Conditions: End-Stage Renal Disease Kidney Failure, Chronic
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 12
Healthy volunteers: no

Brief summary:
MK-2060 is being developed for prevention of thrombotic complications in end-stage renal disease (ESRD). The purpose of this study is to conduct a preliminary evaluation of the safety and tolerability of MK-2060 treatment in combination with a commonly used P2Y12 receptor inhibitor, clopidogrel, in ESRD patients.

Detailed description:

Arms:
arm 1: Participants continued their established background therapy of daily 75 mg clopidogrel for 2 weeks (days -14 to 0). Participants then continued background therapy while receiving 25 mg MK-2060 intravenous (IV) infusion on days 1, 3, 5, and 8.

Interventions: intervention 1: MK-2060
Intervention descriptions: intervention 1: MK-2060 administered via IV infusion

Protocol document:
Prot_SAP_000.pdf: 
Official Protocol Title:
NCT number:                NCT05335005
Document Date:            09-Jun-2022 
A Study to Evaluate Safety and Tolerability of
Co-administration of MK-2060 and Clopidogrel
in Participants with End-Stage Renal Disease
on Hemodialysis


PRODUCT: MK-2060  
1
PROTOCOL/AMENDMENT NO.: 008-01
MK-2060-008-01 FINAL PROTOCOL
09-JUN-2022
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 Study to Evaluate Safety and Tolerability of Co-administration of MK-
2060 and Clopidogrel in Participants with End-Stage Renal Disease on Hemodialysis
Protocol Number: 008-01
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
2021-005333-17
IND
142, 237
Approval Date: 09 June 2022
08BRCT


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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
08BRCT


PRODUCT: MK-2060  
3
PROTOCOL/AMENDMENT NO.: 008-01
MK-2060-008-01 FINAL PROTOCOL
09-JUN-2022
DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
MK-2060-008-01
09-JUN-2022
The original protocol is being amended to add standard text on photography of rash, to 
reflect the Sponsor’s entity name and address change, and to correct typographical errors.
MK-2060-008-00
28-JAN-2022
Not applicable
08BRCT


PRODUCT: MK-2060  
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PROTOCOL/AMENDMENT NO.: 008-01
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PROTOCOL AMENDMENT SUMMARY OF CHANGES
Amendment: [01]
Overall Rationale for the Amendments:
The original protocol is being amended to add standard text on photography of rash, to reflect the Sponsor’s entity name and address 
change, and to correct typographical errors. These changes should not impose any undue safety risks to the participant nor have any 
impact on the PK/PD of MK-2060.
Summary of Changes Table:
Section # and Name
Description of Change 
Brief Rationale 
Title Page
IND number added
Additional clinical site in the US will be participating 
in the study
Title Page
Section 10.1.1 Code of 
Conduct for Clinical Trials
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 3 Hypotheses, 
Objectives, and Endpoints
Removed “-008” from the tertiary 
objective “To investigate the relationship 
between the genetic polymorphisms of 
CYP2C19 and the pharmacokinetics of 
MK-2060.”
Correction of typographical error
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Section # and Name
Description of Change 
Brief Rationale 
Section 8.1.9 
Discontinuation and 
Withdrawal
Section 8.5 Adverse Events, 
Serious Adverse Events, and 
Other Reportable Safety 
Events
Section 10.3.1 Definition of 
AE
Section 10.3.5 Reporting of 
AEs, SAEs, and Other 
Reportable Safety Events to 
the Sponsor
Changed references of sections 8.4, 8.4.1, 
8.4.3, and 8.4.6 to 8.5, 8.5.1, 8.5.3, and 
8.5.6, respectively
Correction of typographical errors
Section 8.3.2.1 Resting Vital 
Signs
Revised sentence to read “The same 
method must be used for all measurements 
for each individual participant and should 
be the same for all participants at a given 
site”
Clarified that temperature measurements should be 
taken from the same location for all participants at a 
given site.
Section 8.3.6 Photograph of 
Rash
Added language recommending 
photographs of rash
Addition of Sponsor standard template text 
08BRCT


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Section # and Name
Description of Change 
Brief Rationale 
Section 1.3 Schedule of 
Activities
Section 10.2 Clinical 
Laboratory Tests
Added note that blood or saliva drug 
screen may be done for anuric participants 
Removed barbiturate testing requirement 
from drug screen.
For participants who are unable to provide urine 
samples, blood or saliva samples may be used for drug 
screen.
There is low likelihood of drug interaction between 
barbiturates and either clopidogrel or MK-2060.
08BRCT


PRODUCT: MK-2060  
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Table of Contents
DOCUMENT HISTORY ........................................................................................................3
PROTOCOL AMENDMENT SUMMARY OF CHANGES...............................................4
1
PROTOCOL SUMMARY ............................................................................................14
1.1
Synopsis.................................................................................................................14
1.2
Schema ..................................................................................................................17
1.3
Schedule of Activities...........................................................................................18
2
INTRODUCTION..........................................................................................................22
2.1
Study Rationale....................................................................................................22
2.2
Background ..........................................................................................................22
2.2.1
Pharmaceutical and Therapeutic Background .............................................22
2.2.2
Ongoing Clinical Studies.............................................................................22
2.2.3
Information on Other Study-related Therapy ..............................................24
2.3
Benefit/Risk Assessment......................................................................................25
3
HYPOTHESES, OBJECTIVES, AND ENDPOINTS................................................25
4
STUDY DESIGN............................................................................................................27
4.1
Overall Design......................................................................................................27
4.2
Scientific Rationale for Study Design.................................................................27
4.2.1
Rationale for Endpoints ...............................................................................28
4.2.1.1
Safety Endpoints................................................................................28
4.2.1.2
Pharmacokinetic Endpoints ...............................................................29
4.2.1.3
Pharmacodynamic Endpoints.............................................................30
4.2.1.4
Planned Exploratory Biomarker Research.........................................30
4.2.1.4.1
Planned Genetic Analysis ........................................................30
4.2.1.5
Future Biomedical Research..............................................................30
4.3
Justification for Dose...........................................................................................31
4.3.1
Rationale for Dose Interval and Study Design ............................................31
4.4
Beginning and End-of-Study Definition ............................................................32
4.4.1
Clinical Criteria for Early Study Termination .............................................32
5
STUDY POPULATION ................................................................................................32
5.1
Inclusion Criteria.................................................................................................33
5.2
Exclusion Criteria................................................................................................35
5.3
Lifestyle Considerations......................................................................................38
5.3.1
Meals and Dietary Restrictions....................................................................38
5.3.1.1
Diet Restrictions.................................................................................38
5.3.2
Caffeine, Alcohol, and Tobacco Restrictions ..............................................38
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5.3.2.1
Caffeine Restrictions..........................................................................38
5.3.2.2
Alcohol Restrictions...........................................................................38
5.3.2.3
Tobacco Restrictions..........................................................................39
5.3.3
Activity Restrictions ....................................................................................39
5.4
Screen Failures.....................................................................................................39
5.5
Participant Replacement Strategy......................................................................39
6
STUDY INTERVENTION............................................................................................39
6.1
Study Intervention(s) Administered...................................................................39
6.2
Preparation/Handling/Storage/Accountability .................................................41
6.2.1
Dose Preparation..........................................................................................41
6.2.2
Handling, Storage, and Accountability........................................................41
6.3
Measures to Minimize Bias: Randomization and Blinding..............................42
6.3.1
Intervention Assignment..............................................................................42
6.3.2
Stratification.................................................................................................42
6.3.3
Blinding........................................................................................................42
6.4
Study Intervention Compliance..........................................................................42
6.5
Concomitant Therapy..........................................................................................42
6.5.1
Rescue Medications and Supportive Care ...................................................45
6.6
Dose Modification (Escalation/Titration/Other)...............................................46
6.6.1
Stopping Rules.............................................................................................46
6.7
Intervention After the End of the Study............................................................47
6.8
Clinical Supplies Disclosure................................................................................47
6.9
Standard Policies..................................................................................................47
6.9.1
Study Site Retention Samples......................................................................47
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL............................................................................................................47
7.1
Discontinuation of Study Intervention...............................................................47
7.2
Participant Withdrawal From the Study...........................................................48
7.3
Lost to Follow-up .................................................................................................49
8
STUDY ASSESSMENTS AND PROCEDURES........................................................49
8.1
Administrative and General Procedures ...........................................................50
8.1.1
Informed Consent.........................................................................................50
8.1.1.1
General Informed Consent.................................................................50
8.1.1.2
Consent and Collection of Specimens for Future Biomedical 
Research.............................................................................................50
8.1.2
Inclusion/Exclusion Criteria ........................................................................51
8.1.3
Participant Identification Card.....................................................................51
8.1.4
Medical History ...........................................................................................51
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8.1.5
Prior and Concomitant Medications Review...............................................51
8.1.5.1
Prior Medications...............................................................................51
8.1.5.2
Concomitant Medications..................................................................51
8.1.6
Assignment of Screening Number...............................................................51
8.1.7
Assignment of Treatment/Randomization Number.....................................52
8.1.8
Study Intervention Administration ..............................................................52
8.1.8.1
Timing of Dose Administration.........................................................52
8.1.9
Discontinuation and Withdrawal .................................................................52
8.1.9.1
Withdrawal From Future Biomedical Research ................................52
8.1.10
Participant Blinding/Unblinding..................................................................53
8.1.11
Domiciling ...................................................................................................53
8.1.12
Calibration of Equipment.............................................................................53
8.2
Efficacy/Immunogenicity Assessments ..............................................................53
8.3
Safety Assessments...............................................................................................54
8.3.1
Physical Examinations.................................................................................54
8.3.1.1
Body Weight and Height ...................................................................54
8.3.1.2
Body Mass Index (BMI)....................................................................54
8.3.2
Vital Signs....................................................................................................54
8.3.2.1
Resting Vital Signs ............................................................................55
8.3.2.2
Orthostatic Vital Signs.......................................................................55
8.3.3
Electrocardiograms ......................................................................................55
8.3.4
Assessment of Time to Hemostasis .............................................................56
8.3.5
Clinical Safety Laboratory Assessments .....................................................57
8.3.6
Photograph of Rash......................................................................................57
8.4
Management of Infusion Reaction During and Post-dose ...............................57
8.4.1
Systemic Infusion Reaction Assessment .....................................................58
8.4.2
Local Infusion Reaction Assessment...........................................................58
8.5
Adverse Events, Serious Adverse Events, and Other Reportable Safety 
Events....................................................................................................................59
8.5.1
Time Period and Frequency for Collecting AE, SAE, and Other 
Reportable Safety Event Information ..........................................................59
8.5.2
Method of Detecting AEs, SAEs, and Other Reportable Safety Events......61
8.5.3
Follow-up of AE, SAE, and Other Reportable Safety Event Information...61
8.5.4
Regulatory Reporting Requirements for SAE .............................................61
8.5.5
Pregnancy and Exposure During Breastfeeding ..........................................61
8.5.6
Disease-related Events and/or Disease-related Outcomes Not Qualifying 
as AEs or SAEs............................................................................................62
8.5.7
Events of Clinical Interest............................................................................62
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09-JUN-2022
8.6
Treatment of Overdose........................................................................................62
8.7
Pharmacokinetics.................................................................................................63
8.7.1
Blood Collection for Plasma MK-2060 and Clopidogrel ............................63
8.8
Pharmacodynamics..............................................................................................63
8.9
Biomarkers ...........................................................................................................63
8.9.1
Planned Genetic Analysis Sample Collection..............................................63
8.9.2
Blood Collection for PT, aPTT, FXI Activity .............................................63
8.9.3
Blood for Plasma ADA................................................................................64
8.10
Future Biomedical Research Sample Collection...............................................64
8.11
Visit Requirements...............................................................................................64
8.11.1
Screening and Run-in Period .......................................................................64
8.11.2
Treatment Period..........................................................................................64
8.11.3
Poststudy......................................................................................................65
8.11.4
Participants Discontinued From Study Intervention but Continuing to be 
Monitored in the Study ................................................................................65
8.11.5
Critical Procedures Based on Study Objectives: Timing of Procedure.......65
8.11.6
Study Design/Dosing/Procedures Modifications Permitted Within 
Protocol Parameters .....................................................................................67
9
STATISTICAL ANALYSIS PLAN .............................................................................68
9.1
Statistical Analysis Plan Summary.....................................................................68
9.2
Responsibility for Analyses.................................................................................68
9.3
Hypotheses/Estimation ........................................................................................68
9.4
Analysis Endpoints...............................................................................................69
9.5
Analysis Populations............................................................................................69
9.6
Statistical Methods...............................................................................................70
9.7
Interim Analyses ..................................................................................................71
9.8
Multiplicity ...........................................................................................................71
9.9
Sample Size and Power Calculations .................................................................71
10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.....................................................................................................72
10.1
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations........72
10.1.1
Code of Conduct for Clinical Trials.............................................................72
10.1.2
Financial Disclosure.....................................................................................74
10.1.3
Data Protection.............................................................................................75
10.1.3.1
Confidentiality of Data ......................................................................75
10.1.3.2
Confidentiality of Participant Records...............................................75
10.1.3.3
Confidentiality of IRB/IEC Information............................................75
10.1.4
Committees Structure...................................................................................76
08BRCT


PRODUCT: MK-2060  
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09-JUN-2022
10.1.5
Publication Policy........................................................................................76
10.1.6
Compliance with Study Registration and Results Posting Requirements ...76
10.1.7
Compliance with Law, Audit, and Debarment ............................................76
10.1.8
Data Quality Assurance ...............................................................................77
10.1.9
Source Documents .......................................................................................78
10.1.10
Study and Site Closure.................................................................................78
10.2
Appendix 2: Clinical Laboratory Tests..............................................................79
10.3
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting...............................................................80
10.3.1
Definition of AE ..........................................................................................80
10.3.2
Definition of SAE ........................................................................................81
10.3.3
Additional Events Reported.........................................................................82
10.3.4
Recording AE and SAE ...............................................................................82
10.3.5
Reporting of AEs, SAEs, and Other Reportable Safety Events to the 
Sponsor ........................................................................................................86
10.4
Appendix 4: Medical Device and Drug-device Combination Products: 
Product Quality Complaints/Malfunctions: Definitions, Recording, and 
Follow-up ..............................................................................................................87
10.5
Appendix 5: Contraceptive Guidance................................................................88
10.5.1
Definitions....................................................................................................88
10.5.2
Contraception Requirements........................................................................89
10.6
Appendix 6: Collection and Management of Specimens for Future 
Biomedical Research............................................................................................90
10.7
Appendix 7: Country-specific Requirements....................................................95
10.8
Appendix 8: Blood Volume Table ......................................................................96
10.9
Appendix 9: Algorithm for Assessing Out of Range Laboratory Values .......97
10.10 Appendix 10: Abbreviations ...............................................................................98
11
REFERENCES.............................................................................................................101
08BRCT


