Clinical trial NCT05769595
Conditions: End-Stage Renal Disease (ESRD) End-Stage Kidney Disease (ESKD) Kidney Failure, Chronic
Sponsor: Merck Sharp & Dohme LLC
Start date: 2023-06-14; Completion date: 2024-02-15
Enrollment: 17 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of MK-2060 after a single dose intravenous (IV) administration in Japanese older participants with end stage renal disease (ESRD) on dialysis. There is no primary hypothesis for this study.

Detailed description:

Arms: arm 1: Participants receive MK-2060 50 mg via a single intravenous (IV) infusion over 60-minutes. arm 2: Participants receive a single IV saline infusion over 60 minutes.
Interventions: intervention 1: MK-2060 intervention 2: Placebo
Intervention descriptions: intervention 1: Lyophilized powder diluted in normal saline for IV infusion intervention 2: IV infusion

Protocol documents:
Prot_SAP_000.pdf: 
Official Protocol Title:
NCT number:                NCT05769595
Document Date:           09-Dec-2022
A Single-Dose Clinical Study to Evaluate the 
Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of MK-2060 in Japanese 
Older Participants with End-Stage Renal 
Disease on Dialysis


PRODUCT: MK-2060  
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PROTOCOL/AMENDMENT NO.: 012-00
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09-DEC-2022
Title Page
THIS PROTOCOL AND ALL OF THE INFORMATION RELATING TO IT ARE 
CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK SHARP & 
DOHME LLC, RAHWAY, NJ, USA (MSD).
Protocol Title: A single-dose clinical study to evaluate the safety, tolerability, 
pharmacokinetics and pharmacodynamics of MK-2060 in Japanese older participants with 
end-stage renal disease on dialysis.
Protocol Number: 012-00
Compound Number: MK-2060
Sponsor Name:
Merck Sharp & Dohme LLC
(hereafter called the Sponsor or MSD)
Legal Registered Address:
126 East Lincoln Avenue
P.O. Box 2000
Rahway, NJ 07065 USA
Regulatory Agency Identifying Number(s):
Approval Date: 09 December 2022
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Sponsor Signatory
Typed Name:
Title:
Date
Protocol-specific Sponsor contact information can be found in the Investigator Study
File Binder (or equivalent).
Investigator Signatory
I agree to conduct this clinical study in accordance with the design outlined in this protocol 
and to abide by all provisions of this protocol.
Typed Name:
Title:
Date
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DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
Original Protocol
09-DEC-2022
Not applicable
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Table of Contents
DOCUMENT HISTORY ........................................................................................................3
1
PROTOCOL SUMMARY ............................................................................................11
1.1
Synopsis.................................................................................................................11
1.2
Schema ..................................................................................................................14
1.3
Schedule of Activities...........................................................................................15
2
INTRODUCTION..........................................................................................................19
2.1
Study Rationale....................................................................................................19
2.2
Background ..........................................................................................................19
2.2.1
Pharmaceutical and Therapeutic Background .............................................19
2.2.2
Clinical Studies............................................................................................19
2.2.3
Ongoing Clinical Studies.............................................................................20
2.3
Benefit/Risk Assessment......................................................................................20
3
HYPOTHESES, OBJECTIVES, AND ENDPOINTS................................................21
4
STUDY DESIGN............................................................................................................22
4.1
Overall Design......................................................................................................22
4.2
Scientific Rationale for Study Design.................................................................22
4.2.1
Rationale for Endpoints ...............................................................................24
4.2.1.1
Safety Endpoints................................................................................24
4.2.1.2
Pharmacokinetic Endpoints ...............................................................25
4.2.1.3
Pharmacodynamic Endpoints.............................................................26
4.2.1.4
Planned Exploratory Biomarker Research.........................................26
4.2.1.4.1
Planned Genetic Analysis ........................................................26
4.2.1.5
Future Biomedical Research..............................................................26
4.2.2
Rationale for the Use of Placebo .................................................................26
4.3
Justification for Dose...........................................................................................27
4.3.1
Rationale for Dose Interval and Study Design ............................................28
4.4
Beginning and End-of-Study Definition ............................................................28
4.4.1
Clinical Criteria for Early Study Termination .............................................29
5
STUDY POPULATION ................................................................................................29
5.1
Inclusion Criteria.................................................................................................30
5.2
Exclusion Criteria................................................................................................31
5.3
Lifestyle Considerations......................................................................................34
5.3.1
Meals and Dietary Restrictions....................................................................34
5.3.1.1
Diet Restrictions.................................................................................34
5.3.2
Caffeine, Alcohol, and Tobacco Restrictions ..............................................34
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5.3.2.1
Caffeine Restrictions..........................................................................34
5.3.2.2
Alcohol Restrictions...........................................................................34
5.3.2.3
Tobacco Restrictions..........................................................................35
5.3.3
Activity Restrictions ....................................................................................35
5.4
Screen Failures.....................................................................................................35
5.5
Participant Replacement Strategy......................................................................35
6
STUDY INTERVENTION............................................................................................35
6.1
Study Intervention(s) Administered...................................................................35
6.2
Preparation/Handling/Storage/Accountability .................................................37
6.2.1
Dose Preparation..........................................................................................37
6.2.2
Handling, Storage, and Accountability........................................................37
6.3
Measures to Minimize Bias: Randomization and Blinding..............................38
6.3.1
Intervention Assignment..............................................................................38
6.3.2
Stratification.................................................................................................38
6.3.3
Blinding........................................................................................................38
6.4
Study Intervention Compliance..........................................................................38
6.5
Concomitant Therapy..........................................................................................39
6.5.1
Rescue Medications and Supportive Care ...................................................39
6.6
Dose Modification (Escalation/Titration/Other)...............................................40
6.6.1
Stopping Rules.............................................................................................40
6.7
Intervention After the End of the Study............................................................41
6.8
Clinical Supplies Disclosure................................................................................41
6.9
Standard Policies..................................................................................................41
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL............................................................................................................41
7.1
Discontinuation of Study Intervention...............................................................41
7.2
Participant Withdrawal From the Study...........................................................42
7.3
Lost to Follow-up .................................................................................................42
8
STUDY ASSESSMENTS AND PROCEDURES........................................................42
8.1
Administrative and General Procedures ...........................................................43
8.1.1
Informed Consent.........................................................................................43
8.1.1.1
General Informed Consent.................................................................43
8.1.1.2
Consent and Collection of Specimens for Future Biomedical 
Research.............................................................................................44
8.1.2
Inclusion/Exclusion Criteria ........................................................................44
8.1.3
Participant Identification Card.....................................................................44
8.1.4
Medical History ...........................................................................................44
8.1.5
Prior and Concomitant Medications Review...............................................44
8.1.5.1
Prior Medications...............................................................................44
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8.1.5.2
Concomitant Medications..................................................................45
8.1.6
Assignment of Screening Number...............................................................45
8.1.7
Assignment of Randomization Number.......................................................45
8.1.8
Study Intervention Administration ..............................................................45
