regular aspirin use up to 150 mg daily at baseline (yes/no)
Note: ‘As needed’ aspirin use should not be considered for stratification. 
These strata have been selected for their importance as prognostic factors for AVG 
thrombosis to ensure balance in these characteristics between treatment groups. 
Hemodialysis outcomes vary across regions based on difference in baseline characteristics of 
dialysis populations in each region and regional variations in dialysis prescriptions. An AVG 
that has had a thrombotic event is at a higher risk of developing a subsequent thrombotic 
event than one without prior thrombosis. Since a significant proportion of the study 
participants are expected to have a prior AVG thrombosis at enrollment it is important to 
balance this risk factor between treatment arms with stratification of randomization. Aspirin 
use is expected to be associated with an increased bleeding risk and potentially decreased 
AVG thrombosis risk in ESRD patients therefore it is important to have aspirin use balanced 
between treatment arms. 
6.3.3
Blinding
A double-blinding technique with in-house blinding will be used. MK-2060 and placebo will 
be prepared by an unblinded pharmacist or designee so that study intervention has an 
identical presentation regardless of treatment assignment. This will maintain blinding to 
treatment assignment of the participant, the investigator, and Sponsor personnel or 
delegate(s) who are involved in the study intervention administration, clinical evaluation of 
the participants and recording of study data. If local dialysis center guidance requires 
medications to be prepared and administered by the same individual, the unblinded 
pharmacist or designee may administer blinded study medication to participants but will 
otherwise have no role in the study, including interaction with study participants. The 
infusion bags and IV line (through which study intervention is administered) do not require 
opaque coverings as the differences between the clinical materials are not visually 
distinguishable within the infusion bags, tubing, or syringe.
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The allocation schedule will be blinded in the study database. See Section 8.1.10 for a 
description of the method of unblinding a participant during the study, should such action be 
warranted. 
6.4
Study Intervention Compliance
Interruptions from the protocol-specified treatment for more than 4 consecutive doses require 
consultation between the investigator and the Sponsor and written documentation of the 
collaborative decision on participant management.
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded in the 
appropriate eCRF. The dose of study intervention will be confirmed by the unblinded 
pharmacist or designee. The study participant identification will be confirmed at the time of 
dosing by the blinded study staff. Refer to the Study Operations Manual.
6.5
Concomitant Therapy
Medications specifically prohibited in the exclusion criteria are not allowed during the 
ongoing study unless there is a clinical indication to initiate a prohibited medication. In those 
cases, discontinuation from study intervention may be required. The investigator should 
discuss any questions regarding this with the Sponsor Clinical Director. The final decision on 
any supportive therapy rests with the investigator and/or the participant’s primary physician. 
However, the decision to continue the participant on study intervention requires the mutual 
agreement of the investigator, the Sponsor, and the participant.
Any medication (including over the counter or prescription medicines, vitamins, and/or 
herbal supplements or other specific categories of interest) that the participant is receiving at 
the time of enrollment or receives during the study must be recorded along with:

Reason for use

Dates of administration including start and end dates

Dosage information including dose and frequency (route will be captured for 
concomitant medication taken at the time of an SAE)
Participants previously receiving intradialytic heparin to prevent clotting in the blood circuit 
are permitted to continue with intradialytic heparin use during the study. 
The Sponsor should be contacted if there are any questions regarding concomitant or prior 
therapy.
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PROHIBITED MEDICATIONS
Listed below are specific restrictions for concomitant therapy during the study, from 
providing documented informed consent to the Final Efficacy Visit (or Premature 
Discontinuation Visit):
Oral Anticoagulants (intradialytic heparin is permitted in the study)

Warfarin

Apixaban

Dabigatran

Rivaroxaban

Edoxaban

Betrixaban
IV/SC Anticoagulants:

IV/SC Heparin and LMWH

IV Warfarin

IV Argatroban

IV Bivalirudin

IV Lepirudin

SC fondaparinux 

IV antithrombin III
Note: Participants on medically indicated anticoagulants (other than intradialytic heparin, 
periprocedural heparin, or low dose heparin for DVT prophylaxis while hospitalized) are 
excluded from the study (ie, participants may not discontinue prescribed anticoagulant 
therapy to meet study eligibility criteria in order to enroll in the study). If a participant has 
prior anticoagulant use, they must have discontinued the anticoagulant for 7 days prior to 
randomization.
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Antiplatelet Medications (Aspirin use up to 150 mg per day is allowed, P2Y12 inhibitor use 
is excluded)

Aspirin in doses >150 mg per day (regular use)

Clopidogrel

Prasugrel

Ticagrelor

Ticlopidine
Note: Participants taking any antiplatelet agent (except for aspirin in doses ≤150 mg per day) 
will undergo a 7-day washout period prior to reinitiation of study medication. Participants 
may not discontinue prescribed antiplatelet therapy to meet study eligibility criteria.
NSAIDs (eg, ibuprofen)
Note: topical NSAIDs are permitted.
6.5.1
Rescue Medications and Supportive Care
The mechanism of MK-2060 is expected to provide substantial anticoagulant benefits with 
very minimal additional bleeding risk. Management of all bleeding events in the study is 
under the discretion of the treating physician and may be directed by the local guidelines
and consultation with a hematologist.
Management of bleeding events in participants receiving MK-2060 may be guided by 
the experience of treatments proven effective in patients with inherited FXI deficiency or 
endogenous FXI inhibitors (see Section 6.5.2). In these conditions, treatment with
tranexamic acid alone or in combination with either FFP or recombinant FVIIa has 
proven efficacious in managing bleeding risk. 
Major and clinically relevant non-major bleeding events will prompt interruption of 
study intervention and a hematology consult. Usual means to achieve hemostasis should 
be applied and, if required, treatment with IV tranexamic acid with use of recombinant
FVIIa or FFP reserved for recalcitrant bleeding events.
Sites will be required to capture details of the use of any rescue medications during the study.
Participants may be allowed to begin treatment again if, following a discussion with the 
Sponsor, it is agreed to be medically appropriate.
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6.5.2
Surgery Guidance
Perioperative management of bleeding in study participants should follow local guidance 
with consultation from a hematologist if needed. 
For participants undergoing minor procedures, no change in study intervention
administration or reversal of study drug is recommended; however, for major surgeries with 
increased risk for post-operative hemorrhage or surgeries involving tissues with high 
fibrinolytic activity (oral mucosa or genitourinary tract), temporary discontinuation of study 
treatment is recommended until the participant has recovered from the procedure and the 
post-procedure risk of bleeding has resolved. 
Additional management of participants at high risk for perioperative bleeding who have 
received MK-2060 is based on published experience of successful peri-surgical management 
of patients with inherited FXI deficiency or endogenous FXI inhibitors. In surgeries 
involving tissue with high fibrinolytic turnover and at risk for bleeding in the setting of 
reduced FXI activity, tranexamic acid alone (1 g QID) started 12 hours pre-surgery and 
continued for 7 days prevented bleeding events in 19 patients with FXI deficiency 
undergoing dental extractions [Berliner, S., et al 1992]. In similar patients undergoing 
major surgeries, a very low dose of recombinant factor VIIa (10 µg/kg to 15 µg/kg) 
given at the end of surgery along with tranexamic acid (1 g QID initiated 2 hours before 
surgery for 3 to 5 days) provided simple and effective control of hemostasis [Salomon, 
O., et al 2019]. In addition, in vitro and in vivo data have demonstrated that aPTT 
prolongation resulting from administration of MK-2060 is reversed with administration 
of FFP (see Appendix 9).
If there is a concern about the risk of bleeding in a participant who requires urgent or 
emergency surgery, unblinding may be considered, but should only be performed if 
knowledge of randomized treatment allocation will influence clinical management 
(Section 8.1.10).
6.6
Dose Modification
There are no dose modifications in this study.
6.7
Intervention After the End of the Study
There is no study-specified intervention following the end of the study.
6.8
Clinical Supplies Disclosure
MK-2060 and placebo treatment arms are blinded but clinical supplies will be provided open 
label to study pharmacies for preparation. An unblinded pharmacist or qualified study site 
personnel will be used to blind supplies. Treatment identity (name, strength, or potency) is 
included in the label text; random code/disclosure envelopes or lists are not provided.
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The emergency unblinding call center will use treatment/randomization schedule for the 
study to unblind participants and to unmask treatment. 
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL
7.1
Discontinuation of Study Intervention
Discontinuation of study intervention does not represent withdrawal from the study.
As certain data on clinical events beyond study intervention discontinuation may be 
important to the study, they must be collected through the participant’s last scheduled follow-
up, even if the participant has discontinued study intervention. Therefore, all participants 
who discontinue study intervention prior to completion of the protocol-specified treatment 
period will still continue to participate in the study as specified in Section 1.3 and 
Section 8.11.3, unless the participant has withdrawn from the study (Section 7.2).
Participants may discontinue study intervention at any time for any reason or be discontinued 
from the study intervention at the discretion of the investigator should any untoward effect 
occur. In addition, a participant may be discontinued from study intervention by the 
investigator or the Sponsor if study intervention is inappropriate, the study plan is violated, or 
for administrative and/or other safety reasons. Specific details regarding procedures to be 
performed at study intervention discontinuation are provided in Section 8.1.9 and 
Section 8.11.6.
A participant must be discontinued from study intervention but continue to be monitored in 
the study for any of the following reasons:
1. The participant or participant’s legally acceptable representative requests to 
discontinue study intervention.
2. The participant has a confirmed positive serum pregnancy test.
3. Upon site learning the participant will undergo a kidney transplant during the study.
4. The participant has a major non-traumatic bleed.
5. The participant has a medical condition or personal circumstance that, in the opinion 
of the investigator and/or Sponsor, places the participant at unnecessary risk through 
continued participation in the study, while on study treatment, or does not allow the 
participant to adhere to the requirements of the protocol.
6. The participant requires ongoing treatment with a prohibited medication 
(Section 6.5).
7. The participant permanently transitions from AVG to an alternative hemodialysis
access.
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8. The participant interrupted study intervention for >4 consecutive doses and is not a 
candidate for reloading after consultation with the Sponsor (refer to the Operations 
Manual for reloading).
Any time a participant’s vital status is in question, the investigator should explore all possible 
options to contact the participant per local regulations (unless the participant has explicitly 
withdrawn his/her consent to any type of follow-up). The site must document all attempts to 
try to contact the participant in the medical records/source documents. The vital status will be 
collected for all randomized participants who have not withdrawn consent, irrespective of 
completion of study procedures. 
If the participant does not attend scheduled study visits, follow-up of clinical events specified 
as endpoints may continue by phone, unless the participant explicitly withdraws his/her 
consent to any type of follow-up. In such cases, the phone contact will not be considered a 
protocol deviation. 
In all cases, the reason for temporary interruption or permanent study intervention 
discontinuation must be recorded in the eCRF and in the participant’s medical records.
Participants may be allowed to begin treatment again if deemed medically appropriate.
7.2
Participant Withdrawal From the Study
A participant must be withdrawn from the study if the participant or participant’s legally 
acceptable representative withdraws consent from the study.
If a participant withdraws from the study, they will no longer receive study intervention or be 
followed at scheduled protocol visits.
Specific details regarding procedures to be performed at the time of withdrawal from the 
study, as well as specific details regarding withdrawal from future biomedical research, are 
outlined in Section 8.1.9. The procedures to be performed should a participant repeatedly fail 
to return for scheduled visits and/or if the study site is unable to contact the participant are 
outlined in Section 7.3.
7.3
Lost to Follow-up
If a participant fails to return to the clinic for a required study visit and/or if the site is unable 
to contact the participant, the following procedures are to be performed:

The site must attempt to contact the participant and reschedule the missed visit. If the 
participant is contacted, the participant should be counseled on the importance of 
maintaining the protocol-specified visit schedule.

The investigator or designee must make every effort to regain contact with the 
participant at each missed visit (eg, telephone calls and/or a certified letter to the 
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participant’s last known mailing address or locally equivalent methods). These 
contact attempts should be documented in the participant’s medical record.

Note: A participant is not considered lost to follow-up until the last scheduled visit for the 
individual participant. The missing data for the participant will be managed via the 
prespecified statistical data handling and analysis guidelines.
8
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the SoA.

Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.

The investigator is responsible for ensuring that procedures are conducted by 
appropriately qualified (by education, training, and experience) staff. Delegation of study 
site personnel responsibilities will be documented in the Investigator Trial File Binder (or 
equivalent).

All study-related medical decisions must be made by an investigator who is a qualified 
physician.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.

Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of ICF may be used for screening or baseline purposes 
provided the procedures meet the protocol-specified criteria and were performed within 
the time frame defined in the SoA.

Additional evaluations/testing may be deemed necessary by the investigator and or the 
Sponsor for reasons related to participant safety. In some cases, such evaluation/testing 
may be potentially sensitive in nature (eg, HIV, Hepatitis C), and thus local regulations 
may require that additional informed consent be obtained from the participant. In these 
cases, such evaluations/testing will be performed in accordance with those regulations.

Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples.
8.1
Administrative and General Procedures
8.1.1
Informed Consent
The investigator or medically qualified designee (consistent with local requirements) must 
obtain documented consent from each potential participant or each participant’s legally 
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acceptable representative prior to participating in a clinical study or future biomedical 
research. If there are changes to the participant’s status during the study (eg, health or age of 
majority requirements), the investigator or medically qualified designee must ensure the 
appropriate consent is in place.
8.1.1.1
General Informed Consent
Informed consent given by the participant or their legally acceptable representative must be 
documented on a consent form. The form must include the trial protocol number, trial 
protocol title, dated signature, and /agreement of the participant (or his/her legally acceptable 
representative) and of the person conducting the consent discussion.
A copy of the signed and dated informed consent form should be given to the participant (or 
their legally acceptable representative) before participation in the study.
The initial ICF, any subsequent revised ICF, and any written information provided to the 
participant must receive the IRB/IEC’s approval/favorable opinion in advance of use. The 
participant or his/her legally acceptable representative should be informed in a timely manner 
if new information becomes available that may be relevant to the participant’s willingness to 
continue participation in the study. The communication of this information will be provided 
and documented via a revised consent form or addendum to the original consent form that 
captures the participant’s or the participant’s legally acceptable representative’s dated 
signature.
Specifics about the study and the study population are to be included in the study informed
consent form.
Informed consent will adhere to IRB/IEC requirements, applicable laws and regulations, and 
Sponsor requirements.
8.1.1.2
Consent and Collection of Specimens for Future Biomedical Research
The investigator or medically qualified designee will explain the future biomedical research 
consent to the participant, or the participant’s legally acceptable representative, answer all of 
his/her questions, and obtain documented informed consent before performing any procedure 
related to future biomedical research. A copy of the informed consent will be given to the 
participant before performing any procedure related to future biomedical research.
8.1.1.3
Consent for PK Substudy
The investigator or medically qualified designee will explain the PK substudy consent to the 
participant, or the participant’s legally acceptable representative, answer all of his/her 
questions, and obtain documented informed consent before performing any procedure related 
to the PK substudy. A copy of the informed consent will be given to the participant before 
performing any procedure related to the PK substudy.
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8.1.1.4
Consent for Quality of Life Questionnaires
At preselected sites, the investigator or qualified designee will explain the QoL 
questionnaires consent to the participant, or the participant’s legally acceptable 
representative, answer all of his/her questions, and obtain documented informed consent 
before administration of the QoL questionnaires. A copy of the informed consent will be 
given to the participant before administration of the QoL questionnaires.
8.1.2
Inclusion/Exclusion Criteria
All inclusion and exclusion criteria will be reviewed at the Screening and Randomization 
Visits as outlined in the SoA (Section 1.3) by the investigator, who is a qualified physician,
to ensure that the participant qualifies for the study.
8.1.3
Participant Identification Card
All participants will be given a participant identification card identifying them as participants 
in a research study. The card will contain study site contact information (including direct 
telephone numbers) to be used in the event of an emergency. The investigator or qualified 
designee will provide the participant with a participant identification card immediately after 
the participant provides documented informed consent. At the time of intervention
randomization, site personnel will add the treatment/randomization number to the participant 
identification card.
The participant identification card also contains contact information for the emergency 
unblinding call center so that a healthcare provider can obtain information about study 
intervention in emergency situations where the investigator is not available.
8.1.4
Medical History
Medical history will be obtained by the investigator or qualified designee with a focus on 
defining the participant’s history of renal disease, cardiovascular morbidities, and bleeding 
events.
8.1.5
Prior and Concomitant Medications Review
8.1.5.1
Prior Medications
The investigator or qualified designee will review prior medication use, including antiplatelet 
and anticoagulant medications which are protocol-specified prohibited medications (Section 
6.5), and record prior medication taken by the participant within 28 days before starting the 
study.
8.1.5.2
Concomitant Medications
The investigator or qualified designee will record medication, if any, taken by the participant 
during the study in accordance with the Data Entry Guidelines. Refer to Section 6.5 for 
guidelines on concomitant medication use.
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8.1.6
Assignment of Screening Number
All consented participants will be given a unique screening number that will be used to 
identify the participant for all procedures that occur prior to randomization. Each participant 
will be assigned only 1 screening number. Screening numbers must not be re-used for 
different participants.
Rescreening is allowed once per participant. Any participant that is rescreened, will retain the 
original screening number assigned at the initial Screening Visit. Specific details on the 
Screening Visit/ Visit 1 requirements are provided in Section 8.11.1.
8.1.7
Assignment of Treatment/Randomization Number
All eligible participants will be randomly allocated and will receive a randomization number. 
The randomization number identifies the participant for all procedures occurring after 
randomization. Once a randomization number is assigned to a participant, it can never be 
reassigned to another participant.
A single participant cannot be assigned more than 1 randomization number.
8.1.8
Study Intervention Administration
Study intervention will be administered intravenously to participants during routine 
hemodialysis sessions. The first 3 study intervention doses will be administered during 
routine hemodialysis on study Days 1, 3, and 5. This loading period will be followed by a 
maintenance period. During the maintenance period, participants will receive study 
intervention on a once weekly schedule beginning on study Day 8 following the 
specifications within the study pharmacy manual until the participant completes the treatment
or is discontinued from the study. Timing of dose administration is found in Section 8.1.8.1.
Some administration of study intervention will take place during routine dialysis sessions that 
are not study visits. Every effort should be made to administer study intervention once 
weekly on the same day each week (Section 8.11.3).
8.1.8.1
Timing of Dose Administration
Study intervention will be prepared and dosed per the instructions outlined in the study 
pharmacy manual. All doses of study intervention will be given 30 minutes after initiation of 
hemodialysis and administered over approximately 60 minutes.
8.1.9
Discontinuation and Withdrawal
Participants who discontinue study intervention prior to completion of the treatment period
should be encouraged to continue to be followed for all remaining study visits as outlined in 
the SoA and Section 8.11.6.
Participants who withdraw from the study should be encouraged to complete all applicable 
activities scheduled for the Discontinuation Visit at the time of withdrawal. Any AEs that are 
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present at the time of withdrawal should be followed in accordance with the safety 
requirements outlined in Section 8.4.
8.1.9.1
Withdrawal From Future Biomedical Research
Participants may withdraw their consent for future biomedical research. Participants may 
withdraw consent at any time by contacting the investigator for the main study. If medical 
records for the main study are still available, the investigator will contact the Sponsor using 
the designated mailbox (clinical.specimen.management@MSD.com). Subsequently, the 
participant's consent for future biomedical research will be withdrawn. A letter will be sent 
from the Sponsor to the investigator confirming the withdrawal. It is the responsibility of the 
investigator to inform the participant of completion of withdrawal. Any analyses in progress 
at the time of request for withdrawal or already performed prior to the request being received 
by the Sponsor will continue to be used as part of the overall research study data and results. 
No new analyses would be generated after the request is received.
In the event that the medical records for the main study are no longer available (eg, if the 
investigator is no longer required by regulatory authorities to retain the main study records) 
or the specimens have been completely anonymized, there will no longer be a link between 
the participant’s personal information and their specimens. In this situation, the request for 
specimen withdrawal cannot be processed.
8.1.10
Participant Blinding/Unblinding
STUDY INTERVENTION IDENTIFICATION INFORMATION IS TO BE UNMASKED 
ONLY IF NECESSARY FOR THE WELFARE OF THE PARTICIPANT. EVERY 
EFFORT SHOULD BE MADE NOT TO UNBLIND.
For emergency situations where the investigator or medically qualified designee (consistent 
with local requirements) needs to identify the intervention used by a participant and/or the 
dosage administered, he/she will contact the emergency unblinding call center by telephone 
and make a request for emergency unblinding. As requested by the investigator or medically 
qualified designee, the emergency unblinding call center will provide the information to 
him/her promptly and report unblinding to the Sponsor. Prior to contacting the emergency 
unblinding call center to request unblinding of a participant’s intervention assignment, the 
investigator who is a qualified physician should make reasonable attempts to enter the 
intensity of the AEs observed, the relation to study intervention, the reason thereof, etc., in 
the medical chart. If it is not possible to record this assessment in the chart prior to the 
unblinding, the unblinding should not be delayed.
In the event that unblinding has occurred, the circumstances around the unblinding (eg, date, 
reason, and person performing the unblinding) must be documented promptly, and the 
Sponsor Clinical Director notified as soon as possible.
Once an emergency unblinding has taken place, the investigator, site personnel, and Sponsor 
personnel may be unblinded so that the appropriate follow-up medical care can be provided 
to the participant.
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Participants whose treatment assignment has been unblinded by the investigator or medically 
qualified designee and/or nonstudy treating physician must be discontinued from study 
intervention, but should continue to be monitored in the study.
Additionally, the investigator or medically qualified designee must go into the IRT system 
and perform the unblind in the IRT system to update drug disposition. In the event that the 
emergency unblinding call center is not available for a given site in this study, the IRT 
system should be used for emergency unblinding in the event that this is required for 
participant safety.
At the end of the study, random code/disclosure envelopes or lists and unblinding logs are to 
be returned to the Sponsor or designee.
8.1.11
Calibration of Equipment
The investigator or qualified designee has the responsibility to ensure that any device or 
instrument used for a clinical evaluation/test during a clinical study that provides information 
about inclusion/exclusion criteria and/or safety or efficacy parameters shall be suitably 
calibrated and/or maintained to ensure that the data obtained are reliable and/or reproducible. 
Documentation of equipment calibration must be retained as source documentation at the 
study site.
Critical equipment for this study includes, but it is not limited to:

Infusion pumps

Vital signs and ECG instruments

All equipment to process study intervention and samples such as, but not limited to, 
centrifuge equipment, pipettes, and freezers for MK-2060 or placebo and sample 
storage.
8.1.12
Identification of External Contact Person
All participants will be asked to identify a person to be contacted by the study site to collect 
the participant’s vital status if the participant cannot be reached (eg, spouse, family, friend, 
neighbor, etc.).
8.2
Efficacy Assessments
The primary endpoint for the study is the time to first occurrence of AVG thrombosis
(Section 4.2.1.1). Study staff is expected to report all AVG thrombosis events as AEs and 
identify them as potential primary endpoints upon learning of the event’s occurrence either 
during routine care of study participants or at study visits. 
Events constituting the tertiary/exploratory endpoint of major thrombotic CV events will be 
reported as AEs upon study staff learning of these events’ occurrence during routine care of 
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study participants or at study visits. These events include fatal and non-fatal MI, ischemic 
stroke, PE, DVT, and acute limb ischemia. 
At selected study sites, KDQOL-SF and EQ-5D-5L questionnaires will be administered by 
the interviewer (investigator or qualified designee) at the visits outlined in the SoA. The 
questionnaires should be administered before administration of study intervention.
8.3
Safety Assessments
Details regarding specific safety procedures/assessments to be performed in this study are 
provided. 
Planned time points for all safety assessments are provided in the SoA.
8.3.1
Physical Examinations
Complete and directed physical examinations will be conducted during the visits outlined in 
the SoA (Section 1.3) by an investigator or medically qualified designee (consistent with 
local requirements) as per institutional standard.
Clinically significant abnormal findings during screening should be recorded as medical 
history.
Directed physical examination performed throughout the treatment period will at a minimum 
include assessment of the cardiovascular system and hemodialysis access site.
8.3.1.1
Height
Height will be measured without shoes using a stadiometer or other appropriate device at 
screening/Visit 1.
8.3.1.2
Weight
Body weight will be measured without shoes, jacket or coat removed, using a standardized 
scale at each time point specified in the SoA (Section 1.3) post-dialysis.
8.3.2
Systemic Infusion Reaction Assessment
Participants will be monitored for up to 1 hour after the administration of study intervention
during the loading phase (first 3 treatment visits) as outlined in the SoA (Section 1.3). During 
this time, signs and symptoms of a systemic infusion reaction including, but not limited to,
fever, vital sign changes (tachycardia/hypotension), pruritis, urticarial (hives), lip swelling, 
angioedema, bronchospasm, stridor, hoarseness, and shortness of breath will be monitored. 
Infusion reactions must be assessed, managed promptly, and reported as AEs.
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Infusion Reaction Management
The risk of infusion reactions to MK-2060 is considered low since the molecule contains 
primarily human sequences; however, infusion reactions may be observed. Due to the 
expected low risk and since one of the objectives of the study is to characterize the safety 
profile of MK-2060, no prophylactic pre-medications to reduce the minimal risk of infusion 
reactions will be given prior to MK-2060 administration.
Participants who experience infusion or hypersensitivity reactions in conjunction with the 
infusion of study intervention should receive appropriate supportive care measures as 
deemed necessary by the treating physician. If a reaction occurs, participants should be 
carefully observed until complete resolution of all signs and symptoms. Report any AEs
according to the guidelines in Section 8.4. 
8.3.3
Vital Signs
Vital signs will be measured at each study visit before initiation of hemodialysis and 
administration of study intervention as outlined in the SoA (Section 1.3). Vital signs assessed 
will include body temperature, respiratory rate, heart rate, and BP. Participants should be 
resting in the semi-recumbent position for at least 10 minutes prior to having vital signs 
measurements obtained.
8.3.3.1
Body Temperature
Body temperature will be a single measurement. Temperature will be measured according to 
standard of practice.
8.3.3.2
Heart Rate and Blood Pressure
Heart rate and BP will be performed in triplicate measurements, obtained at least 1 to 
2 minutes apart and before initiation of hemodialysis and administration of study 
intervention. The mean of these measurements will be recorded and used as the baseline to 
calculate change from baseline for safety evaluations (and for rechecks, if needed). 
The correct size of the BP cuff and the correct positioning on the participant’s limb is 
essential to increase the accuracy of BP measurements. Whenever possible, BP 
measurements should be obtained using the same arm or leg, same BP monitoring device, 
and same examiner at each visit. 
8.3.4
Electrocardiograms
A standard supine 12-lead ECG will be obtained and reviewed by an investigator or 
medically qualified designee (consistent with local requirements) at the visits outlined in the 
SoA (Section 1.3). The ECG should be recorded with a paper speed of 25 mm/sec and 
equivalence of 1 mV signal to 10 mm vertical deflection in the ECG.
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Clinically significant abnormal findings during the screening period should be recorded as 
medical history. Assessments may be repeated during the study, as clinically indicated.

Participants should avoid the ingestion of caffeine and nicotine-containing products 
for at least 30 minutes before the scheduled ECGs.

ECGs should be performed after the participant has rested quietly for at least 
10 minutes in a supine position and before the assessment of blood pressure and heart 
rate as well as before blood collection.
All ECGs performed should be reviewed at the investigative site for participant safety 
monitoring. The investigator is responsible for retaining all copies of the ECG reports.
8.3.5
Clinical Safety Laboratory Assessments

Refer to Appendix 2 for the list of clinical laboratory tests to be performed and to the 
SoA for the timing and frequency.

The investigator or medically qualified designee (consistent with local requirements) 
must review the laboratory report, document this review, and record any clinically 
relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents. Clinically significant 
abnormal laboratory findings are those which are not associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the 
participant's condition.

All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA.

If laboratory values from nonprotocol-specified laboratory assessments performed at 
the institution’s local laboratory require a change in study participant management or 
are considered clinically significant by the investigator (eg, SAE or AE or dose 
modification), then the results must be recorded in the appropriate CRF (eg, SLAB).