PRODUCT: MK-2060  
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LIST OF TABLES
Table 1
Study Schema...................................................................................................17
Table 2
Preliminary Part 2 Plasma Pharmacokinetic Parameters [Geometric Mean 
(%GCV)] of MK-2060 Following Multiple 60-minute IV infusion Doses 
of 25 mg QW ...................................................................................................23
Table 3
Study Interventions..........................................................................................40
Table 4
Local Infusion Reaction Assessment...............................................................58
Table 5
Reporting Time Periods and Time Frames for Adverse Events and Other 
Reportable Safety Events.................................................................................60
Table 6
Pharmacokinetic (Blood), Pharmacodynamic and Biomarker Collection 
Windows ..........................................................................................................66
Table 7
Postdose Safety Evaluation Windows .............................................................66
Table 8
Protocol-required Safety Laboratory Assessments..........................................79
08BRCT


PRODUCT: MK-2060  
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09-JUN-2022
LIST OF FIGURES
Figure 1
Study Diagram ...........................................................................................17
08BRCT


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09-JUN-2022
1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Study to Evaluate Safety and Tolerability of Co-administration of MK-
2060 and Clopidogrel in Participants with End-Stage Renal Disease on Hemodialysis
Short Title: MK-2060 and Clopidogrel Co-administration Safety and Tolerability Study
Acronym: NA
Hypotheses, Objectives, and Endpoints:
Hypotheses are aligned with objectives in the Objectives and Endpoints table.
This study is to be conducted in adult participants with End-Stage Renal Disease on 
Hemodialysis. 
Objectives
Endpoints
Primary
•
Objective: To assess the safety and 
tolerability following multiple doses of 
concomitant treatment of MK-2060 and 
clopidogrel
•
Bleeding related AEs, AEs and 
discontinuations due to AEs
Secondary
•
Objective: To evaluate plasma 
pharmacokinetics of MK-2060 following 
multiple doses of concomitant treatment 
of MK-2060 and clopidogrel 
•
MK-2060 plasma AUC0-168, Cmax, 
C168, Tmax, terminal t1/2, CL, Vz
•
Objective: To evaluate the time required 
to achieve hemostasis following 
completion of dialysis in ESRD patients
following concomitant treatment of MK-
2060 and clopidogrel
•
Hypothesis: Mean time-to-hemostasis for 
MK-2060 treatment is less than 20 
minutes
•
Time to hemostasis
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Overall Design:
Study Phase
Phase 1
Primary Purpose
Treatment
Indication
Graft thrombosis
Population
Patient: adult participants with end-stage renal disease on 
hemodialysis
Study Type
Interventional
Intervention Model
Single Group
This is a multi-site study.
Type of Control
None
Study Blinding
Unblinded Open-label
Blinding Roles
No Blinding
Estimated Duration of Study
The Sponsor estimates that the study will require 
approximately 17 months from the time the first 
participant (or their legally acceptable representative) 
provides documented informed consent until the last 
participant’s last study-related contact.
Number of Participants:
Up to 12 participants will be allocated.
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Intervention Groups and Duration:
Intervention 
Groups
Inter-
vention 
Group 
Name
Drug
Dose 
Strength
Dose 
Frequency
Route of 
Adminis-
tration
Regimen 
Use
NA
MK-2060
25 mg
Week 1: 3
doses 
Week 2: 1 
dose
Intravenous
Week 1: 3
doses
Week 2: 1 
dose
Experimental
Total 
Number of 
Intervention 
Groups/
Arms
There will be 1 intervention group with up to 12 participants.
Duration of 
Participation
Each participant will participate in the study for approximately 21 weeks,
from the time the participant provides documented informed consent 
through the final contact. After a screening phase of approximately 4 weeks
and run-in period of approximately 2 weeks, each participant will receive 
assigned intervention for approximately 2 weeks. After the end-of-
treatment each participant will be followed for approximately 96 days.
Study Governance Committees:
Executive Oversight Committee
No
Data Monitoring Committee
No
Clinical Adjudication Committee
No
Study governance considerations are outlined in Appendix 1.
Study Accepts Healthy Volunteers: No
A list of abbreviations is in Appendix 11.
08BRCT


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1.2
Schema
The study design is depicted in Table 1 and Figure 1.
Table 1
Study Schema
Week 1
Week 2
MK-2060a
25 mg IV MK-2060 x 3
25 mg IV MK-2060 x 1
a The suggested doses may be adjusted downward based on newly available safety, tolerability, pharmacokinetic 
and/or pharmacodynamic data observed in this study as well as other MK-2060 studies. 
Figure 1
Study Diagram
08BRCT


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1.3
Schedule of Activities
Study Period:
Scr
een
-ing
Run-in a
Intervention
Post-
study
Intervention
Notes
Scheduled Day
Day -14
Day -7
Day -3
Day 1
Day2
Day 3
Day 5
Day 8
Day 9
Day 10
Day 12
Day 15
Day 21
Day 29
Day 35
Day 49
Day 67
Day 104
Administrative Procedures
Informed Consent
X
Sec. 8.1.1.1
Informed Consent for 
FBR
X
Sec. 8.1.1.2
Participant ID Card
X
Sec. 8.1.3
Inclusion/Exclusion 
Criteria
X
X
X
X
Sec. 5.1, 5.2, and 8.1.2
Review of IC/EC at Screening and during Run-in period; 
only specific criteria will be reviewed predose prior to 
treatment allocation on Day 1
Participant Bracelet
X
Sec. 4.3.1
Medical History
X
Sec 8.1.4
Prior/Concomitant 
Medication Review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 6.5 & 8.1.5
Assignment of Screening 
Number
X
Sec. 8.1.6
Assignment of 
Allocation Number
X
Sec. 8.1.7
MK-2060 
Administration
X
X
X
X
Sec. 8.1.8
Record the time of the 
last Clopidogrel dose 
X
X
X
X
X
X
X
X
X
X
X
X
Domiciling
X
X
X
X
X
Sec. 8.1.11
On site Hemodialysis
(HD) b
X
X
X
X
X
X
X
X
Safety Procedures
Full physical 
examination
X
X
X
X
X
X
X
Sec. 8.3.1
To be done predose prior to HD on Days 1, 3, 5 and 8
Systemic Infusion 
Reaction Assessment
X
X
X
X
X
X
Sec. 8.4.1
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Study Period:
Scr
een
-ing
Run-in a
Intervention
Post-
study
Intervention
Notes
Scheduled Day
Day -14
Day -7
Day -3
Day 1
Day2
Day 3
Day 5
Day 8
Day 9
Day 10
Day 12
Day 15
Day 21
Day 29
Day 35
Day 49
Day 67
Day 104
Local Infusion Reaction 
Assessment
X
X
X
X
X
X
Sec. 8.4.2
Assessment of Time to 
Hemostasis
X
X
X
X
X
X
X
Sec. 8.3.4. 
Performed immediately at the end of HD
Height
X
Sec. 8.3.1
Height may be measured during Screening or Run-in
period.
Weight
X
X
Sec. 8.3.1, weight for BMI to be taken during Screening or 
Run-in period.
Additional weight measurements can be taken per site 
SOP.
Resting Semi-
Recumbent Vital Signs 
(blood pressure, heart 
rate, respiratory rate, 
body temperature)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.2.1
To be done at predose on Days 1, 3, 5 and 8
Orthostatic VS
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.2.2
To be done at predose on Days 1, 3, 5 and 8.
To be done before start of dialysis on Days -3 and 15.
12-lead ECG
X
X
X
X
X
X
X
X
X
Sec. 8.3.3
To be done at predose on Days 1, 3, 5 and 8
Serum FSH -
(WONCBP only)
X
Serum or Urine 
Pregnancy test (WOCBP 
only)
X
X
X
HIV, hepatitis B and C 
screen 
X
Drug Screen and 
Alcohol Breath Test
X
X
Appendix 2 DS and alcohol breath test is mandatory at 
Screening and predose; any additional DS and alcohol 
breath tests are conducted per site SOP
Blood or saliva DS may be used for anuric participants
08BRCT


PRODUCT: MK-2060  
20
PROTOCOL/AMENDMENT NO.: 008-01
MK-2060-008-01 FINAL PROTOCOL
09-JUN-2022
Study Period:
Scr
een
-ing
Run-in a
Intervention
Post-
study
Intervention
Notes
Scheduled Day
Day -14
Day -7
Day -3
Day 1
Day2
Day 3
Day 5
Day 8
Day 9
Day 10
Day 12
Day 15
Day 21
Day 29
Day 35
Day 49
Day 67
Day 104
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.5
Appendix 2
To be done predose on Days 1, 3 and 8
aPTT/PT at Local Lab
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.5
Appendix 2
Days 1, 3, 5 & 8: predose, 1h and 12h.
Chemistry c
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.5
Appendix 2
To be done at predose on Days 1, 3 and 8
Hemoccult Test d
X
X
X
X
X
X
X
X
Sec. 8.3.5, 8.11.5
AE/SAE review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec 8.5, Appendix 3
Pharmacokinetics
Blood for Plasma 
MK-2060 Assay e, f
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.7
Days 1 & 8: predose, 1h, 12h. 
Days 3 &5: predose, 1h.
See footnotes e, f
Blood for Clopidogrel 
Assay e,f
X
X
X
X
X
X
X
X
Sec. 8.7
See footnote e, f.
Pharmacodynamics
Blood for PT/aPTT/ FXI 
Activity by Central Lab f
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.8, Days 1 & 8: predose and 1h (within 15 min of end 
of infusion).
Days 3 &5: predose
Biomarkers
Blood for Plasma ADA f
X
X
X
X
X
Sec. 8.9.3
Day 1: predose
Blood (DNA) for 
Planned Genetic 
Analysis 
X
See section 8.8 
08BRCT


PRODUCT: MK-2060  
21
PROTOCOL/AMENDMENT NO.: 008-01
MK-2060-008-01 FINAL PROTOCOL
09-JUN-2022
Study Period:
Scr
een
-ing
Run-in a
Intervention
Post-
study
Intervention
Notes
Scheduled Day
Day -14
Day -7
Day -3
Day 1
Day2
Day 3
Day 5
Day 8
Day 9
Day 10
Day 12
Day 15
Day 21
Day 29
Day 35
Day 49
Day 67
Day 104
ADA=antidrug antibody; AE=adverse event; DNA=deoxyribonucleic acid; ECG=electrocardiogram; FBR=future biomedical research; FSH=follicle stimulating hormone; 
hCG=human chorionic gonadotropin; HD= hemodialysis; ID=identification; SAE=serious adverse event; SOP=standard operating procedure; VS=vital signs; WOCBP=women 
of childbearing potential; WONCBP= women of non-childbearing potential.
a Run-in period (Day -14 to Day -3) should be approximately 2 weeks before the initial dose of MK-2060. 
b On site Hemodialysis:  Pre-dose blood sample collections will be collected prior to HD initiation.
c Participants should fast for at least 4 hours prior to glucose measurement. Day 1 pre-dose tests can be conducted up to 24 hours prior to dosing.
d. Hemoccult test will be provided to subjects at Day-7 visit and participants will return the sample at Day-3. Other post-dose hemoccult test samples may be obtained within 
48 hours of specified timepoint or first available sample if not within this time window.
e All pre-dose PK should be taken prior to initiation of dialysis on that day.
f Leftover main study plasma will be stored for future biomedical research if the participant (or their legally acceptable representative) provides documented informed consent 
for FBR.
08BRCT


PRODUCT: MK-2060  
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09-JUN-2022
2
INTRODUCTION
2.1
Study Rationale
MK-2060 is an anti-factor XI monoclonal antibody, being developed for prevention of 
thrombotic complications in end-stage renal disease (ESRD). Many ESRD patients take 
P2Y12 inhibitors as a concomitant antiplatelet therapy. The purpose of this study is to 
conduct a preliminary evaluation of the safety and tolerability of MK-2060 treatment in 
combination with a commonly used P2Y12 receptor inhibitor, clopidogrel, in ESRD patients.
2.2
Background
Refer to the IB for detailed background information on MK-2060.
2.2.1
Pharmaceutical and Therapeutic Background
FXI is a critical component in the intrinsic pathway of the coagulation cascade.  MK-2060 is 
an anti-FXI monoclonal antibody being developed for the prevention of thrombotic 
complications in ESRD.  Based on preclinical and human genetic data, as well as emerging 
clinical data using an anti-sense oligo (ASO) approach [Buller, H. R., et al 2015] [Bethune, 
C., et al 2017], FXI inhibition is predicted to confer a clinically relevant antithrombotic effect 
with a reduced risk of bleeding complications and hence an expanded therapeutic index 
compared to inhibition of more downstream clotting factors such as FXa and thrombin.  
Therefore, FXI/FXIa inhibition is a promising therapeutic approach for the prevention of 
thromboembolic complications.
2.2.2
Ongoing Clinical Studies
MK-2060-004:
MK-2060-004 is a double-blind, randomized, placebo-controlled, multiple site, sequential 
panel, single and multiple dose trial of MK-2060 in adult participants (men and women of 
non-child bearing potential) with ESRD on HD. As of 14-Dec-2021, 41 participants have 
been administered at least one IV dose up to 40 mg MK-2060 or placebo.  To date, single IV 
doses up to 40 mg in Part 1 have been generally well tolerated and there have been no 
treatment related SAEs and no discontinuations due to any drug-related AEs.  There have 
been no AEs suggestive of hypersensitivity.  Refer to IB Edition 5 for a detailed overview of 
Part 1 of the study, and available preliminary PK, PD, and safety results for Part 1.

Updated Pharmacokinetic Data from MK-2060-004 Part 2 since IB Ed 5:
Analysis of preliminary PK from the single dose portion of MK-2060-004 (Part 1) suggested 
that a multiple dose regimen (25 mg dose on Day 1, 3, and 5, followed by 3 once-weekly 
maintenance doses of 25 mg) would result in rapid achievement of the Cmax at steady state. 
The projected Cmax steady state levels were comparable to what was observed for a single 
40 mg IV dose and would provide sufficient PD in ESRD patients.
08BRCT


PRODUCT: MK-2060  
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09-JUN-2022
The IB was revised to include observed multiple dose PK parameters from Part 2 of MK-
2060-004. PK parameters from 18 subjects in Part 2 are presented in [Table 2]. The observed 
PK concentration profiles from the Part 2 multiple-dose participants are consistent with the 
projected PK concentrations using the Part 1 single dose data, suggesting that the PK of MK-
2060 is not time dependent.
Preliminary analysis detected no ADA positive samples over 150 days following a single 
dose of MK-2060 in Part 1 of MK-2060 PN004 in ERSD participants. Also, in Part 2 
following multiple doses of MK-2060, no ADA positive samples were found over 111 days 
after initiation of dosing.
Table 2
Preliminary Part 2 Plasma Pharmacokinetic Parameters [Geometric Mean 
(%GCV)] of MK-2060 Following Multiple 60-minute IV infusion Doses of 25 mg QW
Cmax_day1
(nM)
Cmax_day22
(nM)
Tmax_day1
a
(hr)
Tmax_day22a
(hr)
Cmax 
Ratio 
(Day 22 
Day 1)
Post-wk1 Cpredose (nM)
Post-wk1 Ceoi (nM)
Day 
8
Day 
15
Day 
22
Day 
29
Day 
8
Day 
15
Day 
22
32.4 
(37.7)
93.4 
(31.7)
1.00
(1.00 –
48.00)
b
1.00
(1.00 –
24.00)
b
2.68 
(33.5)
47.1
(28.1)
44.7 
(32.0)
44.8 
(36.0)
44.6 
(32.1)
91.4 
(24.1)
96.8 
(32.2)
93.5 
(33.3)
a Median (Min-Max)
bOn Day 1 one patient had Cmax at 48 hrs and on Day 22 five patients and one patient had Cmax at 12 and 24 hrs 
respectively.