8.1.8.1
Timing of Dose Administration.........................................................45
8.1.9
Discontinuation and Withdrawal .................................................................46
8.1.9.1
Withdrawal From Future Biomedical Research ................................46
8.1.10
Participant Blinding/Unblinding..................................................................46
8.1.11
Domiciling ...................................................................................................47
8.1.12
Calibration of Equipment.............................................................................48
8.2
Efficacy Assessments ...........................................................................................48
8.3
Safety Assessments...............................................................................................48
8.3.1
Physical Examinations.................................................................................48
8.3.2
Management of Infusion Reaction During and Post-dose...........................48
8.3.2.1
Local Infusion Reaction Assessment.................................................49
8.3.2.2
Systemic Infusion Reaction Assessment ...........................................49
8.3.3
Assessment of Time to Hemostasis .............................................................49
8.3.4
Height and Weight .......................................................................................50
8.3.5
Resting Vital Signs ......................................................................................50
8.3.6
Electrocardiograms ......................................................................................50
8.3.7
Clinical Safety Laboratory Assessments .....................................................51
8.3.8
Photograph of Rash......................................................................................51
8.4
Adverse Events, Serious Adverse Events, and Other Reportable Safety 
Events....................................................................................................................52
8.4.1
Time Period and Frequency for Collecting AE, SAE, and Other 
Reportable Safety Event Information ..........................................................52
8.4.2
Method of Detecting AEs, SAEs, and Other Reportable Safety Events......54
8.4.3
Follow-up of AE, SAE, and Other Reportable Safety Event Information...54
8.4.4
Regulatory Reporting Requirements for SAE .............................................54
8.4.5
Pregnancy and Exposure During Breastfeeding ..........................................55
8.4.6
Disease-related Events and/or Disease-related Outcomes Not Qualifying 
as AEs or SAEs............................................................................................55
8.4.7
Events of Clinical Interest............................................................................55
8.5
Treatment of Overdose........................................................................................55
8.6
Pharmacokinetics.................................................................................................56
8.6.1
Blood Collection for Plasma MK-2060 and ADA.......................................56
8.7
Pharmacodynamics..............................................................................................56
8.8
Biomarkers ...........................................................................................................56
8.8.1
Planned Genetic Analysis Sample Collection..............................................56
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8.9
Future Biomedical Research Sample Collection...............................................57
8.10
Medical Resource Utilization and Health Economics.......................................57
8.11
Visit Requirements...............................................................................................57
8.11.1
Screening......................................................................................................57
8.11.2
Treatment Period..........................................................................................57
8.11.3
Poststudy......................................................................................................57
8.11.4
Phone Call Follow-up ..................................................................................57
8.11.5
Critical Procedures Based on Study Objectives: Timing of Procedure.......58
8.11.6
Study Design/Dosing/Procedures Modifications Permitted Within 
Protocol Parameters .....................................................................................59
9
STATISTICAL ANALYSIS PLAN .............................................................................60
9.1
Statistical Analysis Plan Summary.....................................................................60
9.2
Responsibility for Analyses.................................................................................61
9.3
Hypotheses/Estimation ........................................................................................61
9.4
Analysis Endpoints...............................................................................................61
9.5
Analysis Populations............................................................................................62
9.6
Statistical Methods...............................................................................................62
9.7
Interim Analyses ..................................................................................................63
9.8
Multiplicity ...........................................................................................................63
9.9
Sample Size and Power Calculations .................................................................63
10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.....................................................................................................64
10.1
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations........64
10.1.1
Code of Conduct for Clinical Trials.............................................................64
10.1.2
Financial Disclosure.....................................................................................66
10.1.3
Data Protection.............................................................................................67
10.1.3.1
Confidentiality of Data ......................................................................67
10.1.3.2
Confidentiality of Participant Records...............................................67
10.1.3.3
Confidentiality of IRB/IEC Information............................................68
10.1.4
Publication Policy........................................................................................68
10.1.5
Compliance with Study Registration and Results Posting Requirements ...68
10.1.6
Compliance with Law, Audit, and Debarment ............................................69
10.1.7
Data Quality Assurance ...............................................................................69
10.1.8
Source Documents .......................................................................................70
10.1.9
Study and Site Closure.................................................................................71
10.2
Appendix 2: Clinical Laboratory Tests..............................................................72
10.3
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting...............................................................73
10.3.1
Definitions of Medication Error, Misuse, and Abuse..................................73
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10.3.2
Definition of AE ..........................................................................................73
10.3.3
Definition of SAE ........................................................................................74
10.3.4
Additional Events Reported.........................................................................75
10.3.5
Recording AE and SAE ...............................................................................76
10.3.6
Reporting of AEs, SAEs, and Other Reportable Safety Events to the 
Sponsor ........................................................................................................79
10.4
Appendix 4: Medical Device and Drug-device Combination Products: 
Product Quality Complaints/Malfunctions: Definitions, Recording, and 
Follow-up ..............................................................................................................81
10.5
Appendix 5: Contraceptive Guidance................................................................82
10.5.1
Definitions....................................................................................................82
10.6
Appendix 6: Collection and Management of Specimens for Future 
Biomedical Research............................................................................................83
10.7
Appendix 7: Country-specific Requirements....................................................88
10.8
Appendix 8: Blood Volume Table ......................................................................89
10.9
Appendix 9: Abbreviations .................................................................................90
11
REFERENCES...............................................................................................................93
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LIST OF TABLES
Table 1
Study Schema...................................................................................................14
Table 2
Study Interventions..........................................................................................36
Table 3
Sample Allocation Schedule............................................................................38
Table 4
Local Infusion Reaction Assessment...............................................................49
Table 5
Reporting Time Periods and Time Frames for Adverse Events and Other 
Reportable Safety Events.................................................................................53
Table 6
Blood Collection Windows..............................................................................58
Table 7
Safety Evaluations Windows...........................................................................59
Table 8
Protocol-required Safety Laboratory Assessments..........................................72
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LIST OF FIGURES
Figure 1
Study Schema.............................................................................................14
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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A single-dose clinical study to evaluate the safety, tolerability, 
pharmacokinetics and pharmacodynamics of MK-2060 in Japanese older participants with 
end-stage renal disease on dialysis.
Short Title: Single Dose Study of MK-2060 in Japanese Older Participants on Dialysis
Acronym: Not applicable
Hypotheses, Objectives, and Endpoints:
