Clinical trial NCT03873038
Conditions: Renal Dialysis Kidney Failure, Chronic
Sponsor: Merck Sharp & Dohme LLC
Start date: 2019-04-29; Completion date: 2021-12-20
Enrollment: 38 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MK-2060 after intravenous (IV) administration of single and multiple doses in older adult participants with end-stage renal disease (ESRD) on hemodialysis (HD).

Detailed description:

Arms: arm 1: Participants will receive a single 8-mg dose of MK-2060 via intravenous (IV) infusion. arm 2: Participants will receive a single 20-mg dose of MK-2060 via IV infusion. arm 3: Participants will receive a single 40-mg dose of MK-2060 via IV infusion. arm 4: Participants will receive a single dose of placebo via IV infusion. arm 5: Participants will receive three doses of up to 25 mg MK-2060 via IV infusion in the first week (Week 1), followed by a single dose of up to 25 mg MK-2060 via IV infusion weekly for 3 weeks (Weeks 2-4) arm 6: Participants will receive three doses of placebo via IV infusion in the first week and then a single dose of placebo via IV infusion weekly for 3 weeks (Weeks 2-4)
Interventions: intervention 1: MK-2060 intervention 2: Placebo
Intervention descriptions: intervention 1: Part 1: Single doses (8 mg, 20 mg, or 40 mg) of MK-2060 will be administered via IV infusion on Day 1.

Part 2: Three doses of 25 mg of MK- 2060 administered via IV infusion on Days 1, 3 and 5; Followed by single doses of 25 mg of MK-2060 administered via IV infusion on Days 8, 15, and 22. intervention 2: Part 1: Single dose of placebo will be administered via IV infusion on Day 1. Part 2: Three doses of placebo administered via IV infusion on Days 1, 3 and 5; Followed by single doses of placebo administered via IV infusion on Days 8, 15, and 22.

Protocol documents:
Prot_SAP_000.pdf: 
Official Protocol Title: 
NCT number: 
NCT03873038 
Document Date: 
02-Aug-2021
Single and Multiple Dose Clinical Trial to Study the Safety and
Pharmacokinetics of MK-2060 in Older Participants with End-Stage 
Renal Disease on Hemodialysis