For any laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 90-days after the last dose of study 
intervention, every attempt should be made to perform repeat assessments until the 
values return to normal or baseline or if a new baseline is established as determined 
by the investigator.
8.3.5.1
Serum Pregnancy Test
All WOCBP (see Section 10.5.1 for definition) participating in the study will have a serum 
pregnancy test at visits indicated in the SoA and when pregnancy is suspected. Participants 
with a positive pregnancy test must be discontinued from study treatment and followed 
(Section 7.1).
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Germany-specific requirements are in Appendix 7.
8.3.5.2
Serum Follicle Stimulating Hormone
All WOCBP (see Section 10.5.1 for definition) participating in the study will have an FSH 
test at Visit 1. A second FSH test at Visit 2 is required for participants who have less than 
1 year of amenorrhea.
8.3.6
Quality of Life Questionnaires
At preselected sites, the KDQOL-SF and the EQ-5D-5L questionnaires will be administered 
by the interviewer (investigator or qualified designee) at the visits specified in the SoA 
(Section 1.3). The questionnaires should be administered before administration of study 
intervention.
8.3.7
Vital Status Assessment
Vital status will be collected at the timepoints specified in the SoA. This assessment can also 
be performed at any point in the study when vital status of a participant is in question, unless 
the participant has specifically withdrawn consent for all further follow-up.
8.4
Adverse Events, Serious Adverse Events, and Other Reportable Safety Events
The definitions of an AE or SAE, as well as the method of recording, evaluating, and 
assessing causality of AE and SAE and the procedures for completing and transmitting AE, 
SAE, and other reportable safety event reports can be found in Appendix 3.
Adverse events, SAEs, and other reportable safety events will be reported by the participant 
(or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized 
representative).
The investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE as well as other reportable safety events. 
Investigators remain responsible for following up AEs, SAEs, and other reportable safety 
events for outcome according to Section 8.4.3.
The investigator, who is a qualified physician, will assess events that meet the definition of 
an AE or SAE as well as other reportable safety events with respect to seriousness, 
intensity/toxicity and causality.
8.4.1
Time Period and Frequency for Collecting AE, SAE, and Other Reportable 
Safety Event Information
All AEs, SAEs, and other reportable safety events that occur after the participant provides 
documented informed consent but before intervention randomization must be reported by the 
investigator if the event causes the participant to be excluded from the study, or is the result 
of a protocol-specified intervention, including but not limited to washout or discontinuation 
of usual therapy, diet, or a procedure.
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From the time of intervention and randomization through study completion, all AEs, SAEs, 
and other reportable safety events must be reported by the investigator. 
Additionally, any SAEs brought to the attention of an investigator at any time outside of the 
time period specified in the previous paragraph must be reported immediately to the Sponsor 
if the event is considered related to study intervention.
Investigators are not obligated to actively seek AEs or SAEs or other reportable safety events 
in former study participants. However, if the investigator learns of any SAE, including a 
death, at any time after a participant has been discharged from the study, and he/she 
considers the event to be reasonably related to the study intervention or study participation, 
the investigator must promptly notify the Sponsor.
All initial and follow-up AEs, SAEs, and other reportable safety events will be recorded and 
reported to the Sponsor or designee within the time frames as indicated in Table 2.
Table 2
Reporting Time Periods and Time Frames for Adverse Events and Other 
Reportable Safety Events
Type of 
Event
Reporting Time 
Period:
Consent to 
Randomization/ 
Allocation
Reporting Time 
Period:
Randomization/ 
Allocation through 
Protocol-specified 
Follow-up Period
Reporting Time 
Period:
After the 
Protocol-specified 
Follow-up Period
Time Frame to 
Report Event 
and Follow-up 
Information to 
Sponsor:
NSAE
Report if:
- due to protocol-
specified intervention
- causes exclusion
- participant is receiving 
placebo run-in or other 
run-in treatment
Report all
Not required
Per data entry 
guidelines
SAE
Report if:
- due to protocol-
specified intervention
- causes exclusion
- participant is receiving 
placebo run-in or other 
run-in treatment
Report all
Report if:
- drug/vaccine 
related.
(Follow ongoing to 
outcome)
Within 24 hours 
of learning of 
event
Pregnancy/
Lactation 
Exposure
Report if:
- participant has been 
exposed to any protocol-
specified intervention 
(eg, procedure, washout 
or run-in treatment 
including placebo run-
in)
Exception: A positive 
pregnancy test at the 
time of initial screening 
is not a reportable event.
Report all
Previously
reported – Follow 
to completion/
termination; report 
outcome
Within 24 hours 
of learning of 
event
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Type of 
Event
Reporting Time 
Period:
Consent to 
Randomization/ 
Allocation
Reporting Time 
Period:
Randomization/ 
Allocation through 
Protocol-specified 
Follow-up Period
Reporting Time 
Period:
After the 
Protocol-specified 
Follow-up Period
Time Frame to 
Report Event 
and Follow-up 
Information to 
Sponsor:
ECI (require 
regulatory 
reporting)
Report if:
- due to intervention
- causes exclusion
Report
- Potential DILI
- Require regulatory 
reporting
Not required
Within 24 hours 
of learning of 
event
ECI (do not 
require 
regulatory 
reporting)
Report if:
- due to intervention
- causes exclusion
Report
- non-DILI ECIs and 
those not requiring 
regulatory reporting
Not required
Within 5 
calendar days of 
learning of event
Cancer
Report if:
- due to intervention
- causes exclusion
Report all
Not required
Within 5 
calendar days of 
learning of event
(unless serious)
Overdose
Report if:
- receiving placebo run-
in or other run-in 
medication 
Report all
Not required
Within 5 
calendar days of 
learning of event
DILI=drug-induced liver injury; ECI=event of clinical interest; NSAE=nonserious adverse event; SAE=serious adverse 
event
8.4.2
Method of Detecting AEs, SAEs, and Other Reportable Safety Events
Care will be taken not to introduce bias when detecting AEs and/or SAEs and other 
reportable safety events. Open-ended and nonleading verbal questioning of the participant is 
the preferred method to inquire about AE occurrence except for assessment of study 
endpoints. 
Participants will be directly questioned about the occurrence of AVG thrombosis or major 
thrombotic cardiovascular endpoints (Section 8.2) at study visits. These events will be
reported as AEs or SAEs upon study staff learning of the events’ occurrence during routine 
care of study participants or at study visits
8.4.3
Follow-up of AE, SAE, and Other Reportable Safety Event Information
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs, SAEs, and other reportable safety events,
including pregnancy and exposure during breastfeeding, ECIs, cancer, and overdose will be 
followed until resolution, stabilization, until the event is otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.3). In addition, the investigator will 
make every attempt to follow all nonserious AEs that occur in randomized participants for 
outcome. Further information on follow-up procedures is given in Appendix 3.
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8.4.4
Regulatory Reporting Requirements for SAE
Prompt notification (within 24 hours) by the investigator to the Sponsor of SAE is essential 
so that legal obligations and ethical responsibilities towards the safety of participants and the 
safety of a study intervention under clinical investigation are met.
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements and global laws and 
regulations relating to safety reporting to regulatory authorities, IRB/IECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and Sponsor policy and forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAE) from the Sponsor will file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements.
8.4.5
Pregnancy and Exposure During Breastfeeding
Although pregnancy and infant exposure during breastfeeding are not considered AEs, any 
pregnancy or infant exposure during breastfeeding in a participant (spontaneously reported to 
the investigator or their designee) that occurs during the study are reportable to the Sponsor.
All reported pregnancies must be followed to the completion/termination of the pregnancy. 
Any pregnancy complication will be reported as an AE or SAE. 
The medical reason (example: maternal health or fetal disease) for an elective termination of 
a pregnancy will be reported as an AE or SAE. Prenatal testing showing fetus will be born 
with severe abnormalities/congenital anomalies that leads to an elective termination of a 
pregnancy will be reported as an SAE for the fetus.
Pregnancy outcomes of ectopic pregnancy, spontaneous abortion, missed abortion, benign 
hydatidiform mole, blighted ovum, fetal death, intrauterine death, miscarriage, and stillbirth 
must be reported as serious events (Important Medical Events). If the pregnancy continues to 
term, the outcome (health of infant) must also be reported.
8.4.6
Disease-related Events and/or Disease-related Outcomes Not Qualifying as 
AEs or SAEs
Not applicable.
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8.4.7
Events of Clinical Interest
Selected serious and nonserious AEs are also known as ECIs and must be reported to the 
Sponsor.
Events of clinical interest for this study include:
1. Potential DILI events defined as an elevated AST or ALT laboratory value that is greater 
than or equal to 3X the ULN and an elevated total bilirubin laboratory value that is 
greater than or equal to 2X the ULN and, at the same time, an alkaline phosphatase 
laboratory value that is less than 2X the ULN, as determined by way of protocol-
specified laboratory testing or unscheduled laboratory testing.*
*Note: These criteria are based upon available regulatory guidance documents. The 
purpose of the criteria is to specify a threshold of abnormal hepatic tests that may require 
an additional evaluation for an underlying etiology. The study site guidance for 
assessment and follow-up of these criteria can be found in the Investigator Study File 
Binder (or equivalent).
8.5
Treatment of Overdose
In this study, an overdose is defined as any dose higher than the maximal target dose 
prescribed in the protocol. It is up to the investigator or the reporting physician to decide 
whether a dose is to be considered an overdose in consultation with the Sponsor.
8.6
Pharmacokinetics
For the investigation of the systemic exposure to MK-2060, the plasma concentration of 
MK-2060 will be determined at different time points in all participants. 
Blood samples for PK analysis will be collected from all randomized participants at select 
study visits described in the SoA (Section 1.3). Blood samples will be collected prior to 
hemodialysis and administration of study intervention at all specified visits, with additional 
blood samples collected approximately 30 minutes after study intervention administration on 
Day 1 and Day 85. This PK analysis is separate from the PK substudy and it is part of the 
main study.
A separate PK substudy will be available to all study sites (see Appendix 8). Sites should ask 
all main study participants to enter into the PK substudy and enroll those that consent. 
Approximately 100 participants will be enrolled. 
Participants in the PK substudy will have all the PK samples collected per the SoA for the 
main study (Section 1.3), in addition to supplementary PK sample collections (Table 10). 
Participants in the substudy will have trough PK samples collected prior to dialysis on Day 3 
and Day 5, will have PK samples collected 6 hours post-study intervention administration on 
Day 1 and Day 85, and will have PK samples collected prior to dialysis on the 2 dialysis 
visits following Day 85, and at the next dosing visit as described in Table 10, Appendix 8. 
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8.6.1
Blood Collection for Plasma MK-2060
Blood samples will be taken on defined study days for PK analysis from all participants (see 
SoA, Section 1.3). Participants enrolled in the PK substudy will have additional blood draws 
at additional study visits (see Appendix 8: PK Substudy). Sample collection, storage, and 
shipment instruction for plasma samples will be provided in a separate Study Operations 
Manual by the Sponsor. 
Trough samples will be collected immediately pre-dialysis and before any IV heparin is 
administered to the participant. Peak samples will be collected approximately 30 minutes 
after study intervention infusion ends. If study intervention is intravenously dosed outside the 
hemodialysis circuit, blood draws must be taken from a separate intravenous site. If the 
hemodialysis circuit is used for both intervention dosing and blood draws, separate access 
points in the hemodialysis circuit must be used with blood draws taken from an access point 
earlier in the dialysis circuit than the access point used for intervention infusion to infuse 
study intervention or other participant medications. The access point used for blood draws 
must be flushed with saline before sample collection. The time samples were drawn, time 
infusion was started, and time the infusion ended will be recorded.
8.7
Immunogenicity Assessments
ADA samples will be collected from all randomized participants according to the ADA 
sampling scheme outlined in the SoA (Section 1.3). Sample collection, storage, and shipment 
instructions for plasma samples will be provided in the operations/laboratory manual. 
8.8
Pharmacodynamics
Sample collection, storage, and shipment instructions for pharmacodynamic samples will be 
provided in the operations/laboratory manual.
8.9
Biomarkers
Collection of samples for other biomarker research is also part of this study. The following 
samples for biomarker research are required and will be collected from all participants as 
specified in the SoA (Section 1.3): Blood for Genetic Analysis.
8.9.1
Planned Genetic Analysis Sample Collection
The planned genetic analysis sample should be drawn for planned analysis of the association 
between genetic variants in DNA and drug response. This sample will not be collected at the 
site if there is either a local law or regulation prohibiting collection, or if the IRB/IEC does 
not approve the collection of the sample for these purposes. If the sample is collected, 
leftover extracted DNA will be stored for future biomedical research if the participant 
provides documented informed consent for future biomedical research. If the planned genetic
analysis is not approved, but FBR is approved and consent is given, this sample will be 
collected for the purpose of FBR.
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Sample collection, storage, and shipment instructions for planned genetic analysis samples 
will be in the Operations/Laboratory Manual.
8.10
Future Biomedical Research Sample Collection
If the participant provides documented informed consent for future biomedical research, the 
following specimens will be obtained as part of future biomedical research:

Leftover DNA for future research

Leftover main study plasma from PT/aPTT/FXI activity stored for future research
8.11
Visit Requirements
Visit requirements are outlined in Section 1.3. Specific procedure-related details are provided 
in Section 8.
If a participant misses a scheduled visit and study sites are unable to reach the participant, the 
sites will contact the ‘external contact person’ identified by participants during screening 
(Section 8.1.12) to collect participant’s vital status (Section 8.3.7).  
Every effort should be made to align study visits with routine hemodialysis sessions. 
8.11.1
Screening
Up to 30 days prior to intervention randomization, potential participants will be evaluated to 
determine whether they fulfill the entry requirements outlined in Section 5.1 and Section 5.2. 
Informed consent must be documented prior to performing any protocol-specific procedure. 
Participants may be rescreened once, after consultation with the Sponsor. Rescreening should 
include all screening procedures listed in the SoA, including consent review. Participants 
who consent to this study and for any reason do not continue to randomization, will be 
considered a screen failure. 
Note: Local laboratories can be used at Screening.
8.11.2
Randomization
At the Randomization Visit, participants who fulfill all inclusion/exclusion criteria will be 
randomized in a 1:1:1 ratio to MK-2060 20 mg, MK-2060 6 mg, or matching placebo and 
assigned a unique randomization number. Randomization must occur ≤30 days from the 
Screening Visit. 
At the Randomization Visit, prior to initiation of hemodialysis, participants will undergo 
directed physical examination, measurement of vital signs, blood draws, and complete QoL 
questionnaires. After initiation of hemodialysis, they will receive the first dose of study 
intervention as described in Section 8.1.8.1, with assessment for systemic infusion reaction 
for up to 1 hour after completion of the infusion. 
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All procedures and assessments specified for the Randomization Visit will be performed after 
the Screening Visit procedures are performed. 
8.11.3
Treatment Period
Participants in this study are expected to be at the study site several times a week for routine
hemodialysis sessions. Study Visits for this study should be aligned with ongoing dialysis 
sessions (see Section 1.3 for visit windows). 
Throughout the treatment period, participants will receive study intervention once a week 
during a routine dialysis session (Section 8.1.8). Participants will maintain this weekly 
schedule until the required number of overall AVG thrombosis events have occurred in the 
study (Section 9.9.1). 
After Visit 6, study visits vary in frequency but study intervention will continue to be 
administered on a weekly basis during routine dialysis sessions until the participant 
completes the treatment or is discontinued from the study. Due to the weekly dosing, there 
will be many dialysis sessions where study intervention is administered but there will be no 
per-protocol study Visit. Every effort should be made to administer study intervention once 
weekly on the same day each week.
8.11.4
Final Efficacy Visit
The Final Efficacy Visit will be conducted for all participants once the planned number of 
AVG thrombosis events is observed and the efficacy cutoff is declared by the Sponsor. 
If applicable, participants will continue in the study until the Final Efficacy Visit but will no
longer be administered study intervention at this visit or going forward. Participants who 
prematurely discontinued study intervention are required to attend the Final Efficacy Visit for 
collection of clinical events and all assessments and procedures outlined in the SoA.
8.11.5
Safety Follow-up Visit
The Safety Follow-up Visit will take place approximately 90 days ± 7 days after the Final 
Efficacy Visit to assess for clinical events, AEs, and vital status. All assessments and 
procedures outlined in the SoA will be performed. 
8.11.6
Premature Discontinuation Visit
At the Discontinuation Visit, all laboratory testing and procedures outlined in the SoA will be 
completed. Discontinuation Visit procedures will be performed on participants as soon as 
possible after discontinuing study intervention (≤7 days).  
All participants who discontinue study intervention prior to completion of the protocol-
specified treatment period will continue to attend all remaining protocol-specified visits, 
including the Safety Follow-up Visit, which is completed approximately 3 months from the 
date of last dose of study medication, and perform all procedures stipulated in the SoA. In the 
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event a participant specifically withdraws consent for further follow-up, no additional 
information is permitted to be collected. 
If the participant does not attend the Discontinuation Visit, a telephone contact for collection 
of protocol-defined endpoint events should occur. In such cases, the phone contact will not 
be considered a protocol deviation. If the site is unable to reach the participant, the site will 
contact the ‘external contact person’ identified by the participant during screening to collect 
participant’s vital status (Section 8.1.12).
8.11.7
Premature Intervention Discontinuation Safety Follow-up Visit
A Safety Follow-up Visit will be conducted for all participants who discontinue study 
intervention prematurely. This Visit will be conducted 90 days ± 7 days after the Premature 
Discontinuation Visit. All assessments and procedures outlined in the SoA will be performed.
9
STATISTICAL ANALYSIS PLAN
This section outlines the statistical analysis strategy and procedures for the study that are 
considered principal in nature. If changes are made to primary and/or key secondary 
hypotheses or the statistical methods related to those hypotheses after the study has begun but 
before any unblinding, then the protocol will be amended (consistent with ICH 
Guideline E9). Changes to exploratory or other non-confirmatory analyses made after the 
protocol has been finalized will be documented in a sSAP and referenced in the CSR for the 
study. Post hoc exploratory analyses will be clearly identified in the CSR. Other planned 
analyses (ie, those specific to the analysis of PK data and FBR) will be documented in 
separate analysis plans.
9.1
Statistical Analysis Plan Summary
Key elements of the SAP are summarized here. The comprehensive plan is provided in 
Sections 9.2 through 9.12.
Study Design 
Overview
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 
Treatment
Assignment
Participants will be randomized in a 1:1:1 ratio among 3 treatment groups: 
(1) MK-2060 20 mg QW, (2) MK-2060 6 mg QW, and (3) matching placebo.
Primary Analysis 
Populations
Efficacy: ITT
Safety: APaT
Event-Driven 
Study Duration
The study is event-driven. It will continue until ~103 or 171 events have accrued for 
the interim analysis or final analysis.
Primary 
Endpoint
Time from randomization until the first occurrence of an AVG thrombosis event
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Key Secondary 
Endpoint
Time to each AVG thrombosis event (first and recurrent) from randomization until 
the efficacy cutoff date
Statistical 
Methods for Key
Efficacy Analyses
Primary:
The HR and the associated 95% CI and p-values will be provided (MK-2060 vs 
placebo; 2 pairwise comparisons) based on a stratified Cox proportional hazards 
model.  
Statistical 
Methods for Key 
Safety Analyses
For analyses in which 95% CIs will be provided for between-treatment differences 
(MK-2060 minus placebo) in the percentage of participants with events, these 
analyses will be performed using the M&N method.
Interim Analyses
A single IA is planned to assess efficacy and futility. The IA is planned to be 
performed once 60% information (103 events) for the primary endpoint is available.
The study may stop at the IA if the criterion for efficacy is met. At the IA, a p-value 
for the comparison of MK-2060 versus placebo <0.001 (one-sided) will be considered 
statistically significant. If the efficacy criterion is met at the IA, the eDMC may 
recommend study continuation after considering safety factors, including the type and 
quality of bleeding events (Section 4.2.1.3).
The study may stop for futility if the posterior probability is <30% that the true HR 
(MK-2060 vs placebo) in time to first occurrence of an AVG thrombosis event is 
≤0.75 for each dose of MK-2060.
Multiplicity
At the IA and final analysis, there are 2 pairwise treatment group comparisons that 
may be tested to address the primary hypothesis. Testing will be performed in order 
of descending randomized dose and will stop with the first comparison that has a one-
sided p-value ≥0.001 (or 0.024) for the IA (or final analysis).  
Sample Size and 
Power 
The planned sample size is approximately 489 participants, with 163 participants in 
each group. This study is event-driven and will complete after accumulation of 
sufficient events to determine efficacy for the time from randomization to the first 
occurrence of an AVG thrombosis event. If the true HR is 0.6, the study will have 
80% power. 
9.2
Responsibility for Analyses/In-house Blinding 
The statistical analysis of the data obtained from this study will be the responsibility of the 
Clinical Biostatistics department of the Sponsor.
The Sponsor will generate the randomized allocation schedule for study intervention
assignment for this protocol, and the randomization will be implemented in IVRS.
This study will be conducted as a double-blind study under in-house blinding procedures. 
The official, final database will not be unblinded until medical/scientific review has been 
performed, protocol deviations have been identified, and data have been declared final and
complete.
Blinding procedures related to the planned IA are described in Section 9.7.
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9.3
Hypotheses/Estimation
Objectives and hypotheses are stated in Section 3.
9.4
Analysis Endpoints
9.4.1
Efficacy Endpoints
Primary Efficacy Endpoint

Time from randomization until the first occurrence of an AVG thrombosis event 
Secondary Efficacy Endpoint

Time to each AVG thrombosis event (first and recurrent) from randomization until 
the efficacy cutoff date
Efficacy endpoints are further described in Section 4.2.1.1.
9.4.2
Patient-reported Outcome Endpoints

Mean change from baseline in KDQOL-SF scale scores over time

Mean change from baseline in EQ-5D scores over time
PRO endpoints are described in Section 4.2.1.2. 
9.4.3
Safety Endpoints

The key safety endpoint is time from randomization until the first ISTH major 
bleeding event or a clinically relevant non-major bleeding event 
Safety and tolerability will also be assessed by clinical review of all relevant parameters 
including AEs, laboratory safety tests, and vital signs.
Safety parameters are described in Section 4.2.1.3.
9.4.4
Pharmacokinetic Endpoint
The key exploratory PK endpoints for MK-2060 are Cmax and Ctrough.
Additional details are in Section 4.2.1.4.
9.4.5
Immunogenicity Endpoints
The exploratory immunogenicity endpoints are the incidence and magnitude (titer) of ADA 
to MK-2060.
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Additional details are in Section 4.2.1.5.
9.4.6
Pharmacodynamic Endpoints
aPTT is the key PD endpoint. 
Additional details are in Section 4.2.1.6.
9.5
Analysis Populations
9.5.1
Efficacy Analysis Population
The ITT population will serve as the population for efficacy analyses. All randomized 
participants will be included in this population. Participants will be included in the treatment 
group to which they are randomized.
9.5.2
Patient-reported Outcome Analysis Population
The PRO population will be the subset of the randomized population based on clinical sites 
selected for PRO administration. This population consists of all randomized participants at 
the selected sites who had at least 1 IV administration (including only partial) of study 
intervention and had completed the baseline and at least 1 post-baseline PRO assessment. 
The PRO population definition will be applied separately to each questionnaire. Participants 
will be included in the treatment group to which they are randomized.
9.5.3
Safety Analysis Population
Analyses of safety will be performed in the APaT population, consisting of all randomized 
participants who received at least 1 IV administration (including only partial) of study 
intervention. Participants will be included in the treatment group corresponding to the study 
intervention they received for the analysis of safety data. This will be the randomized 
treatment group for all participants except for those who take incorrect study intervention for 
the entire treatment period. Such participants will be included in the treatment group 
corresponding to the study intervention actually received. Any participant who receives both 
correct and incorrect study intervention will be analyzed according to the randomized 
treatment group and a narrative will be provided for any events that occur during the IV 
administration period for which the participant was incorrectly dosed.
At least 1 laboratory or vital sign measurement obtained after at least 1 dose of study 
intervention is required for inclusion in the analysis of each specific parameter. To assess 
change from baseline, a baseline measurement is also required.
9.5.4
Pharmacokinetic Analysis Population
The population for PK data analysis is defined as all participants with at least 1 measurable 
PK sample following treatment with MK-2060.
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9.5.5
Immunogenicity Analysis Population
The population for immunogenicity analysis includes all participants with at least 1 ADA 
assay result following treatment with MK-2060.
9.5.6
Pharmacodynamic Analysis Population