In Japanese older participants with end-stage renal disease on dialysis,
[Will be populated by selections made in Section 3 Objectives and Endpoints]
Objectives
Endpoints
Primary
•
To evaluate the safety and tolerability 
following a single dose intravenous 
administration of MK-2060.
•
Adverse events
Secondary
•
To evaluate plasma pharmacokinetics of 
MK-2060 following a single dose 
intravenous administration of MK-2060.
•
AUC0-inf, AUC0-last, AUC0-168, 
Cmax, C168, Tmax, Tlast, t1/2, CL 
and Vz
•
To evaluate the effect of MK-2060 on 
activated partial thromboplastin time 
following a single dose intravenous 
administration of MK-2060.
•
Activated partial thromboplastin time
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Overall Design:
Study Phase
Phase 1
Primary Purpose
Treatment
Indication
Risk reduction of major thrombotic cardiovascular
Population
Japanese older participants with end-stage renal disease 
on dialysis
Study Type
Interventional
Intervention Model
Parallel
This is a multi-site study.
Type of Control
Placebo
Study Blinding
Double-blind
Blinding Roles
Investigator, Participants or Subjects, Sponsor
Estimated Duration of Study
The Sponsor estimates that the study will require 
approximately 8 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 up to 16 participants will be randomized as described in Section 9.9.
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Intervention Groups and Duration:
Intervention 
Groups
Intervention 
Group Name
Drug
Dose 
Strength
Dose 
Frequency
Route of 
Adminis-
tration
Regimen
Use
MK-2060
MK-2060
50 mg
Once
Intravenous
Single 60-
minutes 
infusion
Test 
product
Placebo
Placebo
0 mg
Once
Intravenous
Single 60-
minutes 
infusion
Placebo
Total 
Number of 
Intervention 
Groups/ 
Arms
2
Duration of 
Participation
Each participant will participate in the study for approximately up to 192 
days (6.5 months) from the time the participant provides documented 
informed consent through the final contact. After a screening phase of up to 
28 days, each participant will receive a single dose of assigned intervention
and will be followed for approximately 164 days (5.5 months).
Study Governance Committees:
Executive Oversight Committee
No
Data Monitoring Committee
No
Clinical Adjudication Committee
No
There are no governance committees in this study. Regulatory, ethical, and study oversight 
considerations are outlined in Appendix 1.
Study Accepts Healthy Volunteers: No
A list of abbreviations is in Appendix 9.
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1.2
Schema
The study design is depicted in Figure 1 and Table 1.
Figure 1
Study Schema
Table 1
Study Schema
N a
Dose b, c
MK-2060 50 mg
Placebo
a
Japanese older participants with ESRD on HD or HDF. Approximately up to 16
participants will be randomized and a minimum of approximately HDF 
participants should be included.
b
Dosing in this study will be initiated after 
 of safety data from the 
highest IV dose in MK-2060-013 has been reviewed. Available safety, PK and/or 
PD data in other MK-2060 clinical studies might also be reviewed prior to initiate 
dosing in this study.
c
The suggested doses may be adjusted downward based on newly available safety,
PK and/or PD data observed in MK-2060-013 and/or in other MK-2060 clinical 
studies.
Placebo: 0.9% sodium chloride infusion
MK-2060-013: Single Dose Study of MK-2060 in Healthy Japanese Participants
CCI
CCI
C
CI
CCI
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1.3
Schedule of Activities
Screening
Intervention 
Post-
study
Phone 
Call
Note 
Visit Number
1
2
Scheduled Day
Scr1 Scr2
1～2
3
5
8
12
15
22
29
60
90
120
150
164
Scheduled Hour
(0= Initiation of 
Administration)
Pre
dose
0
1
3.5
8
12
24
48
52
96
168
Window (Day)
Window of 
Screening: See 
Section 8.11.1
Administrative 
Procedures
Informed Consent
X
Informed Consent 
FBR
X
Inclusion/
Exclusion Criteria
X
X
X
Participant ID 
Card
X
Medical History
X
Prior/
Concomitant 
Medication 
Review
X ---------------------------------------------------------------------------------------------------------------------------------------------- X
Assignment of 
Screening 
Number
X
Participant 
Registration
X
X
X
At informed 
consent, 
randomization 
and 
administration
Assignment of 
Randomization 
Number
X
CCI
CCI
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Screening
Intervention 
Post-
study
Phone 
Call
Note 
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
Scheduled Day
Scr1 Scr2
1～2
3
5
8
12
15
22
29
60
90
120
150
164
Scheduled Hour
(0= Initiation of 
Administration)
Pre
dose
0
1
3.5
8
12
24
48
52
96
168
Window (Day)
+1
±1
±2
±2
±3
±5
±5
±7
±7
±7
Window of 
Screening: See 
Section 8.11.1
MK-2060/Placebo 
Administration
X -- X
See 
Section 8.1.8.1
Meal
X ---------- X
A meal will be 
provided at 
approximately 4 
hours postdose. At 
the discretion of 
the investigator, 
additional meals 
and/or snack(s) 
will be provided 
(e.g. snack at 
approximately 2 
hours postdose)
Domiciling
See 
Section 8.1.11.
Safety Procedures
Physical 
examination
X
X
X
X
X
X
X
X
X
X
X
A local infusion 
site (i.e., dialysis 
vascular access 
site) examination 
will be included 
in all postdose 
physical 
examination.
Systemic Infusion 
Reaction 
Assessment
X
X
X
X
X
CCI
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Screening
Intervention 
Post-
study
Phone 
Call
Note 
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
Scheduled Day
Scr1 Scr2
1～2
3
5
8
12
15
22
29
60
90
120
150
164
Scheduled Hour
(0= Initiation of 
Administration)
Pre
dose
0
1
3.5
8
12
24
48
52
96
168
Window (Day)
+1
±1
±2
±2
±3
±5
±5
±7
±7
±7
Window of 
Screening: See 
Section 8.11.1
Assessment of 
Time to 
Hemostasis
X
X
X
X
X
X
X
See Section 8.3.3.
Height
X
Weight
X
X
Resting Vital 
Signs (BP, PR and 
RR)
X
X
X ----------------- X
X
X
X
X
X
X
X
X
On Day 1~2, BP, 
PR and RR will 
be measured at 
predose, 15 min, 
30 min, and 1, 2, 
3.5, 12 and 24 
hours postdose.
Predose PR and 
BP will be 
triplicate 
measurements 
obtained at least 1 
to 2 minutes apart 
within 3 hours of 
starting dialysis 
session.
Resting Vital 
Signs (body 
temperature)
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
X
X
X
X
Hematology and 
Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
aPTT and PT
X
X
X
X
X
X
X
X
X
X
X
CCI
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Screening
Intervention 
Post-
study
Phone 
Call
Note 
Visit Number
1
2
3
4
5
6
7
8
9
10
11
12
13
Scheduled Day
Scr1 Scr2
1～2
3
5
8
12
15
22
29
60
90
120
150
164
Scheduled Hour
(0= Initiation of 
Administration)
Pre
dose
0
1
3.5
8
12
24
48
52
96
168
Window (Day)
+1
±1
±2
±2
±3
±5
±5
±7
±7
±7
Window of 
Screening: See 
Section 8.11.1
Hemoccult Test
X
X
X
X
X
X
X
X
X
HIV, hepatitis B 
and C screen
X
Saliva Drug 
Screen
X
FSH
X
X
As needed.
AE/SAE review
X -------------------------------------------------------------------------------------------------------------------------------------------------------- X
Pharmacokinetics
Blood for Plasma 
MK-2060 Assay
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Days 8, 29 and 
120: two draws 
for a pre- dialysis 
and a post-
dialysis sample.
Blood for plasma 
ADA
X
X
X
X
X
X
X
X
Pharmacodynamics
Blood for 
aPTT/PT/FXI 
activity
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Days 8, 29 and 
120: two draws 
for a pre- dialysis 
and a post-
dialysis sample.
Biomarkers
Blood for Genetic 
Analysis
X
See Section 8.8.1.
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2
INTRODUCTION
MK-2060 is an anti-FXI mAb being developed for the prevention of thrombotic vascular 
events in ESRD. FXI is an integral component of the intrinsic pathway of the coagulation 
cascade. Based on preclinical and human genetic data, as well as emerging clinical data using 
an ASO approach (Ionis) and mAb (Bayer), 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.
2.1
Study Rationale
The purpose of this study is to assess the safety, tolerability, PK and PD of MK-2060 after a 
single dose IV administration in Japanese older participants with ESRD on dialysis. Data 
from this study etc. will be used to aid dose selection of MK-2060 in Japanese participants in 
future studies.
2.2
Background
Refer to the IB for detailed background information on MK-2060.
2.2.1
Pharmaceutical and Therapeutic Background
FXI inhibition is predicted to confer a clinically relevant anti-thrombotic effect with a limited 
risk of bleeding complications and hence an expanded therapeutic index compared to 
inhibition of more downstream clotting factors such as FXa and thrombin. Currently, several 
Factor XI inhibitors (ASO, mAb, SMi) are being investigated in either Phase 1 or 2 studies, 
across a range of populations, but limited data has been made available to confirm the proof 
of concept in ESRD patients as a suitable indication.
2.2.2
Clinical Studies
As of 
, MK-2060 has been evaluated in 2 completed Phase 1 studies (MK-2060-
001 and MK-2060-004), 1 ongoing Phase 1 study (MK-2060-008) and 1 ongoing Phase 2 
study (MK-2060-007).
MK-2060-001:
MK-2060-001 was a double-blind, randomized, placebo-controlled, sequential panel, SAD 
study in non-Japanese healthy male participants to evaluate the safety, tolerability, PK and 
PD profiles of MK-2060 administered SC or IV. A total of 45 non-Japanese healthy 
participants received single MK-2060 doses of up to 120 mg administered SC (27 
participants) and up to 40 mg administered IV (18 participants). Refer to the latest IB for 
detailed results.
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MK-2060-004:
MK-2060-004 was a double blind, randomized, placebo-controlled, sequential panel single 
(Part 1) and multiple (Part 2) dose study to evaluate the safety, tolerability, PK and PD 
characteristics of MK-2060 single (up to 40 mg) and multiple (25 mg dose on Days 1, 3, and 
5, followed by 3 once-weekly maintenance doses of 25 mg) IV doses in non-Japanese older 
participants with ESRD on HD. Overall, 38 participants were enrolled in the study: 24 
participants in Part 1 and 21 participants in Part 2 (7 participants in Part 1 also participated in 
Part 2). Refer to the latest IB for detailed results.
2.2.3
Ongoing Clinical Studies
MK-2060-008:
MK-2060-008 is an open label, multi-site, multiple dose trial of MK-2060 in non-Japanese
participants with ESRD on HD to evaluate the safety and tolerability of MK-2060 and 
clopidogrel administered in combination in participants with ESRD on HD. This study will 
enroll up to 12 ESRD participants receiving clopidogrel as background therapy. After an 
approximately 14-day run-in period to enable measurement of baseline time to hemostasis 
and AE monitoring, each participant will receive a loading dose of 25 mg IV MK-2060 for a 
total of 3 doses in week 1 and a single dose of 25 mg IV MK-2060 in week 2.
MK-2060-007:
MK-2060-007 is an event driven, randomized, placebo-controlled, parallel-group, multi-site, 
double-blind study of MK-2060 in non-Japanese participants with ESRD on HD via an AVG. 
This phase 2 study is designed to evaluate the efficacy and safety of MK-2060 
 QW 
and MK 2060
 QW (with three loading doses in Week 1). As of 
 