PRODUCT: MK-2060  
1
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02-AUG-2021
Title Page
THIS PROTOCOL AMENDMENT AND ALL OF THE INFORMATION RELATING 
TO IT ARE CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK 
SHARP & DOHME CORP., A SUBSIDIARY OF MERCK & CO., INC., NJ, U.S.A. 
(MSD).
Protocol Title: Single and Multiple Dose Clinical Trial to Study the Safety and 
Pharmacokinetics of MK-2060 in Older Participants with End-Stage Renal Disease on 
Hemodialysis
Protocol Number: 004-06
Compound Number: MK-2060
Sponsor Name:
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
(hereafter referred to as the Sponsor or MSD)
Legal Registered Address:
One Merck Drive
P.O. Box 100
Whitehouse Station, New Jersey, 08889-0100, U.S.A.
Regulatory Agency Identifying Number(s):
IND
142,237
Approval Date:  02 August 2021
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Sponsor Signatory
Typed Name:
Title:
Date
Protocol-specific Sponsor contact information can be found in the Investigator Study
File Binder (or equivalent).
Investigator Signatory
I agree to conduct this clinical study in accordance with the design outlined in this protocol 
and to abide by all provisions of this protocol.
Typed Name:
Title:
Date
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DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
MK-2060-004-06
02-AUG-2021
The protocol amendment 05 is being amended to allow flexibility in the number of female 
participants, expand the age range (reduce lower limit to 18 years) and expand BMI range
to 45 kg/m2 for Part 2 in order to optimize recruitment in the study.
MK-2060-004-05
08-FEB-2021
The protocol amendment 04 is being amended to allow patients who have completed all 
procedures in Part 1 Panel C to enroll in Part 2 of the study, based on the terminal half-life 
of MK-2060 from preliminary PK analysis, in order to optimize recruitment in the study.
MK-2060-004-04
02-SEP-2020
The protocol amendment 03 is being amended to revise the planned dose and the dose 
regimen for Part 2 based on the newly available preliminary PK and PD analysis of Part 1 
Panels A-C. 
MK-2060-004-03
21-FEB-2020
The protocol amendment 02 is being amended to expand age range (reduce lower limit to 
40 years) and expand BMI range to 42 kg/m2 for Part 1. In addition, smoking exclusion 
criteria (exclusion criteria #22) has been removed in order to optimize recruitment in the 
study.
MK-2060-004-02
21-JAN-2020
The protocol amendment 01 is being amended to revise inclusion criteria #1 (change the 
references 3 months of stable dialysis prior to screening to prior to dosing) and #3 (expand 
BMI range to 42 kg/m2 for Part 2) in order to optimize recruitment in the study.
MK-2060-004-01
03-DEC-2019
The original protocol is being amended to add a multiple dosing study part (Part 2) to 
evaluate the safety and tolerability of MK-2060 following multiple dose IV administration 
including an IV loading dose in older adult participants with ESRD on HD. 
MK-2060-004-00
21-FEB-2019
Not applicable.
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PROTOCOL AMENDMENT SUMMARY OF CHANGES
Amendment: [06]
Overall Rationale for the Amendments:
The protocol amendment 05 is being amended to allow flexibility in the number of female participants and the total number of 
participants enrolled in Part 2 of the study, as well as to revise inclusion criteria #7 (lower age limit to 18 for Part 2), and #3 (expand 
BMI range to 45 kg/m2 for Part 2) in order to optimize recruitment in the study. 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 
1.1 Synopsis
4.1 Overall Design
9.9 Sample Size and Power 
Calculations
Changed the total number of participants 
to be approximately 20 for Part 2.
Enrolling exactly 20 participants in Part 2 is not critical 
to meeting the primary objectives of the study.
4.1 Overall Design
4.2 Scientific Rationale for 
Study Design 
5 Study Population
5.1 Inclusion Criteria
Changed lower age limit from 40 to 18 for 
Part 2.
Removed the following sentence at the end 
of 2nd paragraph in Section 4.2:  In the US 
population ESRD has the highest 
prevalence in the 65 and older age group 
[United States Renal Data System 2018], 
therefore this study is being conducted in 
older adult subjects ages ≥40 and ≤80 
years old.   
Expanding the age range is to optimize recruitment for 
Part 2 of the study. This change adds flexibility for 
participant initial screening and enrollment without 
imposing any undue safety risks to the participant.
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Section # and Name
Description of Change 
Brief Rationale 
5.1 Inclusion Criteria
Inclusion Criteria 3: Changed Body Mass
Index (BMI) f r o m  “ ≥ 18 and ≤ 42
kg/m2” to “≥ 18 and ≤ 45 kg/m2”.
Expand BMI range to 45 kg/m2 for Part 2 to optimize 
recruitment for Part 2. 
5.1 Inclusion Criteria
Inclusion Criteria 6: Removed “)” after 
“Section 5.3”.
Correct typographic error.
5.2 Exclusion Criteria
Add the following bullet under Exclusion 
Criterium #16:
•
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.
In the best of interest of the ESRD patient’s health, the 
patients are recommended to receive COVID-19
vaccine.  Administration of COVID-19 vaccine should 
not have any impact on the PK/PD of MK-2060.  
6.3.2 Stratification
Revised the 2nd sentence to read “A 
minimum of 3 participants of each gender 
will be enrolled in Part 2”.
Enrolling 3 participants of each gender in Part 2 is 
sufficient to meet the primary objectives of the study.
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Table of Contents
DOCUMENT HISTORY ........................................................................................................3
PROTOCOL AMENDMENT SUMMARY OF CHANGES...............................................4
1
PROTOCOL SUMMARY ............................................................................................13
1.1
Synopsis.................................................................................................................13
1.2
Schema ..................................................................................................................17
1.3
Schedule of Activities (SoA)................................................................................19
1.3.1
Part 1............................................................................................................19
1.3.2
Part 2............................................................................................................24
2
INTRODUCTION..........................................................................................................27
2.1
Study Rationale....................................................................................................27
2.2
Background ..........................................................................................................27
2.2.1
Pharmaceutical and Therapeutic Background .............................................27
2.2.2
Ongoing Clinical Studies.............................................................................27
2.3
Benefit/Risk Assessment......................................................................................28
3
HYPOTHESES, OBJECTIVES, AND ENDPOINTS................................................28
4
STUDY DESIGN............................................................................................................31
4.1
Overall Design......................................................................................................31
4.2
Scientific Rationale for Study Design.................................................................33
4.2.1
Rationale for Endpoints ...............................................................................34
4.2.1.1
Safety Endpoints................................................................................34
4.2.1.2
Pharmacokinetic Endpoints ...............................................................35
4.2.1.3
Pharmacodynamic Endpoints.............................................................35
4.2.1.4
Planned Exploratory Biomarker Research.........................................36
4.2.1.4.1
Planned Genetic Analysis ........................................................36
4.2.1.5
Future Biomedical Research..............................................................36
4.2.2
Rationale for the Use of Placebo .................................................................37
4.3
Justification for Dose...........................................................................................37
4.3.1
Rationale for Dose Selection/Regimen/Modification..................................37
4.3.2
Starting Dose for This Study........................................................................37
4.3.3
Maximum Dose/Exposure for This Study ...................................................38
4.3.4
Rationale for Multiple Dose Regimen (Part 2)............................................38
4.3.5
Rationale for Dose Interval and Study Design ............................................39
4.4
Beginning and End of Study Definition .............................................................41
4.4.1
Clinical Criteria for Early Study Termination .............................................41
5
STUDY POPULATION ................................................................................................42
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5.1
Inclusion Criteria.................................................................................................42
5.2
Exclusion Criteria................................................................................................44
5.3
Lifestyle Considerations......................................................................................48
5.3.1
Meals and Dietary Restrictions....................................................................48
5.3.2
Caffeine, Alcohol, and Tobacco Restrictions ..............................................48
5.3.2.1
Caffeine Restrictions..........................................................................48
5.3.2.2
Alcohol Restrictions...........................................................................48
5.3.2.3
Tobacco Restrictions..........................................................................48
5.3.3
Activity Restrictions ....................................................................................49
5.4
Screen Failures.....................................................................................................49
5.5
Participant Replacement Strategy......................................................................49
6
STUDY INTERVENTION............................................................................................49
6.1
Study Intervention(s) Administered...................................................................49
6.2
Preparation/Handling/Storage/Accountability .................................................51
6.2.1
Dose Preparation..........................................................................................51
6.2.2
Handling, Storage, and Accountability........................................................51
6.3
Measures to Minimize Bias: Randomization and Blinding..............................52
6.3.1
Intervention Assignment..............................................................................52
6.3.2
Stratification.................................................................................................53
6.3.3
Blinding........................................................................................................53
6.4
Study Intervention Compliance..........................................................................53
6.5
Concomitant Therapy..........................................................................................53
6.5.1
Rescue Medications and Supportive Care ...................................................56
6.6
Dose Modification (Escalation)...........................................................................56
6.6.1
Stopping Rules.............................................................................................57
6.7
Intervention After the End of the Study............................................................58
6.8
Clinical Supplies Disclosure................................................................................58
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL............................................................................................................58
7.1
Discontinuation of Study Intervention...............................................................58
7.2
Participant Withdrawal From the Study...........................................................59
7.3
Lost to Follow-up .................................................................................................59
8
STUDY ASSESSMENTS AND PROCEDURES........................................................59
8.1
Administrative and General Procedures ...........................................................60
8.1.1
Informed Consent.........................................................................................60
8.1.1.1
General Informed Consent.................................................................60
8.1.1.2
Consent and Collection of Specimens for Future Biomedical 
Research.............................................................................................61
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8.1.2
Inclusion/Exclusion Criteria ........................................................................61
8.1.3
Participant Identification Card.....................................................................61
8.1.4
Medical History ...........................................................................................62
8.1.5
Prior and Concomitant Medications Review...............................................62
8.1.5.1
Prior Medications...............................................................................62
8.1.5.2
Concomitant Medications..................................................................62
8.1.6
Assignment of Screening Number...............................................................62
8.1.7
Assignment of Treatment/Randomization Number.....................................62
8.1.8
Study Intervention Administration ..............................................................62
8.1.8.1
Timing of Dose Administration.........................................................62
8.1.9
Discontinuation and Withdrawal .................................................................63
8.1.9.1
Withdrawal From Future Biomedical Research ................................63
8.1.10
Participant Blinding/Unblinding..................................................................63
8.1.11
Domiciling ...................................................................................................64
8.1.12
Calibration of Equipment.............................................................................64
8.2
Efficacy/Immunogenicity Assessments ..............................................................65
8.3
Safety Assessments...............................................................................................65
8.3.1
Physical Examinations.................................................................................65
8.3.1.1
Body Weight and Height ...................................................................65
8.3.1.2
Body Mass Index (BMI)....................................................................65
8.3.2
Vital Signs....................................................................................................66
8.3.2.1
Resting Vital Signs ............................................................................66
8.3.2.2
Orthostatic Vital Signs.......................................................................66
8.3.3
Electrocardiograms ......................................................................................66
8.3.4
Assessment of Time to Hemostasis .............................................................67
8.4
Management of Infusion Reaction During and Post-dose ...............................68
8.4.1
Systemic Infusion Reaction Assessment .....................................................68
8.4.2
Local Infusion Reaction Assessment...........................................................69
8.4.3
Clinical Safety Laboratory Assessments .....................................................69
8.5
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other 
Reportable Safety Events ....................................................................................70
8.5.1
Time Period and Frequency for Collecting AE, SAE, and Other 
Reportable Safety Event Information ..........................................................70
8.5.2
Method of Detecting AEs, SAEs, and Other Reportable Safety Events......72
8.5.3
Follow-up of AE, SAE, and Other Reportable Safety Event Information...72
8.5.4
Regulatory Reporting Requirements for SAE .............................................72
8.5.5
Disease-related Events and/or Disease-related Outcomes Not Qualifying 
as AEs or SAEs............................................................................................73
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8.5.6
Events of Clinical Interest (ECIs)................................................................73
8.6
Treatment of Overdose........................................................................................73
8.7
Pharmacokinetics.................................................................................................73
8.7.1
Blood Collection for Plasma MK-2060 .......................................................74
8.8
Pharmacodynamics..............................................................................................74
8.9
Biomarkers ...........................................................................................................74
8.9.1
Blood Collection for PT, aPTT, FXI Activity and FGA Assay...................74
8.9.2
Blood for Plasma ADA................................................................................75
8.9.3
5-D Itch Scale ..............................................................................................75
8.9.4
Planned Genetic Analysis Sample Collection..............................................75
8.10
Future Biomedical Research Sample Collection...............................................75
8.11
Visit Requirements...............................................................................................75
8.11.1
Screening......................................................................................................75
8.11.2
Treatment Period..........................................................................................76
8.11.3
Poststudy Visit .............................................................................................76
8.11.4
Discontinued Participants Continuing to be Monitored in the Study ..........76
8.11.5
Safety Phone Call Follow-up (Part 1 Only).................................................76
8.11.6
Critical Procedures Based on Study Objectives: Timing of Procedure.......76
8.11.7
Study Design/Dosing/Procedures Modifications Permitted Within 
Protocol Parameters .....................................................................................78
9
STATISTICAL ANALYSIS PLAN .............................................................................79
9.1
Statistical Analysis Plan Summary.....................................................................79
9.2
Responsibility for Analyses.................................................................................80
9.3
Hypotheses/Estimation ........................................................................................81
9.4
Analysis Endpoints...............................................................................................81
9.5
Analysis Populations............................................................................................82
9.6
Statistical Methods...............................................................................................82
9.7
Interim Analyses ..................................................................................................85
9.8
Multiplicity ...........................................................................................................85
9.9
Sample Size and Power Calculations .................................................................85
10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.....................................................................................................87
10.1
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations........87
10.1.1
Code of Conduct for Clinical Trials.............................................................87
10.1.2
Financial Disclosure.....................................................................................89
10.1.3
Data Protection.............................................................................................89
10.1.3.1
Confidentiality of Data ......................................................................90
10.1.3.2
Confidentiality of Participant Records...............................................90
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10.1.3.3
Confidentiality of IRB/IEC Information............................................90
10.1.4
Committees Structure...................................................................................90
10.1.5
Publication Policy........................................................................................90
10.1.6
Compliance with Study Registration and Results Posting Requirements ...91
10.1.7
Compliance with Law, Audit, and Debarment ............................................91
10.1.8
Data Quality Assurance ...............................................................................92
10.1.9
Source Documents .......................................................................................93
10.1.10
Study and Site Closure.................................................................................93
10.2
Appendix 2: Clinical Laboratory Tests..............................................................94
10.3
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting...............................................................95
10.3.1
Definition of AE ..........................................................................................95
10.3.2
Definition of SAE ........................................................................................96
10.3.3
Additional Events Reported.........................................................................97
10.3.4
Recording AE and SAE ...............................................................................97
10.3.5
Reporting of AEs, SAEs, and Other Reportable Safety Events to the 
Sponsor ......................................................................................................101
10.4
Appendix 4: Device Events, Adverse Device Events, and Medical Device 
Incidents: Definitions, Collection, and Documentation..................................102
10.5
Appendix 5: Contraceptive Guidance and Pregnancy Testing......................103
10.5.1
Definitions..................................................................................................103
10.5.2
Pregnancy Testing......................................................................................103
10.6
Appendix 6: Collection and Management of Specimens for Future 
Biomedical Research..........................................................................................104
10.7
Appendix 7: Country-specific Requirements..................................................109
10.8
Appendix 8: Approximate Blood Volume........................................................110
10.9
Appendix 9: Algorithm for Assessing Out of Range Laboratory Values .....112
10.10 Appendix 10: Abbreviations .............................................................................113
11
REFERENCES.............................................................................................................115
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LIST OF TABLES
Table 1
Study Schema........................................................................................................ 18
Table 2
Study Intervention................................................................................................. 50
Table 3
Sample Allocation Schedule for Part 1................................................................. 52
Table 4
Sample Allocation Schedule for Part 2................................................................. 52
Table 5
Local Infusion Reaction Assessment.................................................................... 69
Table 6
Reporting Time Periods and Time Frames for Adverse Events and Other 
Reportable Safety Events...................................................................................... 71
Table 7
Pharmacokinetic (Blood) Collection Windows .................................................... 77
Table 8
Protocol-required Safety Laboratory Assessments............................................... 94
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LIST OF FIGURES
Figure 1
Study Design for Part 1......................................................................................... 17
Figure 2
Study Design for Part 2......................................................................................... 18
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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: Single and Multiple Dose Clinical Trial to Study the Safety and 
Pharmacokinetics of MK-2060 in Older Participants with End-Stage Renal Disease on 
Hemodialysis
Short Title: Single and Multiple Dose Study of MK-2060 in Older Participants with ESRD
Acronym: N/A
Hypotheses, Objectives, and Endpoints:
This study is to be conducted in adult participants with End-Stage Renal Disease on 
Hemodialysis. 
Primary Objectives
Primary Endpoints
- Objective: 
Part 1: To evaluate the safety and tolerability 
of MK-2060 following single dose IV 
administration in older adult participants 
with ESRD on HD.
Part 2: To evaluate the safety and tolerability 
of MK-2060 following multiple dose IV 
administration including an IV loading dose 
in older adult participants with ESRD on 
HD.
- AEs (including local infusion site 
reactions and systemic reactions to 
infusion), physical examinations, vital 
signs, 12-lead ECGs, laboratory safety tests 
(serum chemistry, hematology), aPTT, PT, 
and endpoints related to bleeding 
(macroscopic bleeding, high sensitivity 
hemoccult) will be assessed throughout the 
dosing intervals. 
Secondary Objectives
Secondary Endpoints
- Objective: 
Part 1: To evaluate plasma pharmacokinetics 
of MK-2060 following a single dose IV 
administration in older adult participants 
with ESRD on HD.
Part 2: To evaluate plasma pharmacokinetics 
of MK-2060 following multiple dose IV 
administration including an IV loading dose 
in older adult participants with ESRD on 
HD.
- Part 1: MK-2060 plasma AUC0-∞, 
AUC0-168, Cmax, C168, Tmax, terminal 
t1/2, CL and Vz
- Part 2: MK-2060 plasma AUC0-168, 
Cmax, C168 (Cmin), Tmax 
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Secondary Objectives
Secondary Endpoints
- Objective: 
Part 1: To evaluate the effect of MK-2060 
on aPTT following single dose IV 
administration in older adult participants 
with ESRD on HD.
Part 2: To evaluate the effect of MK-2060 
on aPTT following multiple dose IV 
administration including an IV loading dose 
in older adult participants with ESRD on 
HD.
- Hypothesis: 
Part 1: The true fold increase from baseline 
for aPTT 168 hours after a single well-
tolerated dose of MK-2060 in older adult 
participants with ESRD on HD is at least 
1.5.
Part 2: The true fold increase from baseline 
for aPTT 168 hours post the last dose 
following an IV loading dose and three 
maintenance IV doses of MK-2060 in older 
adult participants with ESRD on HD is at 
least 1.5.
- aPTT fold change from baseline
Part 1:
- Objective: To compare the plasma 
pharmacokinetics of MK-2060 following a 
single dose IV administration in older adult 
participants with ESRD on HD to 
participants with normal renal function 
(historical controls in PN001).
- Estimation: In older adult participants with 
ESRD on HD, PK parameters (e.g. AUC0-
∞, Cmax) of MK-2060 following 
administration of a single dose will be 
estimated and compared to participants with 
normal renal function (historical controls in 
PN001).  
- Part 1: MK-2060 plasma AUC0-∞, 
AUC0-168, Cmax, C168, Tmax, terminal 
t1/2, CL and Vz
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Overall Design:
Study Phase
Phase 1
Primary Purpose
Treatment
Indication
Prevention of thrombotic complications
Population
Patient: Older adult participants with end-stage renal 
disease on hemodialysis
Study Type
Interventional
Intervention Model
Sequential
This is a multi-site study.
Type of Control
Placebo 
Study Blinding
Double-blind
Masking
Participant or 
Subject
Investigator
Outcomes 
Assessor
Estimated Duration of Study
The Sponsor estimates that the study will require 
approximately 23 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:
Approximately 44 participants will be allocated/randomized.
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Intervention Groups and Duration:
Intervention 
Groups
Inter-
vention 
Group 
Name
Drug
Dose 
Strength
Dose 
Frequency
Route of 
Adminis-
tration
Regimen/ 
Treatment 
Period
Use
Part 1
Panel A
MK-2060
8 mg
Once
IV
Single 60-
minute IV 
infusion
Experimental
Placeboa
Placeboa
Panel B
MK-2060
20 mg
Once
IV
Single 60-
minute IV 
infusion
Experimental
Placeboa
Placeboa
Panel C
MK-2060
40 mg
Once
IV
Single 60-
minute IV 
infusion
Experimental
Placeboa
Placeboa
Part 2
Part 2
MK-2060
Week 1: 
loading 
dose up to 
25 mg x 3 
Weeks 2-4: 
maintenance 
dose up to 
25 mg
Week 1: 
3x
Week 2-4: 
weekly
IV
Week 1: 3x 
Week 2-4: 
weekly 
Experimental
Placeboa
Placeboa
a.
Placebo IV (0.9% sodium chloride infusion, USP sterile saline)
Total 
Number
Total 44 participants.
Part 1:  24 participants (3 panels of 8 participants per panel). Within each 
panel participants will be randomized to receive MK-2060 or placebo in a 
3:1 ratio (6 active and 2 placebo).  In order to ensure 24 evaluable 
participants with at least 21 days of follow-up, we will allow for the 
replacement of participants.
Part 2: Approximately 20 participants will be randomized to a once weekly 
dose of MK-2060 or placebo in a treatment ratio of 3:1 (15 active and 5 
placebo) for 4 weeks. 
In order to ensure approximately 20 evaluable participants with at least 21 
days of follow-up after the last dose, replacement of participants who do not 
complete 21 days of follow-up may be enrolled with joint agreement of the 
investigator and the Sponsor.
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Duration of 
Participation
Part 1:  Each participant will participate in the study for approximately 28
weeks from the time the participant provides documented informed consent 
through the final contact. After a screening phase of approximately 4 weeks, 
each participant will receive the assigned intervention (single dose IV 
infusion). After study drug administration, each participant will be followed 
for approximately 164 days.
Part 2:  Each participant will participate in the study for approximately 20
weeks from the time the participant provides documented informed consent
through the final contact. After a screening phase of approximately 4 weeks, 
each participant will receive the assigned intervention (weekly single dose 
IV infusion for 4 weeks). After the last dose of the study drug 
administration, each participant will be followed for approximately 90 days.
Study Governance Committees:
Steering Committee
No
Executive Oversight Committee
No
Data Monitoring Committee
No
Clinical Adjudication Committee
No
Study Accepts Healthy Volunteers: No
A list of abbreviations used in this document can be found in Appendix 10.
1.2
Schema
The study design is depicted in [Figure 1], [Figure 2] and [Table 1].
Figure 1
Study Design for Part 1
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PRODUCT: MK-2060  
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02-AUG-2021
Figure 2
Study Design for Part 2
Table 1
Study Schema
Part 1
Panel
Doseb
Aa
8 mg IV MK-2060
Placeboc
Ba
20 mg IV MK-2060
Placeboc
Ca
40 mg IV MK-2060d
Placeboc
Part 2e
Dosef
Week 1
Week 2/Week 3/Week 4
Up to 25 mg IV MK-2060 x 3
Up to 25 mg IV MK-2060
Placeboc
Placeboc
a.
8 older adult participants with ESRD on HD per panel. Within each panel participants will be randomized to receive 
a single IV infusion of MK-2060 or placebo in a 3:1 ratio (6 active and 2 placebo)
b.
Part 1: There will be approximately a 28-day period (+/- 2 days) [including 21 days (+/- 2 days) safety data review 
and approximately 7 days for decision to dose next panel] between dosing the last participant in a panel and dose 
administration in the next panel to evaluate safety.  The decision to proceed to the next panel will be based upon 
acceptable safety and tolerability data collected over at least a 21 day (+/- 2 days) observation period for at least 7 
participants in the previous panel, including local lab aPTT, PT, and hemoccult test review.  Plasma pharmacokinetic 
data will be reviewed on an ongoing basis and at least 14 days of PK data from at least 7 participants in Panel A (8 
mg) will be evaluated prior to proceeding to the next panels.  The suggested doses may be adjusted downward based 
on evaluation of safety, tolerability, pharmacokinetic and/or pharmacodynamic data observed in previous treatment 
panels.
c.
Placebo IV (0.9% sodium chloride infusion, USP sterile saline)
d.
Panel C (40 mg dose) will not be dosed until at least 21 days of safety, tolerability, PK, and PD data from the 40 mg 
IV dose in PN001 (Panel I) has been reviewed. 
e.
Approximately 20 older participants with ESRD will be randomized to receive MK-2060 or placebo in a 3:1 ration 
(15 active and 5 placebo).
f.
Part 2 will not be dosed until at least 14 days of safety, tolerability data and available PK data from at least 6 
participants in Part 1 Panel C 40 mg IV dose in this study has been reviewed.
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1.3
Schedule of Activities (SoA)
1.3.1
Part 1
Study 
Panelsa A, B, and C
Notes
Study Day within 
Period
≤28 days pre-
doseb
Day 1 (hour post dose)
D2
D3
D5
D8
D12 w
(±1D)
D15 w
(±2D)
D22 w
(±2 D)
D29
(±3 D)
D60 w
(±5 D)
D90 w
(±5 D)
D120
(±7 D)
D150
Post-
trialc,w
(±7 D)
D164
Phone 
Call
(±7 D)
Scheduled Hour
Scn
1
Scn
2
Scn3b Pre-
dose 0
1
3.5 8 12
24
48 52
96
168
Administrative Procedures
Informed Consent
X
Informed Consent 
for Future 
Biomedical 
Research
X
Participant 
Identification 
Card/Braceletd
X
X
Assignment of 
Screening Number
X
Assignment of 
Allocation 
Numbere
X
Inclusion/
Exclusion Criteria
X
X
X
X
Clinic Procedures 
Medical History
X
Prior/Concomitant 
Medication 
Review
X--------------------------------------------------------------------------------------------------------------------------------------------------------------------X
On site 
Hemodialysisv
X
X
X-------X
X---X
X
X
X
MK-2060/Placebo 
X
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Study 
Panelsa A, B, and C
Notes
Study Day within 
Period
≤28 days pre-
doseb
Day 1 (hour post dose)
D2
D3
D5
D8
D12 w
(±1D)
D15 w
(±2D)
D22 w
(±2 D)
D29
(±3 D)
D60 w
(±5 D)
D90 w
(±5 D)
D120
(±7 D)
D150
Post-
trialc,w
(±7 D)
D164
Phone 
Call
(±7 D)
Scheduled Hour
Scn
1
Scn
2
Scn3b Pre-
dose 0
1
3.5 8 12
24
48 52
96
168
Administrationf
Standard Mealsg
X----------X
Participant 
Domiciling in 
Clinical Research 
Unit
X----------------------------------X
Safety Procedures
Full Physical 
Examination h
X
X
X
X
X
X
X
X
X
X
X
Systemic Infusion
Reaction 
Assessmenti
X
X
X
X
X
Assessment of 
time to adequate 
hemostasisu
X
X
X
X
X
X
X
Height
X
X
Weight
X
X
X
Pre-HD
12-lead ECG j
X
X
X
X
X
X
X
Semirecumbent
Vital Signs (heart
rate, blood
pressure,
respiratory rate,
body 
temperature) k
X
X
X-------------X
X
X
X
X
X
X
X
X
Orthostatic Vital 
Signs (heartrate, 
blood pressurel
X
X
X
X
X
X
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PRODUCT: MK-2060  
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Study 
Panelsa A, B, and C
Notes
Study Day within 
Period
≤28 days pre-
doseb
Day 1 (hour post dose)
D2
D3
D5
D8
D12 w
(±1D)
D15 w
(±2D)
D22 w
(±2 D)
D29
(±3 D)
D60 w
(±5 D)
D90 w
(±5 D)
D120
(±7 D)
D150
Post-
trialc,w
(±7 D)
D164
Phone 
Call
(±7 D)
Scheduled Hour
Scn
1
Scn
2
Scn3b Pre-
dose 0
1
3.5 8 12
24
48 52
96
168
AE/SAE reviewm
X-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------X
Serum β-Human 
Chorionic 
Gonadotropin (β-
hCG) 
X
X
X
Female 
particip-
ants only
Serum Follicle 
Stimulating 
Hormone (FSH) 
X
Post-
meno-
pausal/ 
oophorec
-tomized 
female 
partici-
pants 
only
Laboratory Procedures/Assessments
HIV/hepatitis 
screen 
X
Per site 
SOP
Serum/saliva Drug 
and Alcohol 
Breath test n
X
X
X
Per site 
SOP
Hematology, 
Chemistry,o
X
X
X
X
X
X
X
X
X
X
X
X
aPTT and PT at 
Local Lab
X
Xp
X
X
X
Xy
X
X
X
X
Hemoccult Test q
X
X
X
X
X
X
X
X
X
Blood for Genetic 
Analysis r
X
Pharmacokinetics Evaluations
Blood for Plasma 
MK-2060s,x
X
Xt
X
X
X X
X
XX
X
X
X
XX
X
X
XX
X
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PRODUCT: MK-2060  
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PROTOCOL/AMENDMENT NO.: 004-06 
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Study 
Panelsa A, B, and C
Notes
Study Day within 
Period
≤28 days pre-
doseb
Day 1 (hour post dose)
D2
D3
D5
D8
D12 w
(±1D)
D15 w
(±2D)
D22 w
(±2 D)
D29
(±3 D)
D60 w
(±5 D)
D90 w
(±5 D)
D120
(±7 D)
D150
Post-
trialc,w
(±7 D)
D164
Phone 
Call
(±7 D)
Scheduled Hour
Scn
1
Scn
2
Scn3b Pre-
dose 0
1
3.5 8 12
24
48 52
96
168
Pharmacodynamic Evaluations
Blood for
PT/aPTT/ FXI
Activity by
Central Labx
X
Xt
X
X
X X
X
XX
X
X
X
XX
X
X
XX
X
Blood for Fibrin 
Generation Assayx
X
Xt
X
X
X X
X
XX
X
X
X
XX
X
X
XX
X
Blood for 
biomarker(s) of 
inflammation 
(e.g., hsCRP) 
Assay t, x
X
Xt
X
X
X X
X
XX
X
X
X
XX
X
X
XX
X
Blood for plasma 
ADA
X
X
X
X
X
X
X
X
5-D Pruritus Scale 
(Panel C only)
X
a.
Participants may only participate in 1 Panel.
b.
Screening 3 should occur within 80 hours prior to Day 1.
c.
The Post-trial visit will occur approximately 150 days following administration of study drug. Procedures outlined in the Post-trial visit may be obtained on Day 150 (±7 days). However, follow up
on any clinical or laboratory AEs should occur in person if the post-trial visit occurs prior to 150 days following administration of study drug. If a participant discontinues for any reason at any
time during the course of the trial the subject may be asked to return to the clinic to complete the post-trial visit. The investigator may decide to perform the post-trial visit at the time of 
discontinuation or as soon as possible after discontinuation as outlined in Section 7 and 8.1.9.
d.
Participants will be giving a Participants Identification Card at screening visit. In addition, participants will be given a bracelet at randomization and wear it until the post-trial visit. The bracelet is 
to identify participants as participants in an anti-coagulant research trial.
e.
The allocation (randomization) number is assigned at the time of study drug administration.
f.
MK-2060/placebo will be administered 30 minutes after the initiation of hemodialysis and will be infused over approximately1 hour. Infusion time may increase or pause, and restart based upon on
tolerability. Refer to the Study Pharmacy Manual for additional information on the preparation and administration of study drug.
g.
A light breakfast will be administered approximately 2 hours post-dose; a lunch and dinner will be provided at ~4 and ~10 hours post-dose respectively. Additional meals and snack(s) will be 
provided by the investigator (See Section 5.3.1).
h.
All postdose PEs will include a local IV infusion reaction assessment for all panels. Refer to Section 8.4.
i.
Participants will be monitored during the administration of MK-2060/placebo and after the initiation of the administration for signs and symptoms of a systemic infusion reaction. This assessment
may be combined with the scheduled physical exam on Day 2 and Day 3. Note: Participants who call the CRU to report an infusion site reaction on Days 4, 5 and/or 7 may be asked to
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02-AUG-2021
Study 
Panelsa A, B, and C
Notes
Study Day within 
Period
≤28 days pre-
doseb
Day 1 (hour post dose)
D2
D3
D5
D8
D12 w
(±1D)
D15 w
(±2D)
D22 w
(±2 D)
D29
(±3 D)
D60 w
(±5 D)
D90 w
(±5 D)
D120
(±7 D)
D150
Post-
trialc,w
(±7 D)
D164
Phone 
Call
(±7 D)
Scheduled Hour
Scn
1
Scn
2
Scn3b Pre-
dose 0
1
3.5 8 12
24
48 52
96
168
return to the CRU as soon as possible for an additional local infusion site reaction assessment.
j.
Day 1 pre-dose ECGs will be obtained in triplicate at least 1-2 minutes apart (within 24 hours prior to trial drug administration). The median of these measurements will be used as the baseline.
Screening and post-dose ECG measurements will be single measurements. ECG will be performed after participants have been in a semi-recumbent position for at least 10 minutes.
k.
Pre-dose HR and BP will be triplicate measurements obtained at least 1-2 minutes apart within 3 hours of dosing MK-2060/placebo (i.e., within 3 hours of starting the infusion). The median of these 
measurements will be used as the baseline. Screening and post-dose vital sign measurements will be single measurement. HR and BP will be measured at pre- dose, 15 min, 30 min, and 1, 2, 3.5 and 
12 hours post-dose on Day 1.  Body temperature and respiratory rate will be single measurements per timepoint (pre-dose and post- dose).
l.
Orthostatic vital sign measurements (heart rate, blood pressure) should follow the last semi-recumbent vital sign measurement. Measurements should be obtained after participants have been 
standing for 2 minutes.
m.
All Adverse Events non-serious (NSAEs)] and serious adverse events (SAEs) will be recorded up to 164 days post-dose (inclusive).
n.
Screening and pre-dose drug screen is mandatory (pre-dose drug screen may occur in the evening prior to Day 1 at the time of admission); any additional drug screen is conducted per site SOP.
o.
Hematology/Chemistry will be obtained after an 8 hour fast. Pre-dose tests can be conducted up to 24 hours prior to dosing.
p.
Local aPTT and PT tests will be performed on Day 1 at 1 hour (end of infusion).  This sample will be obtained immediately prior to the end of infusion (i.e., no more than 5 min before anticipated 
time of the end of the infusion).
q.
Hemoccult test will be provided to participants at screening 1 visit and participants will return the sample at screening visit 2. Other post-dose hemoccult test samples may be obtained within 48 
hours of specified timepoint.
r.
This sample should be drawn for planned analysis of the association between genetic variants in DNA and drug response. This sample will not be collected at the site if there is either a local law
or regulation prohibiting collection, or if the IRB/IEC does not approve the collection of the sample for these purposes. If the sample is collected,
leftover extracted DNA will be stored for future
biomedical research if the participant (or their legally acceptable representative) provides documented informed consent for future biomedical research. If the planned genetic analysis is not
approved, but FBR is approved and consent is given, this sample will be collected for the purpose of FBR. Blood for genetic analysis should be collected only once per participant
after randomization.
s.
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.
t.
The 1-hour PK and PD samples will be obtained immediately prior to the end of infusion (i.e. no more than 5 min before anticipated time of the end of the infusion).
u.
Assessment of time to adequate hemostasis will be conducted at the conclusion of the dialysis session. 
v.
Onsite hemodialysis sessions will be 4 hours in duration.  Pre-dose and 48hr blood sample collections will be collected prior to HD initiation and 4hr and 52hr samples collected immediately after the 
conclusion of HD.  
w.
Day 12, 15, 22, 60, 90 and 150 clinic visits must occur within 12 hours prior to a hemodialysis session.
x.
All the PK/PD draws for on-site HD on Day 8, 29 and 120 must have two draws for a pre-HD and a post-HD sample.
y.
Local lab aPTT/PT will be drawn prior to initiation of onsite HD on Day 8.
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1.3.2
Part 2
Study Period
Screening
≤28 days 
to Day 1
Intervention
Post-
study
Notes
Sec. 8.11 for Visit Requirements 
and Sec. 8.11.6 for Timing of 
Procedure
Scheduled Week/Day
Scn1
Scn2d
Week 1
Week 2
Week 3
Week 4
Post Week 4
111
1
2
3
5
8
10
15
17
22
23
24
26
29
35 42 49 63 81
Visit Window (Day)
NA
NA
NA
NA
NA
±1
NA
±1
NA
NA NA +1 NA ±2 ±2 ±2 ±3 ±3
±7
Administrative Procedures
Informed Consent
X
Sec. 8.1.1, 8.9 and 10.6 
(Appendix 6)
Informed Consent for 
Future Biomedical Research
X
Inclusion/Exclusion Criteria
X
X
X
Sec. 5.1, 5.2 and 8.1.2, Day 1 at 
predose
Participant Identification 
Card
X
Sec. 8.1.3
Participant Bracelet
X
Sec. 4.3.5
Assignment of Screening 
Number
X
Sec. 8.1.6
Assignment of Allocation 
Number
X
See Section 8.1.7, at Day 1 
predose
Clinic Procedures
Medical History
X
Sec. 8.1.4
Prior/Concomitant 
Medications Review
  X----------------------------------------------------------------------------------------------------------------------------------X
Sec. 6.5 and 8.1.5
MK-2060 or Placebo 
Administration
X
X
X
X
X
X
Sec. 8.1.8 and 8.6
On site Hemodialysis
X
X
X
X
X
X
X
X
See footnote b
Meals
X
X
X
X
Sec. 5.3.1
Domiciling
X
X
X
X
X
X
X
Sec. 8.1.11
Safety Procedures
Physical Examinations
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.1, include a local IV 
infusion reaction assessment at 
all postdose PE
Systemic Infusion Reaction 
Assessment
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.4.1 
Assessment of Time to 
Hemostasis
X
X
X
X
X
X
X
X
Sec. 8.3.4. ~4 hrs postdose on 
each dosing days
Height
X
X
Sec. 8.3.1
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Study Period
Screening
≤28 days 
to Day 1
Intervention
Post-
study
Notes
Sec. 8.11 for Visit Requirements 
and Sec. 8.11.6 for Timing of 
Procedure
Scheduled Week/Day
Scn1
Scn2d
Week 1
Week 2
Week 3
Week 4
Post Week 4
111
1
2
3
5
8
10
15
17
22
23
24
26
29
35 42 49 63 81
Visit Window (Day)
NA
NA
NA
NA
NA
±1
NA
±1
NA
NA NA +1 NA ±2 ±2 ±2 ±3 ±3
±7
Weight
X
X
X
Resting 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
X
X
Sec. 8.3.2
Predose, 15 min, 30 min, and 1, 
2, 3.5 and 12 hrs postdose on 
each dosing days
Orthostatic Vital Signs 
(blood pressure, heart rate)
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.2. Predose and 12 hrs 
postdose on each dosing days
12-lead electrocardiogram
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.3. Predose and 3.5 hrs 
postdose on each dosing days
Laboratory Procedures/Assessments
Safety Lab
Hematology and 
Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.4.3, 10.2 (Appendix 2) 
and 10.9 (Appendix 9). 
aPTT/PT at Local Lab
X
X(3)
X(2) X(2) X(2)
X
X(2)
X
X(2)
X
X
X
X
X
X
X
X
X
Day 1: Predose, 1 and 12 hrs
postdose. Predose may be 
performed within 3 days of 
dosing. Days 3, 5, 8, 15 and 22: 
1 and 12 hrs postdose.
Hemoccult Test
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.4.3, 8.11.6, 10.2 
(Appendix 2) and 10.9 
(Appendix 9).  
HIV/hepatitis Screen
X
Per site SOP
Serum/saliva Drug and 
Alcohol Breath Test 
X
X
X
Per site SOP
Serum Follicle 
Stimulating Hormone 
(FSH)
X
Postmeno-pausal/ 
oophorectomized female 
participants only
Serum β-Human 
Chorionic 
Gonadotropin (β-hCG)
X
X
Female participants only
AE/SAE review
 X----------------------------------------------------------------------------------------------------------------------------------X
Sec. 8.5 and 10.3 (Appendix 3)
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Study Period
Screening
≤28 days 
to Day 1
Intervention
Post-
study
Notes
Sec. 8.11 for Visit Requirements 
and Sec. 8.11.6 for Timing of 
Procedure
Scheduled Week/Day
Scn1
Scn2d
Week 1
Week 2
Week 3
Week 4
Post Week 4
111
1
2
3
5
8
10
15
17
22
23
24
26
29
35 42 49 63 81
Visit Window (Day)
NA
NA
NA
NA
NA
±1
NA
±1
NA
NA NA +1 NA ±2 ±2 ±2 ±3 ±3
±7
Pharmacokinetics  
Blood for Plasma MK-2060 
Assay
X(3)
X
X(2) X(2) X(2)
X
X(2)
X
X(3)
X
X
X
X
X
X
X
X
X
X
Sec. 8.7
Days 1 & 22: predose, 1h (within 
5 min end of infusion), 12h. 
Days 3, 5, 8 & 15: predose, 1h 
(end of infusion).
See footnote e, f.
Pharmacodynamics
Blood for PT/aPTT/ FXI 
Activity by Central Lab
X(2)
X
X
X
X
X
X
X
X(2)
X
X
X
X
X
X
X
X
X
Sec. 8.8, Days 1 and 22 (2 
draws): predose and 1h (within 5 
min end of infusion.
Blood for Fibrin Generation 
Assay
X(2)
X
X
X
X
X
X
X
X(2)
X
X
X
X
X
X
X
X
X
Blood for biomarker(s) of 
inflammation (e.g., hsCRP) 
Assay
X
X
X
X
X
X
X
X
X
X
Biomarkers
Blood for plasma anti-drug 
antibody
X
X
X
X
X
X
X
See Section 8.9
On dosing Days 1, 15, and 22: 
draw sample at predose.
Blood for Genetic Analysis 
X
See footnote c.
5-D Pruritus Scale
X
X
a.
Blood samples at each dosing day (i.e. Days 1, 3, 5, 8, 15 and 22 postdose will be collected in the opposite arm from the dialysis vascular access site.
b.
On site Hemodialysis:  Pre-dose blood sample collections will be collected prior to HD initiation and 4hr samples collected immediately after the conclusion of HD.
c.
Blood for Genetic Analysis:  This sample should be drawn for planned analysis of the association between genetic variants in DNA and drug response. This sample will not be collected at that site 
if there is either a local law or regulation prohibiting collection, or if the IRB/IEC does not approve the collection of the sample for these purposes. If the sample is collected, leftover extracted 
DNA will be stored for future biomedical research if the participant (or their legally acceptable representative) provides documented informed consent for future biomedical research. If the planned 
genetic analyses are not approved, but future biomedical research is approved and consent is given, this sample will be collected for the purpose of future biomedical research. Blood for genetic 
analysis should be collected only once per participant after randomization. If a participant re-enrolled into Part 2, a blood for genetic analysis sample is not needed if collected in Part 1.
d.
Screening 2 may be performed within 80 hours prior to Day 1.
e.
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.
f.
All pre-dose PK should be taken prior to initiation of dialysis on that day.
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2
INTRODUCTION
2.1
Study Rationale
MK-2060 is an anti-FXI monoclonal antibody being developed for the prevention of
thrombotic complications in end-stage renal disease (ESRD). The purpose of this study is to 
assess the safety, tolerability, PK, and PD of MK-2060 after IV administration of single
and multiple doses in older adult participants with ESRD on HD. Data from this trial will 
be used to aid dose selection of MK-2060 in future trials.
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
Protocol 001
Protocol MK-2060-001 is a double-blind, randomized, placebo-controlled, single site, 
sequential panel study to evaluate the safety, tolerability, PK, and PD of single ascending 
dose administration of SC and IV doses of MK-2060 in healthy male participants.  The 
clinical conduct of PN001 is complete. 36 healthy male participants received single SC doses 
of MK-2060 up to 120 mg and 24 healthy male subjects received single IV doses of MK-
2060 up to 40 mg.  MK-2060 was generally well-tolerated and there were no SAEs or 
discontinuations due to AEs.  Refer to the IB Edition 4 for a detailed overview of the study, 
and available preliminary PK, PD, and safety results.
Protocol 004 Part 1 Panels A, B and C:
As of 09-Oct-2020, 24 participants have been administered one IV dose up to 40 mg MK-
2060 or placebo.  To date, single IV doses up to 40 mg have been generally well tolerated 
and there have been no treatment emergent SAEs and no discontinuations due to any drug-
related AEs.  There have been no AEs suggestive of hypersensitivity.  Refer to IB Edition 4
for a detailed overview of preliminary safety, PK and PD results for Part 1 Panels A, B and 
C. 
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2.3
Benefit/Risk Assessment
Participants in clinical trials generally cannot expect to receive direct benefit from treatment 
during participation, as clinical studies are designed to provide information about the safety 
and effectiveness 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
This study is to be conducted in adult participants with End-Stage Renal Disease on 
Hemodialysis. 
Objectives
Endpoints
Primary