Updated Pharmacodynamic Activity Data from MK-2060-004 Part 2 since IB Ed 5:
In patients with ESRD on HD, following multiple doses of 25 mg of MK-2060, aPTT 
prolongation was observed with maximum mean fold change of approximately 2.95. The 
maximum aPTT prolongation occurred at ~ 1 hour post dose on Day 22 (end of infusion at 
the last dose). The multiple 25 mg doses inhibited FXI to a maximum level of approximately 
2% of normal activity (based upon normal range of FXI activity standardized in the assay). 
The maximum inhibition of FXI activity was observed at 1 hour on Day 22.

Updated Safety Data from MK-2060-004 Part 2 since IB Ed 5:
As of 14-Dec-2021, 20 participants have received multiple doses of MK-2060 25 mg or 
placebo IV, and 1 participant received only 1 dose of 25 mg IV in Part 2. This participant 
was discontinued from the study after the first dose due to not meeting Inclusion Criterion #1 
(the participant is not being dialyzed via AVF or AVG).
Multiple IV doses of 25 mg have been generally well tolerated. There have been no deaths 
reported. There were no AEs suggestive of hypersensitivity.  A total of two participants 
08BRCT


PRODUCT: MK-2060  
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09-JUN-2022
discontinued the study drug due to AEs. One participant discontinued study drug due to the 
drug-related SAE lower gastrointestinal hemorrhage (additional information provided below)
and another participant discontinued from the study drug due to a nonstudy drug related AE 
(COVID-19 infection). and did not receive the last dose on Day 22.
A total of 7 participants in Part 2 reported total 8 non-serious AEs (7 mild AEs, 1 moderate 
AE diarrhea) and 4 SAEs. Two AEs reported in one participant (mild nausea and mild 
sneezing) were considered as study drug related by the investigator. All other non-serious 
AEs were considered as not study drug related by the investigator. 
A total of 4 participants in Part 2 reported total 4 SAEs, in which 1 SAE was considered as 
drug-related by the investigator and 3 SAEs were considered as not study drug related by the 
investigator. One participant reported a drug-related SAE of lower gastrointestinal 
hemorrhage after Day 5 dosing. This patient experienced bright red blood per rectum and 
was hospitalized overnight as a precaution.  During the hospitalization blood counts were 
closely monitored and there was no decrease in hemoglobin or hematocrit, no blood 
transfusion or other blood products were required, and the bleeding resolved with 
conservative therapy.  A lower gastrointestinal endoscopy revealed the source of the bleed 
was from internal hemorrhoids.  One participant reported a nonstudy drug related SAE of 
pneumonia (hospitalized) approximately 6 weeks post the last dose. One participant reported 
a nonstudy drug related SAE of myocardial infarction (hospitalized and had triple bypass 
surgery coronary artery bypass graft) approximately 11 weeks post the last dose. One 
participant reported a nonstudy drug related SAE of arteriovenous graft thrombosis 
approximately 11 weeks post the last dose. All 4 participants recovered from the SAEs.
Across all treatments for 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 labs, 
and no changes in hematology labs suggestive of bleeding aside from the lower 
gastrointestinal haemorrhage summarized above. Similarly, an exploratory assessment of 
time to vascular access site hemostasis after removal of the hemodialysis catheters remained 
unchanged from baseline.
MK-2060-007:
MK-2060-007 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 phase 2 study is designed to evaluate the efficacy and safety of MK-2060 20 mg 
QW and MK 2060 6 mg QW (with three loading doses in Week 1). As of 14-Dec-2021, 32 
participants enrolled in MK-2060-007 with a maximum exposure of 78 days. MK-2060-007 
is ongoing and safety data are blinded and preliminary. 
2.2.3
Information on Other Study-related Therapy
Clopidogrel is an inhibitor of platelet aggregation. Clopidogrel selectively inhibits the 
binding of adenosine diphosphate (ADP) to its platelet receptor (P2Y12) and the subsequent 
ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet 
aggregation. Biotransformation of clopidogrel is necessary to produce inhibition of platelet 
08BRCT


PRODUCT: MK-2060  
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09-JUN-2022
aggregation, but an active metabolite responsible for the activity of the drug has not been 
isolated. Clopidogrel also inhibits platelet aggregation induced by agonists other than ADP 
by blocking the amplification of platelet activation by released ADP. Clopidogrel does not 
inhibit phosphodiesterase activity.
Clopidogrel acts by irreversibly modifying the platelet ADP receptor. Consequently, platelets 
exposed to clopidogrel are affected for the remainder of their lifespan. Dose dependent 
inhibition of platelet aggregation can be seen 2 hours after single oral doses of clopidogrel. 
Repeated doses of 75 mg clopidogrel per day inhibit ADP-induced platelet aggregation on 
the first day, and inhibition reaches steady state between Day 3 and Day 7. At steady state, 
the average inhibition level observed with a dose of 75 mg clopidogrel per day was between 
40% and 60%. 
Platelet aggregation and bleeding time gradually return to baseline values after treatment is 
discontinued, generally in about 5 days. After repeated 75-mg oral doses of clopidogrel 
(base), plasma concentrations of the parent compound, which has no platelet inhibiting 
effect, are very low and are generally below the quantification limit beyond 2 hours after 
dosing. Clopidogrel is extensively metabolized by the liver. Administration of clopidogrel 
with meals did not show a meaningful effect on the bioavailability of clopidogrel as assessed 
by the pharmacokinetics of the main circulating metabolite. Clopidogrel is rapidly absorbed 
after oral administration of repeated doses of 75 mg clopidogrel, with peak plasma levels of 
the main circulating metabolite occurring approximately 1 hour after dosing. 
The use of clopidogrel is contraindicated in hypersensitivity to it and in active pathological 
bleeding such as peptic ulcer or intracranial hemorrhage. Thrombotic thrombocytopenic 
purpura has been reported rarely following use of clopidogrel, sometimes after a short 
exposure (<2 weeks). Clopidogrel prolongs the bleeding time and therefore should be used 
with caution in patients who may be at risk of increased bleeding from trauma, surgery, or 
other pathological conditions (particularly gastrointestinal and intraocular).
2.3
Benefit/Risk Assessment
Participants in clinical studies will not receive direct benefit from treatment during 
participation as clinical studies are designed to provide information about the safety and 
properties of an investigational medicine. 
Additional details regarding specific benefits and risks for participants participating in this 
clinical study may be found in the accompanying IB and informed consent documents.
3
HYPOTHESES, OBJECTIVES, AND ENDPOINTS
Hypotheses are aligned with objectives in the Objectives and Endpoints table.
This study is to be conducted in adult participants with End-Stage Renal Disease on 
Hemodialysis
08BRCT


PRODUCT: MK-2060  
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09-JUN-2022
Objectives
Endpoints
Primary
•
Objective: To assess the safety and 
tolerability following multiple doses of 
concomitant treatment of MK-2060 and 
clopidogrel
•
Bleeding related AEs, AEs and 
discontinuations due to AEs
Secondary
•
Objective: To evaluate plasma 
pharmacokinetics of MK-2060 following 
multiple doses of concomitant treatment 
of MK-2060 and clopidogrel 
•
MK-2060 plasma AUC0-168, Cmax, 
C168, Tmax, terminal t1/2, CL, Vz
•
Objective: To evaluate the time required 
to achieve hemostasis following 
completion of dialysis in ESRD patients
following concomitant treatment of MK-
2060 and clopidogrel
•
Hypothesis: Mean time-to-hemostasis for 
MK-2060 treatment is less than 20 
minutes
•
Time to hemostasis
Tertiary/Exploratory
•
Objective: To explore the effect of 
concomitant treatment of MK-2060 and 
clopidogrel on aPTT.
•
aPTT fold change from baseline
•
Objective: To explore the effect of 
concomitant treatment of MK-2060 and 
clopidogrel on prothrombin time.
•
Prothrombin time fold change from 
baseline
•
Objective: To evaluate plasma 
pharmacokinetics of clopidogrel 
(clopidogrel carboxylic acid) following 
multiple doses of concomitant treatment 
of MK-2060 and clopidogrel
•
Clopidogrel (clopidogrel carboxylic 
acid) plasma concentration
•
Objective: To explore the development of 
ADAs measured in blood samples 
following multiple doses of concomitant 
treatment of MK-2060 and clopidogrel
•
ADA
08BRCT


PRODUCT: MK-2060  
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09-JUN-2022
Objectives
Endpoints
•
Objective: To investigate the relationship 
between the genetic polymorphisms of 
CYP2C19 and the pharmacokinetics of 
MK-2060. Variation in CYP2C19 may be 
analyzed for association with any 
laboratory or clinical data collected in this 
study
•
Germline genetic variation in 
CYP2C19 and association to clinical 
data collected in this study
4
STUDY DESIGN
4.1
Overall Design
This is an open label, multi-site, multiple dose trial of MK-2060 in adult participants (men 
and women) with ESRD on HD to be conducted in conformance with Good Clinical Practice.  
The study will evaluate the safety and tolerability of MK-2060 and clopidogrel administered
in combination in adult participants with ESRD on HD.
The study will enroll up to 12 ESRD participants receiving clopidogrel as background 
therapy. After an approximately 14-day run-in period to enable measurement of baseline time 
to hemostasis and AE monitoring, each participant will receive a loading dose of 25 mg IV 
MK-2060 for a total of 3 doses in week 1 and a single dose of 25 mg IV MK-2060 in week 2.
Participants will be closely monitored for safety and tolerability, including safety labs, local 
lab aPTT and PT results, physical exam to check bleeding related AEs, vital signs (VS) and 
12-lead ECG, as well as local infusion site reactions and systemic reactions to MK-2060 
infusion.  All participants in this study will be followed through approximately 96 days after 
the last study dose for safety and tolerability, including all adverse experiences, safety labs, 
local lab aPTT and PT results, physical exam to check bleeding related AEs, VS, and 12-lead 
ECG.
Because this is a Phase 1 assessment of MK-2060 in humans, the PK, pharmacodynamic, and 
safety profiles of the compound are still being elucidated. This protocol is therefore written 
with flexibility to accommodate the inherent dynamic nature of Phase 1 clinical studies. 
Refer to Section 8.11.6 for examples of modifications permitted within the protocol 
parameters.
Specific procedures to be performed during the study, including prescribed times and 
associated visit windows, are outlined in Section 1.3 of the SoA. Details of each procedure 
are provided in Section 8.
4.2
Scientific Rationale for Study Design
MK-2060 has been generally well-tolerated both in GLP toxicity studies and in Phase 1 
clinical trials, which have included single dose assessment in normal healthy volunteers 
08BRCT


PRODUCT: MK-2060  
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09-JUN-2022
(PN001) and single/multiple dose assessment in ESRD/HD patients. Preliminary safety data 
from PN004 suggests that MK-2060 does not prolong time to hemostasis following HD 
catheter removal. The purpose of this study is to evaluate the safety of MK-2060 in 
ESRD/HD patients taking clopidogrel as concomitant antiplatelet therapy, since such patients 
require antiplatelet/P2Y12 inhibitor treatment for variety of comorbidities occurring in 
conjunction with their renal disease and hemodialysis treatment. Pertinent to this study 
design, a study of clopidogrel in chronic HD patients showed no impact of clopidogrel on 
time-to-hemostasis following removal of dialysis catheters [Kaufman, J. S., et al 2000]. 
Furthermore, a recent publication suggested that use of clopidogrel in patients with severe 
FXI deficiency/hemophilia type C does not add to the bleeding risk in that particular 
population [Perek, S., et al 2017]. Other FXI inhibitors in clinical development have
demonstrated low risk of bleeding with FXI inhibition. Taken together, these data support 
conducting this study with MK-2060 in ESRD/HD patients receiving clopidogrel as 
background therapy.
4.2.1
Rationale for Endpoints
4.2.1.1
Safety Endpoints
Based on the data from PN001 (healthy subject study) and PN004, it is expected that
multiple dose IV administration of MK-2060 will be well-tolerated in participants with 
ESRD on HD. However, the safety and tolerability following multiple doses of concomitant 
treatment of MK-2060 and clopidogrel are primary endpoints for this trial and will be
carefully monitored. Physical examinations, VS, ECGs, laboratory safety tests (serum
chemistry and hematology), aPTT, PT, and AEs related to bleeding will be assessed
throughout the treatment period. AEs, including local infusion site reactions and systemic
reactions to MK-2060 infusion, will be assessed throughout the treatment period.
Bleeding related AEs will include any sign or symptom of bleeding, even if not requiring 
intervention by a medical/healthcare professional, as well as clinically-relevant non major 
bleeding or major bleeding.
As with all biologic medications, MK-2060 carries a risk of acute reactions upon exposure,
particularly with IV administration. These reactions can be categorized as common acute
infusion reactions, acute hypersensitivity reactions, and high cytokine release reactions.
Common acute infusion reactions are usually mild, can occur even with the first dose, and
manifest with rigors, back pain, abdominal pain, nausea, vomiting, diarrhea, dyspnea,
flushing, pruritus, and changes in heart rate or blood pressure. Acute hypersensitivity
reactions typically occur after repeated exposures but can occur with the first dose. In
addition to signs similar to common infusion reactions, participants may develop
urticaria, wheezing, coughing, facial swelling, angioedema and more significant changes in
VS. Cytokine release reactions are exceedingly rare but severe. They manifest as severe
headache, nausea, vomiting, back pain, fever, hypotension and multiorgan failure. The risk
of any of these infusion reactions to MK-2060 is considered low given its profile in
preclinical safety studies. There were no infusion reactions, no acute hypersensitivity 
reactions, and no cytokine release reactions observed so far in any MK-2060 clinical studies
(see Investigator’s Brochure for more information on the Phase 1 clinical trial experience 
08BRCT