participants enrolled in MK-2060-007 with a maximum exposure of 
. MK-2060-007 
is ongoing and safety data are blinded and preliminary.
2.3
Benefit/Risk Assessment
Participants in clinical studies will not receive direct benefit from treatment during 
participation as clinical studies are designed to provide information about the safety and 
properties of an investigational medicine.
Additional details regarding specific benefits and risks for participants participating in this 
clinical study may be found in the accompanying IB and informed consent documents.
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3
HYPOTHESES, OBJECTIVES, AND ENDPOINTS
In Japanese older participants with end-stage renal disease on dialysis,
Objectives
Endpoints
Primary
•
To evaluate the safety and tolerability 
following a single dose intravenous 
administration of MK-2060.
•
Adverse events
Secondary
•
To evaluate plasma pharmacokinetics of 
MK-2060 following a single dose 
intravenous administration of MK-2060.
•
AUC0-inf, AUC0-last, AUC0-168, 
Cmax, C168, Tmax, Tlast, t1/2, CL 
and Vz
•
To evaluate the effect of MK-2060 on 
activated partial thromboplastin time 
following a single dose intravenous 
administration of MK-2060.
•
Activated partial thromboplastin time
Tertiary/Exploratory
•
To explore the effect of MK-2060 given 
as a single dose intravenous 
administration on Factor XI activity 
levels.
•
Factor XI activity
•
To explore the effect of MK-2060 given 
as a single dose intravenous
administration on prothrombin time.
•
Prothrombin time
•
To explore the effect of MK-2060 given 
as a single dose intravenous 
administration on time to hemostasis after 
decannulation of the dialysis vascular 
access site.
•
Time to hemostasis after decannulation 
of vascular access
•
To explore the presence and titer of anti-
drug antibodies in plasma samples 
following a single dose intravenous 
administration of MK-2060.
•
Presence and titer of anti-drug 
antibodies
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Objectives
Endpoints
•
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.
•
Germline genetic variation and 
association to clinical data collected in 
this study
4
STUDY DESIGN
4.1
Overall Design
This is a randomized, placebo-controlled, parallel-group, multi-site, double-blind study of 
MK-2060 in Japanese older participants with ESRD on dialysis. The study will evaluate the 
safety, tolerability, PK and PD of a single dose IV administration of MK-2060 in Japanese 
older participants with ESRD on dialysis (participants assigned male sex at birth or 
WONCBP between the age of 50 to 80 years).
The study design is depicted in Figure 1 and Table 1.
Approximately up to 16 participants will be randomized in a ratio of 
 and receive a single 
dose of MK-2060 or placebo (0.9% sodium chloride infusion). All participants will be 
domiciled until approximately 
hours postdose (completion of dialysis on Day
 Blood 
samples for PK, PD and ADA assay will be obtained predose and at selected time points up 
to 150 days postdose. All participants will be closely monitored for safety and tolerability for 
approximately 164 days.
Because this is a Phase 1 assessment of MK-2060 in humans, the PK, pharmacodynamic, and 
safety profiles of the compound are still being elucidated. This protocol is therefore written 
with flexibility to accommodate the inherent dynamic nature of Phase 1 clinical studies. 
Refer to Section 8.11.6 for examples of modifications permitted within the protocol 
parameters.
Specific procedures to be performed during the study, including prescribed times and 
associated visit windows, are outlined in Section 1.3 of the SoA. Details of each procedure 
are provided in Section 8.
4.2
Scientific Rationale for Study Design
MK-2060 is being developed for the prevention of thrombotic vascular events in ESRD 
patients, thus the objectives of this study are to evaluate safety, tolerability, PK, and PD of 
MK-2060 after a single dose IV administration in Japanese patient population [older 
participants with ESRD on dialysis (participants assigned male sex at birth or WONCBP
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between the age of 50 to 80 years)]. Approximately up to 16 participants with ESRD on 
dialysis who meet study eligibility criteria may be enrolled in this study.
Dialysis modality in this study includes HD and HDF. The Japanese patients treated by HDF 
have been increasing in number rapidly since 2012. HD and HDF accounted for 49.3% and 
47.1% of all dialysis patients, respectively in 2020 [JSDT Renal Data Registry 2020]. 
Therefore, this study will enroll both HD and HDF participants. Since only HD participants 
were enrolled in MK-2060-004 (Phase 1 study in non-Japanese participants), this study will 
mainly enroll HD participants and a minimum of approximately HDF participants will be 
enrolled.
 