Objective: 
Part 1: To evaluate the safety and 
tolerability of MK-2060 following single 
dose IV administration in older adult 
participants with ESRD on HD.
Part 2: To evaluate the safety and 
tolerability of MK-2060 following 
multiple dose IV administration including 
an IV loading dose in older adult 
participants with ESRD on HD.

AEs (including local infusion site 
reactions and systemic reactions to 
infusion), physical examinations, vital 
signs, 12-lead ECGs, laboratory safety 
tests (serum chemistry, hematology), 
aPTT, PT, and endpoints related to 
bleeding (macroscopic bleeding, high 
sensitivity hemoccult) will be assessed 
throughout the dosing intervals. 
Secondary

Objective: 
Part 1: To evaluate plasma 
pharmacokinetics of MK-2060 following 
a single dose IV administration in older 
adult participants with ESRD on HD.
Part 2: To evaluate plasma 
pharmacokinetics of MK-2060 following 
multiple dose IV administration including 
an IV loading dose in older adult 
participants with ESRD on HD.

Part 1: MK-2060 plasma AUC0-∞, 
AUC0-168, Cmax, C168, Tmax, 
terminal t1/2, CL and Vz

Part 2: MK-2060 plasma AUC0-168, 
Cmax, C168 (Cmin), Tmax 
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Objectives
Endpoints

Objective: 
Part 1: To evaluate the effect of MK-2060 
on aPTT following single dose IV 
administration in older adult participants 
with ESRD on HD.
Part 2: To evaluate the effect of MK-2060 
on aPTT following multiple dose IV 
administration including an IV loading 
dose in older adult participants with 
ESRD on HD.

Hypothesis: 
Part 1: The true fold increase from 
baseline for aPTT 168 hours after a single 
well-tolerated dose of MK-2060 in older 
adult participants with ESRD on HD is at 
least 1.5.
Part 2: The true fold increase from 
baseline for aPTT 168 hours post the last 
dose following an IV loading dose and 
three maintenance IV doses of MK-2060 
in older adult participants with ESRD on 
HD is at least 1.5.

aPTT fold change from baseline
Part 1:

Objective: To compare the plasma 
pharmacokinetics of MK-2060 following 
a single dose IV administration in older 
adult participants with ESRD on HD to 
participants with normal renal function 
(historical controls in PN001).

Estimation: In older adult participants 
with ESRD on HD, PK parameters (e.g. 
AUC0-∞, Cmax) of MK-2060 following 
administration of a single dose will be 
estimated and compared to participants 
with normal renal function (historical 
controls in PN001).  

Part 1: MK-2060 plasma AUC0-∞, 
AUC0-168, Cmax, C168, Tmax, 
terminal t1/2, CL and Vz
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Objectives
Endpoints
Tertiary/Exploratory

Objective:
Part 1: To explore the effect of MK-2060 
given as a single IV dose on Factor XI 
(FXI) activity levels.
Part 2: To explore the effect of MK-2060 
given as multiple IV doses on Factor XI 
(FXI) activity levels.
a.
FXI activity level fold change from 
baseline

Objective:
Part 1: To explore the effect of MK-2060 
given as a single IV dose on fibrin 
generation. 
Part 2: To explore the effect of MK-2060 
given as multiple IV doses on fibrin 
generation.
b. Fibrin Generation Assay (FGA)

Objective:
Part 1: To explore the effect of MK-2060 
given as a single IV dose on prothrombin 
time (PT).
Part 2: To explore the effect of MK-2060 
given as multiple IV doses on 
prothrombin time (PT).
c.
PT fold change from baseline

Objective:
Part 1: To explore the effect of MK-2060 
given as a single IV dose on biomarker(s) 
of inflammation (e.g., hsCRP).
Part 2: To explore the effect of MK-2060 
given as multiple IV doses on 
biomarker(s) of inflammation (e.g., 
hsCRP).
d. hsCRP reduction from baseline
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Objectives
Endpoints

Objective:
Part 1: To explore the effect of MK-2060 
given as a single IV dose on time to 
hemostasis after decannulation of the 
hemodialysis vascular access site in ESRD 
patients.
Part 2: To explore the effect of MK-2060 
given as multiple IV doses on time to 
hemostasis after decannulation of the 
hemodialysis vascular access site in ESRD 
patients.
e.
Time to adequate hemostasis after 
decannulation of vascular access 
compared to baseline

Objective: To explore the relationship 
between genetic variation and response to 
the treatment(s) administered, and 
mechanisms of disease.  Variation across 
the human genome may be analyzed for 
association with clinical data collected in 
this study.
f.
Germline genetic variation

To explore the development of ADAs 
measured in blood samples after single 
and multiple IV doses of MK-2060 are 
administered in older adult participants 
with ESRD on HD.
g. ADA