The primary analysis population for the PD endpoints will be all randomized participants 
who have at least 1 infusion (including only partial) of study intervention and have at least 
1 PD marker assessment. Participants will be included in the treatment group to which they 
are randomized.
9.6
Statistical Methods
This section describes the statistical methods that address the primary and secondary 
objectives. Methods related to the exploratory objectives will be described in the sSAP.
P-values for the key secondary efficacy endpoint may be provided as an assessment of 
strength of evidence without intent to make inferential claims.
For analysis purposes, the baseline assessment is considered the one closest to but before or 
on the day of randomization (Day 1).
For stratified analyses, the stratification factors used for randomization (Section 6.3.2) will 
be applied to the analysis. Small strata will be combined in a way specified by a blinded 
statistician before the analysis, if needed.
Event accrual will be monitored throughout the course of the study. An efficacy cutoff date 
for the IA or final analysis will be declared when approximately 103 or 171 events, 
respectively, have accrued for the primary efficacy endpoint. If the study stops at the IA, the 
Final Efficacy Visits will be scheduled to occur within 14 days of Sponsor’s notification to 
stop the study. If the study continues, the Final Efficacy Visits will be scheduled to occur in 
the 14 days following the final analysis efficacy cutoff date. All participants still on study 
treatment at the time of the efficacy cutoff date (Sponsor’s notification to stop the study at IA 
or final analysis) will attend the Final Efficacy Visit with no further administration of study 
treatment and will have a scheduled Safety Follow-up Visit 90 days after the Final Efficacy 
Visit. Two database locks will then occur: one using the efficacy cutoff date and another after 
all safety follow-up data are available. Analyses addressing all efficacy objectives will be 
performed based on data up to the efficacy cutoff date. Supportive efficacy analyses will be 
performed including data through the Safety Follow-up Visit. The primary assessment of 
safety will use all data through the Safety Follow-up Visit. Supportive safety summaries will 
be provided based on data through the efficacy cutoff date.  
9.6.1
Statistical Methods for Efficacy Analyses
This section describes the statistical methods that address the primary and key secondary 
objectives related to the efficacy endpoints.
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The primary efficacy estimand following the guidance in ICH E9 (R1) [European Medicines 
Agency 2020] has the following 5 attributes:
1. The treatment condition of interest and the alternative treatment condition to which 
comparison will be made: intervention with MK-2060 or placebo.
2. The population of participants targeted by the clinical question: individuals with 
ESRD.
3. The variable (or endpoint) to be obtained for each participant that is required to 
address the clinical question: first occurrence of an AVG thrombosis event.
4. The specification of how to account for other intercurrent events to reflect the 
scientific question of interest: a treatment policy approach will be used for the 
intercurrent events of discontinuation of study intervention and/or initiation of 
non-study intervention. No observed data will be excluded from analyses because of 
these intercurrent events.
5. The population-level summary for the endpoint which provides the basis for a 
comparison between treatment conditions: the HR (MK-2060 vs placebo) for the time 
to first occurrence of an AVG thrombosis event.
9.6.1.1 Primary Efficacy Endpoint 
The nonparametric Kaplan-Meier method will be used to estimate the time from 
randomization until the first occurrence of an AVG thrombosis event curve in each treatment 
group. The treatment effect will be assessed by the stratified log-rank test. A stratified Cox 
proportional hazard model with Efron's method of tie handling will be used to assess the 
magnitude of the treatment effect (ie, HR) between the treatment arms. The HR and its 95% 
CI from the stratified Cox model with Efron's method of tie handling and with a single 
treatment covariate will be reported. P-values will be provided to address the primary 
objective and associated hypothesis (2 pairwise comparisons). Kaplan-Meier figures will also
be provided.
Censoring will occur at the last follow-up contact where an AVG thrombosis event could be 
assessed on or prior to the cutoff date. Any participant who undergoes a kidney transplant 
during the study will be censored on the date of the kidney transplant.
Efficacy results that will be deemed to be statistically significant after consideration of the 
Type I error control strategy are described in Section 9.8.
Sensitivity analyses will be described in the sSAP.
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9.6.1.2 Secondary Efficacy Endpoints 
Time to each AVG thrombosis event (first and recurrent) 
The primary approach for time to each AVG thrombosis event analysis will be the Andersen-
Gill model [Andersen, P. K. 1982] to compare the MK-2060 each dose group to placebo. The 
Andersen-Gill model is an extension of the Cox proportional hazard model including both 
first and recurrent events.
For each comparison (MK-2060 vs placebo), treatment group and the stratification factors 
used for randomization will be included in the model as fixed effects. Robust standard errors 
will be used to account for correlations of event times within a participant.
Estimates of treatment comparisons and effect size including 95% confidence intervals will 
be provided based on the fitted model.
The analysis strategy for key efficacy endpoints is outlined in Table 3.
Table 3
Analysis Strategy for Key Efficacy Endpoints
Endpoint
Statistical Method
Analysis 
Population
Missing Data 
Approach
Primary Endpoint
Time from randomization until the first 
occurrence of an AVG thrombosis event
Test: Stratified log-rank test
Estimation: Stratified Cox 
model with Efron’s tie 
handling method
ITT
Censor
Key Secondary Endpoint
   Time to each AVG thrombosis event (first 
and recurrent) from randomization until the 
efficacy cutoff 
Andersen-Gill modela
ITT
Censor
AVG=arteriovenous graft; ITT=Intent-to-Treat (all randomized participants).
a Treatment group and the stratification factors used for randomization will be included in the model as fixed 
effects.
9.6.2
Analysis Methods for Safety Analyses
Safety and tolerability will be assessed by clinical review of all relevant parameters including 
AEs, laboratory tests, vital signs, and ECGs. The primary approach to analysis of safety will 
include all data through treatment including the 3-month follow-up assessment. The analysis 
will compare safety events in each MK-2060 group to the placebo group.
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Adverse Events
AEs will be coded using the standard MedDRA and grouped according to SOC.
The analysis of safety results will follow a tiered approach (Table 4). The tiers differ with 
respect to the analyses that will be performed.
For the safety analyses, any participant who undergoes a kidney transplant during the study 
will be censored at 3 months after the date of the kidney transplant.
Tier 1 Events
Safety parameters or AEs of special interest that are identified a priori constitute “Tier 1” 
safety endpoints that will be subject to inferential testing for statistical significance with 
p-values and 95% CIs. For this protocol, the time to the composite endpoint of an ISTH 
major bleeding event or a clinically relevant non-major bleeding event (adjudicated) is a 
Tier 1 event and will be analyzed following the analysis approach for the primary efficacy 
analysis.
Tier 2 Events
Tier 2 parameters will be assessed via point estimates with 95% CIs provided for between-
treatment differences in the proportion of participants with events.
Membership in Tier 2 requires that at least 4 participants in any treatment group exhibit the 
event; all other AEs and PDLCs will belong to Tier 3. The threshold of at least 4 events was 
chosen because the 95% CI for the between-group difference in percent incidence will 
always include zero when the treatment groups each have fewer than 4 events and thus would 
add little to the interpretation of potentially meaningful differences. Because many 95% CIs
may be provided without adjustment for multiplicity, the CIs should be regarded as a helpful 
descriptive measure to be used in review, not a formal method for assessing the statistical 
significance of the between-group differences in AEs and PDLCs.
In addition, summary measures of AEs consisting of the percentage of participants with any 
AE, with a drug-related AE, with an SAE, with an AE which is both drug-related and serious, 
who discontinued due to an AE, and who died will be considered Tier 2 endpoints.
For AEs prespecified for adjudication (cardiovascular, AVG thrombotic, bleeding events, 
and death), results of adjudication are also considered Tier 2 endpoints. 
The 95% CIs will be provided for between-treatment differences in the percentage of 
participants with each Tier 2 event; these analyses will be performed using the M&N
method.
Tier 3 Events
Safety endpoints that are not Tier 2 events will be considered Tier 3 events. Only point 
estimates by treatment group will be provided for Tier 3 safety parameters.
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Continuous Safety Measures
For continuous measures such as changes from baseline in laboratory and vital signs 
parameters, summary statistics for baseline, on treatment, and change from baseline values 
will be provided by treatment group.
Table 4
Analysis Strategy for Safety Parameters
Safety 
Tier
Safety Endpoint
P-Value for 
Treatment 
Comparison
95% CI for 
Treatment 
Comparison
Descriptive 
Statistics
Tier 1
Time to first ISTH major bleeding event or 
clinically relevant non-major bleeding event
(adjudicated)
X
X
X
Tier 2
Any AE
X
X
Any serious AE 
X
X
Any drug-related AE
X
X
Any serious and drug-related AE
X
X
Discontinuation due to AE
X
X
Death
Adjudicated major thrombotic CV events
Adjudicated AVG thrombotic events
Adjudicated ISTH major bleeding events
X
X
X
X
X
X
X
X
Specific AEs, SOCs, PDLCs (incidence ≥4 of 
participants in 1 of the treatment groups)
X
X
Tier 3
Specific AEs, SOCs, PDLCs (incidence <4 of 
participants in all the treatment groups)
X
Change from baseline results (laboratory tests, 
ECGs, vital signs) 
X
AE=adverse event; AVG=arteriovenous graft; CI=confidence interval; CV=cardiovascular; 
ECGs=electrocardiogram(s); ISTH=International Society on Thrombosis and Haemostasis; 
PDLC=predefined limit of change; SOC=system organ class; X=results will be provided.
9.7
Interim Analyses
A single IA will be performed to assess efficacy and futility (non-binding). The IA will be 
conducted by an external unblinded statistician and an external unblinded programmer not 
otherwise involved in study conduct. Results of the IA will be reviewed by the external 
DMC, with recommendations provided to an internal executive oversight committee. If the 
eDMC recommends modifications to the design of the study or discontinuation of the study, 
the executive committee (and potentially other limited sponsor personnel) may be unblinded 
to results at the treatment level in order to act on these recommendations. The extent to 
which individuals are unblinded with respect to results of the IA will be documented by the 
unblinded statistician. Additional logistical details will be provided in the eDMC Charter.
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CCI
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9.8
Multiplicity
At the IA and final analysis, there are 2 pairwise treatment group comparisons that may be 
made to test the primary hypothesis. 
CCI
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9.9
Sample Size and Power Calculations
9.9.1
Efficacy
An HR=0.6 is assumed for each MK-2060 vs placebo group comparison with respect to time 
to first occurrence of an AVG thrombosis event. This effect estimate is a conservative 
estimate based on published literature for pharmacological inhibition of FXa and FXIa. Large 
studies of FXa inhibitors compared to aspirin or placebo for prevention of DVT/PE in a high-
risk population reported HR 0.26 to 0.36 [Agnelli, G., et al 2013] [Weitz, J. I., et al 2017]. 
Smaller studies of pharmacological agents targeting FXI activity compared to enoxaparin for
prevention of DVTs in orthopedic surgical populations reported reductions in DVTs 
equivalent to RR 0.14 to 0.43 [Buller, H. R., et al 2015] [Weitz, J. I., et al 2020]
(conservative estimate based on a several placebo-controlled FXa studies).
The planned sample size is approximately 489 participants, with 163 participants in each 
group. If the true HR is 0.6, with approximately 103 and 171 first AVG thrombosis events 
among 3 groups at the planned IA and final analysis, respectively, the study will have 80% 
power at one-sided alpha = 0.025.
Power and interim analysis calculations were performed using R (“gsDesign” package).
9.9.2
Safety
Given the sample size of 163 per group, Table 8 provides examples of minimum differences 
in proportions in AEs between each MK-2060 dose and placebo that would have a 95% CI 
that excludes zero based on the M&N method.
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Table 8
Examples of AE Incidences for Which The 95% CI for the Difference Would 
Exclude Zero
MK-2060
n/N (%)
Placebo
n/N (%)
4/163 (2.5%)
9/163 (5.5%)
24/163 (14.7%)
0/163 (0.0%)
2/163 (1.2%)
12/163 (7.4%)
AE= adverse event; n=number of participants with an adverse event; N=population size.
Based on the M&N method
9.10
Subgroup Analyses
The primary efficacy endpoint will be summarized for each of the following baseline defined 
subgroups:

Region (US, non-US)

Previous thrombosis of active AVG (yes/no)

Regular aspirin use up to 150 mg daily at baseline (Yes or No)

Concurrent diagnosis of diabetes (type 1 or type 2) at the time of randomization 
(Yes or No)

Medical history of peripheral vascular disease (Yes or No)

Age (≥65 years vs <65 years)

Sex (male vs female)

Race (White, Black or African American, Asian, Other)
9.11
Compliance (Medication Adherence)
A participant’s percentage compliance will be calculated as the proportion of IV infusions 
over the total IV infusions they should have received. Summary statistics will be provided on 
percent compliance for the APaT population.  
9.12
Extent of Exposure
The extent of exposure will be summarized as duration of treatment in terms of number of IV 
infusions and duration of exposure defined as the time between first and last IV infusion. IV 
infusion interruption will be summarized. Summary statistics will be provided on extent of 
exposure for the APaT population.
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10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS
10.1
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1
Code of Conduct for Clinical Trials
Merck Sharp & Dohme LLC, Rahway, NJ, USA (MSD)
I. Introduction
A. Purpose
Merck Sharp & Dohme LLC, Rahway, NJ, USA (MSD), through its subsidiaries, conducts clinical trials 
worldwide to evaluate the safety and effectiveness of our products. As such, we are committed to designing, 
planning, conducting, analyzing, and reporting these trials in compliance with the highest ethical and scientific 
standards. Protection of participants in clinical trials is the overriding concern in the design and conduct of clinical 
trials. In all cases, MSD clinical trials will be conducted in compliance with MSD’s global standards, local and/or 
national regulations (including all applicable data protection laws and regulations), and International Council for 
Harmonisation Good Clinical Practice (ICH GCP) E6 and ICH General Considerations for Clinical Studies E8, 
and in accordance with the ethical principles that have their origin in the Declaration of Helsinki.
B. Scope
Highest ethical and scientific standards shall be endorsed for all clinical interventional investigations sponsored by 
MSD irrespective of the party (parties) employed for their execution (e.g., contract research organizations, 
collaborative research efforts). This Code is not intended to apply to trials that are observational in nature, or 
which are retrospective. Further, this Code does not apply to investigator-initiated trials, which are not under the 
full control of MSD.
II. Scientific Issues
A. Trial Conduct
1. Trial Design
Except for pilot or estimation trials, clinical trial protocols will be hypothesis-driven to assess safety, efficacy 
and/or pharmacokinetic or pharmacodynamic indices of MSD or comparator products. Alternatively, MSD 
may conduct outcomes research trials, trials to assess or validate various endpoint measures, or trials to 
determine patient preferences, etc.
The design (i.e., participant population, duration, statistical power) must be adequate to address the specific 
purpose of the trial and shall respect the data protection rights of all participants, trial site staff and, where 
applicable, third parties. All trial protocols are and will be assessed for the need and capability to enroll 
underrepresented groups. Participants must meet protocol entry criteria to be enrolled in the trial. 
2. Site Selection
MSD’s clinical trials are conducted globally in many different countries and in diverse populations, including 
people of varying age, race, ethnicity, gender, and accounting for other potential disease related factors. MSD 
selects investigative sites based on medical expertise, access to appropriate participants, adequacy of facilities 
and staff, previous performance in clinical trials, as well as budgetary considerations. Prior to trial initiation, 
sites are evaluated by MSD personnel (or individuals acting on behalf of MSD) to assess the ability to 
successfully conduct the trial.
Where appropriate, and in accordance with regulatory authority guidance, MSD will make concerted efforts 
to raise awareness of clinical trial opportunities in various communities. MSD will seek to engage 
underrepresented groups and those disproportionately impacted by the disease under study.  MSD will 
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support clinical trial investigators to enroll underrepresented groups and expand access to those who will 
ultimately use the products under investigation.
3. Site Monitoring/Scientific Integrity
Investigative trial sites are monitored to assess compliance with the trial protocol and Good Clinical Practice 
(GCP). MSD reviews clinical data for accuracy, completeness, and consistency. Data are verified versus 
source documentation according to standard operating procedures. Per MSD policies and procedures, if
potential fraud, scientific/research misconduct, privacy incidents/breaches or Clinical Trial-related 
Significant Quality Issues are reported, such matters are investigated. When necessary, appropriate corrective 
and/or preventative actions are defined and regulatory authorities and/or ethics review committees are 
notified.
B. Publication and Authorship
Regardless of trial outcome, MSD commits to publish the primary and secondary results of its registered trials of 
marketed products in which treatment is assigned, according to the pre-specified plans for data analysis. To the 
extent scientifically appropriate, MSD seeks to publish the results of other analyses it conducts that are important 
to patients, physicians, and payers. Some early phase or pilot trials are intended to be hypothesis-generating rather 
than hypothesis testing; in such cases, publication of results may not be appropriate since the trial may be 
underpowered and the analyses complicated by statistical issues such as multiplicity.
MSD’s policy on authorship is consistent with the recommendations published by the International Committee of 
Medical Journal Editors (ICMJE). In summary, authorship should reflect significant contribution to the design and 
conduct of the trial, performance or interpretation of the analysis, and/or writing of the manuscript. All named 
authors must be able to defend the trial results and conclusions. MSD funding of a trial will be acknowledged in 
publications.
III. Participant Protection
A. Regulatory Authority and Ethics Committee Review (Institutional Review Board [IRB]/Independent Ethics 
Committee [IEC])
All protocols and protocol amendments will be submitted by MSD for regulatory authority 
acceptance/authorization prior to implementation of the trial or amendment, in compliance with local and/or 
national regulations.
The protocol, protocol amendment(s), informed consent form, investigator’s brochure, and other relevant trial 
documents must be reviewed and approved by an IRB/IEC before being implemented at each site, in compliance 
with local and/or national regulations. Changes to the protocol that are required urgently to eliminate an 
immediate hazard and to protect participant safety may be enacted in anticipation of ethics committee approval. 
MSD will inform regulatory authorities of such new measures to protect participant safety, in compliance with 
local and/or national regulations.
B. Safety
The guiding principle in decision-making in clinical trials is that participant welfare is of primary importance. 
Potential participants will be informed of the risks and benefits of, as well as alternatives to, trial participation. At 
a minimum, trial designs will take into account the local standard of care.
All participation in MSD clinical trials is voluntary. Participants enter the trial only after informed consent is 
obtained. Participants may withdraw from an MSD trial at any time, without any influence on their access to, or
receipt of, medical care that may otherwise be available to them.
C. Confidentiality
MSD is committed to safeguarding participant confidentiality, to the greatest extent possible, as well as all 
applicable data protection rights. Unless required by law, only the investigator, Sponsor (or individuals acting on 
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behalf of MSD), ethics committee, and/or regulatory authorities will have access to confidential medical records 
that might identify the participant by name.
D. Genomic Research
Genomic research will only be conducted in accordance with a protocol and informed consent authorized by an 
ethics committee.
IV. Financial Considerations
A. Payments to Investigators
Clinical trials are time- and labor-intensive. It is MSD’s policy to compensate investigators (or the sponsoring 
institution) in a fair manner for the work performed in support of MSD trials. MSD does not pay incentives to 
enroll participants in its trials. However, when enrollment is particularly challenging, additional payments may be 
made to compensate for the time spent in extra recruiting efforts.
MSD does not pay for participant referrals. However, MSD may compensate referring physicians for time spent 
on chart review and medical evaluation to identify potentially eligible participants.
B. Clinical Research Funding
Informed consent forms will disclose that the trial is sponsored by MSD, and that the investigator or sponsoring 
institution is being paid or provided a grant for performing the trial. However, the local ethics committee may 
wish to alter the wording of the disclosure statement to be consistent with financial practices at that institution. As 
noted above, all publications resulting from MSD trials will indicate MSD as a source of funding.
C. Funding for Travel and Other Requests
Funding of travel by investigators and support staff (e.g., to scientific meetings, investigator meetings, etc.) will be 
consistent with local guidelines and practices.
V. Investigator Commitment
Investigators will be expected to review MSD’s Code of Conduct as an appendix to the trial protocol, and in signing the 
protocol, agree to support these ethical and scientific standards.
10.1.2
Financial Disclosure
Financial Disclosure requirements are outlined in the US Food and Drug Administration 
Regulations, Financial Disclosure by Clinical Investigators (21 CFR Part 54). It is the 
Sponsor's responsibility to determine, based on these regulations, whether a request for 
Financial Disclosure information is required. It is the investigator's/subinvestigator's 
responsibility to comply with any such request.
The investigator/subinvestigator(s) agree, if requested by the Sponsor in accordance with 21 
CFR Part 54, to provide his/her financial interests in and/or arrangements with the Sponsor to 
allow for the submission of complete and accurate certification and disclosure statements. 
The investigator/subinvestigator(s) further agree to provide this information on a 
Certification/Disclosure Form, commonly known as a financial disclosure form, provided by 
the Sponsor. The investigator/subinvestigator(s) also consent to the transmission of this 
information to the Sponsor in the United States for these purposes. This may involve the 
transmission of information to countries that do not have laws protecting personal data.
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10.1.3
Data Protection
The Sponsor will conduct this study in compliance with all applicable data protection 
regulations.
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names 
or any information that would make the participant identifiable will not be transferred.
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
10.1.3.1
Confidentiality of Data
By signing this protocol, the investigator affirms to the Sponsor that information furnished to 
the investigator by the Sponsor will be maintained in confidence, and such information will 
be divulged to the IRB, IEC, or similar or expert committee; affiliated institution and 
employees, only under an appropriate understanding of confidentiality with such board or 
committee, affiliated institution and employees. Data generated by this study will be 
considered confidential by the investigator, except to the extent that it is included in a 
publication as provided in the Publications section of this protocol.
10.1.3.2
Confidentiality of Participant Records
By signing this protocol, the investigator agrees that the Sponsor (or Sponsor representative), 
IRB/IEC, or regulatory authority representatives may consult and/or copy study documents to 
verify worksheet/CRF data. By signing the consent form, the participant agrees to this 
process. If study documents will be photocopied during the process of verifying 
worksheet/CRF information, the participant will be identified by unique code only; full 
names/initials will be masked prior to transmission to the Sponsor.
By signing this protocol, the investigator agrees to treat all participant data used and 
disclosed in connection with this study in accordance with all applicable privacy laws, rules 
and regulations.
10.1.3.3
Confidentiality of IRB/IEC Information
The Sponsor is required to record the name and address of each IRB/IEC that reviews and 
approves this study. The Sponsor is also required to document that each IRB/IEC meets 
regulatory and ICH GCP requirements by requesting and maintaining records of the names 
and qualifications of the IRB/IEC members and to make these records available for 
regulatory agency review upon request by those agencies.
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10.1.4
Committees Structure
10.1.4.1
Executive Oversight Committee
The EOC is comprised of members of the therapeutic area management. The EOC will 
receive and decide on any recommendations made by the DMC regarding the study.
10.1.4.2
External DMC
To supplement the routine study monitoring outlined in this protocol, an external DMC will 
monitor the safety and efficacy data throughout the study. The voting members of the DMC 
are external to the Sponsor. The members of the DMC must not be involved in the study in 
any other way (eg, they cannot be study investigators) and must have no competing interests 
that could affect their role with respect to the study. The DMC will monitor the study at an 
appropriate frequency for evidence of adverse effects to study intervention and for evidence 
of efficacy and futility at the interim analysis (see Section 9.7), to be detailed in monitoring 
guidelines. 
The DMC will recommend whether the study should continue (or other modifications, 
prespecified or otherwise, should be made) according to the protocol, considering the overall 
risk and benefit to study participants. The DMC will make recommendations to the EOC
regarding steps to ensure both participant safety and the continued ethical integrity of the 
study. 
Specific details regarding the DMC’s composition, responsibilities, and governance structure,
including roles, responsibilities of various members, meeting facilitation, required 
documentation of DMC reports, and recommendations will be described in a separate charter 
that is reviewed and approved by the external DMC.
10.1.4.3
Clinical Adjudication Committee
A CAC will evaluate the following events for the purposes of confirming them according to 
the criteria in Sections 4.2.1.1 and 4.2.1.3, as well as evaluating the presence of confounding 
factors:
1. AVG thrombosis 
2. Major thrombotic CV events
3. Bleeding events
4. Deaths
All personnel involved in the adjudication process will remain blinded to study intervention 
allocation throughout the study. The CAC will be comprised of an external panel of 
independent physicians experienced in assessing AVG thrombosis, CV events, and bleeding
events. The members of the CAC will not be investigators in the MK-2060 study.
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Criteria to define all these events will be detailed in the CAC charter. 
10.1.4.4
Scientific Advisory Committee
This study was developed in collaboration with a SAC. The SAC is comprised of both 
Sponsor and non-Sponsor scientific experts who provide input with respect to study design, 
interpretation of study results, and subsequent peer-reviewed scientific publications.
10.1.5
Publication Policy
The results of this study may be published or presented at scientific meetings. The Sponsor 
will comply with the requirements for publication of study results. In accordance with 
standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement.
If publication activity is not directed by the Sponsor, the investigator agrees to submit all 
manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect 
proprietary information and to provide comments.
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements.
10.1.6
Compliance with Study Registration and Results Posting Requirements
Under the terms of the FDAAA of 2007 and the EMA clinical trial Directive 2001/20/EC, the 
Sponsor of the study is solely responsible for determining whether the study and its results 
are subject to the requirements for submission to http://www.clinicaltrials.gov, 
www.clinicaltrialsregister.eu or other local registries. MSD, as Sponsor of this study, will 
review this protocol and submit the information necessary to fulfill these requirements. MSD 
entries are not limited to FDAAA or the EMA clinical trial directive mandated trials. 
Information posted will allow participants to identify potentially appropriate studies for their 
disease conditions and pursue participation by calling a central contact number for further 
information on appropriate study locations and study site contact information.
By signing this protocol, the investigator acknowledges that the statutory obligations under 
FDAAA, the EMA clinical trials directive, or other locally mandated registries are that of the 
Sponsor and agrees not to submit any information about this study or its results to those 
registries.
10.1.7
Compliance with Law, Audit, and Debarment
By signing this protocol, the investigator agrees to conduct the study in an efficient and 
diligent manner and in conformance with this protocol; generally accepted standards of GCP
(eg, International Council on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use GCP: Consolidated Guideline and other generally accepted 
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standards of GCP); and all applicable federal, state and local laws, rules and regulations 
relating to the conduct of the clinical study.
The Code of Conduct, a collection of goals and considerations that govern the ethical and 
scientific conduct of clinical investigations sponsored by MSD, is provided in this appendix 
under the Code of Conduct for Clinical Trials.
The investigator agrees not to seek reimbursement from participants, their insurance 
providers, or from government programs for procedures included as part of the study 
reimbursed to the investigator by the Sponsor.
The investigator will promptly inform the Sponsor of any regulatory authority inspection 
conducted for this study.
The investigator agrees to provide the Sponsor with relevant information from inspection 
observations/findings to allow the Sponsor to assist in responding to any citations resulting 
from regulatory authority inspection and will provide the Sponsor with a copy of the 
proposed response for consultation before submission to the regulatory authority. 
Persons debarred from conducting or working on clinical studies by any court or regulatory 
authority will not be allowed to conduct or work on this Sponsor’s studies. The investigator 
will immediately disclose in writing to the Sponsor if any person who is involved in 
conducting the study is debarred or if any proceeding for debarment is pending or, to the best 
of the investigator’s knowledge, threatened.
10.1.8
Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The investigator 
or qualified designee is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF.
Detailed information regarding Data Management procedures for this protocol will be 
provided separately.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.
Study documentation will be promptly and fully disclosed to the Sponsor by the investigator 
upon request and also shall be made available at the study site upon request for inspection, 
copying, review, and audit at reasonable times by representatives of the Sponsor or any 
regulatory authorities. The investigator agrees to promptly take any reasonable steps that are 
requested by the Sponsor or any regulatory authorities as a result of an audit or inspection to 
cure deficiencies in the study documentation and worksheets/CRFs.
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The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data.
Study monitors will perform ongoing source data review and verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that the 
study is being conducted in accordance with the currently approved protocol and any other 
study agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including participants’ documented informed consent, pertaining to 
the conduct of this study must be retained by the investigator for 15 years after study 
completion unless local regulations or institutional policies require a longer retention period. 
No records may be destroyed during the retention period without the written approval of the 
Sponsor. No records may be transferred to another location or party without written 
notification to the Sponsor.
10.1.9
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. The investigator/institution should maintain adequate and 
accurate source documents and study records that include all pertinent observations on each 
of the site’s participants. Source documents and data should be attributable, legible, 
contemporaneous, original, accurate, and complete. Changes to source data should be 
traceable, should not obscure the original entry, and should be explained if necessary (eg, via 
an audit trail). Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator/institution may need to request previous medical records or transfer records, 
depending on the study. Also, current medical records must be available.
10.1.10
Study and Site Closure
The Sponsor or its designee may stop the study or study site participation in the study for 
medical, safety, regulatory, administrative, or other reasons consistent with applicable laws, 
regulations, and GCP.
In the event the Sponsor prematurely terminates a particular study site, the Sponsor or 
designee will promptly notify that study site’s IRB/IEC as specified by applicable regulatory 
requirement(s).
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10.2
Appendix 2: Clinical Laboratory Tests
The tests detailed in Table 9 will be performed by the central laboratory. Local laboratories 
can be used at Screening. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol.
Additional tests may be performed at any time during the study as determined necessary by 
the investigator or required by local regulations.
Table 9
Protocol-required Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet count 
RBC indices:
MCV
MCH
%Reticulocytes
WBC count with 
differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
RBC count
Hemoglobin
Hematocrit
Chemistry
Nitrogen (BUN)
AST/ SGOT
Total bilirubin (and direct 
bilirubin, if total bilirubin is 
elevated above the ULN)
Albumin
Bicarbonate
Chloride
Potassium
Sodium
ALT/ SGPT
Glucose 
Calcium
Alkaline phosphatase
Total Protein
Phosphorous
Other Tests

FSH (as needed for WOCBP)

Serum hCG pregnancy test (as needed for WOCBP)

Immunogenicity assay (ADA)

Coagulation test: INR, PT, aPTT

Factor XI activity

Serology (HIV antibody, hepatitis B surface antigen, and hepatitis C virus 
antibody) 
ADA= anti-drug antibodies; ALT= alanine aminotransferase; aPTT= activated partial thromboplastin time; 
AST= aspartate aminotransferase; BUN= blood urea nitrogen; FSH= follicle stimulating hormone; hCG= 
human chorionic antigen; HIV= human immunodeficiency virus; MCH= mean corpuscular hemoglobin; 
MCV= mean corpuscular volume; PT= prothrombin time; RBC= red blood cells; SGOT= serum glutamic-
oxaloacetic transaminase; SGPT= serum glutamic-pyruvic transaminase; ULN= upper limit of normal; 
WBC= white blood cells; WOCBP= women of childbearing potential. 
The investigator (or medically qualified designee) must document their review of each 
laboratory safety report.
Coagulation test results such as PT, INR, and aPTT need to remain blinded to the site and 
Sponsor staff involved in the study. Laboratory results that could unblind the study will not 
be reported to investigative sites or other blinded personnel until the study has been 
unblinded.
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10.3
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1
Definition of AE
AE definition
    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.
    NOTE: 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.
    NOTE: For purposes of AE definition, study intervention includes any pharmaceutical 
product, biological product, vaccine, diagnostic agent, medical device, combination 
product, or protocol specified procedure whether investigational or marketed (including 
placebo, active comparator product, or run-in intervention), manufactured by, licensed 
by, provided by, or distributed by the Sponsor for human use in this study.
Events meeting the AE definition
    Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the investigator.
    Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
    New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.
    Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
    Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.
    For all reports of overdose (whether accidental or intentional) with an associated AE, the 
AE term should reflect the clinical symptoms or abnormal test result. An overdose 
without any associated clinical symptoms or abnormal laboratory results is reported using 
the terminology “accidental or intentional overdose without adverse effect.”
•
Any new cancer or progression of existing cancer.
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Events NOT meeting the AE definition
    Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.
    Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
    Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
    Surgery planned prior to informed consent to treat a pre-existing condition that has not 
worsened.
    Refer to Section 8.4.6 for protocol-specific exceptions.
10.3.2
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met.
An SAE is defined as any untoward medical occurrence that, at any dose:
a.   Results in death
b.   Is life-threatening

The term “life-threatening” in the definition of “serious” refers to an event in which 
the participant was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe.
c.   Requires inpatient hospitalization or prolongation of existing hospitalization

Hospitalization is defined as an inpatient admission, regardless of length of stay, even 
if the hospitalization is a precautionary measure for continued observation. (Note: 
Hospitalization for an elective procedure to treat a pre-existing condition that has not 
worsened is not an SAE.) A pre-existing condition is a clinical condition that is 
diagnosed prior to the use of an MSD product and is documented in the participant’s 
medical history.
d.   Results in persistent or significant disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
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and accidental trauma (eg, sprained ankle) that may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.   Is a congenital anomaly/birth defect

In offspring of participant taking the product regardless of time to diagnosis.
f.   Other important medical events

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that may 
not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 1 
of the other outcomes listed in the above definition. These events should usually be 
considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse.
10.3.3
Additional Events Reported
Additional events that require reporting
In addition to the above criteria, AEs meeting either of the below criteria, although not 
serious per ICH definition, are reportable to the Sponsor.