 is not 
removed by both HD and HDF, it is anticipated that there is no PK difference between HD 
and HDF patients.
The mean age of prevalent dialysis patients in Japan was 69.40 years, indicating a gradual 
annual increase.  The age group of 70 to 74 had the highest percentage both in males and 
females [JSDT Renal Data Registry 2020]. The mean age of HD and HDF patients was 70.00 
years and 67.21 years, respectively. The mean dialysis vintage of HD patient was 6.99 years 
and 50.7% was less than 5 years of dialysis vintage. On the other hand, the mean dialysis 
vintage of HDF patient was 8.44 years and 40.9% was less than 5 years of dialysis vintage.
HDF is applied to relatively young patients with a longer dialysis vintage than HD in 2018 
[JSDT Renal Data Registry 2018]. Therefore, this study is being conducted in older 
participants ages from 50 years to 80 years.
In the Part 1 of MK-2060-004, the exposure (AUC0-inf and Cmax) after single IV dose at 8 
mg MK-2060 in non-Japanese ESRD participants on HD is comparable to non-Japanese
healthy participants (MK-2060-001) while the exposure after single IV dose at 20 mg and 40 
mg in non-Japanese ESRD participants on HD are slightly lower than that in non-Japanese
healthy participants due to higher clearance. The terminal t1/2 ranged from ~14 days for MK-
2060 8 mg to ~21 days for MK-2060 40 mg in non-Japanese ESRD participants on HD 
. PK samples were also collected 
pre- and post-dialysis, with the post-dialysis PK concentration approximately
 
higher than pre-dialysis indicting that MK-2060 is not cleared via dialysis and the reduction 
in volume due to dialysis slightly increases the MK-2060 concentration. Based on single dose 
PK and aPTT or FXIa activity data,
 