PRODUCT: MK-2060  
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with MK-2060). Participants will be monitored closely during the infusion with scheduled
VS and physical examinations as indicated in the Schedule of Activities. In
addition to monitoring for acute reactions to MK-2060, the infusion site will be assessed
for signs of reactogenicity, including pain, tenderness, erythema and swelling by study staff,
particularly during the first week after infusion. AEs and SAEs will be collected through
Day 104.
Time to adequate hemostasis after decannulation of vascular access
A secondary objective of this study is to explore the effect of MK-2060 given as a single and 
multiple IV dose on time to hemostasis after decannulation of the hemodialysis vascular 
access site in ESRD patients on clopidogrel therapy.  In the dialysis unit after the completion 
of hemodialysis the dialysis catheters are removed from the dialysis access site (i.e., AV 
fistula or AV graft).  Upon decannulation, pressure is held until adequate hemostasis has 
been obtained for both the arterial and venous sites. In this study the process is standardized 
such that change in time to hemostasis from baseline (i.e., average of values obtained from 
the run-in period) can be assessed (see the operations manual for details).
On three dialysis visits prior to dosing, time to adequate hemostasis for both the arterial and 
venous sites will be assessed to establish a baseline (mean of three run-in period 
assessments). Should time to hemostasis be different for arterial and venous sites, the longer 
of the two should be recorded. This endpoint will then be assessed at the end of the dialysis 
sessions after each dosing days as specified in the SoA. Change from baseline will be 
calculated. 
Anti-drug antibodies (ADAs) to MK-2060
The presence and titer of ADAs will be measured using validated assays. ADAs can develop
to biologics like MK-2060. ADAs may be clinically inconsequential or may change the PK
and/or drug efficacy. Moreover, ADAs may lead to safety events, such as acute or delayed
hypersensitivity reactions. Thus, the titer of ADAs will be correlated with PK and safety
events. If needed, positive ADAs will be further evaluated to determine whether they are able
to neutralize MK-2060 activity against FXI. If MK-2060-specific antibodies are confirmed
to be present, additional tests will be performed to determine if the antibodies have the ability
to neutralize the action of MK-2060.
4.2.1.2
Pharmacokinetic Endpoints
Plasma PK of MK-2060
The evaluation of MK-2060 PK will include determination of non-compartmental PK 
parameters including AUC0-168, Cmax, C168, Tmax,terminal t1/2, CL and Vz.
08BRCT


PRODUCT: MK-2060  
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4.2.1.3
Pharmacodynamic Endpoints
aPTT and FXI activity (performed by Central Lab)
In order to assess PD, this study will include an assessment of aPTT prolongation levels
(relative to baseline), and FXI activity levels, with assays being performed at a Central
Laboratory. For PK/PD modeling, aPTT and FXI activity levels will be related to plasma
exposure. The time points for PD data collection are based on the projected PK profile of
MK-2060. Estimation of the aPTT effects of MK-2060 following multiple well-tolerated
doses is an exploratory objective of this study.
4.2.1.4
Planned Exploratory Biomarker Research
4.2.1.4.1
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 ADME; 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.
In addition to studying variation across the human genome, CYP2C19 genotyping will be 
specifically investigated for association of variations with any clinical data.
4.2.1.5
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.
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4.3
Justification for Dose
The dosing regimen for MK-2060 (25 mg IV on days 1, 3, 5 of week 1 as loading phase, and 
25 mg IV once in week 2) is the same as the first two weeks dosing of the high dose arm in 
the ongoing Ph2 study (PN007) and first two weeks of dosing of part 2 of MK-2060-004 in 
ESRD patients. This dose is projected to result in ~90% of participants with an aPTT of 
>1.5X baseline at Cmin during steady state (C168). The observed median Cmax is 93.4 nM 
and median Cmin is 44.8 nM at steady state after multiple dose of MK-2060 at 25 mg in 
ESRD patients receiving hemodialysis (MK-2060-004, incomplete data of Part 2) which 
achieved similar exposures as the projected steady state exposures of 25 mg in PN007 
(median Cmax of 77 nM and median Cmin of 42 nM). As this is a Phase 1 assessment of 
MK-2060 in humans, and the PK, pharmacodynamic and safety profiles of the compound are 
still being evaluated, modifications to the dose or dosing regimen may be required to achieve 
the scientific goals of the study objectives and/or to ensure appropriate safety monitoring of 
the study participants. Details of allowed modifications are provided in Section 8.11.6.
4.3.1
Rationale for Dose Interval and Study Design
The ESRD/HD population is the target patient population for MK-2060, and a proportion of 
ESRD patients are taking antiplatelet therapy, such as clopidogrel. Dosing of MK-2060 with 
the 1 week loading regimen followed by 1 maintenance dose on Day 8 provides a duration of 
time where MK-2060 exposures are highest and FXI inhibition/aPTT prolongation is 
maximized (but not exceeding exposures observed in previous trials in ESRD/HD patients). 
With the slow clearance of MK-2060, there will be prolonged pharmacology during washout, 
during which time safety and bleeding-related AEs will continue to be monitored. 
Each participant will be dosed and observed until discharge (~24 hours post-dose) for 
safety/tolerability.  24 hours is sufficient to monitor for initial safety/tolerability and local 
infusion site reactions and for systemic reactions to infusion. Following discharge, the
following measures are being taken in this protocol to ensure the safety of study
participants:

Participants will be informed that they are taking an anticoagulant as a
participant in this trial, and that this might increase the risk of bleeding as might 
occur in surgery, dental procedures, or strenuous exercise/contact sport activities.

Participants will be excluded if they have planned significant dental procedures,
including surgery, or other planned surgical procedures within duration of
participation in the trial.

Participants will be required to avoid scheduling any non-urgent/elective 
surgical or dental procedures, and to avoid strenuous physical activity and contact
sport activities for the duration of the trial.

Participants will be provided with an identification card and a medical alert
bracelet, both of which identify them as participants in an anti-coagulant
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research trial and, in the event of an emergency, will serve to notify healthcare
providers that they might be at risk for provoked bleeding.

If local lab aPTT values are > 3-fold above baseline, or local lab PT values are >
1.5 fold above baseline (at any time point), participants will be asked to remain in
the clinic for at least 24 hours, and until aPTT/PT values are no longer increasing
(upon retest) and at the discretion of the investigator.
Due to the physio-chemical properties of monoclonal antibody (mAb) therapeutics, transfer 
to the seminal compartment and subsequent vaginal uptake of a mAb is essentially zero, as 
demonstrated in rabbits, monkeys, and humans [Breslin, W. J., et al 2014], [Moffat, G. J., et 
al 2014], and [Sohn, W., et al 2015].  In addition, in an embryofetal developmental toxicity 
study in pregnant rabbits administered MK-2060, there was no evidence of embryofetal 
lethality or teratogenicity up to 120 mg/kg/day (the highest dose evaluated; 1 dose QW for 2 
weeks) providing an estimated systemic exposure margin of 234-fold the observed AUC0-
168hr of 63 day•μg/mL after multiple 60-minute IV infusion doses of 25 mg IV at steady 
state in ESRD patients.  Therefore, there is no risk to pregnant partners of male participants 
receiving MK-2060, and male contraception during clinical studies with MK-2060 is not 
warranted.
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 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).
A study may be paused during review of newly available preclinical/clinical safety, PK, 
pharmacodynamic, efficacy, or biologic data or other items of interest, prior to a final 
decision on continuation or termination of the study. It may be necessary to keep the study 
open for gathering/reviewing of additional supportive data to optimally complete the 
objective(s) of the study. If necessary, the appropriate amendment(s) to the protocol and/or 
appropriate communication(s) will be generated. If the decision has been made to end the 
study following this review period, the study end will be defined as the date of the Sponsor 
decision, and this end of study date supersedes the definitions outlined above. The 
Competent Authority(ies) and IRB(s)/IEC(s) will be apprised of the maximum duration of 
the study beyond the last participant out and the justification for keeping the study open.
4.4.1
Clinical Criteria for Early Study Termination
There are no prespecified criteria for terminating the study early.
5
STUDY POPULATION
Male and Female participants with ESRD on HD between the ages of 18 and 80 years 
(inclusive) will be enrolled in this study.
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Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1
Inclusion Criteria
A participant will be eligible for inclusion in the study if the participant meets all of the 
following criteria:
Type of Participant and Disease Characteristics
1. ESRD maintained on stable outpatient HD regimen at a healthcare center for > 3 months
prior to dosing, using an established and normally functioning, regular flow, uninfected 
mature AV fistula or AV graft and skin consistent with standard chronic HD access 
injuries, and HD stability defined as Kt/V ≥1.2 within 3 months prior to dosing.
2. On HD regimen at least 3 times per week for a minimum of 3 hours per dialysis session, 
using a complication-free well-maintained AV fistula or AV graft, expected and plan to 
continue this throughout and at least up to poststudy.
3. Is taking clopidogrel for a minimum of 2 weeks prior to the first dosing of MK-2060
administration and will continue to take clopidogrel for at least the duration of MK-2060 
treatment.
4. Have a Body Mass Index (BMI) ≥ 18 and ≤ 45 kg/m2. BMI = weight (kg)/height (m)2.
Dry weight (body weight after hemodialysis) should be used for BMI calculations.
5. Baseline health is judged to be stable based on medical history, physical examination, 
vital sign measurements and ECG performed prior to treatment allocation.
6. Liver function test (serum alanine aminotransferase [ALT] and aspartate 
aminotransferase [AST]) must be equal to or below 1.5X upper limit of normal (ULN) 
and deemed not clinically significant by the investigator.
7. Be willing to comply with the trial restrictions (see Section 5.3) for a complete summary 
of trial restrictions).
Demographics
8. Is male or female, from 18 years to 80 years of age inclusive, at the time of providing
informed consent.
Female Participants
9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and 
at least one of the following conditions applies: 
•
Not a WOCBP
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OR
•
A WOCBP and:
-
Uses 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 96 days 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. Contraceptive use by 
women should be consistent with local regulations regarding the methods of 
contraception for those participating in clinical studies
-
Has a negative highly sensitive pregnancy test (urine or serum as required by local 
regulations) within 76 hours before the first dose of study intervention. If a urine test 
cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is 
required. In such cases, 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 in Section 8.5.5.
-
Medical history, menstrual history, and recent sexual activity has been reviewed by 
the investigator to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.
Informed Consent
10.
The participant (or legally acceptable representative) has provided documented
informed consent/assent for the study. The participant may also provide 
consent/assent for FBR. However, the participant may participate in the study without 
participating in FBR.
Additional Categories
Consent must be documented by the participant’s dated signature or by the participant’s
legally acceptable representative’s dated signature on a consent form along with the dated
signature of the person conducting the consent discussion.
A copy of the signed and dated consent form should be given to the participant before
participation in the trial.
The initial informed consent form, any subsequent revised written informed consent form
and any written information provided to the participant must receive the IRB/ERC’s
approval/favorable opinion in advance of use. The subject 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 trial.
The communication of this information will be provided and documented via a revised
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consent form or addendum to the original consent form that captures the subject’s dated
signature or by the participant’s legally acceptable representative’s dated signature.
Specifics about a trial and the trial population will be added to the consent form template at
the protocol level.
The informed consent will adhere to IRB/IEC requirements, applicable laws and regulations
and Sponsor requirements.
5.2
Exclusion Criteria
The participant must be excluded from the study if the participant meets any of the following 
criteria:
Medical Conditions
1. History of any clinically significant concomitant disease or condition (including 
treatment for such conditions) or diseases whose current condition is considered 
clinically unstable that, in the opinion of the investigator, could either interfere with the 
study drug, compromise interpretation of study data, or pose an unacceptable risk to the 
patient. Participants with a remote history of uncomplicated medical events (e.g.,
uncomplicated kidney stones, as defined as spontaneous passage and no recurrence in the 
last 5 years, or childhood asthma) may be enrolled in the study at the discretion of the 
investigator.
2. Institutionalized, mentally or legally incapacitated at the time of prestudy (screening) 
visit or expected during the conduct of the study or has a history of clinically significant 
psychiatric disorder in the last 5 years. Participants who have had situational depression 
may be enrolled in the study at the discretion of the investigator.
3. History of cancer (malignancy), including adenocarcinoma,
Exceptions: (1) Adequately treated nonmelanomatous skin carcinoma or carcinoma in 
situ of the cervix or (2) Other malignancies that have been successfully treated with 
appropriate follow up and therefore unlikely to recur for the duration of the study, in the 
opinion of the investigator and with agreement of the Sponsor (eg, malignancies that have 
been successfully treated ≥10 years prior to the screening visit).
4. Has blood coagulation test from local lab (aPTT, PT) ≥ 20 % outside of normal range in 
screening period (confirmed by recheck)..
5. Any other clinically significant abnormalities in laboratory test results at screening that 
would, in the opinion of the investigator, increase the patient's risk of participation, 
jeopardize complete participation in the study, or compromise interpretation of study 
data.
6. Has a history of deep vein thrombosis or pulmonary embolism. Has a history of vascular 
access thrombosis within 1 month prior to enrollment. Has a personal or family history of 
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bleeding disorder (e.g., hemophilia, Factor V Leiden, prothrombin gene mutation, protein 
C or S deficiency, ATIII deficiency, anti- phospholipid Ab syndrome).
7. Has a history of GI bleeding, duodenal polyps or gastric ulcer in the last 5 years or severe 
hemorrhoidal bleed in last 3 months prior to screening.
8. Has a clinically significant history of or current frequent epistaxis within the last 3 
months or active gingivitis prior to screening.
9. At the time of screening or pre-dose, has planned significant dental procedures
(including planned dental surgery), or other planned surgical procedures within duration 
of participation in the trial.
10. Is positive for hepatitis B surface antigen or HIV.  Participants positive for hepatitis C 
antibodies may be enrolled with agreement of both investigator and sponsor.
11. The participant had a major surgery and/or donated or lost 1 unit of blood (approximately 
500 mL) within 4 weeks prior to the screening visit
12. History of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or 
has had an anaphylactic reaction or significant intolerability (ie, systemic allergic 
reaction) to prescription or nonprescription drugs or food.
13. Has a tattoo, scar, or other physical finding at the area of the infusion site that would 
interfere with infusion or a local tolerability assessment.
Prior/Concomitant Therapy
14. Unable to refrain from or anticipates the use of any medication, including prescription 
and nonprescription drugs or herbal remedies (except clopodigrel) beginning 
approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study 
intervention, throughout the study, until the poststudy visit. There may be certain 
medications that are permitted (see Section 6.5).
15. Has ongoing anticoagulant therapy (warfarin, apixaban, dabigatran, rivaroxaban, 
edoxaban, betrixaban) or antiplatelet therapy which does not include clopidogrel (ie. 
prasugrel, ticagrelor, ticlopidine, and aspirin). Intradialytic heparin is permitted.
16. Has a history (subject recall) of receiving any human immunoglobulin preparation
such as IVIG or RhoGAM within the last year.
17. Has a history (subject recall) of receiving any biological therapy (including human
blood products or monoclonal antibodies; excluding erythropoietin and insulin) within
the last 3 months or 5 half-lives (whichever is longer), or vaccination within the last 
month.
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Exceptions: 

Participants who have received seasonal flu vaccine and/or pneumococcal vaccine 
within one month prior to Day 1 dosing may be enrolled at the discretion of the 
investigator.