Is a cancer

Is associated with an overdose
10.3.4
Recording AE and SAE
AE and SAE recording
    When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory, and diagnostics reports) related to 
the event.
    The investigator will record all relevant AE/SAE information on the AE 
CRFs/worksheets at each examination.
    It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to the Sponsor in lieu of completion of the AE CRF page.
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    There may be instances when copies of medical records for certain cases are requested by 
the Sponsor. In this case, all participant identifiers, with the exception of the participant 
number, will be blinded on the copies of the medical records before submission to the 
Sponsor.
    The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of intensity
    An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, not when it is rated as severe.
•
The investigator will make an assessment of intensity for each AE and SAE (and other 
reportable safety event) reported during the study and assign it to 1 of the following 
categories:
- Mild: An event that is easily tolerated by the participant, causing minimal discomfort, 
and not interfering with everyday activities (for pediatric studies, awareness of 
symptoms, but easily tolerated).
- Moderate: An event that causes sufficient discomfort to interfere with normal 
everyday activities (for pediatric studies, definitely acting like something is wrong).
- Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. Severe is a category used for rating the 
intensity of an event; and both AE and SAE can be assessed as severe (for pediatric 
studies, extremely distressed or unable to do usual activities).
Assessment of causality
•
Did the study intervention cause the AE?
•
The determination of the likelihood that the study intervention caused the AE will be 
provided by an investigator who is a qualified physician. The investigator’s signed/dated 
initials on the source document or worksheet that supports the causality noted on the AE 
form, ensures that a medically qualified assessment of causality was done. This initialed 
document must be retained for the required regulatory time frame. The criteria below are 
intended as reference guidelines to assist the investigator in assessing the likelihood of a 
relationship between the test product and the AE based upon the available information.
•
The following components are to be used to assess the relationship between the 
study intervention and the AE; the greater the correlation with the components and 
their respective elements (in number and/or intensity), the more likely the study 
intervention caused the AE:
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- Exposure: Is there evidence that the participant was actually exposed to the study 
intervention such as: reliable history, acceptable compliance assessment (pill count, 
diary, etc.), expected pharmacologic effect, or measurement of drug/metabolite in 
bodily specimen?
- Time Course: Did the AE follow in a reasonable temporal sequence from 
administration of the study intervention? Is the time of onset of the AE compatible 
with a drug-induced effect (applies to studies with investigational medicinal 
product)?
- Likely Cause: Is the AE not reasonably explained by another etiology such as 
underlying disease, other drug(s)/vaccine(s), or other host or environmental factors.
- Dechallenge: Was the study intervention discontinued or dose/exposure/frequency 
reduced?
◦
If yes, did the AE resolve or improve?
◦
If yes, this is a positive dechallenge.
◦
If no, this is a negative dechallenge.
(Note: This criterion is not applicable if: (1) the AE resulted in death or permanent 
disability; (2) the AE resolved/improved despite continuation of the study 
intervention; (3) the study is a single-dose drug study; or (4) study intervention(s) 
is/are only used 1 time.)
- Rechallenge: Was the participant re-exposed to the study intervention in this study?
◦
If yes, did the AE recur or worsen?
◦
If yes, this is a positive rechallenge.
◦
If no, this is a negative rechallenge.
(Note: This criterion is not applicable if: (1) the initial AE resulted in death or 
permanent disability, or (2) the study is a single-dose drug study; or (3) study 
intervention(s) is/are used only 1 time.)
NOTE: IF A RECHALLENGE IS PLANNED FOR AN AE THAT WAS SERIOUS AND 
MAY HAVE BEEN CAUSED BY THE STUDY INTERVENTION, OR IF RE-
EXPOSURE TO THE STUDY INTERVENTION POSES ADDITIONAL POTENTIAL 
SIGNIFICANT RISK TO THE PARTICIPANT THEN THE RECHALLENGE MUST BE 
APPROVED IN ADVANCE BY THE SPONSOR CLINICAL DIRECTOR, AND IF 
REQUIRED, THE IRB/IEC.
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•
Consistency with study intervention profile: Is the clinical/pathological presentation of 
the AE consistent with previous knowledge regarding the study intervention or drug class 
pharmacology or toxicology?
•
The assessment of relationship will be reported on the case report forms/worksheets by 
an investigator who is a qualified physician according to his/her best clinical judgment, 
including consideration of the above elements.
•
Use the following scale of criteria as guidance (not all criteria must be present to be 
indicative of a study intervention relationship).
- Yes, there is a reasonable possibility of study intervention relationship:
◦
There is evidence of exposure to the study intervention. The temporal sequence 
of the AE onset relative to the administration of the study intervention is 
reasonable. The AE is more likely explained by the study intervention than by 
another cause.
- No, there is not a reasonable possibility of study intervention relationship:
◦
Participant did not receive the study intervention OR temporal sequence of the 
AE onset relative to administration of the study intervention is not reasonable 
OR the AE is more likely explained by another cause than the study 
intervention. (Also entered for a participant with overdose without an associated 
AE.)
•
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.
•
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important 
that the investigator always make an assessment of causality for every event before the 
initial transmission of the SAE data to the Sponsor.
•
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.
•
The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements.
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Follow-up of AE and SAE
    The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Sponsor to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals.
    New or updated information will be recorded in the CRF.
    The investigator will submit any updated SAE data to the Sponsor within 24 hours of 
receipt of the information.
10.3.5
Reporting of AEs, SAEs, and Other Reportable Safety Events to the Sponsor
AE, SAE, and other reportable safety event reporting to Sponsor via electronic data 
collection tool
    The primary mechanism for reporting to the Sponsor will be the EDC tool.
-
Electronic reporting procedures can be found in the EDC data entry guidelines (or 
equivalent).
-
If the electronic system is unavailable for more than 24 hours, then the site will 
use the paper AE Reporting form.
◦
Reference Section 8.4.1 for reporting time requirements.
    The site will enter the SAE data into the electronic system as soon as it becomes 
available.
    After the study is completed at a given site, the EDC tool will be taken off-line to prevent 
the entry of new data or changes to existing data.
    If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the EDC tool has been taken off-line, then the site can 
report this information on a paper SAE form or by telephone (see next section).
    Contacts for SAE reporting can be found in the Investigator Study File Binder (or 
equivalent).
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SAE reporting to the Sponsor via paper CRF
    If the EDC tool is not operational, facsimile transmission or secure e-mail of the SAE 
paper CRF is the preferred method to transmit this information to the Sponsor.
    In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service.
    Initial notification via telephone does not replace the need for the investigator to complete 
and sign the SAE CRF pages within the designated reporting time frames.
    Contacts and instructions for SAE reporting and paper reporting procedures can be found 
in the Investigator Study File Binder (or equivalent).
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10.4
Appendix 4: Device Events, Adverse Device Events, and Medical Device 
Incidents: Definitions, Collection, and Documentation
Not applicable. 
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10.5
Appendix 5: Contraceptive Guidance
10.5.1
Definitions
Women of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below):
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:

Premenarchal

Premenopausal female with 1 of the following:
- Documented hysterectomy
- Documented bilateral salpingectomy
- Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than the 
above (eg, Mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview.

Postmenopausal female
- A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.
◦
A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or HRT. 
However, in the absence of 12 months of amenorrhea, confirmation with two 
FSH measurements in the postmenopausal range is required.
- Females on HRT and whose menopausal status is in doubt will be required to use one 
of the nonhormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment.
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Women of Nonchildbearing Potential (WONCBP)
Women in the following categories are considered WONCBP:

Premenopausal female with 1 of the following:
- Documented hysterectomy
- Documented bilateral salpingectomy
- Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than the 
above (eg, Mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview.

Postmenopausal female
- A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
◦
A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or HRT. 
However, in the absence of 12 months of amenorrhea, confirmation with two 
FSH measurements in the postmenopausal range is required. 
- Females on HRT and whose menopausal status is in doubt must discontinue HRT to 
allow confirmation of postmenopausal status before study enrollment.
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10.5.2
Contraception Requirements
Contraceptives allowed during the study includea:
Highly Effective Contraceptive Methods That Have Low User Dependencyb
Failure rate of <1% per year when used consistently and correctly.

Progestogen- only contraceptive implantc,d

IUSc,e

Non-hormonal IUD

Bilateral tubal occlusion

Azoospermic partner (vasectomized or secondary to medical cause)
This is a highly effective contraception method provided that the partner is the sole male sexual 
partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly 
effective method of contraception should be used. A spermatogenesis cycle is approximately 90 days.
Note: Documentation of azoospermia can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview.
Highly Effective Contraceptive Methods That Are User Dependentb
Failure rate of <1% per year when used consistently and correctly.

Combined (estrogen- and progestogen- containing) hormonal contraceptionc,d
- Oral
- Intravaginal
- Transdermal
- Injectable

Progestogen-only hormonal contraceptionc,d
- Oral
- Injectable
Sexual Abstinence

Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the participant.
Acceptable Contraceptive Methods
Failure rate of >1% per year when used consistently and correctly.

Progesterone-only hormonal contraception where inhibition of ovulation is not the primary mode of 
action