The PK and aPTT or FXI activity (relative of baseline) data from MK-2060-001 
and following single IV doses from MK-2060-004 suggests a comparable but 
 
 for participants 
with ESRD and healthy participants.
It is also not anticipated that race significantly alter the PK and PD of MK 2060. As mAbs 
are primarily eliminated via catabolism, there is expected to be no ethnic differences of the 
clearance between Japanese and non-Japanese participants. Since the PK and PD values were 
corelated 
 in non-Japanese, PD responses in Japanese participants 
are also expected to be similar to that in non-Japanese participants The impact of race on 
MK-2060 PK and PD will be further assessed by conducting single dose study in Japanese 
healthy participants (MK-2060-013).  
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In MK-2060-001, in general, a single SC dose of MK-2060 up to 120 mg or a single IV dose 
of MK-2060 up to 40 mg in non-Japanese healthy participants assigned male sex at birth was 
well tolerated. There were no SAEs, ECIs, or deaths reported, no participants discontinued 
from the study due to an AE. There were no AEs suggestive of hypersensitivity. In Part 1 of 
MK-2060-004, a single IV dose up to 40 mg has been generally well-tolerated in non-
Japanese participants with ESRD on HD. There were no ECIs or deaths reported, no 
participants discontinued from the study due to an AE. There were no AEs suggestive of 
hypersensitivity. In Part 2 of MK-2060-004, multiple IV doses of 25 mg have been generally 
well tolerated in non-Japanese participants with ESRD on HD. There were no deaths 
reported. There were no AEs suggestive of hypersensitivity. Two participants receiving 
placebo were discontinued from study intervention due to AEs including lower 
gastrointestinal hemorrhage (SAE, related) and COVID-19 infection (nonserious, not 
related). Four (4) participants experienced SAEs: 1 (6.3%) in MK-2060 (severe myocardial 
infarction on Day 103, not related) and 3 (60.0%) in placebo. All SAEs resolved by the end 
of the study. In addition, IONIS has demonstrated using a FXI ASO that inhibition of the FXI 
pathway in ESRD participants on HD (mean age of 61 years) is generally safe and well-
tolerated [Bethune, C., et al 2017].  
Therefore, the study of MK-2060 in Japanese older participants with ESRD on dialysis is 
supported.
4.2.1
Rationale for Endpoints
4.2.1.1
Safety Endpoints
This will be the first introduction of MK-2060 to Japanese older participants with ESRD on 
dialysis. Based on the data from MK-2060-004, it is expected that IV administration of MK-
2060 will be well-tolerated in participants with ESRD on dialysis. However, the safety and 
tolerability of MK-2060 are primary endpoints and will be carefully monitored. PEs, VSs, 
12-lead ECGs, laboratory safety tests (hematology, chemistry, aPTT and PT) and bleeding 
related AEs will be assessed. AEs, including local infusion site reactions and systemic 
reactions to infusion, will be collected through Day 164.
As with all biologic medications, MK-2060 carries a risk of acute reactions upon exposure, 
particularly with IV administration. The risk of any of infusion reactions to MK-2060 is 
considered low given its profile in preclinical safety studies and available safety data in MK-
2060-001 and MK-2060-004. However, given potential safety risks, participants will be 
monitored closely for systemic reactions to infusion with scheduled VSs and PEs. In addition 
to monitoring for acute reactions to MK-2060, the infusion site reactions will be assessed for 
signs of reactogenicity.
Time to hemostasis after decannulation of vascular access:
An exploratory objective of this study is to explore the effect of MK-2060 given as a single 
dose IV administration on time to hemostasis after decannulation of the dialysis vascular 
access site in Japanese ESRD patients. In the dialysis unit after the completion of dialysis 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, which was used in MK-2060-004 and MK-2060-008, is standardized such 
that change in time to hemostasis from baseline (i.e., Screening 1 and 2) can be assessed. 
This exploratory analysis may allow for a very preliminary read on bleeding risk with 
administration of MK-2060 in the Japanese ESRD patient population.
In general, both single dose and multiple doses of MK-2060 in non-Japanese participants 
with ESRD on HD (MK-2060-004) had no effect on time to hemostasis at the end of HD 
after dosing. In Parts 1 and 2, the maximum observed fold-change for time to hemostasis was 
mostly around 1 across all doses of MK-2060 and placebo throughout the study.
Anti-drug antibodies to MK-2060:
The amino acid sequence of MK-2060 is highly similar to standard human 
 
The mechanism of action of MK-2060 is not immunomodulatory and the ESRD population is 
less likely to have a robust immune response.
The presence and titer of ADAs will be measured using validated assays. ADAs can develop 
to biologics like MK-2060. If needed, positive ADAs will be further evaluated to determine 
whether they are able to neutralize MK-2060 activity against FXI.
From MK-2060-001, a total of 45 participants were evaluable for immunogenicity 
assessment. One participant had a single positive sample at the Day 90 timepoint. The 
remaining 44 participants did not have positive samples.
From MK-2060-004, overall, 
participants were evaluable for immunogenicity assessment: 
 participants in Part 1 and 
 participants in Part 2. Of the 
 participants,
 were 
treatment emergent positive. All other participants were negative for ADA. In Part 1,  
 treatment emergent positive with 
 
 reported no AEs 
 
 treatment emergent positive with 
 
no reported AEs. The magnitude of response 
(ie, maximum postdose titer value) in both participants with a positive response to MK-2060 
was near the limit of detection of the ADA assay (titer value of
 In both ADA positive 
participants, the presence of ADA did not affect the MK-2060 safety and PK profile.
Based on the PK profiles observed to date and available ADA analysis data from both MK-
2060-001 and MK-2060-004, 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.
4.2.1.2
Pharmacokinetic Endpoints
In order to characterize the PK profile of MK-2060 in Japanese older participants with ESRD 
on dialysis, non-compartmental PK parameters AUC0-inf, AUC0-last, AUC0-168, Cmax, 
C168, Tmax, Tlast, t1/2, CL and Vz will be summarized following a single dose IV 
administration. Evaluation of plasma PK data of MK-2060 following a single dose IV 
administration in Japanese older participants with ESRD on dialysis is a secondary objective 
of this study.
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4.2.1.3
Pharmacodynamic Endpoints
In order to assess PD, this study will include an assessment of aPTT/PT prolongation levels, 
and FXI activity levels, with assays being performed at a central laboratory for PD. For 
PK/PD modeling, aPTT and FXI activity levels will be related to plasma exposure. The time 
points for PD data collection are based on the projected PK profile of MK-2060. Evaluation
of the effects of MK-2060 on aPTT following a single dose IV administration in Japanese 
older participants with ESRD on dialysis is a secondary objective of this study. 
4.2.1.4
Planned Exploratory Biomarker Research
4.2.1.4.1
Planned Genetic Analysis
Genetic variation may impact a participant’s response to therapy, susceptibility to, severity, 
and progression of disease. Variable response to therapy may be due to genetic determinants 
that impact drug ADME; mechanism of action of the drug; disease etiology; and/or 
molecular subtype of the disease being treated. Therefore, where local regulations and 
IRB/IEC allow, a sample will be collected for DNA analysis from consenting participants.
DNA samples may be used for research related to the study intervention(s), the disease under 
study, or related diseases. They may also be used to develop tests/assays including diagnostic 
tests related to the disease under study, related diseases, and study intervention(s). Genetic 
research may consist of the analysis of 1 or more candidate genes, the analysis of genetic 
markers throughout the genome, or analysis of the entire genome. Analysis may be 
conducted if it is hypothesized that this may help further understand the clinical data.
The samples may be analyzed as part of a multistudy 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 FBR on DNA specimens for which consent was provided during 
this clinical study.
Such research is for biomarker testing to address emergent questions not described elsewhere 
in the protocol and will only be conducted on specimens from appropriately consented 
participants. The objective of collecting/retaining specimens for FBR is to explore and 
identify biomarkers that inform the scientific understanding of diseases and/or their 
therapeutic treatments. The overarching goal is to use such information to develop safer, 
more effective drugs/vaccines, and/or to ensure participants receive the correct dose of the 
correct drug/vaccine at the correct time. The details of FBR 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 
Japanese older participants with ESRD on dialysis. A placebo-controlled study will allow for 
an unbiased assessment of safety and tolerability of MK-2060. Secondary and exploratory 
outcomes are also supported by the use of placebo, including evaluation of the effect of MK-
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2060 on aPTT following single IV dose, which should only be observed in participants with 
active treatment.
4.3
Justification for Dose
The dose to be administered in this study will not exceed 50 mg.
The single IV dose of 50 mg in this study would cover the exposures at the steady state 
obtained from the possible maximum dose of Phase 3 study (i.e. 
 mg IV or lower QW).
This is also the planned highest dose in a single IV dose study in Japanese healthy 
participants (MK-2060-013) and dose in this study may be adjusted downward based on 
available safety, PK and/or PD data in MK-2060-013 and/or other MK-2060 clinical studies.
In MK-2060-004, a single IV dose up to 40 mg and multiple IV doses of 25 mg QW have
been generally well-tolerated in non-Japanese participants with ESRD on HD. Apart from 
mechanism-based aPTT increases, there were no clinically significant changes from baseline 
for ECGs, safety labs. Similarly, an exploratory assessment of time to vascular access site 
hemostasis after removal of the hemodialysis catheters remained unchanged from baseline.
Given dose proportionality in exposures generally observed in previous clinical studies, a
single IV dose of 50 mg in Japanese older participants with ESRD on dialysis in this study is 
projected to result in a Cmax of 
 