To explore biomarkers of pruritis in 
plasma samples of patients, and evaluate 
their relationship to patient-reported 
pruritic symptoms as registered by the 5-D 
Itch Scale.
h. biomarkers of pruritis, pruritic 
symptoms
4
STUDY DESIGN
4.1
Overall Design  
This is a double-blind, randomized, placebo-controlled, multiple site, sequential panel, single 
and multiple dose trial of MK-2060 in older adult participants (age ≥40 and ≤80 for Part 1 
and ≥18 and ≤80 for Part 2; men and women of non-child bearing potential) with ESRD on 
HD to be conducted in conformance with Good Clinical Practice.  The study will evaluate the 
safety and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and 
multiple dose IV administration of MK-2060 in older adult participants with ESRD.
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Part 1:  Part 1 of the trial will consist of up to 3 panels. In all panels, 8 participants will be 
randomized to receive a single dose of MK-2060 or placebo (0.9% sodium chloride infusion, 
USP sterile saline) in a treatment ratio of 3:1 (6 active and 2 placebo).  Each participant may 
only participate in one panel of the study. 
Participants in all panels will be domiciled for ~52 hours after study drug administration for 
safety/tolerability monitoring. Participants in all groups/panels will be closely monitored for 
safety and tolerability, including safety labs, local lab aPTT and PT results, physical exam to 
check incidence of bleeding, vital signs (VS) and 12-lead ECG, as well as local infusion site 
reactions and for systemic reactions to infusion.
There will be approximately a 28-day period (+/- 2 days) [including 21 days (+/- 2 days)] 
safety data review and approximately 7 days for dosing escalation decision)] between dosing 
the last cohort in a panel and dose administration in the next panel to evaluate safety, 
tolerability, and available PK data.  The decision to proceed to the next panel will be based 
upon acceptable safety and tolerability data collected over at least a 21-day (+/- 2 days) 
observation period for at least 7 participants in the previous panel, including local lab aPTT, 
PT, and hemoccult test review.  Plasma pharmacokinetic data will be reviewed on an ongoing 
basis and at least 14 days of PK data from at least 7 participants in Panel A (8 mg dose) will 
be evaluated prior to proceeding to the next panels.  Panel C (40 mg dose) will not be dosed 
until at least 21 days of safety, tolerability, PK, and PD data from the 40mg IV panel in the 
ongoing PN001 (Panel I) has been reviewed.
Part 2:  Part 2 will be the first study of multiple dosing of MK-2060 in older adult patients 
with ESRD on HD. In this part, approximately 20 participants will be randomized to a 3 
times per week for the 1st week and then once weekly dose for 3 weeks of MK-2060 or 
placebo (0.9% sodium chloride infusion, USP sterile saline) in a treatment ratio of 3:1 (15 
active and 5 placebo) for total of 4 weeks of dosing.  Participants will receive a loading dose 
up to 25 mg IV MK-2060 or placebo for a total of 3 doses in week 1 and a weekly 
maintenance dose up to 25 mg IV MK-2060 or placebo in weeks 2-4.  Participants will not be 
dosed until 14 days of safety data and available PK data from at least 6 participants in the 
40mg IV panel (Part 1 Panel C) of this trial has been reviewed.  Participants who have 
completed Part 1 Panel A, B, or C may be enrolled in Part 2 of the study with joint agreement 
of the Investigator and the Sponsor.  
Participants will be domiciled for the 1st week until ~ 24 hours post the third dose and for 
~24 hours after each study drug administration in weeks 2-4 for safety/tolerability 
monitoring.   Participants may be domiciled longer pending the investigator requirements 
and/or the preference of the participant.  Participants will be closely monitored for safety and 
tolerability, including safety labs, local lab aPTT and PT results, physical exam to check 
incidence of bleeding, vital signs (VS) and 12-lead ECG, as well as local infusion site 
reactions and for systemic reactions to infusion.  All participants in this study will be 
followed through approximately 3 months after the last study dose (Dose #6) for safety and 
tolerability, including all adverse experiences, safety labs, local lab aPTT and PT results, 
physical exam to check incidence of bleeding, vital signs (VS) and 12-lead ECG.
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The trial design is depicted in [Figure 1, Figure 2 and Table 1]. For all panels in Part 1 and 
Part 2, participants will be followed for approximately 164 days or 90 days post the last dose 
of study drug respectively.  Blood samples will be collected for MK-2060 plasma PK and PD 
to assess aPTT/PT levels, fibrin generation, and FXI activity levels.
The precise timing of safety and tolerability measurements, PK and PD samples may be 
altered during the course of the study based on newly available data (i.e., to obtain data 
closer to the time of peak concentrations or to better describe the half-life of the compound). 
Because this is a Phase 1 assessment of MK-2060 in humans, the pharmacokinetic (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 8.11.7 for examples of modifications permitted 
within the protocol parameters.
Specific procedures to be performed during the study, as well as their prescribed times and 
associated visit windows, are outlined in the SoA in Section 1.3. Details of each procedure 
are provided in Section 8.
4.2
Scientific Rationale for Study Design
The main objectives of this study are to evaluate safety, tolerability, PK, and PD of MK-2060 
after IV administration of single and multiple doses in older adult (ages ≥ 40 and ≤ 80 for 
Part 1 and ≥ 18 and ≤ 80 for Part 2) men and women of non-child bearing potential 
(WONCBP) with ESRD on HD.  PD effects on aPTT, PT, FXI activity, and fibrin generation 
will be explored.  Up to approximately 44 older adult participants with ESRD on HD who 
meet study eligibility criteria may be enrolled in this study. 
MK-2060 is being developed for the prevention of thrombotic complications in ESRD 
patients, thus the primary aim of this study is to evaluate safety, tolerability, PK, and PD of 
MK-2060 in this patient population.  
We do not anticipate renal impairment, HD, or age to significantly alter the PK and PD of 
MK-2060.  As discussed above, PN001 has demonstrated MK-2060 to be generally safe and 
well-tolerated in normal healthy subjects.  Based on preliminary analysis, MK-2060 achieved 
mean maximum concentration at 1hr (end of infusion) after IV infusion, followed by a bi-
phasic terminal phase with apparent mean half-life of ~29 to 39 days.  MK-2060 clearance 
was ~0.23 L/day, consistent with reported CL of mAb.  As renal elimination is typically an 
insignificant pathway for IgG mAbs due to their large size, the clearance of MK-2060 is not 
expected to change in renal impaired subjects or subjects on hemodialysis. Furthermore, 
assessment of the clotting cascade in subjects with ESRD has demonstrated that FXI levels 
are not significantly altered [Vaziri, N. D., et al 1994].  In PN001, MK-2060 volume of 
distribution was estimated as 11 L, slightly larger than the reported volume of distribution for 
mAb. [Dirks, N. L. 2010].  It could be possible that kidney failure or HD might impact 
volume of distribution, due to fluid retention, although we do not anticipate this to have a 
major effect.  As MK-2060 is a monoclonal antibody age is also unlikely to alter PK and PD.  
The impact of renal impairment, HD, and age on MK-2060 PK and PD will be further 
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assessed by comparing data in this study to the data in young normal healthy subjects in 
PN001.  IONIS has demonstrated using an FXI anti-sense oligo (ASO) that inhibition of the 
FXI pathway in ESRD patients on HD (mean age of 61 years) is generally safe and well-
tolerated [Bethune, C., et al 2017]. Thus, the study of MK-2060 in older adult patients with 
ESRD on HD is well supported.
The rationale to limit recruitment to males and WONCBP is that developmental and 
reproductive toxicology studies in animals have not been completed.
4.2.1
Rationale for Endpoints
4.2.1.1
Safety Endpoints
This will be the first introduction of MK-2060 to participants with ESRD on HD. Based on
the data from PN001, it is expected that IV administration of MK-2060 will be well-
tolerated in participants with ESRD on HD. However, the safety and tolerability of MK-
2060 are primary endpoints and will be carefully monitored. Physical examinations, VS,
ECGs, laboratory safety tests (serum chemistry and hematology), aPTT, PT, and endpoints
related to bleeding (macroscopic bleeding and high sensitivity hemoccult) will be assessed
throughout the dosing intervals. AEs, including local infusion site reactions and systemic
reactions to infusion, will be assessed throughout the dosing intervals.
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. However, given potential safety risks, participants will be
monitored closely during the infusion with scheduled VS and physical examinations as
needed. 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 164 for all panels in Part 1 and Day 111 for Part 2.
Time to adequate hemostasis after decannulation of vascular access
An exploratory 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.  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).  
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Upon decannulation pressure is held until adequate hemostasis has been obtained.  In this 
study the process is standardized such that change in time to hemostasis from baseline (i.e., 
pre-dose) can be assessed (see the operational manual for details).
Twice for Part 1 and once for Part 2 during the screening period (i.e., prior to dosing) time to 
adequate hemostasis will be assessed to establish a baseline (mean of two screening period 
assessments; Screen 2 and Screen 3 for Part 1).  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. This exploratory analysis may allow for a very preliminary read 
on bleeding risk with administration of MK-2060 in the ESRD patient population.
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
In order to characterize the PK profile of MK-2060 in older adult participants with 
ESRD on HD, for Part 1 non-compartmental PK parameters AUC0-∞, AUC0-168, Cmax,
C168hr, Tmax, apparent terminal t1/2, CL and Vz will be summarized after single dose IV 
administration; for Part 2, non-compartmental PK parameters AUC0-168, Cmax, C168, 
Tmax will be summarized for the first and last dose. Estimation of plasma PK data of MK-
2060 following a single and multiple dose in older participants with ESRD on HD is a 
secondary objective of this study. Another secondary objective is to compare single dose 
plasma PK data of MK-2060 in older adult participants with ESRD on HD to participants
with normal renal function studied in PN001.
4.2.1.3
Pharmacodynamic Endpoints
aPTT and FXI activity (performed by Central Lab); fibrin generation assay (FGA)
and high sensitivity C-reactive protein (hsCRP)
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. FGA and hsCRP will also be measured as exploratory PD biomarkers. 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 a single and multiple well-tolerated
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dose is a secondary objective of this study. For this secondary objective, the hypothesis
that is being tested is: The true fold-increase in aPTT 168 hours after a single well-
tolerated dose of MK-2060 in older adult participants with ESRD on HD is at
least 1.5 (Part 1) and the true fold increase from baseline for aPTT 168 hours post the last 
dose following an IV loading dose and three maintenance IV doses of MK-2060 in older 
adult participants with ESRD on HD is at least 1.5 (Part 2). A 1.5-fold aPTT prolongation
corresponds to the in vitro PD effect that is observed when using a concentration of MK-
2060 that was demonstrated to inhibit clot formation in nonhuman primates to a similar
extent as a clinically relevant comparator (apixaban, 5 mg bid).  In plasma from severe FXI-
deficient patients, aPTT prolongation up to 3.9-fold is observed, using the same PD assay 
described above [Ellsworth K 2018]. aPTT prolongation up to approximately 3.5-fold was 
also reported in FXI-deficient subjects in a published study [Asakai, R., et al 1991]. aPTT 
prolongation up to ~4-fold would be expected for almost complete FXI inhibition, and aPTT 
prolongation greater than 4-fold would represent unexpected pharmacology, which is part of 
the basis for the aPTT-based stopping rules described in Section 6.6.1
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 absorption, distribution, metabolism, and excretion; mechanism of action of 
the drug; disease etiology; and/or molecular subtype of the disease being treated. Therefore, 
where local regulations and IRB/IEC allow, a sample will be collected for DNA analysis 
from consenting participants.
DNA samples may be used for research related to the study intervention(s), the disease under 
study, or related diseases. They may also be used to develop tests/assays including diagnostic 
tests related to the disease under study, related diseases, and study intervention(s). Genetic 
research may consist of the analysis of 1 or more candidate genes, the analysis of genetic 
markers throughout the genome, or analysis of the entire genome. Analysis may be 
conducted if it is hypothesized that this may help further understand the clinical data.
The samples may be analyzed as part of a multi-study assessment of genetic factors involved 
in the response to understand study disease or related conditions.
4.2.1.5
Future Biomedical Research
The Sponsor will conduct future biomedical research 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 analyses, depending on which specimens are consented for future 
biomedical research.
Such research is for biomarker testing to address emergent questions not described elsewhere 
in the protocol (as part of the main study) and will only be conducted on specimens from 
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appropriately consented participants. The objective of collecting/retaining specimens for 
future biomedical research 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 future biomedical research are presented in Appendix 6.
4.2.2
Rationale for the Use of Placebo
The primary goal of the study is to evaluate the safety and tolerability of MK-2060 in older 
adult participants with ESRD on HD. A placebo-controlled study will allow for an unbiased
assessment of safety and tolerability of MK-2060, including local infusion site reactions.
Secondary and exploratory outcomes are also supported by the use of placebo, including 
evaluation of the effect of MK-2060 on aPTT following single and multiple dose IV 
administration, which should only be observed in participants with active treatment.
4.3
Justification for Dose
4.3.1
Rationale for Dose Selection/Regimen/Modification
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 8.11.7 - Study Design/Dosing/Procedures 
Modifications Permitted within Protocol Parameters.
The primary objective of the current study is to assess the safety and tolerability profile of 
MK-2060 after IV single and multiple dose administration in older adult participants with 
ESRD on HD under IND guidance limitations for dose.  The purpose of this trial is not to 
determine maximum tolerated dose but rather to investigate the pharmacology of MK-2060 
at relevant exposures, consistent with the guidance of the IND.
4.3.2
Starting Dose for This Study
The clinical conduct of the Phase I study in healthy male participants (PN001) evaluating 
safety, tolerability, and PK of MK-2060 has completed.  The highest single IV dose of 40 
mg has been well tolerated.
In healthy participants the 8 mg IV dose was well-tolerated and lacked a significant 
pharmacodynamic effect (maximum observed aPTT increase was 1.4-fold compared to 
baseline), thus it has been selected as the starting dose for Panel A in the current trial. 
Selection of this dose will allow the assessment of the impact of renal impairment and HD on 
MK-2060 PK by direct comparison of the data from the 8 mg IV dose in normal healthy 
subjects in PN001.  Please refer to Section 4.2 above for further discussion of why significant 
PK differences with MK-2060 in older adult participants with ESRD on HD is not 
anticipated.
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4.3.3
Maximum Dose/Exposure for This Study
The maximum dose to be administered in this study will not exceed 40 mg and will be based 
on review of emerging data from earlier panels within the current study, and from the 
ongoing PN001.  Panel C (40 mg dose) will not be dosed until at least 21 days of safety, 
tolerability, and PK and PD data from the 40 mg IV dose in PN001 (Panel I) has been 
reviewed.
The safety of MK-2060 was evaluated in a cardiovascular safety pharmacology study and a
4-week repeat-dose toxicity study, both in Rhesus monkeys. The NOAEL for the
multiple dose study was ≥60 mg/kg/week (AUC0-168hrat 60mg/kg = 7920g/mL * day).
Assuming dose proportionality, a single dose of 40 mg MK-2060 IV is predicted to result in 
a mean Cmax ~80 nM (plasma concentrations of MK-2060 that does not exceed those 
observed in previous panels of PN001), C168 ~20 nM and a mean AUC0-168hr of 5800 
nM*hr, 220-fold below the NOAEL of 7920 μg/mL*day (1.28 x 106 nM*hr) in healthy male 
subjects.  At this dose the mean aPTT change from baseline is predicted to be ~2.75 fold at 
Cmax and ~2 fold at C168. Please refer to Section 4.2 above for further discussion of why 
significant PK differences with MK-2060 in older adult participants with ESRD on HD is not 
anticipated.
4.3.4
Rationale for Multiple Dose Regimen (Part 2)
The primary intent of Part 2 is to evaluate the safety, tolerability, PK, and PD of an MK-2060 
multiple dose regimen that will achieve target anticoagulation. For anticoagulants, it is 
desirable to achieve near target anticoagulation as soon as therapy is initiated so a loading 
dose is being used for this portion of the study. 40 mg IV is the highest dose assessed in 
PN001 in NHVs and in ESRD patients in Part 1 of PN004.  In PN001 with a single 40 mg IV 
dose Cmax and AUC0-168hr the geometric mean (GCV) were 78.2 (11.8) nM and 6350 
(17.6) nM*hr , respectively.  Preliminary dose modelling based on PK/PD data from the 
available 8, 20, and 40 mg single dose data in ESRD patients in Part 1 of PN004 projects that 
a regimen of 25 mg dosed on Days 1, 3, and 5 followed by 3 maintenance doses of 25 mg 
QW is projected to have a median Cmax (post first maintenance dose) of 91 nM and AUC0-
168hr (post last dose) of 8868 nM*hr.  From a safety perspective, the steady state Cmax of 
the 25 mg IV QW dose is projected to be ~25% higher than the Cmax achieved with the 40 
mg IV single dose in PN001. Due to the slight increase in projected steady state Cmax in Part 
2, the domiciling period has been increased during the first week of dosing for additional 
safety monitoring. As discussed above, all doses of MK-2060 have been generally well 
tolerated with no dose related SAEs, discontinuations due to AEs, or AEs suggestive of 
hypersensitivity, therefore no safety issues are anticipated in Part 2 with this slightly higher 
exposure. 25 mg QW is projected to result in >90% of participants with aPTT of 1.5 fold 
baseline at trough.  The multiple dose regimen of Part 2 (3 doses for week 1 plus 3 
maintenance doses) steady state is projected to be achieved by end of week 1 (concentration 
~90% of steady state).
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4.3.5
Rationale for Dose Interval and Study Design
MK-2060 is a fully human monoclonal antibody and is not considered a compound with
high potential for risk of harm to participants according to the publication “Guideline
on Strategies to Identify and Mitigate Risks for First-in-Human and Early Clinical Trials 
with Investigational Medicinal Products” (European Medicine Agency guidance released
July 2017). The degree of uncertainty was determined by careful evaluation of the following: 
mode of action of MK-2060, presence or absence of biomarkers, the nature of the target, the 
relevance of available animal models and/or findings in nonclinical safety studies, and the 
study population.  MK-2060 does not exhibit highly species-specific action, nor is it
directed towards immune system targets. Safety assessment studies and ancillary
pharmacology studies with MK-2060 provide no contraindications to the initiation of
clinical studies in humans with this compound via the IV route. No dose-limiting toxicities
were observed in the 4-week nonhuman primate toxicity trial, and substantial preclinical
safety margins were obtained over initial human doses. These considerations suggest that
the risk of unanticipated severe reactions is low. However, due to uncertainties inherent in
early phase clinical testing, this study will include a period of observation on a clinical
research unit (CRU) after dosing. CRUs will be staffed and equipped to manage
unanticipated severe adverse effects and have appropriate access to a full service acute-
care hospital to facilitate rapid institution of medical intervention as indicated.
Part 1 of the trial will include up to 3 sequential IV panels with up to 8 participants each,
including up to 6 participants on active drug and up to 2 participants on placebo, per panel.
The 3 panels will include dose levels administered via the IV route [Panel A: 8 mg; Panel B: 
20 mg; Panel C: 40 mg] to explore the intravenous PK and PD profile of MK-2060.  
Participants may only participate in one panel in Part 1 of the study. All IV doses will be
delivered via a continuous infusion. In each panel, participants will be enrolled and dosed
on a rolling basis. Each participant in each panel will be dosed and observed until
discharge (~52 hours post-dose) for safety/tolerability.  52 hours is sufficient to monitor for
initial safety/tolerability and local infusion site reactions and for systemic reactions to
infusion. There will be approximately a 28-day (+/- 2 days) period between dosing the last
participants in a panel and dose administration in the next panel to evaluate safety,
tolerability, and available PK data.
Within each group, all participants are planned to be administered MK-2060 or placebo by 
Phase 1 Clinical Research standards for compounds not considered to have a high degree of 
uncertainty related to the potential risk of harm to participants. The dosing regimen was
determined based on the following: the presence of preclinical safety margins for MK-
2060, the inclusion of extensive safety monitoring in the clinic, and the fact that MK-2060
is not considered a compound with a high potential for risk of harm. There will be
frequent, careful assessments of adverse events throughout the post-dose period. This
recommendation is in keeping with the projected safety profile and the ability of the Phase I
unit to monitor each subject closely.
In Part 1, the decision to proceed to the next panel will be based upon acceptable safety and
tolerability data collected over at least a 21-day (+/- 2 days) observation period for at 
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least 7 participants in the previous panel, including local lab aPTT, PT, and hemoccult test
review. In Part 2, participants will not be dosed until 14 days of safety data and available PK 
data from at least 6 participants in the 40mg IV panel (Part 1 Panel C) of this trial has been 
reviewed. Considering that the major safety concerns are local tolerability and acute infusion 
reactions, 21 days of safety data is sufficient to advance the trial between panels in Part 1.
Based on observed safety from PN001 and PN004 (Panel A and B) and PK data from PN001 
and PN004 (Panel A), 14 days after a single 40 mg IV dose of MK-2060 the exposure will be 
below the highest exposure observed with the 8 mg and 20 mg IV doses.  Therefore 14 days 
of safety, tolerability data and available PK data from at least 6 participants in Part 1 Panel C 
40 mg IV dose will be sufficient to determine the safety of proceeding to Part 2.  PK and PD
data will be reviewed on an ongoing basis and will be used to inform on decisions to modify
the subsequent dose level. When available, plasma PK data will be reviewed to aid in
dose escalation decisions; at least 14 days of PK data from at least 7 participants in Panel A 
(8 mg) will be evaluated prior to proceeding to the next panels.  In addition, Panel C (40 mg 
dose) will not be dosed until 21 days of safety, tolerability, and PK and PD data from the 40 
mg dose in PN001 has been reviewed.
In Part 2 (multiple dose), in order to mimic the therapeutic setting, 3 doses given on Days 1, 
3, and 5 will be studied in addition to the weekly maintenance dose. A weekly maintenance
dosing frequency was selected to reduce the peak to trough ratio without posing a significant
burden to ESRD patients who undergo dialysis 3 times a week and can receive an IV infusion 
concurrent with dialysis. A less frequent dosing interval would result in higher peak 
concentrations and patients being sustained at maximal FXI inhibition levels longer, which 
could potentially increase bleeding risk in this vulnerable population. For anticoagulants, it is 
desirable to achieve near target anticoagulation as soon as therapy is initiated. Given the half-
life of ~18 days observed in Part 1 of PN004 and the dosing frequency of QW, without the 3 
doses given during week 1 (loading dose) it would take weeks to achieve steady state 
exposure and target anticoagulation.  Thus, the 3 doses during week 1 are introduced to help 
achieve desired anticoagulation immediately after initiation of therapy. 
Participants will be discharged following the ~52- or ~24-hour (24 hours after last dose for 
Week 1 and 24 hours after each dose in Weeks 2-4) in-clinic period after dosing for Part 1 or 
Part 2 accordingly, but they will continue to be monitored throughout the trial period and
return to the site post-dose as specified in the SoA (safety evaluations as indicated in the
flow chart (including repeat physical examinations, infusion reaction assessments,
laboratory safety assessments, hemoccult, local lab aPTT and PT tests).
Following discharge, the following measures are being taken in this protocol to ensure the
safety of study participants:

Participants will be informed that they could be 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.
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
Participants will be required to avoid scheduling any 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
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 48 hours for Part 1 and 24 hours for Part 2, and until
aPTT/PT values are no longer increasing (upon retest at 48 hours) and according 
to the discretion of the investigator.
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 from the study, 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 Institutional Review Board(s)/Independent Ethics 
Committee(s) [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 pre-specified criteria for terminating the trial early.
A primary objective of this early Phase I trial is to identify a safe and well-tolerated dose 
and/or dosing regimen that achieve pharmacokinetic, pharmacodynamic and/or biologic 
targets in humans based on preclinical or early clinical data.  Therefore, it is possible that 
trial participants may not receive all doses specified in the protocol if this objective is 
achieved at lesser dose levels in this trial.  This would not be defined as early termination of 
the trial, but rather an earlier than anticipated achievement of the trial objective(s).  If a 
finding (e.g., pharmacokinetic, pharmacodynamic, efficacy, biologic targets, etc.) from 
another preclinical or clinical trial using the trial treatment(s), comparator(s), drug(s) of the 
same class, or methodology(ies) used in this trial, results in the trial(s) or program being 
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stopped for non-safety reasons, this also does not meet the definition of early trial 
termination.
Early trial termination is defined as a permanent discontinuation of the trial due to 
unanticipated concerns of safety to the trial participants arising from clinical or preclinical 
trials with the trial treatment(s), comparator(s), drug(s) of the same class or methodology(ies) 
used in this trial.
The clinical study may be terminated early if the extent (incidence and/or severity) of 
emerging effects is such that the risk/benefit ratio to the study population as a whole is 
unacceptable. In addition, further recruitment in the study or at a particular study site(s) may 
be stopped due to insufficient compliance with the protocol, GCP, and/or other applicable 
regulatory requirements, procedure-related problems or the number of discontinuations for
administrative reasons is too high.
5
STUDY POPULATION
Male and Female of non-child bearing potential (WONCBP) participants with ESRD on HD
between the ages of 18 and 80 years (ages ≥ 40 and ≤ 80 for Part 1 and ≥ 18 and ≤ 80 for Part 
2) will be enrolled in this study.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1
Inclusion Criteria
A participant will be eligible for inclusion in the study if the participant:
Type of Participant and Disease Characteristics
1. ESRD maintained on stable outpatient HD regimen, using an established (>3 
months) 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 at a healthcare 
center for > 3 month from 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 for at least 3 months beyond the 
study.
3. Have a Body Mass Index (BMI) ≥ 18 and ≤ 45 kg/m2. BMI = weight (kg)/height
(m)2.
4. Baseline health is judged to be stable based on medical history, physical
examination, vital sign measurements and ECG performed prior to
randomization.
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5. 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 both the investigator and the 
Sponsor.
6. Be willing to comply with the trial restrictions (see Section 5.3) for a
complete summary of trial restrictions).
Demographics
7. Be male or female, of non-child bearing potential (WONCBP) from 40 years to 80 
years of age inclusive for Part 1, and 18 years to 80 years of age inclusive for Part 2, 
at the time of signing the informed consent.
Male Participants
Contraceptive use by men should be consistent with local regulations regarding the methods
of contraception for those participating in clinical studies.
8. Agree to use a male condom plus partner use of an additional contraceptive method 
when having penile-vaginal intercourse with a WOCBP who is not currently 
pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain 
abstinent from penile-vaginal intercourse or use a male condom during each episode 
of penile-vaginal penetration.
Female Participants
Contraceptive use by women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.
9. A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and one of the following conditions applies:
a.
She is not a woman of childbearing potential (WOCBP), satisfying one of the two 
criteria below:
i.
If the participant is a postmenopausal female: she is without menses 
for at least 1 year and has a follicle stimulating hormone (FSH) value 
in the postmenopausal range upon pre-study (screening) evaluation.
ii.
If the participant is a surgically sterile female: she is status post 
hysterectomy, bilateral salpingectomy, oophorectomy or tubal ligation. 
NOTE: These procedures must be confirmed with medical records. In 
the absence of documentation, hysterectomy may be confirmed by 
pelvic exam or if necessary by ultrasound; oophorectomy may be 
confirmed by hormone levels, particularly follicle stimulating hormone 
(FSH) in the post-menopausal range, but tubal ligation without records 
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should be excluded. Information must be captured appropriately within 
the site's source documents.
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
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:
Medical Conditions
1. Has a 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.
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2. Is mentally or legally incapacitated, has significant emotional problems at the time of pre-
study (screening) visit or expected during the conduct of the study or has a history of 
clinically significant psychiatric disorder of the last 5 years. Participants who have had 
situational depression may be enrolled in the study at the discretion of the investigator.
3. Has a history of cancer (malignancy), including adenocarcinoma,
Exceptions: (1) Subjects with adequately treated non-melanomatous skin carcinoma
may participate in the trial; (2) Subjects with other malignancies which have been
successfully treated ≥10 years prior to the pretrial (screening) visit where, in the
judgment of both the investigator and treating physician, appropriate follow-up has
revealed no evidence of recurrence from the time of treatment through the time of the
pretrial (screening) visit (except those cancers identified at the beginning of exclusion
criterion 10); or, (3) Subjects, who, in the opinion of the trial investigator, are highly
unlikely to sustain a recurrence for the duration of the trial.
4. Has blood coagulation test (aPTT, PT) ≥20 % outside of normal range on pretrial
(screening), which are considered clinically significant by both the investigator and
the sponsor.
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 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.
8. Has a history of or current frequent epistaxis within the last 3 months or active gingivitis.
9. Has ongoing anticoagulant therapy (warfarin, apixaban, dabigatran, rivaroxaban, 
edoxaban, betrixaban) or antiplatelet therapy (clopidogrel, prasugrel, ticagrelor, 
ticlopidine). Intradialytic heparin and aspirin are permitted.
10. 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.
11. 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.
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12. Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 
4 weeks prior to the pre-study (screening) visits.
13. Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex
allergy), or has had an anaphylactic reaction or significant intolerability (i.e. systemic
allergic reaction) to prescription or non-prescription drugs or food.
14. 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.
15. Has a history (subject recall) of receiving any human immunoglobulin preparation
such as IVIG or RhoGAM within the last year.
16. 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 1 
month.
Exceptions: 

Participants who have received seasonal flu vaccine and pneumococcal vaccine 
within the last 1 month 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.
17. 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.

Non-sustained or sustained ventricular tachycardia (> 2 consecutive ventricular 
ectopic beats at a rate of > 1.7/second).
Prior/Concomitant Therapy
18. Is unable to refrain from or anticipates the use of medication, including prescription and 
nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-
lives) prior to administration of the initial dose of study drug, throughout the study until 
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the poststudy visit. Allowed and prohibited concomitant meds are discussed in Section 
6.5.
Prior/Concurrent Clinical Study Experience
19. Has participated in another investigational study within 4 weeks (or 5 half-lives, 
whichever is greater) prior to sponsor’s investigational drug (MK2060/placebo) 
administration. The window will be derived from the date of the last dose in the previous 
study.
Diagnostic Assessments
20. Has a blood pressure >190 mmHg systolic or >110 mmHg diastolic.
Other Exclusions
21. Is under the age of legal consent.
22. Consumes greater than 3 glasses of alcoholic beverages (1 glass 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 glasses 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. Is a regular user of any illicit drugs or has a history of drug (including alcohol) abuse 
within approximately 2 years. Participants must have a negative serum or saliva drug 
screen prior to randomization. Participants with a positive drug screen due to the use of 
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. Presents any concern by the investigator 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.
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5.3
Lifestyle Considerations
5.3.1
Meals and Dietary Restrictions
Fasting requirements for trial procedures, such as, but not limited to, laboratory safety
evaluations are specified in Section 8.
All meals on study dosing days will be served as to not interfere with the study procedures.
On dosing days, subjects will fast from all food and drinks, except water, for at least 8 hours 
prior to study drug administration.  Subjects will continue to fast until 2 hours after study 
drug administration when they will be given a light breakfast.  A lunch and dinner will be 
provided at time points indicated in the trial flowchart.  Additional meals and snack(s) will be 
provided by the investigator as per the CRUs standard procedures.  Subjects will fast from all 
food and drinks except water between meals and snacks.  After 24-hour post-dose procedures 
on dosing days have been completed, subsequent meals and snacks will be unrestricted in 
caloric content, composition and timing.
Instructions on whether to take MK-2060 with or without food and/or drink may be modified 
during the trial based on newly available data.
5.3.2
Caffeine, Alcohol, and Tobacco Restrictions
5.3.2.1
Caffeine Restrictions
Participants will refrain from consumption of caffeinated beverages and xanthine-containing 
products from 12 hours prior to the pre- and post-trial visits, from 12 hours prior to and 12 
hours after study drug administration, and 12 hours prior to scheduled outpatient visits. At all 
other times, caffeinated beverages or xanthine-containing products will be limited to no more 
than 6 units per day amounts (>6 units: 1 unit=120 mg of caffeine).
5.3.2.2
Alcohol Restrictions
Participants will refrain from consumption of alcohol 24 hours prior to the pre- and post-
trial visits, from 24 hours prior to and after study drug administration.
Participants will refrain from consumption of alcohol 12 hours prior to scheduled
outpatient visits.
At all other times, alcohol consumption is limited to no more than approximately 3 alcoholic
beverages or equivalent (1 glass is approximately equivalent to: beer [~355 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.
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5.3.3
Activity Restrictions
Participants will avoid unaccustomed strenuous physical activity (ie, weight lifting, running, 
bicycling, etc.) from the pre-study (screening) visit until administration of the initial dose of 
study drug, 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 randomized in the study. A minimal set of screen failure information 
may be included, as outlined in the electronic case report forms (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 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. The 
study site should contact the Sponsor for the replacement participant’s 
treatment/randomization number.
The replacement participant may begin dosing at the subsequent dose level for that panel, 
based on investigator and Sponsor review and discussion.
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 prior to dosing the replacement supplies. Clinical supplies will be 
affixed with a clinical label in accordance with regulatory requirements.
6.1
Study Intervention(s) Administered
The study intervention to be used in this study are outlined in Table 2.
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Table 2
Study Intervention
Arm 
Name
Arm Type
Intervention 
Name
Type
Dose 
Formu-
lation
Unit Dose 
Strength(s)
Dosage 
Level(s)
Route of 
Administration
Regimen/
Treatment 
Period/
Vaccination 
Regimen
Use
IMP/
NIMP
Sourcing
MK-
2060
Experimental
MK-2060
Drug
Solution 
for 
Infusion
100mg/mL
8 mg
20 mg
25 mg
40 mg
IV Infusion
Part 1: Day 1
Part 2: Days 1, 
3, 5, 8, 15 and 
22
Experimental
IMP
Provided 
Centrally 
by 
sponsor
Placebo
Placebo 
Comparator
Placebo
Drug
Solution 
for 
Infusion
Saline
0 mg
IV Infusion
Part 1: Day 1
Part 2: Days 1, 
3, 5, 8, 15 and 
22
Placebo
IMP
Locally
Definition Investigational Medicinal Product (IMP) and Non-Investigational Medicinal Product (NIMP) is based on guidance issued by the European Commission. Regional 
and/or Country differences of the definition of IMP/NIMP may exist. In these circumstances, local legislation is followed.
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All supplies indicated in Table 2 will be provided per the "Sourcing" column depending upon 
local country operational requirements. If local sourcing, every attempt should be made to 
source these supplies from a single lot/batch number where possible (e.g., 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 in order to administer the 
proper dose to each subject are outlined in a separate document provided by the Sponsor.
6.2.2
Handling, Storage, and Accountability
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received, and any discrepancies are 
reported and resolved before use of the study intervention.
Only participants enrolled in the study may receive study intervention, and only authorized 
site staff may supply or administer study intervention. All study interventions must be stored 
in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff.
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records).
For all study sites, the local country Sponsor personnel or designee will provide appropriate 
documentation that must be completed for drug accountability and return, or local discard 
and destruction if appropriate. Where local discard and destruction is appropriate, the 
investigator is responsible for ensuring that a local discard/destruction procedure is 
documented.
The study site is responsible for recording the lot number, manufacturer, and expiry date for 
any locally purchased product (if applicable) as per local guidelines unless otherwise 
instructed by the Sponsor.
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution, and usage of study 
interventions in accordance with the protocol and any applicable laws and regulations.
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6.3
Measures to Minimize Bias: Randomization and Blinding
6.3.1
Intervention Assignment
In each panel in Part 1 and Part 2, participants will be assigned randomly according to a 
computer-generated allocation schedule.  A sample allocation schedule is shown below in
Table 3 and Table 4 for Part 1 and Part 2 respectively.
Table 3
Sample Allocation Schedule for Part 1
Subjectsa
Doseb
Panel A
N=6
8 mg IV
N=2
PBO
Panel B
N=6
20 mg IV
N=2
PBO
Panel C
N=6
40 mg IV
N=2
PBO
PBO=Placebo
a Subjects will be ESRD on HD and randomized to receive an intravenous (IV) dose of MK-2060 (n=6) or 
placebo (n=2).
b The suggested doses may be adjusted downward based on evaluation of safety, tolerability, 
pharmacokinetic, and/or pharmacodynamic data observed in previous treatment panels.
Table 4
Sample Allocation Schedule for Part 2
Subjectsa
Doseb
N=15
Week 1: up to 25 mg IV x 3 /
Weeks 2-4: up to 25 mg IV
N=5
PBO
PBO=Placebo
a Subjects will be ESRD on HD and randomized to a once weekly IV dose of MK-2060 (n=15) or placebo 
(n=5) for 4 weeks. Males will be assigned allocation numbers in ascending order, starting with the lowest 
number.  Females will be assigned allocation numbers in descending order, starting with the highest 
number.
b The suggested doses may be adjusted downward based on evaluation of safety, tolerability,
pharmacokinetic, and/or pharmacodynamic data observed in Part 1.
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6.3.2
Stratification
A minimum of 2 participants of each gender will be enrolled in each panel in Part 1.  A 
minimum of 3 participants of each gender will be enrolled in Part 2.
6.3.3
Blinding
A double-blinding technique with in-house blinding will be used. MK-2060 and placebo will 
be packaged identically by an unblinded pharmacist so that blind is maintained. The infusion 
bags, IV line (through which the infusion is administered) do not require opaque covering as 
the differences between the clinical materials are not visually distinguishable within the 
infusion bags, tubing or syringe. The participant, the investigator, and Sponsor personnel or 
delegate(s) who are involved in the study intervention administration or clinical evaluation of 
the participants are unaware of the intervention assignments.
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
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 and is able to withhold the use within four hours prior to 
administration of the first dose of study drug in each panel of the study. 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 
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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
2.
Angiotensin II Receptor Antagonists
Candesartan
Eprosartan 
Irbesartan
Olmesartan
Telmisartan 
Valsartan 
3.
Diuretics
Hydrochlorothiazide 
Chlorothiazide 
Amiloride 
Triamterene 
Spironolactone 
Loop-diuretics, e.g., furosemide
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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
6.
DPP-4 Inhibitors
Linagliptin 
Saxagliptin 
Sitagliptin 
Vildagliptin
7.
GLP-1 Analogs
Exenatide
Liraglutide
Aspirin 
Low-dose aspirin is permitted in the study. 
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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
Clopidogrel
Prasugrel
Ticagrelor
Ticlopidine
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.
Clinical Research Units (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)
Prior to each treatment, the clinical and laboratory safety parameters from the previous dose 
level will be reviewed by the investigator and discussed with the Sponsor to permit a 
decision on whether to advance to the next higher dose level.  No dose escalation will occur 
without the joint agreement of the investigator and the Sponsor.
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6.6.1
Stopping Rules
If any of the following events occur, dose escalation in Part 1 or subsequent dosing in Part 2 
will be stopped to review additional safety data:

If one or more treatment related infusion adverse events of severe intensity occurs. 

If one or more treatment related SAEs occurs, dose escalation will be stopped and a 
meeting to review available safety data by the investigator and Sponsor will be 
required.

Two (2) or more participants within a Panel in Part 1 (at the same dose level) or Part 
2 report Severe Non-Serious Adverse Events considered related to the study drug by 
the investigator.

An increase in local lab aPTT > 4.0-fold versus screening baseline as confirmed after 
repeat measurement in 2 or more subjects in a panel in Part 1 or in Part 2.  Local lab 
aPTT measured at Screening Visit 1 should be used as baseline value.

An increase in local lab PT > 1.5-fold versus screening baseline as confirmed after 
repeat measurement in 2 or more subjects in a panel in Part 1 or in Part 2. Local lab 
PT measured at Screening Visit 1 should be used as baseline value.
In severe FXI-deficient populations, aPTT prolongations greater than 3-fold have been 
observed (050RJ8). 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 doses in PN001.  These aPTT 
prolongations occurred in the absence 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 subjects in a 
panel. 
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.
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The safety of participants will be assessed on an ongoing basis, and while conditions that 
could warrant stopping dose escalation in Part 1 or subsequent dosing in Part 2 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 within the same panel or dose escalation will be 
stopped and a meeting to review 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 following the end of the study.
6.8
Clinical Supplies Disclosure
The emergency unblinding call center will use the intervention allocation schedule for the 
study to unblind participants and to unmask study intervention identity. The emergency 
unblinding call center should only be used in cases of emergency (see Section 8.1.10). The 
Sponsor will not provide random code/disclosure envelopes or lists with the clinical supplies.
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL
7.1
Discontinuation of Study Intervention
Discontinuation of study intervention does not represent withdrawal from the study.
As certain data on clinical events beyond study intervention discontinuation may be 
important to the study, they must be collected through the participant’s last scheduled follow-
up, even if the participant has discontinued study intervention. Therefore, all participants 
who discontinue study intervention prior to completion of the protocol-specified treatment 
period regimen will still continue to participate in the study as specified in Section 7.1 and 
Section 8.1.9, or if available, a protocol clarification letter. In Part 2, 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, semirecumbent 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 Sections 8.1.9.
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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’s treatment assignment has been unblinded by the investigator, MSD, or 
through the emergency unblinding call center.

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.
7.2
Participant Withdrawal From the Study
Specific details regarding procedures to be performed at the time of withdrawal from the 
study, as well as specific details regarding withdrawal from future biomedical research, are 
outlined in Section 8.1.9. The procedures to be performed should a participant repeatedly fail 
to return for scheduled visits and/or if the study site is unable to contact the participant are 
outlined in Section 7.3. 
7.3
Lost to Follow-up
If a participant fails to return to the clinic for a required study visit and/or if the site is unable 
to contact the participant, the following procedures are to be performed:

The site must attempt to contact the participant and reschedule the missed visit. If the 
participant is contacted, the participant should be counseled on the importance of 
maintaining the protocol-specified visit schedule.