COVID-19 vaccine may be administered. Study intervention must be given at least 
72 hours following or at least 48 hours prior to any COVID-19 vaccination.
Investigational COVID-19 vaccines (i.e., those not licensed or approved for 
Emergency Use) are not allowed.
Prior/Concurrent Clinical Study Experience
18. Participated in another investigational study within 4 weeks (or 5 half-lives, whichever is 
greater) prior to the screening visit. The window will be derived from the date of the last 
dose in the previous study.
Diagnostic Assessments
19. Has a blood pressure >190 mmHg systolic or >110 mmHg diastolic.
20. Exclusion criteria for ECG:

Heart rate < 40 or > 110 bpm 

QTc interval > 500 msec 

Any significant arrhythmia or conduction abnormality, (including but not specific to 
atrioventricular block [2nd degree or higher], Wolff Parkinson White syndrome 
[unless curative radio ablation therapy]), which, in the opinion of the investigator and 
sponsor, could interfere with the safety for the individual patient.
Other Exclusions
21. Under the age of legal consent.
22. Consumes greater than 3 servings of alcoholic beverages (1 serving is approximately 
equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits 
[29.5 mL/1 ounce]) per day. Participants who consume 4 servings of alcoholic beverages 
per day may be enrolled at the discretion of the investigator.
23. Consumes excessive amounts, defined as greater than 6 servings (1 serving is 
approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or 
other caffeinated beverages per day.
24. A regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) 
abuse within approximately 2 years. Participants must have a negative drug screen prior 
to treatment allocation. Participants with a positive drug screen due to the use of 
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physician prescribed medications (e.g., opioids, benzodiazepines, antidepressants) may 
be enrolled at the discretion of the investigator.  In addition, participants with a positive 
THC may be enrolled at the discretion of the investigator if the participants’ THC use is 
under 4 times/month and the participants agree to not use during their study participation.  
Participants with positive THC on screening may have rechecks performed at the 
discretion of the investigator to ensure compliance with abstinence from THC use during 
study participation.
25. The investigator has any concern regarding safe participation in the study or for any other 
reason the investigator considers the participant inappropriate for participation in the 
study.
26. 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.
5.3
Lifestyle Considerations
5.3.1
Meals and Dietary Restrictions
5.3.1.1
Diet Restrictions
Fasting requirements for laboratory safety evaluations are specified in Section 10.2.
All meals on study dosing days will be served as to not interfere with the study procedures.
Meals and snack(s) will be provided by the investigator as per the CRUs standard procedures 
when domiciling.
Participants will be instructed to avoid ingesting certain foods (such as red meat, broccoli, 
turnips etc.) and certain medications and supplements (such as vitamin C supplements etc.) 
for about three days prior to feces sample collection to avoid false positive hemoccult test.
5.3.2
Caffeine, Alcohol, and Tobacco Restrictions
5.3.2.1
Caffeine Restrictions
Participants will refrain from consumption of caffeinated beverages or xanthine-containing 
products from 12 hours before the prestudy and poststudy visits and from 12 hours prior to 
and after study intervention administration. At all other times, caffeinated beverages or 
xanthine-containing products will be limited to no more than 6 units per day (1 unit = 120 mg 
of caffeine).
5.3.2.2
Alcohol Restrictions
Participants will refrain from consumption of alcohol 24 hours before the prestudy and 
poststudy visits and from 24 hours prior to and after study intervention administration. 
Participants will refrain from consumption of alcohol 12 hours prior to scheduled outpatient 
visits.
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At all other times, alcohol consumption is limited to no more than approximately 3 alcoholic 
beverages or equivalent servings (1 serving is approximately equivalent to: beer 
[354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) per day.
5.3.2.3
Tobacco Restrictions
Smoking (and/or the use of nicotine/nicotine-containing products) is permitted during the 
study. Participant should follow CRU’s smoking restrictions during domiciling.
5.3.3
Activity Restrictions
Participants will avoid unaccustomed strenuous physical activity (ie, weight lifting, running, 
bicycling, etc) from the prestudy (screening) visit throughout the study and until the 
poststudy visit.
5.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently enrolled in the study. A minimal set of screen-failure information may 
be included, as outlined in the eCRF entry guidelines. Minimal information may include 
demography, screen-failure details, eligibility criteria, and any AEs or SAEs meeting 
reporting requirements.
5.5
Participant Replacement Strategy
If a participant discontinues from study intervention or withdraws from the study within 21 
days after the first dosing, a replacement participant may be enrolled if deemed appropriate 
by the investigator and Sponsor. The replacement participant will generally receive the same 
intervention or intervention sequence (as appropriate) as the participant being replaced. The 
replacement participant will be assigned a unique treatment/randomization number.
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 MK-2060 will be packaged to support enrollment and replacement 
participants as required. When a replacement participant is required, the Sponsor or designee 
needs to be contacted before dosing the replacement participant. Clinical supplies will be 
affixed with a clinical label in accordance with regulatory requirements.
6.1
Study Intervention(s) Administered
The study interventions to be used in this study are outlined in Table 3.
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Table 3
Study Interventions
Arm 
Name
Arm 
Type
Intervention 
Name
Inter-
vention 
Type
Dose 
Formulation
Unit Dose 
Strength(s)
Dosage 
Level(s)
Route of 
Adminis-
tration
Regimen/
Treatment Period/
Vaccination 
Regimen
Use
IMP/
NIMP
Sourcing
MK-2060
Experi
mental
MK-2060
Drug
Lyophilized 
Powder
7.5 mg/vial
25 mg
IV 
Infusion
Week 1: Days 1, 3, 
5
Week 2: Day 8
Experi
mental
IMP
Provided 
centrally 
by 
SponsorP
EEA =European Economic Area; IMP=investigational medicinal product; IV = intravenous; NIMP=noninvestigational medicinal product.
The classification of IMP and NIMP 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/NIMP may exist. In these circumstances, local legislation is followed.
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All supplies indicated in Table 3 will be provided per the “Sourcing” column depending on 
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 a separate document provided by the Sponsor. The rationale 
for selection of doses to be used in this study is in Section 4.3.
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
Participants in this study will be allocated by nonrandom assignment.
6.3.2
Stratification
No stratification based on age, sex, or other characteristics will be used in this study.
6.3.3
Blinding
This is an open-label study; therefore, the Sponsor, investigator, and participant will know 
the intervention administered.
6.4
Study Intervention Compliance
Interruptions from the protocol-specified treatment plan require consultation between the 
investigator and the Sponsor and written documentation of the collaborative decision on 
participant management.
6.5
Concomitant Therapy
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed
during time periods specified by this protocol for that medication or vaccination. If there is a 
clinical indication for any medications or vaccinations specifically prohibited, 
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 or vaccination 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 or vaccine (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
The Sponsor Clinical Director should be contacted if there are any questions regarding 
concomitant or prior therapy.
Concomitant use of the following medications will be allowed during the conduct of the 
study as long as the subject has been on a stable dose and treatment regimen for at least 
approximately 2 weeks prior to screening and is able to withhold the use within four hours 
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prior to administration of the first dose of study drug. The name (generic and brand), dose 
and regimen for all concomitant medications should be recorded on the appropriate CRF. 
All medications must be reviewed and approved by the Sponsor clinical monitor prior to 
enrollment of an individual patient.  This list is not exhaustive, but serves as a guideline to 
facilitate the approval process between the investigator and the Sponsor clinical monitor
ALLOWED MEDICATIONS
Lipid Lowering Agents: Statins
Atorvastatin 
Simvastatin 
Pravastatin 
Lovastatin
Rosuvastatin
Pravastatin 
Lipid Lowering Agents: Fibrates
Fenofibrate 
Gemfibrozil
Lipid Lowering Agents: Other
Ezetimibe
Anti-Hypertensive Medications:
Monotherapy and combination therapy with an angiotensin converting enzyme (ACE) 
inhibitor, an angiotensin II receptor antagonist, beta blockers, calcium channel blockers, or a 
diuretic is allowed in the study.
Specific therapeutic categories include:
1.
ACE inhibitors
Benazepril 
Captopril
Enalapril
Fosinopril
Lisinopril 
Moexipril 
Perindopril
Quinapril 
Ramipril 
Trandolapril
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2.
Angiotensin II Receptor Antagonists
Candesartan
Eprosartan 
Irbesartan
Olmesartan
Telmisartan 
Valsartan 
3.
Diuretics
Hydrochlorothiazide 
Chlorothiazide 
Amiloride 
Triamterene 
Spironolactone 
Loop-diuretics, e.g., furosemide
4.
Beta-blockers
5.
Calcium channel-blockers
Diabetes Medications 
Specific therapeutic categories include: 
1.
Insulin 
2.
Metformin
3.
Sulfonylureas 
Glipizide 
Glyburide 
Glimepiride
4.
Meglitinides 
Repaglinide
Nateglinide 
5.
Thiazolidinediones
Pioglitazone 
Rosiglitazone
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6.
DPP-4 Inhibitors
Linagliptin 
Saxagliptin 
Sitagliptin 
Vildagliptin
7.
GLP-1 Analogs
Exenatide
Liraglutide
Iron 
Phosphate Binders 
Vitamin D 
Erythropoietin
PROHIBITED MEDICATIONS
Listed below are specific restrictions for concomitant therapy during the course of the trial, 
from signing consent to the poststudy visit:
Oral Anticoagulants (Intradialytic heparin is permitted in the study)
Warfarin
Apixaban
Dabigatran
Rivaroxaban
Edoxaban
Betrixaban
Antiplatelet Medications
Prasugrel
Ticagrelor
Ticlopidine
Aspirin 
NSAIDs (e.g., ibuprofen); however, the non-NSAID paracetamol/acetaminophen may be 
used for minor ailments without prior consultation with the Sponsor.
6.5.1
Rescue Medications and Supportive Care
No rescue or supportive medications are specified for use in this study.
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CRUs will be staffed with medically trained personnel with appropriate access to full service 
acute-care hospitals to facilitate rapid institution of medical intervention.
6.6
Dose Modification (Escalation/Titration/Other)
The dose and administration of the study intervention to any participant may be modified
based on newly available safety, tolerability, pharmacokinetic and/or pharmacodynamic data 
observed in other MK-2060 studies. If necessary, a participant must be discontinued for the 
reasons described in Section 7
6.6.1
Stopping Rules
The following stopping rules will be used during the conduct of this study.
If any of the below stopping rules are met, the study will be paused, and no further dosing 
will occur until the Sponsor has reviewed the totality of data available. To continue the study 
(on joint agreement with the Sponsor and investigator), a substantial amendment will be 
submitted for approval.
1. An individual participant reports an SAE considered related to the study intervention 
by the investigator.
2. Two (2) or more participants report Severe Nonserious AEs considered related to the 
study intervention by the investigator.
3. If one or more treatment-related infusion adverse events of severe intensity occurs in 
2 or more participants.
4. An increase in local lab aPTT >4.0-fold versus screening baseline as confirmed after 
repeat measurement in 2 or more participants. Local lab aPTT measured at the 
Screening Visit should be used as baseline value.
5. An increase in local lab PT >1.5-fold versus screening baseline as confirmed after 
repeat measurement in 2 or more participants. Local lab PT measured at the 
Screening Visit should be used as baseline value.
In severe FXI-deficient populations, aPTT prolongations greater than 3-fold have been 
observed [Asakai, R., et al 1991]. Using the same PD aPTT assay utilized in PN001 and to be 
used by the central lab in this study, samples of pooled normal human plasma were compared 
to those from FXI-deficient patients, which were tested individually [Ellsworth K 2018].  In 
normal human plasma, the clot time ranged between 31.8 and 36.4 seconds.  In plasma from 
FXI deficient patients, the clot time ranged between 99.5 and 128.1 seconds, which 
corresponded to a range of 2.9 to 3.9-fold prolongation in aPTT compared to that of the 
normal human plasma.  From data collected in PN001, it appears that higher doses of MK-
2060 provide similar inhibition as the severe FXI-deficient phenotype, evidenced by MK-
2060-associated increases in aPTT (local lab) up to 3.9-fold at the highest dose in PN001
(120 mg administered subcutaneously).  These aPTT prolongations occurred in the absence 
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of prolongation of PT and were associated with >95% inhibition of FXI activity, with no 
evidence of MK-2060-related AE. Therefore, the stopping criteria based upon an aPTT is >4-
fold after repeat measurement in 2 or more participants. 
Participants who receive intradialytic heparin will likely have an increased local lab aPTT at 
the 1-hour timepoint post dosing due to the pharmacologic effects of heparin.  In order to 
allow for the evaluation of the pharmacologic effects of MK-2060 alone, the 12-hour post-
dose local lab aPTT will be the first timepoint used to assess aPTT stopping criteria for 
participants who receive intradialytic heparin.  Heparin dosed at the time of hemodialysis 
should not interfere with aPTT at this 12-hour post-dose timepoint (heparin t1/2 is ~1hr).  All 
other local safety labs throughout the course of the trial will be drawn pre-hemodialysis and 
in the absence of heparin.
The safety of participants will be assessed on an ongoing basis, and while conditions that 
could warrant stopping dosing are not limited to those noted above, these criteria are meant 
to pre-specify circumstances under which the trial may be stopped to review the available 
safety data.  Importantly, if any criterion listed above occurs, further dosing will be stopped 
and review of available safety data by the investigator and Sponsor will be required prior to 
continuing the trial, which might include modification of safety monitoring procedures.  
6.7
Intervention After the End of the Study
There is no study-specified intervention after the end of the study.
6.8
Clinical Supplies Disclosure
This study is open-label; therefore, the participant, the study-site personnel, the Sponsor, 
and/or designee are not blinded. Study intervention (name, strength, or potency) is included 
in the label text; random code/disclosure envelopes or lists are not provided.
6.9
Standard Policies
MK-2060 will be provided by the Sponsor in sufficient quantity to complete the study.
6.9.1
Study Site Retention Samples
Not applicable.
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 before completion of the protocol-specified treatment period 
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will still continue to participate in the study as specified in Section 1.3 and Section 8.1.9, or 
if available, a PCL. If a participant discontinues at any point during the dosing period, all 
safety follow-ups and PK, PD sample collections should continue weekly post the last dose. 
Safety procedures include full physical examination, systemic infusion reaction assessment, 
semi-recumbent vital signs, orthostatic vital signs, safety lab measurements, AE reviews and 
assessment of time to hemostasis if on-site dialysis. The poststudy timing and assessments 
should be performed as outlined in Section 1.3.2
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.
A participant must be discontinued from study intervention, but continue to be monitored in 
the study, for any of the following reasons:
•
The participant or participant’s legally acceptable representative requests to discontinue 
study intervention.
•
The participant has a medical condition or personal circumstance which, in the opinion of 
the investigator and/or Sponsor, placed the participant at unnecessary risk from continued 
administration of study intervention.
•
The participant has a confirmed positive serum pregnancy test.
•
The participant has a positive drug screen at any time during the course of the study and 
after confirmation by recheck.
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 FBR, 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.
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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 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 procedure met 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.
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The maximum amount of blood collected from each participant over the duration of the study
will not exceed ~453 mL (Appendix 8).
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 informed consent from each potential participant (or their legally 
acceptable representative) prior to participating in this clinical study or FBR. 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 
documented informed 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 study protocol number, study 
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 FBR 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 
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to FBR. A copy of the informed consent will be given to the participant before performing 
any procedure related to FBR.
8.1.2
Inclusion/Exclusion Criteria
All inclusion and exclusion criteria will be reviewed 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 allocation,
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 health care provider can obtain information about study 
intervention in emergency situations where the investigator is not available.
8.1.4
Medical History
A medical history will be obtained by the investigator or qualified designee.
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 any 
protocol-specified washout requirement, 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.
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 before allocation. Each participant will 
be assigned only 1 screening number. Screening numbers must not be reused for different 
participants.
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8.1.7
Assignment of Treatment/Randomization Number
All eligible participants will be randomly allocated and will receive a 
treatment/randomization number. The treatment/randomization number identifies the 
participant for all procedures occurring after treatment allocation. Once a 
treatment/randomization number is assigned to a participant, it can never be reassigned to 
another participant.
A single participant cannot be assigned more than 1 treatment/randomization number.
8.1.8
Study Intervention Administration
Study intervention(s) will be administered by the investigator and/or study staff according to 
the specifications within the pharmacy manual.
8.1.8.1
Timing of Dose Administration
MK-2060 will be prepared and dosed per the instructions outlined in the Study Pharmacy
Manual. All doses of MK-2060 will be given 30 minutes after initiation of hemodialysis and 
administered over approximately 60 minutes.
8.1.9
Discontinuation and Withdrawal
The investigator or study coordinator must notify the Sponsor when a participant has been 
discontinued/withdrawn from the study and/or intervention. If a participant discontinues for 
any reason at any time during the course of the study, the participant may be asked to return 
to the clinic (or be contacted) for a poststudy visit as per the number of days described in
Section 8.11.4 to have the applicable procedures conducted. However, the investigator may 
decide to perform the poststudy procedures at the time of discontinuation or as soon as 
possible after discontinuation. If the poststudy visit occurs prior to the safety follow-up time 
frame as specified in Section 8.5.1, the investigator should perform a follow-up telephone 
call at the end of the follow-up period (Section 8.5.1) to confirm if any AEs have occurred 
since the poststudy clinic visit. Any AEs that are present at the time of 
discontinuation/withdrawal should be followed in accordance with the safety requirements 
outlined in Section 8.5.
8.1.9.1
Withdrawal From Future Biomedical Research
Participants may withdraw their consent for FBR. Participants may withdraw consent at any 
time by contacting the study investigator. If medical records for the 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 
FBR 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 before the request being received by the Sponsor will continue to be used 
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as part of the overall research study data and results. No new analyses would be generated 
after the request is received.
If the medical records for the study are no longer available (eg, if the investigator is no longer 
required by regulatory authorities to retain the 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
This is an open-label study; there is no blinding for this study. The emergency unblinding 
call center will be available so that a health care provider can obtain information about study 
intervention in emergency situations where the investigator is not available.
8.1.11
Domiciling
Participants will report to the CRU the evening prior to the scheduled day of trial drug 
administration and remain in the unit for 24 hours after each MK-2060 administration. At the 
discretion of the investigator or at the request of the participant, participants may  remain in 
the CRU longer. 
8.1.12
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 trial includes:

Infusion pumps

VS and ECG instruments

All equipment to process study drug and samples, such as but not limited to, 
centrifuge equipment, pipettes, and freezers for MK-2060 and sample storage.
8.2
Efficacy/Immunogenicity Assessments
The amino acid sequence of MK-2060 is highly similar to standard human IgG4 sequences.  
The mechanism of action of MK-2060 is not immunomodulatory and the ESRD population is 
less likely to have a robust immune response. 
Following analysis for ADA from PN001, one out of 45 (2.2%) had positive ADA test result 
(50 mg SC dose, at the Day 90 post dose time point). The presence of ADA did not appear to 
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have an effect on the PK of MK-2060. Determining the impact of ADA on PD was not 
possible as there was no measurable PD effect at the Day 90 time point. 
From the ongoing PN004, no ADA positive samples were found over 150 days following a 
single dose of MK-2060 in Part 1 of MK-2060 PN004 in ERSD participants. In Part 2 of 
PN004, following multiple repeat dosing of MK-2060, no ADA positive samples were found 
over 111 days after initiation of dosing. Based on the PK profiles observed to date and 
available ADA analysis data from both PN001 and PN004, it is unlikely that ADA have 
affected the current PK profiles. Therefore, the overall risk of immunogenicity is expected to 
be low for MK-2060.
8.3
Safety Assessments
Details regarding specific safety procedures/assessments to be performed in this study are 
provided. The total amount of blood/tissue to be drawn/collected over the course of the study 
(from prestudy to poststudy visits), including approximate blood/tissue volumes 
drawn/collected by visit and by sample type per participant, can be found in Appendix 8. 
Planned time points for all safety assessments are provided in the SoA.
8.3.1
Physical Examinations
A complete physical examination will be conducted by an investigator or medically qualified 
designee (consistent with local requirements) per institutional standard. Height and weight 
will also be measured and recorded.
Investigators should pay special attention to clinical signs related to previous serious 
illnesses.
8.3.1.1
Body Weight and Height
Body height and weight will be obtained with the subjects shoes off, jacket or coat removed.
8.3.1.2
Body Mass Index (BMI)
BMI equals a person's weight in kilograms divided by height in meters squared 
(BMI=kg/m2). BMI will be rounded to the nearest whole number according to the standard 
convention of 0.1 to 0.4 round down and 0.5 to 0.9 round up.
Dry weight (body weight after hemodialysis) should be used for BMI calculations.
8.3.2
Vital Signs
•
Body temperature, HR, RR, and BP will be assessed.
•
BP and pulse measurements will be assessed semi-recumbent with a completely 
automated device. Manual techniques will be used only if an automated device is not 
available.
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•
VS will be measured in a semi-recumbent position after at least 10 minutes rest and will 
include temperature, systolic and diastolic BP, and pulse and RR.
8.3.2.1
Resting Vital Signs
Vital Sign Measurements (Heart Rate and Blood Pressure)
Participants should be resting in a quiet setting without distractions in a semi-recumbent
position for at least 10 minutes before having VS measurements obtained. Semi-recumbent
VS will include HR, systolic and diastolic BP, RR, and body temperature at timepoints 
indicated in the SoA. The correct size of the BP cuff and the correct positioning on the 
participants' arm is essential to increase the accuracy of BP measurements.
The Day 1 predose (baseline) resting HR and BP will be in triplicate measurements, obtained 
at least 1 to 2 minutes apart within 3 hours of dosing MK-2060. The median of these 
measurements will be used as the baseline to calculate change from baseline for safety 
evaluations (and for rechecks, if needed). All other VS measurements will be single 
measurements.
Participants will continue to rest semi-recumbent from dosing until 4 hours postdose except 
to stand for any study-related procedure.
Body Temperature
Body temperature will be measured. The same method must be used for all measurements for 
each individual participant and should be the same for all participants at a given site.
Respiratory Rate
Respiratory rate (breaths per minute) will be measured and recorded as single measurements.
8.3.2.2
Orthostatic Vital Signs
Orthostatic VS (HR and systolic and diastolic BP) will also be obtained. Participants should 
be semi-recumbent for at least 10 minutes and then stand upright for approximately 
2 minutes before measurement of orthostatic VS.
8.3.3
Electrocardiograms
Special care must be taken for proper lead placement by qualified personnel. Skin should be 
clean and dry before lead placement. Participants may need to be shaved to ensure proper 
lead placement. Female participants may need to remove interfering garments.
Participants should be resting in the semi-recumbent position for at least 10 minutes before
each ECG measurement.
The correction formula to be used for QTc is Fridericia.
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If repeat ECGs are required, the clinical site will decide whether to leave the electrodes in 
place or mark the position of the electrodes for subsequent ECGs. To mark the position of the 
electrodes, 12-lead electrode sites will be marked on the skin of each participant with an 
ECG skin-marker pen to ensure reproducible electrode placement.
The Day 1 predose ECGs will be obtained in triplicate at least 1 to 2 minutes apart within 
3 hours before dosing MK-2060. The median of these measurements will be used as the 
baseline to calculate change from baseline for safety evaluations (and for rechecks, if 
needed). Unless otherwise designated in the flow chart, all other ECG measurements will be 
single measurements.
If a participant demonstrates an increase in QTc interval ≥60 msec compared with median 
predose baseline measurement, the ECG will be repeated twice within 5 minutes. The median 
value of the QTc interval from the 3 ECGs will represent the value at that time point. If the 
median QTc interval increase from baseline for any postdose time point is ≥60 msec, the 
participant will continue to be monitored by repeat 12-lead ECGs every 15 minutes for at 
least 1 hour or until the QTc is within 60 msec of baseline. If prolongation of the QTc 
interval ≥60 msec persists, a consultation with a study cardiologist may be appropriate and 
the Sponsor should be notified.
If the median QTc interval is ≥500 msec, the Sponsor should be notified and the ECGs 
should be reviewed by a cardiologist. The participant should be telemetry monitored (until 
the QTc is <500 msec) or should be considered for transfer to a location where closer 
monitoring and definitive care (eg, a CCU or ICU) is available.
If the participant has unstable hemodynamics, or has any clinically significant dysrhythmias 
noted on telemetry, the participant should be immediately transferred to an acute care setting 
for definitive therapy.
If prolongation of the QTc is noted, concomitant medications that prolong QTc should be 
held until the QTc is within 60 msec of baseline and the QTc is <500 msec.
A cardiologist will be consulted by the investigator as needed to review ECG tracings with 
significant abnormalities.
8.3.4
Assessment of Time to Hemostasis
Assessment of time to adequate hemostasis will be conducted at the conclusion of each onsite 
hemodialysis session. Procedure for assessment of time to hemostasis will be provided in a 
separate trial Study Operations Manual by the Sponsor. Baseline time to hemostasis will be 
established by the assessments performed during the Run-in period.
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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 96 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.
8.3.6
Photograph of Rash
Photographs of the rash are highly recommended to be taken immediately, along with any 
additional information that may assist the investigator to evaluate the skin reaction, skin 
eruption or rash occurrence in determining etiology and drug relationship.
8.4
Management of Infusion Reaction During and Post-dose
As outlined in the IB, the risk of infusion reactions to MK-2060 is considered low since the 
molecule contains primarily human sequences. However, infusion reactions may be 
observed. Since the purpose of the study is to characterize the safety profile of MK-2060, no 
prophylactic pre-medications to reduce the risk of infusion reactions will be given prior to 
MK-2060 administration.
In rare instances, systemic infusion reactions are severe and may have a fatal outcome. It is 
likely that most infusion reactions will occur within the first 30-60 minutes of administration, 
though they may be observed up to 24-30 hours post-dose. An anaphylactic reaction is a 
severe type of infusion reaction that is characterized by cutaneous and mucosal symptoms, 
such as generalized hives, pruritis or flushing, swollen lip-tongue-uvula and angioedema, 
accompanied by respiratory compromise (bronchospasm, stridor or hoarseness) and/or 
changes in blood pressure (hypotension). Severe infusion reactions, including cytokine 
release syndrome and hypersensitivity reactions must be promptly treated with interruption 
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of the infusion, medical management, appropriate monitoring, and life-saving measures. 
Appropriate resuscitation equipment and a physician should be readily available during the 
period of drug administration. Less severe infusion reactions may respond to a reduction in 
the infusion rate and medical management.
8.4.1
Systemic Infusion Reaction Assessment
Participants will be monitored during the administration of MK-2060 for 24 hours post-dose 
at CRU after the initiation of administration. During this time, signs and symptoms of a 
systemic injection/infusion reaction, including but no limited to fever, VS changes 
(tachycardia/hypotension), pruritis, urticarial (hives), lip swilling, angioedema, 
bronchospasm, stridor, hoarseness, and shortness of breath will be monitored. 
Injection/infusion reactions must be assessed and managed promptly. 
8.4.2
Local Infusion Reaction Assessment
A local infusion site examination will be obtained as outlined in Section 1.3 and will include 
an assessment of any pain, tenderness, erythema/redness and induration/swelling. These 
events will be evaluated based upon the system outlined in the guidance for the industry 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials in Table 4. Infusion reactions must be assessed and managed 
promptly per site procedure.
Participants who call the CRU to report an infusion site reaction within 7 days postdose may 
be asked to return to the CRU as soon as possible for an additional local infusion site reaction 
assessment.
Table 4
Local Infusion Reaction Assessment
Local Site 
Reaction
Mild
Moderate
Severe
Potentially Life
Threatening
Pain
Does not 
interfere with 
activity
Repeated use of non-
narcotic pain reliever > 
24 hr or interferes with 
activity
Any use of narcotic 
pain reliever or 
prevents daily 
activity
Emergency room (ER) 
visit or hospitalization
Tenderness
Mild discomfort 
to touch
Discomfort with 
movement
Significant 
discomfort at rest
ER visit or 
hospitalization
Erythema/
Redness
2.5-5 cm
5.1 – 10 cm
> 10 cm
Necrosis or exfoliative 
dermatitis 
Induration/
Swelling
2.5 – 5 cm and 
does not 
interfere with 
activity
5.1 – 10 cm or 
interferes with activity
> 10 cm or prevents 
daily activity
Necrosis
Adapted from the guidance for the industry Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials.
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8.5
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 8.5.3.
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.
8.5.1
Time Period and Frequency for Collecting AE, SAE, and Other Reportable 
Safety Event Information
AEs, SAEs, and other reportable safety events that occur after the participant provides 
documented informed consent, but before intervention allocation, must be reported by the 
investigator under any of the following circumstances:
•
if the participant is receiving placebo run-in or other run-in treatment,
•
if the event causes the participant to be excluded from the study,
•
if it is the result of a protocol-specified intervention, including, but not limited to washout 
or discontinuation of usual therapy, diet, placebo, or a procedure.
From the time of intervention allocation through ~96 days after cessation of intervention, all 
AEs, SAEs and other reportable safety events must be reported by the investigator.
Additionally, any SAE brought to the attention of an investigator any time outside the period 
specified in the previous paragraph also 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 5.
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Exception: A positive pregnancy test at the time of initial screening is not a reportable event 
unless the participant has received study intervention.
Table 5
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
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 24 
hours of 
learning of 
event
DILI=drug-induced liver injury; ECI=event of clinical interest; NSAE=nonserious adverse event; SAE=serious adverse 
event.
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8.5.2
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.
8.5.3
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 allocated participants for 
outcome. Further information on follow-up procedures is given in Appendix 3.
8.5.4
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.
8.5.5
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.
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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.
8.5.6
Disease-related Events and/or Disease-related Outcomes Not Qualifying as 
AEs or SAEs
Not applicable.
8.5.7
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. An overdose of Sponsor's product, as defined in Section 8.6.
2. 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 on 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).
It may also be appropriate to conduct additional evaluation for an underlying etiology in the 
setting of abnormalities of liver blood tests including AST, ALT, bilirubin, and alkaline 
phosphatase that do not meet the criteria noted above. In these cases, the decision to proceed 
with additional evaluation will be made through consultation between the study investigators 
and the Sponsor Clinical Director. However, abnormalities of liver blood tests that do not 
meet the criteria noted above are not ECIs for this study.
8.6
Treatment of Overdose
For purposes of this study, an overdose will be defined as any dose of any drug administered 
as part of the study exceeding the dose prescribed by 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.
Sponsor does not recommend specific treatment for an overdose. Decisions regarding dose 
interruptions or modifications will be made by the investigator in consultation with the 
Sponsor Clinical Director based on the clinical evaluation of the participant.
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8.7
Pharmacokinetics
The decision as to which plasma and/or urine samples collected will be measured for 
evaluation of PK/pharmacodynamics will be collaboratively determined by the Sponsor (eg, 
samples at lower doses may not be measured if samples at higher doses reveal undetectable 
drug concentrations). If indicated, these samples may also be measured and/or pooled for 
assay in an exploratory manner for metabolites and/or additional pharmacodynamic markers.
8.7.1
Blood Collection for Plasma MK-2060 and Clopidogrel
Sample collection, storage, and shipment instructions for plasma samples will be provided in 
the Study Operations Manual by the Sponsor. Samples taken on the day of infusion will be 
collected in the opposite arm from the infusion site. The 1-hour PK sample will be obtained 
immediately prior to the end of infusion (i.e. no more than 15 min before anticipated time of 
the end of infusion). As plasma concentrations of the parent compound of clopidogrel are 
very low and are generally below the quantification limit beyond 2 hours after dosing, 
concentrations of the main circulating metabolite clopidogrel carboxylic acid will be assessed 
to monitor clopidogrel therapy. 
8.8
Pharmacodynamics
Sample collection, storage, and shipment instructions for PT/aPTT/ FXI activity by central 
lab samples will be in the operations 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.
8.9.1
Planned Genetic Analysis Sample Collection
The planned genetic analysis sample will be drawn for CYP2C19 genotyping and for planned 
analysis of the association between genetic variants in DNA and drug response. If the 
IRB/IEC does not approve of the planned analysis of the association between DNA variation 
and drug response, or if there is a local law or regulation prohibiting the same, data analysis 
will be limited to CYP2C19.  Leftover extracted DNA will be stored for FBR if the 
participant provides documented informed consent for FBR. 
Sample collection, storage, and shipment instructions for planned genetic analysis samples 
will be in the Operations/Laboratory Manual.
8.9.2
Blood Collection for PT, aPTT, FXI Activity
PT and aPTT at screening, predose, and postdose specified in the SoA will be performed 
locally for safety monitoring. All other predose and postdose PT and aPTT, as well as FXI
activity will be performed at a central vendor for PK/PD analysis. Sample collection, storage, 
and shipment instructions for the PT, aPTT, FXI activity will be provided in a separate Study 
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Operations Manual by the Sponsor. The primary data for statistical analysis and modeling 
will be based on the information from the central vendor.
8.9.3
Blood for Plasma ADA
Sample collection, storage, and shipment instruction for plasma samples will be provided in a 
separate Study Operations Manual by the Sponsor.
8.10
Future Biomedical Research Sample Collection
If the participant provides documented informed consent for FBR, the following specimens 
will be obtained as part of FBR:

Leftover DNA for future research.

Leftover main study plasma for future research.
8.11
Visit Requirements
Visit requirements are outlined in Section 1.3. Specific procedure-related details are provided 
in Section 8.
8.11.1
Screening and Run-in Period
Screening Visit:
Within 6 weeks before intervention allocation, potential participants will be evaluated to 
determine that they fulfill the entry requirements as set forth in Section 5.
Participants may be rescreened after consultation with the Sponsor. Rescreening should 
include all screening procedures listed in the SoA, including consent review. 
Run-in Period:
Approximately 14 days before intervention allocation, potential participants who meet 
inclusion/exclusion criteria at the Screening Visit will report to the clinical research unit to 
perform on site hemodialysis on the days per SoA. Baseline Time to hemostasis will be 
measured during the run-in period. Refer to the SoA for other procedures required for the 
run-in period.
8.11.2
Treatment Period
Refer to the Schedule of Activities (Section 1.3) and Administrative and General Procedures 
(Section 8.1).
After all predose procedures have been completed, participants will be assigned a unique 
allocation number in a computer-generated allocation schedule. 
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Participants will be administered study drug as indicated in Section 6. Participants who on 
Day 1 have a significant acute illness or fever prior to the administration of study drug may 
be rescheduled.
8.11.3
Poststudy
The poststudy visit will occur approximately 96 days following administration of the last 
dose of study drug. Procedures outlined in the poststudy visit may be obtained on Day 104
(±7 days). However, follow up on any clinical or laboratory AEs should occur in person if 
the poststudy visit occurs prior to 96 days following administration of the last dose of study 
drug.
8.11.4
Participants Discontinued From Study Intervention but Continuing to be 
Monitored in the Study
At any point if a participant discontinues from treatment but continues to be monitored in the 
study, all of study procedures specified in the SoA may be completed upon joint agreement 
between the investigator and the Sponsor. The subset of study procedures completed will be 
communicated in a PCL.
8.11.5
Critical Procedures Based on Study Objectives: Timing of Procedure
For this study, the blood sample for MK-2060 is the critical procedure.
At any postdose time point, the blood sample for MK-2060 needs to be collected as close to 
the exact time point as possible. All other procedures should be completed as close to the 
prescribed/scheduled time as possible. Study procedures can be performed before or after the 
prescribed/scheduled time.
The order of priority can be changed during the study with joint agreement of the investigator 
and the Sponsor Clinical Director.
Any nonscheduled procedures required for urgent evaluation of safety concerns take 
precedence over all routine scheduled procedures.
The following variance in procedure collection times will be permitted.
•
Postdose PK and PD sample collection, standard safety evaluations (VS, ECG, laboratory 
safety tests (including chemistry/hematology, aPTT, PT), physical exam (full, symptom 
driven, systemic injection/infusion, local injection/infusion)) as outlined in 
Table 6 and Table 7 below.
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Table 6
Pharmacokinetic (Blood), Pharmacodynamic and Biomarker Collection Windows
PK, PD and ADA Collection
PK, PD and ADA Collection Window
Days 1, 3, 5, 8: predose 
Within 2 hr of dosing (samples to be 
collected before dialysis)
Day 1, 3, 5, 8: 1 hr post each dose
± 15 min (within 15 min of end of infusion)
Days 1, 3, 5, 8: 12 hr post dose
± 30 min
Days 2, 9,10 
± 4 hr of theoretical sampling time
Days 12, 15, 21, 29, 35
± 1 day 
Days 49, 67 
± 3 days 
Day 104
± 7 days 
•
Predose standard safety evaluations: VS and ECG within 3 hours of MK-2060 dosing; 
laboratory safety tests (including aPTT and PT at local lab), drug screen and physical 
exam within 24 hours of MK-2060 dosing.
Table 7
Postdose Safety Evaluation Windows
Postdose Standard Safety Evaluations (VS, 
ECG, laboratory safety tests, and physical 
exam)
Postdose Evaluation Window
Days 1, 3, 5, and 8: all postdose
± 30 min of theoretical sampling time
Days 2, 9, and 10 
± 4 hr of theoretical sampling time
Days 12, 15, 21, 29, 35
± 1 day 
Days 49, 67
± 3 days 
Day 104
± 7 days  
•
Assessment of time to adequate hemostasis: at the conclusion of the onsite hemodialysis 
session, after hemodialysis catheters are removed from the dialysis access site.
•
Hemoccult test: samples may be obtained within 48 hours of specified timepoint or first 
available sample if not within the specified time window.
•
Postdose evaluations: weight (Day 104), serum or urine pregnancy test (Day 104): use 
windows indicated in Table 7.
•
Study intervention administration: +/- 1 hour relative to time of dosing on Day 1.
•
Run-in (Day -14 to Day -3 Visits): ± 1 day is allowed.
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8.11.6
Study Design/Dosing/Procedures Modifications Permitted Within Protocol 
Parameters
This is a Phase 1 assessment of MK-2060 in participants with ESRD on HD, and the PK, 
pharmacodynamic, and safety profiles of the compound are still being elucidated. This 
protocol is written with some flexibility to accommodate the inherent dynamic nature of 
Phase 1 clinical studies. Modifications to the dose, dosing regimen, and/or clinical or 
laboratory procedures currently outlined may be required to achieve the scientific goals of 
the study and/or to ensure appropriate safety monitoring of the study participants.
As such, some alterations from the currently outlined dose and/or dosing regimen may be 
permitted based on newly available data, but the maximum daily dose may not exceed those 
currently outlined in the protocol.
•
Decrease in the duration of study intervention administration (eg, number of days)
•
Adjustment of the dosing interval (eg, divided doses [bid to qd, qd to bid, tid, or vice 
versa])
•
Lengthening of the washout period between doses
•
Addition of PK pause
•
Instructions to take study intervention with or without food or drink may also be modified 
based on newly available data
•
Modification of the PK/pharmacodynamic sample processing and shipping details based 
on newly available data
The PK/pharmacodynamic sampling scheme currently outlined in the protocol may be 
modified during the study based on newly available PK or pharmacodynamic data (eg, to 
obtain data closer to the time of peak plasma concentrations). If indicated, these collected 
samples may also be assayed in an exploratory manner for metabolites and/or additional 
pharmacodynamic markers.
Up to additional 50 mL of blood may be drawn for safety, PK, and/or pharmacodynamic 
analyses. The total blood volume withdrawn from any single participant will not exceed the 
maximum allowable volume during his/her participation in the entire study (Appendix 8).
The timing of procedures for assessment of safety procedures (eg, vital signs, ECG, safety 
laboratory tests, etc) may be modified during the study based on newly available data. 
Additional laboratory safety tests may be added to blood samples previously drawn to obtain 
additional safety information. These changes will not increase the number of study 
procedures for a given participant during his/her participation in the entire study.
It is understood that the current study may use some or none of the alterations described 
above. Any alteration made to this protocol to meet the study objectives must be detailed by 
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the Sponsor in a letter to the Study File and forwarded to the investigator for retention. The 
letter may be forwarded to the IRB/IEC at the discretion of the investigator.
9
STATISTICAL ANALYSIS PLAN
9.1
Statistical Analysis Plan Summary
This section contains a summary of the statistical analyses for this trial. Full details can be 
found in the subsequent sections. Since this is an exploratory study, statistical analyses will 
consist of presenting the descriptive statistics in shape of appropriate plots and summary 
tables (mean, standard deviation, median, min, max). 
9.2
Responsibility for Analyses
The statistical analysis of the data obtained from this study will be conducted by, or under the 
direct auspices of, the Early Clinical Development Statistics Department in collaboration 
with the Quantitative Pharmacology and Pharmacometrics Department and Translational 
Pharmacology Department of the Sponsor.
If, after the study has begun, changes are made to the statistical analysis plan stated below, 
then these deviations to the plan will be listed, along with an explanation as to why they 
occurred, in the Clinical Study Report.
9.3
Hypotheses/Estimation
Objectives of the study are stated in Section 3.
Primary Objective: To assess the safety and tolerability following multiple doses of 
concomitant treatment of MK-2060 and clopidogrel by measuring the bleeding 
related AEs
Secondary Objective 1: To evaluate plasma pharmacokinetics of MK-2060 and 
clopidogrel following multiple doses of concomitant treatment of MK-2060 and 
clopidogrel
Estimation:

Estimate plasma AUC0-168, Cmax, C168, Tmax, terminal t1/2, CL, Vz. 
Secondary Objective 2: To determine whether the increase in time required to 
achieve hemostasis in ESRD patients treated with MK-2060 and following 
completion of dialysis remains below 20 minutes 
Hypothesis:

Mean time-to-hemostasis for MK-2060 treatment is less than 20 minutes. 
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Tertiary/Exploratory Objective 1: To explore the effect of concomitant treatment 
of MK-2060 and clopidogrel on aPTT.
Estimation:

Estimate aPTT fold change from baseline.
Tertiary/Exploratory Objective 2: To explore the effect of concomitant treatment 
of MK-2060 and clopidogrel on prothrombin time.
Estimation:

Estimate PT fold change from baseline.
9.4
Analysis Endpoints
Primary Endpoints
1. Safety and tolerability following multiple doses of concomitant treatment of MK-
2060 and clopidogrel are the primary endpoints. Thus all AEs including bleeding 
related AEs (as defined in Section 4.2.1.1) are the primary endpoints for this study.
Secondary Endpoints (Pharmacokinetic)
1. Pharmacokinetics: The pharmacokinetic variables of secondary interest for MK-2060 
are plasma AUC0-168, Cmax, C168, Tmax, terminal t1/2, CL, and Vz.
2. Time to hemostasis
Exploratory Endpoints:
1. Pharmacodynamics: The PD variable of exploratory interest is aPTT (change from 
baseline). Baseline is defined as the pre-dose value.
2. ADA
9.5
Analysis Populations
The following populations are defined for the analysis and reporting of data.  All subjects 
will be reported, and their data analyzed, according to the treatment(s) they actually received.
All Subjects as Treated: The All Subjects as Treated Population consists of all subjects who 
received at least one dose of treatment.  This population will be used for assessments of 
safety and tolerability.
Per-Protocol: The Per-Protocol Population consists of the set of data generated by the subset 
of subjects who comply with the protocol sufficiently to ensure that these data will be likely 
to exhibit the effects of treatment, according to the underlying scientific model. Compliance 
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covers such considerations as exposure to treatment, availability of measurements and 
absence of important protocol deviations. Important protocol deviations will be identified to 
the extent possible prior to unblinding by individuals responsible for data 
collection/compliance, and its analysis and interpretation.  Any subjects or data values 
excluded from analysis will be identified, along with their reason for exclusion, in the CSR.  
At the end of the study, all subjects who are compliant with the study procedure as 
aforementioned and have available data from at least one treatment will be included in the 
Per-Protocol dataset. 
9.6
Statistical Methods
Safety 
Summary statistics and plots will be generated for raw laboratory safety tests, ECGs, and/or 
VS as well as for change from baseline, as deemed clinically appropriate.  For the primary 
endpoint, i.e., the bleeding related AEs, descriptive summary (total counts, percentage) will 
be provided. Same will be provided for all AEs as well as for the secondary and exploratory 
endpoints wherever appropriate. For continuous measurements, mean, standard deviation, 
median, min, max will be provided. Depending on the safety parameter, the difference from 
baseline will either be computed on the original scale (raw change from baseline) or on the 
log scale and back-transformed for reporting (percent change from baseline) as appropriate. 
Values will be listed for each PK parameter (including Tmax and apparent terminal t1/2), and 
appropriate non-model based descriptive statistics will be provided.
Secondary Hypothesis:
To determine whether the mean time-to-hemostasis recorded from patients treated with MK-
2060 is lower than the cut-off time of 20 minutes, a Bayesian approach will be used. 
Utilizing a non-informative flat prior, the posterior probability that the observed mean of 
time-to-hemostasis of participants is less than 20 will be calculated, and the criteria for 
success will be met if the following condition is satisfied. 
Posterior-probability (PP) (µTH < 20) ≥ 0.60
Where 
µTH = mean of the time-to-hemostasis measurements for ESRD patients treated with MK-
2060
MK-2060 PK parameters including plasma AUC0-168, Cmax, C168, Tmax, terminal t1/2, 
CL, Vz with the following (non-model-based) descriptive statistics will be provided: N 
(number of subjects with non-missing data), geometric mean, and geometric percent CV 
(calculated as 100 x sqrt(exp(s2 ) - 1), where s2 is the observed variance on the natural log-
scale). 
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Exploratory Estimation:
Descriptive statistics as well as appropriate plots will be displayed for aPTT fold change 
from baseline. To describe the subject distribution using a contingency table for various time-
to-hemostasis measurements with respect to treatments by clopidogrel and clopidogrel+MK-
2060, respectively. 
Time-to-hemostasis (mins)
Clopidogrel 
Clopidogrel + MK-2060
<10
10-20
> 20
9.7
Interim Analyses
No interim analysis is planned for this study. 
9.8
Multiplicity
Since there are no pre-specified primary hypotheses, no adjustments for multiplicity are 
needed.
9.9
Sample Size and Power Calculations
Approximately 12 subjects will be enrolled for this study. The success criterion is that the 
posterior probability (PP) for the mean time-to-hemostasis less than 20 min, is greater than 
60%. Based on the assumed prior mean and standard deviation calculated from data for MK-
2060-004, the PP is calculated based on 10,000 simulations, and is found to be reasonably 
high (>X%) that PP is above 60%. 
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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)
Code of Conduct for Interventional Clinical Trials
I. Introduction
A. Purpose
MSD, through its subsidiaries, conducts clinical trials worldwide to evaluate the safety and effectiveness of our 
products. As such, we are committed to designing, implementing, 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 local and/or national regulations (including all applicable data protection laws and
regulations), and International Council for Harmonisation Good Clinical Practice (ICH-GCP), and also 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.
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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 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.
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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 
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, frequently known as a financial disclosure form, provided by 
the Sponsor. The investigator/subinvestigator(s) also consent to the transmission of this 
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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.
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 before 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 
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and qualifications of the IRB/IEC members and to make these records available for 
regulatory agency review upon request by those agencies.
10.1.4
Committees Structure
Not applicable.
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 ICMJE 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 trials 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, ICH GCP: Consolidated Guideline and other generally accepted standards of GCP); and 
all applicable federal, state and local laws, rules and regulations relating to the conduct of the 
clinical study.
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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.
The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data.
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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 8 will be performed by the local laboratory.
•
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 8
Protocol-required Safety 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
Chemistrya
BUN
Potassium
AST/SGOT
Total bilirubin (and 
direct bilirubin, if 
total bilirubin is 
above the ULN)
Albumin
Bicarbonate
Chloride
Phosphorous
Creatinine
Sodium
ALT/SGPT
Total Protein
Glucose
Calcium
Alkaline 
phosphatase
Other Screening 
Tests
•
aPTT, PT (collection according to the trial schedule of activities Section 1.3 for 
aPTT and PT collected at local lab)
•
FSH (as needed in WONCBP only)
•
Serum or urine β human chorionic gonadotropin (β hCG) will be carried out on Day 
1 predose. At all other timepoints urine or serum pregnancy test will be carried out 
(as needed for WOCBP) (Serum β hCG pregnancy test will be carried out if there is 
a positive urine test)
•
alcohol breath test and drug screen (to include at minimum: amphetamines, cocaine, 
opiates, cannabinoids and benzodiazepines) 
•
Serology (HIV antibody, HBsAg, and hepatitis C virus antibody)]
ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; FSH=follicle-stimulating 
hormone; [HBsAg=hepatitis B surface antigen]; hCG=human chorionic gonadotropin; [HIV=human immunodeficiency 
virus]; MCH=mean corpuscular hemoglobin; MCV=mean corpuscular volume; RBC=red blood cell; SGOT=serum 
glutamic-oxaloacetic transaminase; SGPT=serum glutamic-pyruvic transaminase; ULN=upper limit of normal; 
WBC=white blood cell; WOCBP=women of childbearing potential; WONCBP=women of nonchildbearing potential
a Fasting: Participants should fast for at least 4 hours prior to glucose measurement.
The investigator (or medically qualified designee) must document their review of each 
laboratory safety report.
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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 (also referred to as Sponsor’s 
product) 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 preexisting 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 preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
•
Surgical procedure(s) planned prior to informed consent to treat a preexisting condition 
that has not worsened.
•
Refer to Section 8.5.6 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:

Results in death

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.

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 preexisting condition that has not 
worsened is not an SAE.) A preexisting 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.

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.

Is a congenital anomaly/birth defect
•
In offspring of participant taking the product regardless of time to diagnosis.

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.
•
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 
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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 /toxicity
•
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 Sponsor’s product cause the AE?
•
The determination of the likelihood that the Sponsor’s product 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 
Sponsor’s product and the AE; the greater the correlation with the components and 
their respective elements (in number and/or intensity), the more likely the Sponsor’s 
product caused the AE:
- Exposure: Is there evidence that the participant was actually exposed to the 
Sponsor’s product such as: reliable history, acceptable compliance assessment (pill 
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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 Sponsor’s product? 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 Sponsor’s product 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 Sponsor’s 
product; (3) the study is a single-dose drug study; or (4) Sponsor’s product(s) is/are 
only used 1 time.)
- Rechallenge: Was the participant re-exposed to the Sponsor’s product 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) Sponsor’s 
product(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 SPONSOR’S PRODUCT, OR IF RE-EXPOSURE 
TO THE SPONSOR’S PRODUCT 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.
•
Consistency with study intervention profile: Is the clinical/pathological presentation of 
the AE consistent with previous knowledge regarding the Sponsor’s product or drug class 
pharmacology or toxicology?
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•
The assessment of relationship will be reported on the CRFs/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 Sponsor’s product relationship).
- Yes, there is a reasonable possibility of Sponsor’s product relationship:
◦
There is evidence of exposure to the Sponsor’s product. The temporal sequence 
of the AE onset relative to the administration of the Sponsor’s product is 
reasonable. The AE is more likely explained by the Sponsor’s product than by 
another cause.
- No, there is not a reasonable possibility of Sponsor’s product relationship:
◦
Participant did not receive the Sponsor’s product OR temporal sequence of the 
AE onset relative to administration of the Sponsor’s product is not reasonable 
OR the AE is more likely explained by another cause than the Sponsor’s 
product. (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.
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.
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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 8.5.1 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).
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: Medical Device and Drug-device Combination Products: Product 
Quality Complaints/Malfunctions: Definitions, Recording, and Follow-up
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 non-hormonal 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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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 for a male participant 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.
Methods That Are Not Considered Highly Effective
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).
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).
08BRCT


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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 using 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 FBR and ask that their biospecimens not be 
used for FBR. Participants may withdraw consent at any time by contacting the study 
investigator. If medical records for the 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 study use only. If specimens were 
collected from study participants specifically for FBR, 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 before 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.
If the medical records for the study are no longer available (eg, if the investigator is no 
longer required by regulatory authorities to retain the 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 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 
operates to assure the integrity of the specimens. Specimens will be destroyed according 
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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/
08BRCT


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10.7
Appendix 7: Country-specific Requirements
Not applicable.
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10.8
Appendix 8: Blood Volume Table
Prestudy
Treatment 
Periods
Poststudy
Total 
Collections
mL Per 
Collection
Total mL/ 
Test
Laboratory Safety Tests
2
9
1
12
12.5
150
HIV/Hepatitis Screen 
1
1
5
5
FSH (Females only)
1
1
3.5
3.5
Serum β-hCG pregnancy test 
(Females only)
2
1
3
3.5
10.5
Blood (DNA) for genetic analysis 
1
1
8.5
8.5
Blood for PT and aPTT at local lab
1
19
1
21
3
63
Blood for plasma ADA and MK-
2060
4
1
5
2.7
13.5
Blood for MK-2060 only
16
16
1.8
28.8
Blood for Clopidogrel Assay
3
5
8
4
32
Blood for PT, aPTT, FXI activity by
central lab
16
1
17
8.1
137.7
Total Blood Volume per Male Participanta 438.5 mL
Total Blood Volume per Female Participanta 452.5 mL
a If additional pharmacokinetic/pharmacodynamic and/or safety analysis is necessary, additional blood (no more than 
50 mL in total) may be obtained.
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10.9
Appendix 9: Algorithm for Assessing Out of Range Laboratory Values
For all laboratory values obtained at prestudy (screening) visit and/or predose evaluation:
A. If all protocol-specified laboratory values are normal, the participant may enter the study.
B. If a protocol specified laboratory value is outside of the parameter(s) outlined in the 
inclusion/exclusion criteria (including a repeat if performed), the participant will be 
excluded from the study.
C. If ≥1 protocol-specified laboratory value not specified in the inclusion/exclusion criteria 
is outside the normal range, the following choices are available:
a.
The participant may be excluded from the study;
b. The participant may be included in the study if the abnormal value(s) is NCS (the 
investigator must annotate the laboratory value “NCS” on the laboratory safety 
test source document).
c.
The participant may be included in the study if the abnormality is consistent with 
a pre-existing medical condition which is not excluded per protocol (eg, elevated 
eosinophil count in a participant with asthma or seasonal allergies), the medical
condition should be annotated on the laboratory report.
OR
d. The abnormal test may be repeated (refer items a. and b. below for continuation of 
algorithm for repeated values).
a.
If the repeat test value is within the normal range, the participant may 
enter the study.
b. If the repeat test value is still abnormal, the study investigator will 
evaluate the potential participant with a complete history and physical 
examination, looking especially for diseases that could result in the 
abnormal laboratory value in question. If such diseases can be ruled out, 
and if the abnormal laboratory value is not clinically relevant, then the 
participant may enter the study.
D. If there is any clinical uncertainty regarding the significance of an abnormal value, the 
participant will be excluded from the study.
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10.10 Appendix 10: Abbreviations
Abbreviation
Expanded Term
ADA
anti drug antibodies
AE
adverse event 
ALT
alanine aminotransferase
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AUC
area under the curve
AV
arteriovenous
bid
twice daily
BMI
body mass index
BP
blood pressure
CCU
Cardiac care unit
Cmax
maximum plasma concentration
CL
clearance
CRF
Case Report Form 
CRU
clinical research unit
CSR
Clinical Study Report
CYP
cytochrome P450
DILI
drug-induced liver injury
DNA
deoxyribonucleic acid 
ECG
electrocardiogram 
ECI
event of clinical interest
eCRF
electronic Case Report Form
EDC
electronic data collection 
EMA
European Medicines Agency
ESRD
End-stage renal disease
FDA
Food and Drug Administration
FDAAA
Food and Drug Administration Amendments Act
FSH
follicle-stimulating hormone 
FXI
Factor XI
FXIa
Factor XIa
GCP
Good Clinical Practice 
GI
gastrointestinal
GLP
Good Laboratory Practice
GLP-1
Glucagon-like peptide-1
HBsAg
hepatitis B surface antigen
hCG
human chorionic gonadotropin
HD
hemodialysis
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
IB
Investigator’s Brochure 
ICF
Informed Consent Form
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Abbreviation
Expanded Term
ICH
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
ICMJE
International Committee of Medical Journal Editors
ICU
intensive care unit
IEC
Independent Ethics Committee
IgG4
immunoglobulin G4
IRB
Institutional Review Board
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IV
intravenous
Kt/V
A number used to quantify hemodialysis.
K – dialyzer clearance of urea
t – dialysis time
V – volume of distribution of urea, approximately equal to patient's total 
body water
mAb
monoclonal antibody
NCS
not clinically significant
NSAE
Nonserious adverse event
NSAID
Non-steroidal anti-inflammatory drug
OR
objective response
PCL
Protocol Clarification Letter
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
po
orally
PP
posterior probability
PT
Prothrombin time
QTc
Corrected Q-T interval
QW
Once weekly
RNA
ribonucleic acid
RR
respiratory rate
SAE
serious adverse event 
SD
standard deviation
SGOT
serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic pyruvic transminase
SLAB
Supplemental laboratory test(s)
SoA
schedule of activities
SOP
Standard Operating Procedures
SUSAR
suspected unexpected serious adverse reaction
THC
Tetrahydrocannabinol
Tmax
Time to maximum plasma concentration
t1/2
half life
ULN
upper limit of normal
VS
vital signs
WBC
white blood cell
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100
PROTOCOL/AMENDMENT NO.:  008-01  
MK-2060-008-01 FINAL PROTOCOL
09-JUN-2022
Abbreviation
Expanded Term
WOCBP
woman/women of childbearing potential
WONCBP
woman/women of nonchildbearing potential
08BRCT


PRODUCT:  MK-2060  
101
PROTOCOL/AMENDMENT NO.:  008-01  
MK-2060-008-01 FINAL PROTOCOL
09-JUN-2022
11
REFERENCES
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2014]
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[07W827]
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2015]
Buller HR, Bethune C, Bhanot S, Gailani D, 
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[04T0MV]
[Ellsworth K 2018]
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[0522VM]
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2000]
Kaufman JS, Fiore L, Hasbargen JA, O'Connor 
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[07W3GX]
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2014]
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[07W82F]
08BRCT


PRODUCT:  MK-2060  
102
PROTOCOL/AMENDMENT NO.:  008-01  
MK-2060-008-01 FINAL PROTOCOL
09-JUN-2022
[Perek, S., et al 2017]
Perek S, Kotler A, Cohen S, Rennert G, Stein N, 
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[07W3GW]
[Sohn, W., et al 2015]
Sohn W, Lee E, Kankam MK, Egbuna O, Moffat 
G, Bussiere J, et al. An open-label study in 
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[07W82C]
08BRCT