These predicted Cmax 
) in this study are slightly 
lower compared to the observed values at the steady state at 25 mg QW in MK-2060-004 
(Cmax of 90.9 nM and AUC0-168 of 9880 nM•hr). In addition, these predicted AUC0-168 
 in this study provided an AUC margin of 
approximately 
, to the AUC at the NOAEL (AUC0-168 at 
60mg/kg of 7920 day•μg/mL = 1.28 x 106 hr•nM) in 4 week SC and IV toxicity study in 
rhesus monkeys.
The maximum aPTT change from baseline was
 (around Tmax) at the steady state 
after multiple IV doses of 25 mg QW in MK-2060-004. As mentioned above, the predicted 
Cmax
 in this study is slightly lower than the observed Cmax 
at the 
steady state in MK-2060-004. Given this together with 
 between PK 
and PD responses, maximum aPTT change from baseline in this study is expected to be 
lower than that observed in MK-2060-004.
Please refer to Section 4.2 above for further rationale as to why significant PK and PK-PD
differences with MK-2060 in Japanese older participants with ESRD on dialysis are not 
anticipated.
As this is a Phase 1 assessment of MK-2060 in humans, and the PK, PD and safety profiles 
of the compound are still being evaluated, modifications to the dose or dosing regimen may 
be required to achieve the scientific goals of the study objectives and/or to ensure appropriate 
safety monitoring of the study participants. Details of allowed modifications are provided in 
Section 8.11.6.
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4.3.1
Rationale for Dose Interval and Study Design
This is a single dose study, in which participants will only receive one IV administration.
MK-2060 or placebo will be given 30 minutes after the initiation of dialysis and administered 
via the post-dialyzer line (V side) over approximately 60 minutes. Participants will be 
enrolled and dosed on a rolling basis. 
Dosing in this study will be initiated after at least
 days of safety data from the highest IV 
dose in MK-2060-013 (Single ascending dose study in Japanese healthy participants) has 
been reviewed.
MK-2060 is a fully human mAb and does not exhibit highly species-specific action, nor is it 
directed towards immune system targets. Safety assessment studies and clinical studies (MK-
2060-001 and MK-2060-004) with MK-2060 provide no contraindications to the initiation of 
this study via IV routes. No dose-limiting toxicities were observed in the 4-week nonhuman 
primate toxicity trial. 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 CRU after dosing. CRUs will have 
appropriate access to a full service acute-care hospital to facilitate rapid institution of medical 
intervention as indicated.
There will be frequent, careful assessments of AEs throughout the postdose period. The 
participants will be dosed and observed until discharge 
hours postdose; completion of 
dialysis on Day
 for safety monitoring, and then they will continue to be monitored 
throughout the study period as indicated in Section 1.3. Following discharge, the additional 
measures are being taken in this protocol to ensure the safety of study participants as 
indicated in Section 8.1.11.
Due to the physio-chemical properties of mAb therapeutics, transfer to the seminal 
compartment and subsequent vaginal uptake of a mAb is essentially zero, as demonstrated in 
rabbits, monkeys, and humans [Breslin, W. J., et al 2014], [Moffat, G. J., et al 2014], and 
[Sohn, W., et al 2015]. In addition, in an embryofetal developmental toxicity study in 
pregnant rabbits administered MK-2060, there was no evidence of embryofetal lethality or 
teratogenicity up to 120 mg/kg/day (the highest dose evaluated; 1 dose QW for 2 weeks) 
providing an estimated systemic exposure margin of 234-fold the observed AUC0-168hr of 
63 day•μg/mL after multiple 60-minute IV infusion doses of 25 mg IV at steady state in 
ESRD patients. Therefore, there is no risk to pregnant partners of male participants receiving 
MK-2060, and male contraception during clinical studies with MK-2060 is not warranted.
4.4
Beginning and End-of-Study Definition
The overall study begins when the first participant (or their legally acceptable representative) 
provides documented informed consent. The overall study ends when the last participant 
completes the last study-related contact, withdraws consent, or is lost to follow-up (Section 
7.3). For purposes of analysis and reporting, the overall study ends when the Sponsor 
receives the last laboratory test result or at the time of final contact with the last participant, 
whichever comes last.
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If the study includes countries in the European Economic Area (EEA), the local start of the 
study in the EEA is defined as First Site Ready (FSR) in any Member State.
A study may be paused during review of newly available preclinical/clinical safety, PK, 
pharmacodynamic, efficacy, or biologic data or other items of interest, prior to a final 
decision on continuation or termination of the study. It may be necessary to keep the study 
open for gathering/reviewing of additional supportive data to optimally complete the 
objective(s) of the study. If necessary, the appropriate amendment(s) to the protocol and/or 
appropriate communication(s) will be generated. If the decision has been made to end the 
study following this review period, the study end will be defined as the date of the Sponsor 
decision, and this end of study date supersedes the definitions outlined above. The 
Competent Authority(ies) and IRB(s)/IEC(s) will be apprised of the maximum duration of 
the study beyond the last participant out and the justification for keeping the study open.
4.4.1
Clinical Criteria for Early Study Termination
There are no prespecified criteria for terminating the study early.
A primary objective of this early Phase 1 study is to identify the safe and well-tolerated dose 
and/or dosing regimen that achieve PK, pharmacodynamic, and/or biologic targets in humans 
based on preclinical or early clinical data. Therefore, it is possible that study participants may 
not receive all doses specified in the protocol if this objective is achieved at lesser dose levels 
in this study. This would not be defined as early termination of the study, but rather an earlier 
than anticipated achievement of the study objective(s). If a finding (eg, PK, 
pharmacodynamic, efficacy, biologic targets, etc) from another preclinical or clinical study 
using the study intervention(s), comparator(s), drug(s) of the same class, or methodology(ies) 
used in this study results in the study(ies) or program being stopped for nonsafety reasons, 
this also does not meet the definition of early study termination.
Early study termination is defined as a permanent discontinuation of the study due to 
unanticipated concerns of safety to the study participants arising from clinical or preclinical
studies with the study intervention(s), comparator(s), drug(s) of the same class, or 
methodology(ies) used in this study.
5
STUDY POPULATION
As stated in the Code of Conduct for Clinical Trials (Appendix 1.1), this study includes
participants of varying age (as applicable), race, ethnicity, and sex (as applicable). The 
collection and use of these demographic data will follow all local laws and participant 
confidentiality guidelines while supporting the study of the disease, its related factors, and 
the IMP under investigation.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
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5.1
Inclusion Criteria
An individual is eligible for inclusion in the study if the individual meets all of the following 
criteria:
Type of Participant and Disease Characteristics
1. Japanese descent with all 2 biological parents of Japanese descent.
2. On HD or HDF with spKt/V ≥1.2, using AV fistula or AV graft ≥3 months prior to 
Screening 1 at a healthcare center, and is on the same dialysis regimen [type of dialyzer, 
blood flow rate, dialysate flow rate, dialysis time and dialysis frequency (3 times per 
week)] ≥2 weeks prior to Screening 1.
3. Be judged to plan to continue or anticipate the use of the current AV fistula or AV graft 
until the poststudy visit.
4. BMI ≤40 kg/m2, inclusive. See Section 8.3.4 for criteria on rounding to the nearest 
whole number. BMI = weight (kg)/height (m)2.
Demographics
5. Is male or female, from 50 years to 80 years of age inclusive, at the time of providing
informed consent.
Female Participants
6.
A female participant is eligible to participate if: 
-
She is a WONCBP, as defined in Appendix 5.
Informed Consent
7. The participant (or legally acceptable representative) has provided documented informed 
consent for the study. The participant may also provide consent for FBR. However, the 
participant may participate in the study without participating in FBR.
Additional Categories
8. Willing to comply with the study restrictions (see Section 5.3 for a complete summary of 
study restrictions).
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5.2
Exclusion Criteria
The participant must be excluded from the study if the participant meets any of the following 
criteria:
Medical Conditions
1. On peritoneal dialysis (including the combination of HD or HDF) or other dialysis 
modalities except for HD and HDF.
2. History of any clinically significant concomitant disease or condition (including 
treatment for such conditions) or diseases whose current condition is considered 
clinically unstable in the opinion of the investigator. Participants with a remote history of 
uncomplicated medical events (eg, 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.
3. Mentally incapacitated, has significant emotional problems at the time of Screening 1 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.
4. History of cancer (malignancy).
Exceptions: (1) Adequately treated non-melanomatous skin carcinoma or carcinoma in situ 
of the cervix or; (2) Other malignancies that have been successfully treated with appropriate 
follow up and therefore unlikely to recur for the duration of the study, in the opinion of the 
investigator and with agreement of the Sponsor (eg, malignancies that have been successfully 
treated ≥10 years prior to Screening 1).
5. History of deep vein thrombosis or pulmonary embolism.  History of vascular access 
thrombosis within 1 month prior to Screening 1.  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).
6. History of GI bleeding, duodenal polyps or active gastroduodenal ulcer within 5 years 
prior to Screening 1, or history of severe hemorrhoidal bleed within 3 months prior to 
Screening 1. Patients who had colonic polyps at low risk for bleeding through an 
endoscope performed prior to Screening 1, but who are judged not to require or anticipate 
requiring re-examination until the poststudy visit, may be enrolled at the discretion of the 
investigator.
7. History of frequent epistaxis within 3 months prior to Screening 1 or active gingivitis.
8. At the time of screening or predose, planned significant dental procedures (including 
planned dental surgery), or other planned surgical procedures within duration of 
participation in the trial.
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9. History of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or 
has had an anaphylactic reaction or significant intolerability (ie, systemic allergic 
reaction) to prescription or nonprescription drugs or food.
10. Positive test(s) for hepatitis B surface antigen or HIV antigen and antibody.  Participants 
positive for hepatitis C antibodies may be enrolled with agreement of both the 
investigator and Sponsor. Serology tests will be performed at Screening 1 by the central 
laboratory for safety.
11. The participant had a major surgery and/or donated or lost 1 unit of blood (approximately 
500 mL) within 4 weeks prior to Screening 1.
12. A tattoo, scar, or other physical finding at the area of vascular access site and blood 
collection sites that would interfere with a local tolerability assessment.
Prior/Concomitant Therapy
13. History (participant recall) of receiving any human immunoglobulin preparation such as 
IVIG or RhoGAM within 1 year prior to Screening 1.
14. History (participant recall) of receiving any biological therapy (including human blood 
products or monoclonal antibodies; excluding erythropoietin and insulin) within 3 months 
(or 5 half-lives, whichever is greater) prior to Screening 1, or vaccination within 1 month 
prior to the dose of study intervention.
Exceptions: 