Male or female condom with or without spermicide

Cervical cap, diaphragm, or sponge with spermicide

A combination of male condom with either cervical cap, diaphragm, or sponge with spermicide 
(double barrier methods)f
a   Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for participants of clinical studies.
b   Typical use failure rates are higher than perfect-use failure rates (ie, when used consistently and correctly).
c   Male condoms must be used in addition to hormonal contraception.
d   If locally required, in accordance with CTFG guidelines, acceptable contraceptive implants are limited to 
those which inhibit ovulation.
e   IUS is a progestin releasing IUD.
f   A combination of male condom with either cap, diaphragm, or sponge with spermicide are considered 
acceptable, but not highly effective, birth control methods.
Note: The following are not acceptable methods of contraception:
-  Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and LAM.
-  Male and female condom should not be used together (due to risk of failure with friction).
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10.6
Appendix 6: Collection and Management of Specimens for Future Biomedical 
Research
1.  Definitions
a.   Biomarker: A biological molecule found in blood, other body fluids, or tissues that is a 
sign of a normal or abnormal process or of a condition or disease. A biomarker may be 
used to see how well the body responds to a treatment for a disease or condition.1
b   Pharmacogenomics: The investigation of variations of DNA and RNA characteristics as 
related to drug/vaccine response.2
c.   Pharmacogenetics: A subset of pharmacogenomics, pharmacogenetics is the influence of 
variations in DNA sequence on drug/vaccine response.2
d.   DNA: Deoxyribonucleic acid.
e.   RNA: Ribonucleic acid.
2.  Scope of Future Biomedical Research3,4
The specimens consented and/or collected in this study as outlined in Section 8.10 will be 
used in various experiments to understand:
◦
The biology of how drugs/vaccines work
◦
Biomarkers responsible for how a drug/vaccine enters and is removed by the body
◦
Other pathways with which drugs/vaccines may interact
◦
The biology of disease
The specimen(s) may be used for future assay development and/or drug/vaccine 
development.
It is now well recognized that information obtained from studying and testing clinical 
specimens offers unique opportunities to enhance our understanding of how individuals 
respond to drugs/vaccines, enhance our understanding of human disease and ultimately 
improve public health through development of novel treatments targeted to populations 
with the greatest need. All specimens will be used by the Sponsor or those working for or 
with the Sponsor.
3.  Summary of Procedures for Future Biomedical Research3,4
a.   Participants for Enrollment
All participants enrolled in the clinical study will be considered for enrollment in future 
biomedical research.
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b.   Informed Consent
Informed consent for specimens (ie, DNA, RNA, protein, etc.) will be obtained during 
screening for protocol enrollment from all participants or legal guardians, at a study visit 
by the investigator or his or her designate. Informed consent for future biomedical 
research should be presented to the participants on the visit designated in the SoA. If 
delayed, present consent at next possible Participant Visit. Consent forms signed by the 
participant will be kept at the clinical study site under secure storage for regulatory 
reasons.
A template of each study site’s approved informed consent will be stored in the Sponsor’s 
clinical document repository.
c.   eCRF Documentation for Future Biomedical Research Specimens
Documentation of participant consent for future biomedical research will be captured in 
the eCRFs. Any specimens for which such an informed consent cannot be verified will be 
destroyed.
d.   Future Biomedical Research Specimen(s)
Collection of specimens for future biomedical research will be performed as outlined in 
the SoA. In general, if additional blood specimens are being collected for future 
biomedical research, these will usually be obtained at a time when the participant is 
having blood drawn for other study purposes.
4.  Confidential Participant Information for Future Biomedical Research3,4
In order to optimize the research that can be conducted with future biomedical research 
specimens, it is critical to link participants' clinical information with future test results. In 
fact, little or no research can be conducted without connecting the clinical study data to 
the specimen. The clinical data allow specific analyses to be conducted. Knowing 
participant characteristics like sex, age, medical history and intervention outcomes are 
critical to understanding clinical context of analytical results.
To maintain privacy of information collected from specimens obtained for future 
biomedical research, the Sponsor has developed secure policies and procedures. All 
specimens will be single-coded per ICH E15 guidelines as described below.
At the clinical study site, unique codes will be placed on the future biomedical research 
specimens. This code is a random number which does not contain any personally 
identifying information embedded within it. The link (or key) between participant 
identifiers and this unique code will be held at the study site. No personal identifiers will 
appear on the specimen tube.
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5.  Biorepository Specimen Usage3,4
Specimens obtained for the Sponsor will be used for analyses using good scientific 
practices. Analyses utilizing the future biomedical research specimens may be performed 
by the Sponsor, or an additional third party (eg, a university investigator) designated by 
the Sponsor. The investigator conducting the analysis will follow the Sponsor’s privacy 
and confidentiality requirements. Any contracted third party analyses will conform to the 
specific scope of analysis outlined in future biomedical research protocol and consent. 
Future biomedical research specimens remaining with the third party after specific 
analysis is performed will be reported to the Sponsor.
6.  Withdrawal From Future Biomedical Research3,4
Participants may withdraw their consent for future biomedical research and ask that their 
biospecimens not be used for future biomedical research. Participants may withdraw 
consent at any time by contacting the investigator for the main study. If medical records 
for the main study are still available, the investigator will contact the Sponsor using the 
designated mailbox (clinical.specimen.management@MSD.com). Subsequently, the 
participant's specimens will be flagged in the biorepository and restricted to main study 
use only. If specimens were collected from study participants specifically for future 
biomedical research, these specimens will be removed from the biorepository and 
destroyed. Documentation will be sent to the investigator confirming withdrawal and/or 
destruction, if applicable. It is the responsibility of the investigator to inform the 
participant of completion of the withdrawal and/or destruction, if applicable. Any 
analyses in progress at the time of request for withdrawal/destruction or already 
performed prior to the request being received by the Sponsor will continue to be used as 
part of the overall research study data and results. No new analyses would be generated 
after the request is received.
In the event that the medical records for the main study are no longer available (eg, if the 
investigator is no longer required by regulatory authorities to retain the main study 
records) or the specimens have been completely anonymized, there will no longer be a 
link between the participant’s personal information and their specimens. In this situation, 
the request for withdrawal of consent and/or destruction cannot be processed.
7.  Retention of Specimens3,4
Future biomedical research specimens will be stored in the biorepository for potential 
analysis for up to 20 years from the end of the main study. Specimens may be stored for 
longer if a regulatory or governmental authority has active questions that are being 
answered. In this special circumstance, specimens will be stored until these questions 
have been adequately addressed.
Specimens from the study site will be shipped to a central laboratory and then shipped to 
the Sponsor-designated biorepository. If a central laboratory is not utilized in a particular 
study, the study site will ship directly to the Sponsor-designated biorepository. The 
specimens will be stored under strict supervision in a limited access facility which 
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operates to assure the integrity of the specimens. Specimens will be destroyed according 
to Sponsor policies and procedures and this destruction will be documented in the 
biorepository database.
8.  Data Security3,4
Databases containing specimen information and test results are accessible only to the 
authorized Sponsor representatives and the designated study administrator research 
personnel and/or collaborators. Database user authentication is highly secure, and is 
accomplished using network security policies and practices based on international 
standards to protect against unauthorized access.
9.  Reporting of Future Biomedical Research Data to Participants3,4
No information obtained from exploratory laboratory studies will be reported to the 
participant, family, or physicians. Principle reasons not to inform or return results to the 
participant include: Lack of relevance to participant health, limitations of predictive 
capability, and concerns regarding misinterpretation.
If important research findings are discovered, the Sponsor may publish results, present 
results in national meetings, and make results accessible on a public website in order to 
rapidly report this information to doctors and participants. Participants will not be 
identified by name in any published reports about this study or in any other scientific 
publication or presentation.
10. Future Biomedical Research Study Population3,4
Every effort will be made to recruit all participants diagnosed and treated on Sponsor 
clinical studies for future biomedical research.
11. Risks Versus Benefits of Future Biomedical Research3,4
For future biomedical research, risks to the participant have been minimized and are 
described in the future biomedical research informed consent.
The Sponsor has developed strict security, policies, and procedures to address participant 
data privacy concerns. Data privacy risks are largely limited to rare situations involving 
possible breach of confidentiality. In this highly unlikely situation, there is risk that the 
information, like all medical information, may be misused.
12. Questions
Any questions related to the future biomedical research should be emailed directly to 
clinical.specimen.management@MSD.com.
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13. References
1.  National Cancer Institute [Internet]: Available from 
https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45618
2.   International Council on Harmonisation [Internet]: E15: Definitions for Genomic 
Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding 
Categories. Available from http://www.ich.org/products/guidelines/efficacy/efficacy-
single/article/definitions-for-genomic-biomarkers-pharmacogenomics-pharmacogenetics-
genomic-data-and-sample-cod.html 
3.   Industry Pharmacogenomics Working Group [Internet]: Understanding the Intent, Scope 
and Public Health Benefits of Exploratory Biomarker Research: A Guide for IRBs/IECs 
and Investigational Site Staff. Available at http://i-pwg.org/ 
4.  Industry Pharmacogenomics Working Group [Internet]: Pharmacogenomics 
Informational Brochure for IRBs/IECs and Investigational Site Staff. Available at http://i-
pwg.org/
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10.7
Appendix 7: Country-specific Requirements
10.7.1
Country-specific Requirements for Germany
Section 1.3 and Section 8.3.5.1
Pregnancy testing for participants in Germany must be performed prior to randomization, 
monthly during treatment phase, at the end of study intervention, and monthly for 120 days
after the end of study intervention.
10.7.2
Country-specific Requirements for Canada
Section 5.2 Exclusion Criteria
Exclusion criterion: Participants will rare conditions that may predispose them to 
catastrophic bleeding events are excluded from this study.
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10.8
Appendix 8: PK Substudy
The PK substudy will be available to all study sites. Sites should ask all main study 
participants to enter into the PK substudy and enroll those that consent. The PK substudy will 
enroll approximately 100 participants. The substudy will serve to improve the accuracy of the 
PK modeling for MK-2060 in individuals with ESRD on hemodialysis. Participants in the PK 
substudy will have PK samples collected in the main study (SoA, Section 1.3) and will have 
additional blood sampling collected for PK analysis (Table 10). Further details will be 
specified in a separate Site Procedure Manual and Substudy SAP. 
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Table 10
PK Substudy Schedule of Activities (in addition to the PK Schedule of Activities for the main study)
Study Period
Screening
Treatment Perioda
Visit 
Number/Title
1
Screen
2 
Randomization
3
4
5
6
7
8
9
Visit n
Final 
Efficacy
Visit
Safety 
Follow-
up Visit
Scheduled 
Days/Month
-30 Days
to Day 1
Day 1
Day 3
Day 5
Day 8
Day 15
Day 29
Day 57
Day 85
Every 3 
months
Based 
on 
Efficacy 
Cutoff 
dateb
3 months
after 
Final 
Efficacy 
Visit
Visit Window
±1 day
±1 
day
±1 days
±3
days
±3 days
±5 
days
±7 days
±7
days
±7
days
PK Substudy 
evaluation 
Xc
Xd
Xd
Xc,e
PK= pharmacokinetics
Note: Visit windows are relative to the previous dose.
Visit n= Starting from Visit 9 (Day 85) all subsequent visits will be scheduled every 3 months until study completion is reached. 
a Participants who discontinue study treatment will not continue to participate in the PK Substudy
b Efficacy Cutoff will be declared when the required number of events has accrued for the primary efficacy endpoint (see Section 9.7). If the study stops at IA, the Final Efficacy Visits will be 
scheduled to occur within 14 days of Sponsor’s notification to stop the study. If the study continues, the Final Efficacy Visits will be scheduled to occur in the 14 days following the Final Analysis 
efficacy cutoff date.
c In addition to the main study PK draws, a third draw will be obtained 6 hours after the infusion began at Day 1 and Day 85. 
d Trough sample collection only. To be collected pre-dialysis (before heparin is administered). Record the time the sample was drawn and the time infusion was started.
e PK will be collected prior to dialysis on the 2 dialysis visits post Day 85 and the next dosing visit after Day 85.
PK samples will be taken on the day the participant receives study intervention. 
Note: If the participant misses a dialysis session on the day study intervention was scheduled, the participant will receive study 
intervention at the next hemodialysis session and resume their regular study intervention schedule the following week or as soon as 
possible.
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10.9
Appendix 9: Hemostasis
FXI plays important roles in the coagulation cascade. FXI activation through the intrinsic 
pathway can initiate clot formation and activation of FXI by thrombin and facilitates further 
thrombin production and clot propagation. Clinical evidence from individuals with either FXI 
deficiency or presence of FXI inhibitors indicates that deficiencies in FXI activity lead to 
increased rates of bleeding in certain situations, for example oral surgeries. Prediction of an 
individual’s bleeding risk based on the magnitude of reduction in FXI activity or associated 
aPTT prolongation is difficult, with poor correlation between levels of FXI activity and 
bleeding risk [Peyvandi, F., et al 2012] [Gailani, D. 2016] [Gomez, K. 2008]. 
Empirical evidence suggests that bleeding risk in surgical patients with reduced FXI activity 
is manageable through the addition of clotting factors in the form of either FFP or 
recombinant FVIIa or the use of antifibrinolytic agents, for example tranexamic acid. In 
individuals with FXI deficiency, perioperative infusion of FFP to provide exogenous FXI 
partially normalized aPTT prolongation and maintained adequate hemostasis in the setting of 
invasive orthopedic surgery [Sano, K., et al 2017]. In individuals undergoing major 
surgeries, a very low dose of recombinant FVIIa given at the end of surgery along with 
tranexamic acid provided simple and effective control of hemostasis [Salomon, O., et al 
2019]. By extension, managing patients with reduced FXI activity from the action of MK-
2060 with these therapies is expected to result in a similar reduction in bleeding risk.
The ability of human plasma, human FXI zymogen, and rhesus monkey plasma to reverse 
aPTT prolongation in human plasma and rhesus monkey plasma treated with MK-2060 was 
assessed in vitro. The aPTT prolongation was measured with varying MK-2060 
concentrations: 17 nM (projected Cmin), 30 nM (concentration leading to maximal aPTT 
prolongation), or 60 nM (projected Cmax). Reversal of MK-2060 aPTT prolongation was 
evaluated by addition of human plasma (Figure 2, Panel A), purified human FXI zymogen 
(Figure 2, Panels B and D), and rhesus monkey plasma (Figure 2, Panel C). In human 
plasma, aPTT prolongation caused by 30 nM MK-2060 was reversed by the addition of both 
human plasma and FXI. The addition of 80% human plasma returned aPTT values expected 
from approximately 10% FXI activity levels, while 150% plasma was required to return 
values expected from 30% FXI activity. At 60 nM MK-2060, aPTT prolongation was 
reversed by the addition of 150% plasma and 200% plasma but remained at higher levels 
than the aPTT values expected from 10% FXI activity levels. 
The effects of purified human FXI were also assessed. Previous studies have shown that in 
clinical practice, 2 plasma-derived factor XI concentrates could cause the reversal of aPTT 
prolongation: a high purity FXI protein [Bauduer, F., et al 2015] and a partially purified FX 
protein (Bioproducts Laboratory). Consistently, in this study, full reversal of aPTT 
prolongation could be achieved by the addition of purified human FXI protein: at 60 nM 
MK-2060, addition of FXI at concentrations > 58.1 nM resulted in a full reversal of aPTT 
prolongation. 
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Similar results were observed when additional rhesus monkey plasma or human FXI protein 
was added to aPTT assessed in rhesus monkey plasma. These results suggest that the impact 
of MK-2060-induced aPTT prolongation on hemostasis was similar in rhesus monkeys.
Source: Nonclinical Study Report PD008
In an in vivo study, normovolemic rhesus macaques received a single IV dose of 0.25 mg/kg 
MK-2060 followed, approximately 30 minutes after dosing, by a 4-hour transfusion with 
either FFP obtained from donor rhesus macaques or Plasma-Lyte A (control). MK-2060 
administration resulted in an approximately 150% aPTT prolongation, as measured 
CCI
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approximately 30 minutes after dosing. A partial reversal of MK-2060-induced aPTT 
prolongation was achieved by the FFP transfusion but not by the Plasma-Lyte A (control) 
transfusion (Table 11).
Table 11
Mean aPTT Parameters in Monkeys After Dosing of MK-2060 Followed by 
Plasma-Lyte or Fresh Frozen Plasma Administration
Time (hours)
MK-2060 Dose: 0.25 mg/kg
Group
Plasma-Lytea
FFP
Mean aPTT (sec)
SE (sec)
Mean aPTT (sec)
SE (sec)
-2
20.5
0.69
20.4
0.09
0
21.2
0.75
21.1
0.31
0.5b
50.8
2.1
50.0
1.1
2.5
51.3
1.7
46.7
0.49
4.5c
48.7
1.5
31.4
1.6
24
34.1
6.3
26.7
0.57
aPTT=activated partial thromboplastin time; FFP=fresh frozen plasma; IV=intravenous(ly); mg/kg=milligram per 
kilogram; SE=standard error; sec=seconds.
a Plasma-Lyte A injection pH 7.4 (multiple electrolytes injection, Type 1) is a sterile, nonpyrogenic isotonic solution in a 
single-dose container for IV administration. Each 100-mL container contains 526 mg sodium chloride; 502 mg sodium 
gluconate; 368 mg sodium acetate trihydrate; 37 mg potassium chloride; and 30 mg magnesium chloride.
b Time point denotes initiation of transfusion of FFP or Plasma- Lyte A.
c Time point denotes end of transfusion of FFP or Plasma-Lyte A.
Source: Nonclinical Study Report TT #20-4451.
The MK-2060 concentration at the beginning of the FFP transfusion (0.5 hours) was 
approximately 6 µg/mL (40.5 nM), which is in the range of the Cmax values observed (28.0 to 
61.3 nM) following a single dose of 20 mg or 40 mg MK-2060, respectively, in clinical study 
MK-2060-P004 in participants with ESRD.
These results indicate that FFP transfusion following the administration of a single 
0.25 mg/kg MK-2060 IV dose to rhesus monkeys can partially reverse MK-2060-induced 
aPTT prolongation.
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10.10 Appendix 10: Abbreviations
Abbreviation
Expanded Term
AEs
adverse event (s)
ADA
anti-drug antibodies
ALT
alanine aminotransferase 
APaT
All-Participants-as-Treated
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AUC
area under the curve
AV
arteriovenous
AVF
arteriovenous fistula
AVG
arteriovenous graft
AxMP
auxiliary medicinal product
BP
blood pressure
BUN
blood urea nitrogen
CAC
clinical adjudication committee
CFR
Code of Federal Regulations
CI
confidence interval
Cmax
maximum observed plasma concentration
CL
clearance
Cmin
minimum blood plasma concentration
CONSORT
Consolidated Standards of Reporting Trials
CORE
Center for Observational and Real-world Evidence
CrCl
creatinine clearance
CRF
Case Report Form 
CSR
Clinical Study Report
CTCAE
Common Terminology Criteria for Adverse Events
CTFG
Clinical Trial Facilitation Group 
Ctrough
trough concentration
CV
cardiovascular
DBP
diastolic blood pressure
DILI
drug-induced liver injury
DMC
Data Monitoring Committee 
DNA
deoxyribonucleic acid 
DOACs
direct oral anticoagulants
DVT
deep vein thrombosis
ECG
electrocardiogram 
ECI
event of clinical interest
eCRF
electronic Case Report Form
EDC
electronic data collection 
EEA
European Economic Area
EMA
European Medicines Agency
EOC
Executive Oversight Committee
EQ-5D-5L
Euro quality of life 5-dimensional, 5-level questionnaire 
ESRD
end-stage renal disease
EU CTR
European Union Clinical Trial Regulation
FDAAA
Food and Drug Administration Amendments Act
FBR
future biomedical research
FFP
fresh frozen plasma
FP
first patient
FPE
first patient enrolled 
FSH
follicle stimulating hormone 
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Abbreviation
Expanded Term
FVIIa
factor VIIa
FXa
active factor X
FXI
factor XI
FXIa
active factor XI
GCP
Good Clinical Practice 
GI
gastrointestinal 
GU
genitourinary 
hCG
human chorionic gonadotropin
HIV
human immunodeficiency virus
HR
hazard ratio
HRT
hormone replacement therapy
IA
interim analysis
IB
Investigator’s Brochure 
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IMP
investigational medicinal product
INR
international normalized ratio
IRB
Institutional Review Board
IRT
interactive response technology
ISTH
International Society on Thrombosis and Haemostasis
ITT
intent-to-treat
IUD
intrauterine device
IV
intravenous
IVRS
interactive voice response system
KDQOL-SF
kidney disease quality of life questionnaire-short form
KPS
Karnofsky performance status
LAM
lactational amenorrhoea method
LMWH
low molecular weight heparin
LPLV
last patient last visit
mAb
monoclonal antibody
MCH
mean corpuscular hemoglobin
MCV
mean corpuscular volume
MedDRA
Medical Dictionary for Regulatory Activities
M&N
Miettinen & Nurminen 
NIMP
non-investigational medicinal product
NSAE
nonserious adverse event
NSAIDs
nonsteroidal anti-inflammatory drugs
NOAEL
no observed adverse effect level 
NOEL
no-observed-effect-level
PD
pharmacodynamics
PDLC
predefined limits of change
pEFD
preliminary embryo-fetal development
PE
pulmonary embolism
PK
pharmacokinetic
PRO
patient-reported outcome
PT
prothrombin time
QID
four times a day 
QOD
every other day
QoL
quality of life
CCI
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Abbreviation
Expanded Term
QP2
department of quantitative pharmacology and pharmacometrics
QW
once a week
RBC
red blood cells
RNA
ribonucleic acid
SAC
Scientific Advisory Committee
SAEs
serious adverse event(s)
SAP
Statistical Analysis Plan
SBP
systolic blood pressure
SC
subcutaneous
SGOT
serum glutamic-oxaloacetic transaminase
SGPT
serum glutamic-pyruvic transaminase
SoA
schedule of activities
SOC
system organ class
sSAP
supplemental Statistical Analysis Plan
SUSAR
suspected unexpected serious adverse reaction
SW
study week
Tmax
time to maximum plasma concentration
ULN
upper limit of normal
US
United States
USRDS
United States renal data system
VAS
visual analog scale
Vc
central volume
VTE
venous thromboembolism 
WBC
white blood cells
WOCBP
woman/women of childbearing potential 
WONCBP
woman/women of nonchildbearing potential
ZINB
zero inflated negative binomial
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