The investigator or designee must make every effort to regain contact with the participant 
at each missed visit (eg, telephone calls and/or a certified letter to the 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.
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
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 utilized 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.
The maximum amount of blood collected from each participant over the duration of the study
will not exceed 500 mL for Part 1 and 563.5 mL for Part 2 (Appendix 8 and
operations/laboratory manual).
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 
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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 
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
randomization, site personnel will add the treatment/randomization number to the participant 
identification card.
The participant identification card also contains contact information for the emergency 
unblinding call center so that a health care provider can obtain information about study 
intervention in emergency situations where the investigator is not available.
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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. Refer to Section 6.5 for guidelines on concomitant medication use
8.1.6
Assignment of Screening Number
All consented participants will be given a unique screening number that will be used to 
identify the participant for all procedures that occur prior to randomization. Each participant 
will be assigned only 1 screening number. Screening numbers must not be re-used for 
different participants.
8.1.7
Assignment of Treatment/Randomization Number
All eligible participants will be randomly allocated and will receive a treatment/
randomization number. The randomization number identifies the participant for all 
procedures occurring after randomization. Once a randomization number is assigned to a 
participant, it can never be re-assigned to another participant.
A single participant cannot be assigned more than 1 treatment /randomization number.
8.1.8
Study Intervention Administration
Administration of study medication will be witnessed by the investigator and/or study staff.
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 or placebo will be given in the morning 30 minutes after 
initiation of hemodialysis and after at least an 8-hour fast. The fast will be maintained until 2-
hours postdose, at which time a standard light breakfast will be served. Subjects will also 
remain semi-recumbent for 4 hours postdose except to stand for the measurement of 
orthostatic VS (if needed) or other trial procedures (for example for breakfast).
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8.1.9
Discontinuation and Withdrawal
The investigator or trial coordinator must notify the Sponsor when a participant has been 
discontinued/withdrawn from the trial. If a participant discontinues for any reason at any 
time during the course of the trial, the participant may be asked to return to the clinic (or be 
contacted) for a post-trial visit (approximately 150 or 90 days after the last dose of study drug 
is given for Part 1 and Part 2 respectively) to have the applicable procedures conducted.  
However, the investigator may decide to perform the post-trial procedures at the time of 
discontinuation or as soon as possible after discontinuation.  If the post-trial visit occurs prior 
to 150 or 90 days after the last dose of study drug is given for Part 1 and Part 2 respectively, 
the investigator and/or appropriately trained study site staff should perform a follow-up 
phone call 150 or 90 days after the last dose of study drug for Part 1 and Part 2 respectively 
to determine if any adverse events have occurred since the post-trial clinic visit.  Any adverse 
events which 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 future biomedical research. Participants may 
withdraw consent at any time by contacting the investigator for the main study. If medical 
records for the main study are still available, the investigator will contact the Sponsor using 
the designated mailbox (clinical.specimen.management@merck.com). Subsequently, the 
participant's consent for future biomedical research will be withdrawn. A letter will be sent 
from the Sponsor to the investigator confirming the withdrawal. It is the responsibility of the 
investigator to inform the participant of completion of withdrawal. Any analyses in progress 
at the time of request for withdrawal or already performed prior to the request being received 
by the Sponsor will continue to be used as part of the overall research study data and results. 
No new analyses would be generated after the request is received.
In the event that the medical records for the main study are no longer available (eg, if the 
investigator is no longer required by regulatory authorities to retain the main study records) 
or the specimens have been completely anonymized, there will no longer be a link between 
the participant’s personal information and their specimens. In this situation, the request for 
specimen withdrawal cannot be processed.
8.1.10
Participant Blinding/Unblinding
STUDY INTERVENTION IDENTIFICATION INFORMATION IS TO BE UNMASKED 
ONLY IF NECESSARY FOR THE WELFARE OF THE PARTICIPANT. EVERY 
EFFORT SHOULD BE MADE NOT TO UNBLIND.
For emergency situations where the investigator or medically qualified designee (consistent 
with local requirements) needs to identify the intervention used by a participant and/or the 
dosage administered, he/she will contact the emergency unblinding call center by telephone 
and make a request for emergency unblinding. As requested by the investigator or medically 
qualified designee, the emergency unblinding call center will provide the information to 
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him/her promptly and report unblinding to the Sponsor. Prior to contacting the emergency 
unblinding call center to request unblinding of a participant’s intervention assignment, the 
investigator who is qualified physician should make reasonable attempts to enter the intensity 
of the AEs observed, the relation to study drug, the reason thereof, etc., in the medical chart. 
If it is not possible to record this assessment in the chart prior to the unblinding, the 
unblinding should not be delayed.
In the event that unblinding has occurred, the circumstances around the unblinding (eg, date, 
reason, and person performing the unblinding) must be documented promptly, and the 
Sponsor Clinical Director notified as soon as possible.
Once an emergency unblinding has taken place, the investigator, site personnel, and Sponsor 
personnel may be unblinded so that the appropriate follow-up medical care can be provided 
to the participant.
Participants whose treatment assignment has been unblinded by the investigator or medically 
qualified designee and/or nonstudy treating physician must be discontinued from study 
intervention, but should continue to be monitored in the study.
8.1.11
Domiciling
Part 1:  Participants will report to the clinical research unit (CRU) the evening prior to the
scheduled day of trial drug administration and remain in the unit for ~ 52 hours post-dose. At
the discretion of the investigator, subjects may be requested to remain in the CRU longer. If
local lab aPTT values are >3-fold above baseline (as measured at Screening Visit 1), or
local lab PT values are >1.5-fold above baseline (at any time point), subjects will be asked
to remain in the clinic for at least 48 hours, and until aPTT/PT values are no longer
increasing (upon retest at 48 hours).
Part 2:  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 post the third dose in Week 1 and 
for ~24 hours post-dose in Weeks 2-4. At the discretion of the investigator, subjects may be 
requested to remain in the CRU longer. In Part 2, Week 1, all participants will be domiciled 
until ~ 24 hours post the third dose on Day 5.  Participants may be domiciled longer per 
investigator’s discretion. If local lab aPTT values are >3-fold above baseline (as measured at 
Screening Visit 1), or local lab PT values are >1.5-fold above baseline (at any time point), 
subjects will be asked to remain in the clinic for at least 24 hours, and until aPTT/PT values
are no longer increasing (upon retest at 24 hours postdose).
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.
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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/placebo 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. Although the samples collected for anti-drug 
antibody (ADA) assessment in PN001 are pending analysis, based on the PK profiles 
observed to date, 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 pre-study 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
The physical exam assessments will be defined and conducted per the site SOP. A symptom 
driven physical exam will be conducted based upon any emergent symptoms at the discretion 
of the investigator.
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 0.1-0.4 round down and 0.5-0.9 round up.  
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8.3.2
Vital Signs
8.3.2.1
Resting Vital Signs
Vital Sign Measurements (Heart Rate and Blood Pressure)
Participants should be resting in a semirecumbent for at least 10 minutes prior to having vital 
sign (VS) measurements obtained. Semirecumbent vital signs (VS) will include heart rate 
(HR) and blood pressure (BP). The correct size of the BP cuff and the correct positioning on 
the participants' arm is essential to increase the accuracy of BP measurements.
Pre-dose heart rate (HR) and blood pressure (BP) will be in triplicate measurements, obtained 
at least 1-2 minutes apart within 3 hours of dosing MK-2060/placebo. The median of these 
measurements will be used as the baseline to calculate change from baseline for safety 
evaluations (and for rechecks, if needed). Postdose vital sign (VS) measurements will be 
single measurements.
Participants will continue to rest semi-recumbent from dosing until 4 hours postdose except 
to stand for the measurement of orthostatic vital signs (VS) (if needed) or other study-related 
procedure.
Body Temperature
Body temperature will be single measurement at all timepoints. The same method must be 
used for all measurements for each individual participant and should be the same for all 
participants.
Respiratory Rate
Respiratory rate (breaths per minute) will be measured and recorded as single measurements.
8.3.2.2
Orthostatic Vital Signs
Orthostatic vital signs (VS) (HR and BP) will also be obtained. Participants should be 
semirecumbent for at least 10 minutes and then stand upright for 2 minutes prior to 
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 prior to lead placement.  Participants may need to be shaved to ensure proper 
lead placement. 
Lead placement should be rechecked in cases where unexpected ECG findings are noted.
Participants should be resting in the semi-recumbent position for at least 10 minutes prior to 
ECG measurements being obtained.
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The QTc correction formula to be used at the site (for safety and inclusion/exclusion criteria 
assessments) is Fridericia.
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 subject with an 
ECG skin marker pen to ensure reproducible electrode placement.
Pre-dose ECGs will be obtained in triplicate at least 1-2 minutes apart within 24 hours prior 
to dosing MK-2060/placebo.  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, post-dose ECG measurements will be single 
measurements.
If a participant demonstrates an increase in QTc interval ≥60 msec compared with median
pre-dose 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 post-dose time point is ≥60 msec, 
the subject 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 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 Cardiac or Intensive Care Unit) is available.
If the participant has unstable hemodynamics, or has any clinically significant dysrhythmias 
noted on telemetry, the subject 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 study cardiologist should be arranged by the Principal Investigator to be available as 
needed to review ECG tracings with 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. In Part 1, baseline time to adequate 
hemostasis will be established by the mean of the assessments performed at Screen 2 and 
Screen 3.
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In Part 2, baseline time to adequate hemostasis will be established by the assessments 
performed at Screen 2.  After review of time to hemostasis at Day 42 or any time to 
hemostasis assessments beyond Day 42 and upon agreement of the both the Sponsor and 
investigator, the patient may return for onsite hemodialysis within 30 days until time to 
hemostasis returns to baseline or until the conclusion of the trial, whichever comes first.
8.4
Management of Infusion Reaction During and Post-dose
As outlined in 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, pruritus or flushing, swollen lips-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 
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.
All participants should be evaluated for infusion-type reactions.  Participants who experience 
infusion or hypersensitivity reactions in conjunction with the infusion of study drug should 
receive appropriate supportive care measures as deemed necessary by the treating physician. 
Participants should be carefully observed until complete resolution of all signs and 
symptoms, if a reaction occurs. Report any adverse experiences according to the guidelines 
in Section 8.5.
8.4.1
Systemic Infusion Reaction Assessment
Participants will be monitored during the administration of MK-2060/placebo for 48 hours 
for Part 1 (all single dose panels) and 24 hours for Part 2 (multiple doses) post-dose at CRU 
after the initiation of administration.  During this time, signs and symptoms of a systemic 
injection/infusion reaction, including but not limited to fever, VS changes 
(tachycardia/hypotension), pruritis, urticarial (hives), lip swelling, angioedema, 
bronchospasm, stridor, hoarseness, and shortness of breath will be monitored.  
Injection/infusion reactions must be assessed and managed promptly.  Such assessment and 
management are discussed in Section 8.4.
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8.4.2
Local Infusion Reaction Assessment
A local infusion site examination will be obtained as outlined in the 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 5. 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 5
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.
8.4.3
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 case report form 
(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.
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
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 150 days (Part 1) or 90 days (Part 2) 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.
8.5
Adverse Events (AEs), Serious Adverse Events (SAEs), 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/randomization, must be 
reported by the investigator for randomized participants only if the event is the result of a 
protocol-specified intervention, including but not limited to washout or discontinuation of 
usual therapy, diet, placebo treatment, or a procedure.
From the time of intervention allocation/randomization through 164 days for Part 1 and 90
days for Part 2 following 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 of the time 
period specified in the previous paragraph also must be reported immediately to the Sponsor 
if the event is considered related to study intervention.
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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 6.
Table 6
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:
Nonserious 
Adverse Event 
(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
Serious 
Adverse Event 
(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:
- due to intervention
- causes exclusion
Report all
Previously reported –
Follow to 
completion/termination; 
report outcome
Within 24 
hours of 
learning of 
event
Event of 
Clinical 
Interest 
(require 
regulatory 
reporting)
Report if:
- due to intervention
- causes exclusion
Report
- potential drug-
induced liver injury 
(DILI)
- require regulatory 
reporting
Not required
Within 24 
hours of 
learning of 
event
Event of 
Clinical 
Interest (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
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Type of Event
Reporting Time 
Period:
Consent to 
Randomization/ 
Allocation
Reporting Time 
Period:
Randomization/ 
Allocation through 
Protocol-specified 
Follow-up Period
Reporting Time 
Period:
After the Protocol-
specified Follow-up 
Period
Time Frame 
to Report 
Event and 
Follow-up 
Information 
to Sponsor:
Cancer
Report if:
- due to intervention
- causes exclusion
Report all
Not required
Within 5 
calendar days 
of learning of 
event
Overdose
Report if:
- receiving placebo 
run-in or other run-
in medication
Report all
Not required
Within 24 
hours of 
learning of 
event
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, events of clinical interest (ECIs), 
cancer, and overdose will be followed until resolution, stabilization, until the event is 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). In 
addition, the investigator will make every attempt to follow all nonserious AEs that occur in
randomized participants for outcome. Further information on follow-up procedures is given 
in Appendix 3.
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 wth 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 suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and Sponsor policy and 
forwarded to investigators as necessary.
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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
Disease-related Events and/or Disease-related Outcomes Not Qualifying as 
AEs or SAEs
Not applicable 
8.5.6
Events of Clinical Interest (ECIs)
Selected nonserious and SAEs 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, that is not associated with 
clinical symptoms or abnormal laboratory results.
2. An elevated AST or ALT lab value that is greater than or equal to 3X the upper limit of 
normal and an elevated total bilirubin lab value that is greater than or equal to 2X the 
upper limit of normal and, at the same time, an alkaline phosphatase lab value that is less 
than 2X the upper limit of normal, as determined by way of protocol-specified laboratory 
testing or unscheduled laboratory testing.*
*Note: These criteria are based upon available regulatory guidance documents. The 
purpose of the criteria is to specify a threshold of abnormal hepatic tests that must trigger 
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
The participant has taken (accidentally or intentionally) any drug administered as part of the 
protocol that exceeds the dose as 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.
8.7
Pharmacokinetics
The decision as to which plasma samples collected will be assayed for evaluation of 
PK/pharmacodynamics will be collaboratively determined by the Department of Quantitative 
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Pharmacology and Pharmacometrics and the appropriate department within Early-Stage 
Development, (e.g., samples at lower doses may not be assayed if samples at higher doses 
reveal undetectable drug concentrations).  Plasma samples may be tested for measurement of 
metabolites and/or additional PK/PD parameters.
8.7.1
Blood Collection for Plasma MK-2060
Sample collection, storage, and shipment instruction for plasma samples will be provided in a 
separate trial 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 5 min before anticipated 
time of the end of the infusion). 
8.8
Pharmacodynamics
Sample collection, storage, and shipment instructions for pharmacodynamic samples will be 
provided in operations/laboratory manual.
8.9
Biomarkers
Collection of samples for other biomarker research is also part of this study. Blood samples
for biomarker research are required and will be collected from all participants as specified in 
the SoA.
8.9.1
Blood Collection for PT, aPTT, FXI Activity and FGA Assay
Part 1:  PT and aPTT at screening, 1 hour, 12 hour, 48 hours, Day 5, Day 8, Day 12, Day 15, 
Day 22, and Day 90 post-dose will be performed locally for safety monitoring. All other pre-
dose and post-dose PT and aPTT, as well as FXI activity will be performed at a central 
vendor for PK/PD analysis. FGA assays will be performed by the Sponsor. Sample 
collection, storage, and shipment instructions for the PT, aPTT, FXI activity, and FGA assays 
will be provided in a separate trial Study Operations Manual by the Sponsor. The primary 
data for statistical analysis and modeling will be based on the information from the central 
vendor.
Part 2:  PT and aPTT at screening, predose, 1 hour, 12 hour postdose on each dosing day 
(Days 1, 3, 5, 8, 15 and 22), Day 10, Day 17, Day 23, Day 24, Day 26, Day 29, Day 35, Day 
42, and Day 111 post-dose will be performed locally for safety monitoring.  All other pre-
dose and post-dose PT and aPTT, as well as FXI activity will be performed at a central 
vendor for PK/PD analysis. FGA assays will be performed by the Sponsor. Sample 
collection, storage, and shipment instructions for the PT, aPTT, FXI activity, and FGA assays 
will be provided in a separate trial Study Operations Manual by the Sponsor. The primary 
data for statistical analysis and modeling will be based on the information from the central 
vendor.
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8.9.2
Blood for Plasma ADA
Sample collection, storage, and shipment instruction for plasma samples will be provided in a 
separate trial Study Operations Manual by the Sponsor.
8.9.3
5-D Itch Scale
5-D itch scale [Elman, S., et al 2010] will be collected on Day 120 for Part 1 Panel C only 
and on Days 24 and 42 for Part 2 participants to collect pruritis symptoms, as indicated in the 
SoA.
8.9.4
Planned Genetic Analysis Sample Collection
The planned genetic analysis sample should be drawn for planned analysis of the association 
between genetic variants in DNA and drug response. This sample will not be collected at the 
site if there is either a local law or regulation prohibiting collection, or if the IRB/IEC does 
not approve the collection of the sample for these purposes. If the sample is collected, 
leftover extracted DNA will be stored for FBR if the participant provides documented 
informed consent for FBR. If the planned genetic analysis is not approved, but FBR is 
approved and consent is given, this sample will be collected for the purpose of FBR.
Sample collection, storage, and shipment instructon for planned genetic analysis samples will 
be provided in the operations/laboratory manual.
8.10
Future Biomedical Research Sample Collection
If the participant provides documented consent for FBR, the following specimens will be 
obtained as part of FBR:

Leftover DNA for future research

Leftover main study plasma from MK-2060 assay stored for future research
8.11
Visit Requirements
Visit requirements are outlined in Section 1.3. Specific procedure-related details are provided 
in Section 8.
8.11.1
Screening
Approximately 4 weeks prior to intervention allocation/randomization, potential participants 
will be evaluated to determine that they fulfill the entry requirements as set forth in Section 
5. Screening 2 should occur within 80 hours prior to Day 1 for Part 2.
Participants may be rescreened after consultation with the Sponsor. Rescreening should 
include all screening procedures listed in the SoA, including consent review. Rescreen 
procedures cannot be conducted the day prior to intervention allocation/randomization if 
there are Day -1 procedures planned per protocol.
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8.11.2
Treatment Period
Refer to the Schedule of Activities (Section 1.3) and Administrative and General Procedures 
(Section 8.1).
After all pre-dose procedures have been completed; subjects will be assigned a unique 
randomization number associated with a specific treatment as defined by a 
computer-generated allocation schedule. Subjects will report to the CRU prior to the 
scheduled day of dosing or time specified by the investigator. On all the dosing days, 
subjects will fast from all food and drinks, except water, for at least 8 hours until 2 hours post 
study drug administration, when they will be given a light breakfast (see Section 5.3.1). 
Subjects will be administered study drug as indicated in Section 6. Subjects 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 Visit
The Poststudy visit will occur approximately 150 days or 90 days following administration of 
the last study drug for Part 1 and Part 2 respectively. Procedures outlined in the Poststudy
visit may be obtained on Day 150 (±7 days) for Part 1 and Day 111 (±7 days) for Part 2. 
However, follow up on any clinical or laboratory AEs should occur in person if the poststudy
visit occurs prior to 150 days or 90 days following administration of the last dose of study 
drug for Part 1 and Part 2 respectively. 
8.11.4
Discontinued Participants 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 at the discretion of the 
investigator and with Sponsor agreement. The subset of study procedures completed will be 
communicated in a PCL.
8.11.5
Safety Phone Call Follow-up (Part 1 Only)
A safety follow-up phone call will be performed approximately 14 days after the post-trial 
visit (within the visit windows allowed per protocol) for all panels in Part 1. The safety 
follow-up phone call must be performed by appropriately trained study site staff. If the initial 
call is unsuccessful, the study site staff should make a total of 3 attempts. All attempts to 
contact the subjects will be recorded in the source documents. The calls will facilitate the 
collection of relevant safety information. The subject will be interviewed to obtained 
information relating to AEs and SAEs. All safety information described by the subject must 
be documented in the source documents.
8.11.6
Critical Procedures Based on Study Objectives: Timing of Procedure
For this trial, the plasma sample for MK-2060 is the critical procedure.  
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At any post-dose timepoint, the blood sample for MK-2060 needs to be collected as close to 
the exact timepoint as possible.  All other procedures should be completed as close to the 
prescribed/scheduled time as possible. Trial procedures can be performed prior or after the 
prescribed/scheduled time.  
The order of priority can be changed during the trial 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.
Post-dose PK and PD sample collection, standard safety evaluation (VS, ECG, laboratory 
safety tests (including chemistry/hematology, aPTT, PT), physical exam (full, symptom 
driven, systemic injection/infusion, local injection/infusion, hemoccult test): as outlined in 
[Table 7] below.
Table 7
Pharmacokinetic (Blood) Collection Windows
PK Collection
PK Collection Window
Part 1
0 – 4.0 hr
5 min
4.1 - 24 hr
15 min
24.1 - 96 hr
1 hr
96.1 - 168 hr
2 hr
Day 12
1 Day and within 12 hours prior to receiving dialysis 
Day 15 + Day 22
2 Days and within 12 hours prior to receiving dialysis
Day 29
3 Days and within 12 hours prior to receiving dialysis
Day 60 + Day 90
5 Days and within 12 hours prior to receiving dialysis
Day 120 + Day 150
7 Days and within 12 hours prior to receiving dialysis
Part 2
0 – 4.0 hr post each dose
5 min
Days 1, 2, 3, 5, 8, 15, 22, 23, 24 
and 29
No flexible window for the scheduled PK day
Day 26
Plus 1 day is allowed
Days 10, 17, 
Plus and minus 1 day is allowed
Days 35, 42, and 49, and 63
Plus and minus 2 days is allowed
Days 81 and 111
Plus and minus 3 days is allowed
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
Predose standard safety evaluations: vital signs within 3 hours and ECG, laboratory 
safety tests and physical exam within 24 hours

Postdose standard safety evaluations: vital signs, ECG, laboratory safety tests, and
physical exam
-
<24 hr post each dose may be obtained within 30 min of the theoretical sampling time
-
24 hr - <48 hr post each dose may be obtained within 1 hr of the theoretical sampling 
time
-
48 hr – 168 hr post each dose may be obtained within 2 hr of the theoretical sampling 
time

Hemoccult Test: within 2 days of specified timepoint.

Assessment of time to adequate hemostasis: at the conclusion of the onsite hemodialysis 
session, after hemodialysis catheters are removed from the dialysis access site.

On clinic visits where onsite hemodialysis is not being conducted, visits must not occur 
within 8 hours of the completion of the most recent dialysis session.
8.11.7
Study Design/Dosing/Procedures Modifications Permitted Within Protocol 
Parameters
This is a Phase 1 assessment of MK-2060 in participant with ESRD on HD, and the PK, 
pharmacodynamic, and safety profiles of the compound is 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 objectives 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.

Repeat of or decrease in the dose of the study intervention administered in any given 
period/panel

Interchange of doses between panels

Entire panel may be omitted

Remove a planned PK pause if agreed by Sponsor and investigator if no further 
increases in total daily dose

Addition of PK pause
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
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.

Decrease in the duration of study intervention administration for Part 2 (eg, number 
of weeks) 
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 employ some or none of the alterations described 
above. Any alteration made to this protocol to meet the study objectives must be detailed by 
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 brief summary of the statistical analyses for this trial. Full details can 
be found in the subsequent sections. 
Statistical Analysis Plan
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.  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). 
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Pharmacokinetics
Model-Based PK Summary 
Part 1:
For Part 1, i.e., single ascending dose, SD PK of participants with ESRD from the present 
study will be compared with historical SD PK data (PN001) in healthy participants.
Separately for each PK parameter, for single dose, individual values of AUC0-∞, AUC0-
168hr, Cmax, and C168hr will be natural log-transformed and evaluated with a linear fixed 
effects model containing a categorical effect for population (ESRD on HD Part 1 single dose, 
healthy) and dose (8mg IV, 20mg IV and 40mg IV) and dose by population interaction. The 
fixed effects model will also contain a categorical effect for sex and a continuous effect for 
age. The present study will enroll older male and female subjects, while PN001 enrolled 
younger male subjects. Sex and age are not expected to impact PK. An unstructured 
covariance matrix will be used to allow for unequal population variances via the GROUP
statement in SAS PROC MIXED. Kenward and Roger’s method will be used to calculate the 
denominator degrees of freedom for the fixed population effect (DDFM=KR). Ninety-five 
percent (95%) CIs for the least squares means for each population by dose level will be 
constructed on the natural log scale and will reference the t-distribution. Exponentiating the 
least-squares means and their corresponding 95% CIs will yield estimates for the population 
geometric means and confidence intervals about the geometric means on the original scale.
A sample size of six subjects on active dose and two on placebo per panel is considered to be 
adequate to address the primary objectives of the study.
Part 2:
For Part 2 i.e., multiple IV dose administration, descriptive statistics (mean, median, standard 
deviation, min, max values) for AUC0-168, Cmax, C168, Tmax, terminal t1/2, CL, and Vz 
will be provided. In addition, graphical display such as box plot will be created for AUC0-
168 and Cmax to check for possible outliers.
A sample size of fifteen subjects on active dose and five on placebo is adequate to address 
the primary objectives of the study.
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.
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9.3
Hypotheses/Estimation
Secondary
1. Hypothesis (Part 1):  The true fold increase in aPTT 168 hours after a single well-
tolerated dose of MK-2060 in older subjects with ESRD on HD is at least 1.5.
2. Hypothesis (Part 2):  The true fold increase in aPTT 168 hours after the last dose 
following an IV loading dose and three maintenance doses of MK-20160 in older adult 
participants with ESRD on HD at least 1.5.
9.4
Analysis Endpoints
Primary Endpoints
1. Safety: Primary safety endpoints will include all types of adverse experiences, in addition 
to laboratory safety tests, ECGs, VS. For change from baseline analyses, baseline is 
defined as the panel-specific pre-dose value.  
Secondary Endpoints (Pharmacokinetic)
1. Pharmacokinetics (Part 1): The pharmacokinetic variables of secondary interest for single 
dose MK-2060 are plasma AUC0-∞, AUC 0-168hr, Cmax, C168hr, Tmax, apparent 
terminal t1/2, CL and Vz.
2. Pharmacokinetics (Part 2): The pharmacokinetic variables of secondary interest for 
multiple dose MK-2060 are plasma AUC 0-168hr, Cmax, C168hr, Tmax after the last 
dose.
3. Pharmacodynamics: The PD variable of secondary interest for MK-2060 is aPTT (change 
from baseline). Baseline is defined as the panel-specific pre-dose value.
Exploratory Endpoints:
1. FXI activity levels 
2. FGA 
3. PT
4. hsCRP
5. Time to hemostasis
6. ADA
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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 (PP): 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 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. This population will be used for the PK and PD analyses.
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.  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). 
Pharmacokinetics
Model-Based PK Summary 
Part 1:
SD PK of participants with ESRD from the present study will be compared with historical 
SD PK data (P001) in healthy participants.
Separately for each PK parameter, individual values of AUC0-∞, AUC0-168hr, Cmax, and
C168hr will be natural log-transformed and evaluated with a linear fixed effects model 
containing a categorical effect for population (ESRD on HD, healthy) and dose (8mg IV, 
20mg IV and 40mg IV) and dose by population interaction. The fixed effects model will also 
contain a categorical effect for sex and a continuous effect for age. The present study will 
enroll older male and female subjects, while PN001 enrolled younger male subjects. Sex and 
age are not expected to impact PK. An unstructured covariance matrix will be used to allow 
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for unequal population variances via the REPEATED and GROUP statement in SAS PROC 
MIXED. Kenward and Roger’s method will be used to calculate the denominator degrees of 
freedom for the fixed population effect (DDFM=KR). Ninety-five percent (95%) CIs for the 
least squares means for each population by dose will be constructed on the natural log scale 
and will reference the t-distribution. Exponentiating the least-squares means, and their 
corresponding 95% CIs will yield estimates for the population geometric means and 
confidence intervals about the geometric means on the original scale.
Part 2:
Geometric means and 95% confidence intervals (based on a t-distribution) will be provided 
for AUC0-168, Cmax, and C168 obtained following the last multiple dose. Median, 
minimum, and maximum will be provided for Tmax. 
Secondary Analysis:  Comparison to Healthy Subjects
To compare subjects with ESRD on HD to subjects with normal renal function at the same 
dose level, a two-sided 90% confidence interval for the true difference in means (ESRD on 
HD – normal renal function, at the same dose level) will be calculated for each PK parameter 
using the mean square error from the PK model described above and referencing a t-
distribution. For each dose level of ESRD on HD, these confidence limits will be 
exponentiated to obtain the 90% confidence interval for the true ratio of geometric means 
(ESRD on HD/normal renal function, at the same dose level) for each PK parameter.
Dose Proportionality
An exploratory analysis will be conducted to preliminarily assess dose proportionality of 
MK-2060 AUC0-∞, AUC0-168hr, Cmax and C168hr in ESRD on HD participants, using the 
power law model. Separately for each PK parameter, individual PK values will be natural log 
transformed and evaluated with a linear regression model having ln(dose) as an explanatory 
variable. A least square estimate and 95% confidence interval for the slope associated with 
ln(dose) will be obtained from the model. 
A plot of the observed PK data versus dose will be provided along with an estimated 
regression line on the raw scale and a 95% Schéffe confidence band. 
Descriptive Statistics 
Individual values will be listed for each PK parameter (including Tmax and apparent 
terminal t1/2, CL, Vz) by treatment, and the following (non-model-based) descriptive 
statistics will be provided: N (number of subjects with non-missing data), arithmetic mean, 
standard deviation, arithmetic  percent CV (calculated as 100 x standard deviation/arithmetic 
mean), median, minimum, maximum, 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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Pharmacodynamics
Secondary Hypothesis
Part 1:
Individual aPTT fold-change from baseline values will be natural log-transformed and
evaluated with a linear mixed effects model containing fixed effects for treatment and time 
and treatment by time interaction and random effect for participant. Least squares means and 
95% confidence intervals for each treatment, and for the between-treatment differences (MK-
2060 – placebo) and 90% CI at each dose level, will be obtained by time. These estimates 
will be back-transformed to obtain GM aPTT fold-change from baseline by treatment and 
time and the GMR (MK-2060 fold-change from baseline/placebo fold-change from baseline) 
by dose and time.
The posterior probability that the true fold-increase from baseline in aPTT 168 hours after a 
single dose is at least 1.5 will be calculated for each dose assuming normality and using a 
non-informative (Jeffrey’s) prior. A 60% posterior probability for at least one dose level that 
also exhibits an acceptable safety profile will satisfy the secondary pharmacodynamics 
hypothesis. In addition, the proportion of subjects with a fold-increase in aPTT 168 hours 
after a single dose of at least 1.5 will be tabulated.
FXI activity levels, FGA and PT will be evaluated in a similar fashion. Additional model-
based analysis may be employed to further explore PD endpoints over time.
Descriptive statistics will be provided for PD endpoints by treatment and time.
Part 2:
As in Part 1, individual aPTT fold-change from baseline values will be natural log-
transformed and evaluated with a linear mixed effects model incorporating the longitudinal 
effects of measurements at the three weekly time points. An unstructured covariance matrix 
will be used to model the correlation between different measurements within the same 
subjects. Kenward and Roger’s method will be used to calculate the denominator degrees of 
freedom for the fixed effects. Least squares mean and 95% confidence intervals for each 
treatment, and for the between-treatment differences (MK-2060 – placebo) and 90% CI will 
be obtained. These estimates will be back-transformed to obtain GM aPTT fold-change from 
baseline by treatment and time and the GMR (MK-2060 fold-change from baseline/placebo 
fold-change from baseline) by time.
The posterior probability that the true fold-increase from baseline in aPTT is at least 1.5 will 
be calculated at each of the three weekly time points assuming normality and using a non-
informative prior. A 60% posterior probability for at least one of the three time points that 
also exhibits an acceptable safety profile will satisfy the secondary pharmacodynamics
hypothesis. In addition, the proportion of subjects with at least 1.5 fold increase in aPTT 168 
hours after the last dose will be tabulated.
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FXI activity levels, FGA and PT will be evaluated in a similar fashion. Additional model-
based analysis may be employed to further explore PD endpoints over time.
Descriptive statistics will be provided for PD endpoints by treatment and time.
PK-PD
The relationship between plasma concentrations and aPTT, FXI activity, FGA, and PT will 
be explored graphically. Upon visual inspection, additional model-based analysis may be 
employed to further explore the PK/PD relationship.
General
For all analyses, data will be examined for departures from the assumptions of the statistical 
model(s) as appropriate; e.g., heteroscedasticity, nonnormality of the error terms.  
Distribution-free methods may be used if a serious departure from the assumptions of the 
models(s) is observed, or suitable data transformations may be applied.
9.7
Interim Analyses
During the in-life portion of the trial, descriptive summary level results (PK, PD and/or 
safety (labs, VS, ECGs) may be prepared as needed to support dose escalation meetings. No 
individual level results will be provided, and the aggregate summaries will be presented in a 
blinded manner. There are no planned interim analyses to test any formal hypotheses.
9.8
Multiplicity
Since there are no pre-specified primary hypotheses, no adjustments for multiplicity are 
needed.
9.9
Sample Size and Power Calculations
A sample size of six subjects on active dose and two on placebo per panel is considered to be 
adequate to address the primary objectives of the study. 
Pharmacokinetics
The sample size selected for each dose level to evaluate the effect of ESRD on HD on the PK 
of MK-2060 compared to subjects with normal renal function was not chosen to satisfy any a 
priori statistical requirement. Nevertheless, estimates of the expected precision of the 
estimates, based on these sample sizes and the variability obtained from previous studies are 
presented below.
The precision of the estimated ratios of geometric means (ESRD on HD/normal renal 
function, at the same dose level) of PK parameters obtained from this study can be assessed 
by calculating the half-width of the 90% CIs expected for the given sample size and assumed 
variability. The between-subject standard deviations (on the natural log scale) for MK-2060 
AUC0-168hr and Cmax after administration of 20mg IV MK-2060 observed in a previous 
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study (PN001) are 0.199 ln(μM*hr) and 0.169 ln(nM), respectively. Since the between 
subject variability in subjects with RI has historically been seen to be 2 to 3-fold higher in 
many studies, the between subject variability obtained from normal renal function subjects 
was inflated by a factor of 2 for ESRD on HD and was used for the following calculations. 
With a sample size of 6 subjects per population (6 20mg IV ESRD on HD and 6 20mg IV 
historical normal renal function, at the same dose level) and observed between-subject SDs 
as given above, then the half width of the 90% CIs of GMRs for MK-2060 AUC0-168hr and 
Cmax on the log scale will be 0.329 and 0.279, respectively. The lower and upper 90% 
confidence limits for the true GMRs will be given by OBS/1.39 and OBS*1.39 for AUC0-
168hr and OBS/1.32 and OBS*1.32 for Cmax, respectively, where OBS is the observed 
GMR. Thus, for example, if the observed GMR for AUC0-168hr was 1.50 after 
administration of 20mg IV MK-2060, then the 90% CI for the GMR would be 1.08 to 2.08.
Pharmacodynamics
Part 1:
If the true CV is 30%, there is approximately 72.3% probability of yielding at least 60% 
posterior probability that the true fold increase is at least 1.5 if the true fold increase in aPTT 
after 168 hours of a single well-tolerated subcutaneous dose relative to placebo is at least 1.5.
The total participants per dose is 8 (active = 6, placebo = 2). 
Part 2:
If the true CV is 30%, for a total of approximately 20 participants (active = 15, placebo = 5), 
there is approximately 84% probability of yielding at least 60% posterior probability that the 
true fold increase is at least 1.5. We assume that the true fold increase in aPTT after 168 
hours of a single well-tolerated subcutaneous dose relative to placebo is at least 1.5.
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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 and Dohme Corp., a subsidiary of Merck & Co., Inc. (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 of clinical trials. In all cases, MSD clinical trials will be conducted in compliance 
with local and/or national regulations (eg, International Council for Harmonisation Good Clinical Practice [ICH-
GCP]) and in accordance with the ethical principles that have their origin in the Declaration of Helsinki.
B. Scope
Highest ethical and scientific standards shall be endorsed for all clinical interventional investigations sponsored by 
MSD irrespective of the party (parties) employed for their execution (eg, 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 (ie, participant population, duration, statistical power) must be adequate to address the specific
purpose of the trial. Participants must meet protocol entry criteria to be enrolled in the trial. 
2. Site Selection
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 to assess the ability to successfully conduct the trial.
3. Site Monitoring/Scientific Integrity
Investigative trial sites are monitored to assess compliance with the trial protocol and general principles of 
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 fraud, scientific/research misconduct, or serious GCP-noncompliance is suspected, the issues 
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are investigated. When necessary, the clinical site will be closed, the responsible regulatory authorities and 
ethics review committees notified.
B. Publication and Authorship
Regardless of trial outcome, MSD commits to publish primary and secondary results of its registered trials of 
marketed products in which treatment is assigned, according to the prespecified 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. Ethics Committee Review (Institutional Review Board [IRB]/Independent Ethics Committee [IEC])
All clinical trials will be reviewed and approved by an IRB/IEC before being initiated at each site. Significant 
changes or revisions to the protocol will be approved by the ethics committee prior to implementation, except 
changes required urgently to protect participant safety that may be enacted in anticipation of ethics committee 
approval. For each site, the ethics committee and MSD will approve the participant informed consent form.
B. Safety
The guiding principle in decision-making in clinical trials is that participant welfare is of primary importance. 
Potential participants will be informed of the risks and benefits of, as well as alternatives to, trial participation. At 
a minimum, trial designs will take into account the local standard of care.
All participation in MSD clinical trials is voluntary. Participants enter the trial only after informed consent is 
obtained. Participants may withdraw from an MSD trial at any time, without any influence on their access to, or 
receipt of, medical care that may otherwise be available to them.
C. Confidentiality
MSD is committed to safeguarding participant confidentiality, to the greatest extent possible. Unless required by 
law, only the investigator, Sponsor (or representative), 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 to identify potentially eligible participants.
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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 (eg, to scientific meetings, investigator meetings, etc.) will be 
consistent with local guidelines and practices.
V. Investigator Commitment
Investigators will be expected to review MSD’s Code of Conduct as an appendix to the trial protocol, and in signing the 
protocol, agree to support these ethical and scientific standards.
10.1.2
Financial Disclosure
Financial Disclosure requirements are outlined in the US Food and Drug Administration 
Regulations, Financial Disclosure by Clinical Investigators (21 CFR Part 54). It is the 
Sponsor's responsibility to determine, based on these regulations, whether a request for 
Financial Disclosure information is required. It is the investigator's/subinvestigator's 
responsibility to comply with any such request.
The investigator/subinvestigator(s) agree, if requested by the Sponsor in accordance with 21 
CFR Part 54, to provide his/her financial interests in and/or arrangements with the Sponsor to 
allow for the submission of complete and accurate certification and disclosure statements. 
The investigator/subinvestigator(s) further agree to provide this information on a 
Certification/Disclosure Form, commonly known as a financial disclosure form, provided by 
the Sponsor. The investigator/subinvestigator(s) also consent to the transmission of this 
information to the Sponsor in the United States for these purposes. This may involve the 
transmission of information to countries that do not have laws protecting personal data.
10.1.3
Data Protection
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.
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10.1.3.1
Confidentiality of Data
By signing this protocol, the investigator affirms to the Sponsor that information furnished to 
the investigator by the Sponsor will be maintained in confidence, and such information will 
be divulged to the IRB, IEC, or similar or expert committee; affiliated institution and 
employees, only under an appropriate understanding of confidentiality with such board or 
committee, affiliated institution and employees. Data generated by this study will be 
considered confidential by the investigator, except to the extent that it is included in a 
publication as provided in the Publications section of this protocol.
10.1.3.2
Confidentiality of Participant Records
By signing this protocol, the investigator agrees that the Sponsor (or Sponsor representative), 
IRB/IEC, or regulatory authority representatives may consult and/or copy study documents to 
verify worksheet/CRF data. By signing the consent form, the participant agrees to this 
process. If study documents will be photocopied during the process of verifying 
worksheet/CRF information, the participant will be identified by unique code only; full 
names/initials will be masked prior to transmission to the Sponsor.
By signing this protocol, the investigator agrees to treat all participant data used and 
disclosed in connection with this study in accordance with all applicable privacy laws, rules 
and regulations.
10.1.3.3
Confidentiality of IRB/IEC Information
The Sponsor is required to record the name and address of each IRB/IEC that reviews and 
approves this study. The Sponsor is also required to document that each IRB/IEC meets 
regulatory and ICH GCP requirements by requesting and maintaining records of the names 
and qualifications of the IRB/IEC members and to make these records available for 
regulatory agency review upon request by those agencies.
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.
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Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements.
10.1.6
Compliance with Study Registration and Results Posting Requirements
Under the terms of the Food and Drug Administration Amendments Act (FDAAA) of 2007 
and the European Medicines Agency (EMA) clinical trial Directive 2001/20/EC, the Sponsor 
of the study is solely responsible for determining whether the study and its results are subject
to the requirements for submission to http://www.clinicaltrials.gov, 
www.clinicaltrialsregister.eu or other local registries. MSD, as Sponsor of this study, will 
review this protocol and submit the information necessary to fulfill these requirements. MSD 
entries are not limited to FDAAA or the EMA clinical trial directive mandated trials. 
Information posted will allow participants to identify potentially appropriate studies for their 
disease conditions and pursue participation by calling a central contact number for further 
information on appropriate study locations and study site contact information.
By signing this protocol, the investigator acknowledges that the statutory obligations under 
FDAAA, the EMA clinical trials directive, or other locally mandated registries are that of the 
Sponsor and agrees not to submit any information about this study or its results to those 
registries.
10.1.7
Compliance with Law, Audit, and Debarment
By signing this protocol, the investigator agrees to conduct the study in an efficient and 
diligent manner and in conformance with this protocol; generally accepted standards of GCP
(eg, International Conference on Harmonization of Technical Requirements for Registration 
of Pharmaceuticals for Human Use 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.
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 Studies.
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. 
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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.
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.
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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 will 
promptly notify that study site’s IRB/IEC.
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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
Chemistry
Blood Urea 
Nitrogen (BUN)
Potassium
Aspartate 
Aminotransferase
(AST)/ Serum 
Glutamic-
Oxaloacetic 
Transaminase 
(SGOT)
Total bilirubin (and 
direct bilirubin, if 
total bilirubin is 
elevated above the 
upper limit of 
normal)
Albumin
Bicarbonate
Chloride
Phosphorous
Creatinine
Sodium
Alanine 
Aminotransferase
(ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT)
Total Protein
Glucose
Calcium
Alkaline phosphatase
Other Screening 
Tests
Follicle-stimulating hormone (as needed in women of nonchildbearing potential only)
Drug screen (to include at minimum: alcohol amphetamines, barbiturates, cocaine, 
opiates, cannabinoids and benzodiazepines) 
Serum β human chorionic gonadotropin (β hCG) pregnancy test (as needed for female 
participant)
[Serology (HIV antibody, hepatitis B surface antigen [HBsAg], and hepatitis C virus 
antibody)
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, 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, or are considered clinically significant in the 
medical and scientific judgment of the investigator.

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.

For all reports of overdose (whether accidental or intentional) with an associated AE, the 
AE term should reflect the clinical symptoms or abnormal test result. An overdose 
without any associated clinical symptoms or abnormal laboratory results is reported using 
the terminology “accidental or intentional overdose without adverse effect.”

Any new cancer or progression of existing cancer.
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Events NOT meeting the AE definition

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.

Surgery planned prior to informed consent to treat a pre-existing condition that has not 
worsened.

Refer to Section 8.5.1 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:
1. Results in death
2. 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.
3. Requires inpatient hospitalization or prolongation of existing hospitalization

Hospitalization is defined as an inpatient admission, regardless of length of stay, 
even if the hospitalization is a precautionary measure for continued observation. 
(Note: Hospitalization for an elective procedure to treat a pre-existing condition that 
has not worsened is not an SAE. A pre-existing condition is a clinical condition that 
is diagnosed prior to the use of an MSD product and is documented in the 
participant’s medical history.
4. 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.
5. Is a congenital anomaly/birth defect

In offspring of participant taking the product regardless of time to diagnosis.
6. 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:
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- Exposure:  Is there evidence that the participant was actually exposed to the 
Sponsor’s product such as: reliable history, acceptable compliance assessment (pill 
count, diary, etc.), expected pharmacologic effect, or measurement of drug/metabolite 
in bodily specimen?
- Time Course:  Did the AE follow in a reasonable temporal sequence from 
administration of the 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 case report forms/worksheets 
by an investigator who is a qualified physician according to his/her best clinical 
judgment, including consideration of the above elements.

Use the following scale of criteria as guidance (not all criteria must be present to be 
indicative of a 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 electronic data collection 
(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 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: Device Events, Adverse Device Events, and Medical Device 
Incidents: Definitions, Collection, and Documentation
Not applicable
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10.5
Appendix 5: Contraceptive Guidance and Pregnancy Testing
10.5.1
Definitions
Women of Nonchildbearing Potential (WONCBP)
Women in the following categories are considered WONCBP:

Premenopausal female with 1 of the following:
-
Documented hysterectomy
-
Documented bilateral salpingectomy
-
Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than the 
above (eg, Mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview.

Postmenopausal female
-
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
◦
A high follicle stimulating hormone (FSH) level in the postmenopausal range may 
be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT). However, in the absence 
of 12 months of amenorrhea, confirmation with two FSH measurements in the 
postmenopausal range is required. 
Females on HRT and whose menopausal status is in doubt will be required to use one of the 
nonhormonal highly effective contraception methods if they wish to continue their HRT 
during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment.
10.5.2
Pregnancy Testing
Pregnancy testing will be performed whenever an expected menstrual cycle is missed or 
when pregnancy is otherwise suspected.
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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 Research
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 drugs/vaccines may interact with
◦
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 Research.
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 Research
In order to optimize the research that can be conducted with future biomedical research 
specimens, it is critical to link participant' 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 gender, 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 Usage
Specimens obtained for the Sponsor will be used for analyses using good scientific 
practices. Analyses utilizing the future biomedical research specimens may be performed 
by the Sponsor, or an additional third party (eg, a university investigator) designated by 
the Sponsor. The investigator conducting the analysis will follow the Sponsor’s privacy 
and confidentiality requirements. Any contracted third party analyses will conform to the 
specific scope of analysis outlined in future biomedical research protocol and consent. 
Future biomedical research specimens remaining with the third party after specific 
analysis is performed will be reported to the Sponsor.
6. Withdrawal From Future Biomedical Research
Participants may withdraw their consent for future biomedical research and ask that their 
biospecimens not be used for future biomedical research. Participants may withdraw 
consent at any time by contacting the investigator for the main study. If medical records 
for the main study are still available, the investigator will contact the Sponsor using the 
designated mailbox (clinical.specimen.management@merck.com). Subsequently, the 
participant's specimens will be flagged in the biorepository and restricted to main study 
use only. If specimens were collected from study participants specifically for future 
biomedical research, these specimens will be removed from the biorepository and 
destroyed. Documentation will be sent to the investigator confirming withdrawal and/or 
destruction, if applicable. It is the responsibility of the investigator to inform the 
participant of completion of the withdrawal and/or destruction, if applicable. Any 
analyses in progress at the time of request for withdrawal/destruction or already 
performed prior to the request being received by the Sponsor will continue to be used as 
part of the overall research study data and results. No new analyses would be generated 
after the request is received.
In the event that the medical records for the main study are no longer available (eg, if the 
investigator is no longer required by regulatory authorities to retain the main study 
records) or the specimens have been completely anonymized, there will no longer be a 
link between the participant’s personal information and their specimens. In this situation, 
the request for withdrawal of consent and/or destruction cannot be processed.
7. Retention of Specimens
Future biomedical research specimens will be stored in the biorepository for potential 
analysis for up to 20 years from the end of the main study. Specimens may be stored for 
longer if a regulatory or governmental authority has active questions that are being 
answered. In this special circumstance, specimens will be stored until these questions 
have been adequately addressed.
Specimens from the study site will be shipped to a central laboratory and then shipped to 
the Sponsor-designated biorepository. If a central laboratory is not utilized in a particular 
study, the study site will ship directly to the Sponsor-designated biorepository. The 
specimens will be stored under strict supervision in a limited access facility which 
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operates to assure the integrity of the specimens. Specimens will be destroyed according 
to Sponsor policies and procedures and this destruction will be documented in the 
biorepository database.
8. Data Security
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 Participants
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 Population
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 Research
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@merck.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 Conference on Harmonization [Internet]: E15: Definitions for Genomic 
Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample 
Coding Categories. Available from 
http://www.ich.org/products/guidelines/efficacy/efficacy-single/article/definitions-
for-genomic-biomarkers-pharmacogenomics-pharmacogenetics-genomic-data-and-
sample-cod.html 
3. Industry Pharmacogenomics Working Group [Internet]: Understanding the Intent, 
Scope and Public Health Benefits of Exploratory Biomarker Research: A Guide for 
IRBs/IECs and Investigational Site Staff. Available at http://i-pwg.org/ 
4. Industry Pharmacogenomics Working Group [Internet]: Pharmacogenomics 
Informational Brochure for IRBs/IECs and Investigational Site Staff. Available at 
http://i-pwg.org/
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10.7
Appendix 7: Country-specific Requirements
Not applicable
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10.8
Appendix 8: Approximate Blood Volume
Part 1:
Part 1 Panels
Pre-
study
Treatment 
Periods
Post-
trial
Total
Collection
mL Per
Collection
Total
mL/Test
Laboratory safety
tests
2
9
1
12
12.5
150
HIV/Hepatitis 
screen (per site
SOP)
1
1
5
5
Blood for planned
genetic analysis
1
1
8.5
8.5
Blood for PT and
aPTT at local lab
1
9
10
3
30
Blood for MK-2060
only
11
0
11
1.8
19.8
Blood for plasma
ADA and MK-2060
7
1
8
2.7
21.6
Blood for PT,
aPTT, FXI activity, 
hsCRP at central
lab, as well as FGA
18
1
19
10
190
Total Blood Volume Per Subject†
424.9 mL
†If additional pharmacokinetic/pharmacodynamic and/or safety analysis is necessary, additional blood (up to 50 mL) may be 
obtained  
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Part 2:
Pre-
study
Treatment 
Periods
Post-
trial
Total
Collection
mL Per
Collection
Total
mL/Test
Laboratory safety
tests
2
12
1
15
12.5
187.5
HIV/Hepatitis 
screen (per site
SOP)
1
1
5
5
Blood for planned
genetic analysis
1
1
8.5
8.5
Blood for PT and
aPTT at local lab
1
23
1
25
3
75
Blood for MK-2060
only
26
1
27
1.8
46.8
Blood for plasma
ADA and MK-2060
6
1
7
2.7
18.9
Blood for PT,
aPTT, FXI activity, 
hsCRP at central
lab, as well as FGA
19
1
20
11
220
Total Blood Volume Per Subject†
563.5 mL
†If additional pharmacokinetic/pharmacodynamic and/or safety analysis is necessary, additional blood (up to 50 mL) 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:
1.
The participant may be excluded from the study;
2.
The participant may be included in the study if the abnormal value(s) is not 
clinically significant (NCS) (the investigator must annotate the laboratory value 
“NCS” on the laboratory safety test source document).
3.
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
4.
The abnormal test may be repeated (refer items a. and b. below for continuation 
of algorithm for repeated values).
If the repeat test value is within the normal range, the participant may enter the study.
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(s)
Adverse event(s)
ALT
Alanine aminotransferase
aPTT
Activated partial thromboplastin time
AST
Aspartate aminotransferase
AUC
Area under the concentration-time curve
AUC0-∞
Area under the concentration-time curve extrapolated to infinity
AUC0-168
Area under the concentration-time curve from 0 to 168 hours post-dose
AUC0-last
Area under the concentration-time curve to the last measurable concentration
AV
Arteriovenous
ASO
Anti-sense oligo
BMI
Body mass index
BP
Blood pressure
C
Plasma concentration 
CL
Clearance
CFR
Code of Federal Regulations
CL/F
Apparent total clearance
Cmax
Maximum observed plasma concentration
CRU
Clinical research unit
CSR
Clinical study report
CTA
Clinical Trial Application
CV
Coefficient of variation
DEM
Dose escalation meetings
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
ER
Emergency room
ERC
Ethics review committee
ESRD
End-Stage Renal Disease
FBR
Future biomedical research
FXa
Factor Xa
FXI
Factor XI
FXIa
Factor XIa
FDAAA
Food and Drug Administration Amendments Act
FSH
Follicle stimulating hormone 
FGA
Fibrin generation assay
GCP
Good Clinical Practice(s)
GCV
Geometric coefficient of variation
GM
Geometric mean
HR
Heart rate
HD
Hemodialysis
HRT
hormone replacement therapy
hsCRP
High-sentivity C-reactive protein
IB
Investigator’s Brochure 
IgG
Immunoglobulin
IV
Intravenous
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Abbreviation
Expanded Term
ICF
Informed Consent Form 
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IND
Investigational New Drug 
IRB
Institutional Review Board 
IUD
intrauterine device
mAb
Monoclonal antibody
NHV
Normal healthy volunteer
NOAEL
no observed adverse effect level 
PK
pharmacokinetic
PD
Pharmacodynamics
PI
Principal Investigator
PP
Per-protocol Population
PR
PR interval
PT
Prothrombin time
QTc
Q-T corrected (corrected Q-T interval)
RhoGAM
A brand of Rh immunoglobulin
QP2
department of quantitative pharmacology and pharmacometrics
RNA
ribonucleic acid
SAE(s)
Serious adverse event(s)
SBP
Systolic blood pressure
SC
Subcutaneous (ly)
SOP
Standard operating procedures
SoA
schedule of activities
SUSAR
suspected unexpected serious adverse reaction
t1/2
Half-life
TGA
Thrombin generation assay
Tmax
Time to maximum observed plasma concentration
ULN
Upper limit of normal
USP
United States Pharmacopeial Convention
VS
Vital Signs
Vz/F
Apparent volume of distribution
WOCBP
woman/women of childbearing potential 
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11
REFERENCES
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Asakai R, Chung DW, Davie EW, 
Seligsohn U. Factor XI deficiency in 
Ashkenazi Jews in Israel. N Engl J Med. 
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[Bethune, C., et al 2017]
Bethune C, Walsh M, Jung B, Yu R, Geary 
RS, Bhanot S. Pharmacokinetics and 
pharmacodynamics of Ionis-FXI(RX), an 
antisense inhibitor of factor XI, in patients 
with end-stage renal disease on 
hemodialysis. Blood. 2017;130:1116.
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[Buller, H. R., et al 2015]
Buller HR, Bethune C, Bhanot S, Gailani 
D, Monia BP, Raskob GE, et al. Factor XI 
antisense oligonucleotide for prevention of 
venous thrombosis. N Engl J Med. 2015 
Jan 15;372(3):232-40.
[04T0MV]
[Dirks, N. L. 2010]
Dirks NL, Meibohm B. Population 
pharmacokinetics of therapeutic 
monoclonal antibodies. Clin 
Pharmacokinet. 2010;49(10):633-59.
[04XMZG]
[Ellsworth K 2018]
pd002mk2060 - MK-2060: Assessment of 
Human Plasma Coagulation by Activated 
Partial Thromboplastin Time Assay, 27-
Sep-2018.
[0522VM]
[Elman, S., et al 2010]
Elman S, Hynan LS, Gabriel V, Mayo MJ. 
The 5-D itch scale: a new measure of 
pruritus. Br J Dermatol. 2010;162:587-93.
[05CLRF]
[Vaziri, N. D., et al 1994]
Vaziri ND, Gonzales EC, Wang J, Said S. 
Blood coagulation, fibrinolytic, and 
inhibitory proteins in end-stage renal 
disease: effect of hemodialysis. Am J 
Kidney Dis. 1994 Jun;23(6):828-35.
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