Participants who have received seasonal flu vaccine and pneumococcal vaccine within 1 
month prior to the dose of study intervention 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.
15. Requires or anticipates requiring the use of following prohibited medications until the 
poststudy visit.

Anticoagulants (Intradialytic heparin is permitted)

Antiplatelet medications (low dose aspirin is permitted)

NSAIDs (e.g., ibuprofen) (acetaminophen used for minor ailments and topical NSAIDs 
is permitted)
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Prior/Concurrent Clinical Study Experience
16. Participated in another investigational study within 1 month (or 5 half-lives, whichever is 
greater) prior to Screening 1. The window will be derived from the date of the last visit in 
the previous study.
Diagnostic Assessments
17. Has a BP ˃ 190 mmHg systolic or > 110 mmHg diastolic obtained at Screening 2 or 
predose.
18. Has blood coagulation test (aPTT or PT) above 1.2X ULN at Screening 1 (confirmed by 
recheck) from the central laboratory for safety.
19. Has ALT or AST above 1.5X ULN at Screening 1 or 2 which are considered clinically 
significant by the investigator from the central laboratory for safety.
20. Exclusion criteria for ECG performed at Screening 1 or predose:

HR ˂ 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 (greater than 2 consecutive 
ventricular ectopic beats at a rate of greater than 1.7/second).
Other Exclusions
21. Consumes greater than 3 servings of alcoholic beverages (1 serving is approximately 
equivalent to: beer [354 mL], wine [118 mL], or distilled spirits [29.5 mL]) per day. 
Participants who consume 4 servings of alcoholic beverages per day may be enrolled at 
the discretion of the investigator.
22. 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.
23. A regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) 
abuse within approximately 2 years. Participants must have a negative saliva drug screen
at Screening 1.  Participants with a positive drug screen due to the use of physician 
prescribed medications may be enrolled at the discretion of the investigator.
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24. The investigator has any concern regarding safe participation in the study or for any other 
reason the investigator considers the participant inappropriate for participation in the 
study.
25. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or 
child) who is investigational site or Sponsor staff directly involved with this study.
5.3
Lifestyle Considerations
5.3.1
Meals and Dietary Restrictions
5.3.1.1
Diet Restrictions
Fasting requirements for study procedures, such as but not limited to laboratory safety 
evaluations are specified in Appendix 2.
On dosing day, participants will fast from all food and drinks, except water and non-
caffeinated tea (e.g. barley tea), for at least 8 hours before initiation of study intervention
administration. Participants will fast from all food and drinks, except water and non-
caffeinated tea, between initiation of study intervention administration and the first scheduled 
meal. Meals and/or snacks will be provided by the investigator at time points indicated in the 
SoA. Participants will fast from all food and drinks, except water and non-caffeinated tea,
between provided meals and snacks. The meal content should be consistent within a given 
clinical site (if possible). After the 24-hour postdose procedures have been completed, 
subsequent meals and snacks will be unrestricted in caloric content, composition, and timing.
5.3.2
Caffeine, Alcohol, and Tobacco Restrictions
5.3.2.1
Caffeine Restrictions
Participants will refrain from consumption of caffeinated beverages or xanthine-containing 
products from 12 hours before Screening 1 and 2 and poststudy visits and from 12 hours 
before and after initiation of study intervention administration. Participants will follow the 
caffeine restrictions defined by the CRU from 12 hours after initiation of study intervention
administration during domiciling. At all other times, caffeinated beverages or xanthine-
containing products will be limited to no more than 6 units per day (1 unit = 120 mg of 
caffeine).
5.3.2.2
Alcohol Restrictions
Participants will refrain from consumption of alcohol 24 hours before Screening 1 and 2 and 
poststudy visits and from 24 hours before and after initiation of study intervention
administration. Participants will follow the alcohol restrictions defined by the CRU from 
24 hours after initiation of study intervention administration during domiciling. At all other 
times, alcohol consumption is limited to no more than approximately 3 alcoholic beverages 
or equivalent servings (1 serving is approximately equivalent to: beer [354 mL], wine 
[118 mL], or distilled spirits [29.5 mL]) per day.
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5.3.2.3
Tobacco Restrictions
Participants will follow the smoking restrictions (and if applicable, the use of 
nicotine/nicotine-containing products) defined by the CRU during domiciling.
5.3.3
Activity Restrictions
Participants will avoid unaccustomed strenuous physical activity (ie, weightlifting, running, 
bicycling, etc) and contact sports including ones have bleeding risk (ie, boxing, football, etc.)
from Screening 1 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 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 withdraws from the study, a replacement participant may be enrolled if 
deemed appropriate by the investigator and Sponsor. The replacement participant will 
generally receive the same intervention or intervention sequence (as appropriate) as the 
participant being replaced. The replacement participant will be assigned a unique 
treatment/randomization number.
6
STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
Clinical supplies study intervention(s) provided by the Sponsor will be packaged to support 
enrollment and replacement participants as required. When a replacement participant is 
required, the Sponsor or designee needs to be contacted before dosing the replacement 
participant. Clinical supplies will be affixed with a clinical label in accordance with 
regulatory requirements.
6.1
Study Intervention(s) Administered
The study intervention(s) to be used in this study are outlined in Table 2.
Country-specific requirements are noted in Appendix 7.
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Table 2
Study Interventions
Arm 
Name
Arm Type
Intervention 
Name
Inter-
vention 
Type
Dose 
Formulation
Unit Dose 
Strength(s)
Dosage 
Level(s)
Route of 
Adminis-
tration
Regimen
Use
IMP or
NIMP/
AxMP
Sourcing
MK-2060
Experimental
MK-2060
Drug
Lyophilized 
Powder
50 mg
IV 
Infusion
Single 
60-minutes 
infusion
Test 
Product
IMP
Provided 
centrally by 
the Sponsor
Placebo
Placebo 
Comparator
Placebo
Drug
Sterile 
Solution
Saline
0 mg
IV 
Infusion
Single 
60-minutes 
infusion
Placebo
IMP
Provided 
centrally by 
the Sponsor
The classification of IMP and NIMP/AxMP in this table is based on guidance issued by the European Commission and applies to countries in the EEA. Country differences 
with respect to the definition/classification of IMP and NIMP/AxMP may exist. In these circumstances, local legislation is followed.
The normal saline provided by the Sponsor as placebo should be used to reconstitute MK-2060.
Normal saline = 0.9% Sodium Chloride Injection
CCI
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All supplies indicated in Table 2 will be provided per the “Sourcing” column depending on 
local country operational requirements. If local sourcing, every attempt should be made to 
source these supplies from a single lot/batch number where possible (eg, not applicable in the 
case where multiple lots or batches may be required due to the length of the study, etc).
Refer to Section 8.1.8 for details regarding administration of the study intervention.
6.2
Preparation/Handling/Storage/Accountability
6.2.1
Dose Preparation
Specific calculations or evaluations required to be performed to administer the proper dose to 
each participant are outlined in a separate document provided by the Sponsor. The rationale 
for selection of doses to be used in this study is in Section 4.3.
6.2.2
Handling, Storage, and Accountability
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received, and any discrepancies are 
reported and resolved before use of the study intervention.
Only participants enrolled in the study may receive study intervention, and only authorized 
site staff may supply or administer study intervention. All study interventions must be stored 
in a secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff.
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records).
For all study sites, the local country Sponsor personnel or designee will provide appropriate 
documentation that must be completed for drug accountability and return, or local discard 
and destruction if appropriate. Where local discard and destruction is appropriate, the 
investigator is responsible for ensuring that a local discard/destruction procedure is 
documented.
The study site is responsible for recording the lot number, manufacturer, and expiry date for 
any locally purchased product (if applicable) as per local guidelines unless otherwise 
instructed by the Sponsor.
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution, and usage of study 
interventions in accordance with the protocol and any applicable laws and regulations.
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6.3
Measures to Minimize Bias: Randomization and Blinding
6.3.1
Intervention Assignment
Participants will be assigned randomly according to a computer-generated allocation 
schedule.
A sample allocation schedule is shown in Table 3.
Table 3
Sample Allocation Schedule
N a
Dose
MK-2060 50 mg
Placebo
a
Japanese older participants with ESRD on HD or HDF.  Approximately up to 
16 participants will be randomized and a minimum of approximately HDF 
participants should be included.
Placebo: 0.9% sodium chloride infusion
6.3.2
Stratification
No stratification based on age, sex, or other characteristics will be used in this study.
6.3.3
Blinding
A double-blinding technique will be used. MK-2060 and placebo will be prepared and/or 
dispensed in a blinded fashion by an unblinded pharmacist or qualified study-site personnel. 
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.
See Section 8.1.10 for a description of the method of unblinding a participant during the 
study should such action be warranted.
6.4
Study Intervention Compliance
Interruptions from the protocol-specified treatment plan require consultation between the 
investigator and the Sponsor and written documentation of the collaborative decision on 
participant management.
The date and (start and end) time of each dose administered in the clinic will be recorded in 
the source documents and recorded in the CRF. The dose of study intervention and study 
participant identification will be confirmed at the time of dosing by a member of the study-
site staff other than the person administering the study intervention.
CC
I
C
C
I
C
CI
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6.5
Concomitant Therapy
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed 
during time periods specified by this protocol. The investigator should discuss any questions 
regarding concomitant medication or vaccine with the Sponsor.
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 or other anticoagulants for injection (postdose 
only) are permitted]

Antiplatelet medications (low dose aspirin is permitted)

NSAIDs (e.g., ibuprofen) (acetaminophen used for minor ailments and topical NSAIDs 
is permitted)

Other study interventions
RESTRICTED MEDICATIONS 
Concomitant use of the following medications including FDCs 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 dose of study intervention. This list is not exhaustive but serves 
as a guideline.

Lipid Lowering Agents: Statins, Fibrates, Ezetimibe

Anti-Hypertensive Medications: angiotensin converting enzyme (ACE) inhibitor, an 
angiotensin II receptor antagonist, beta blockers, calcium channel blockers, diuretic

Diabetes Medications: Insulin, GLP-1 Analogs, Glinides, DPP-4 Inhibitors, α-GI

Iron 

Phosphate Binders 

Vitamin D 

Erythropoietin

HIF-PH inhibitors
6.5.1
Rescue Medications and Supportive Care
No rescue or supportive medications are specified for use in this study.
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6.6
Dose Modification (Escalation/Titration/Other)
The dose of the study intervention to any participant may be adjusted downward based on 
newly available safety, PK and/or PD data observed in this study and/or other MK-2060 
studies.
6.6.1
Stopping Rules
The following stopping rules will be used during the conduct of this study.
If any of the below stopping rules are met, the study will be paused, and no further dosing 
will occur until the Sponsor has reviewed the totality of data available. The study can be 
restarted based on joint agreement with the Sponsor and investigator. If needed, a substantial 
amendment may be submitted for approval.
1. An individual participant reports an SAE considered related to the study intervention by 
the investigator.
2. Two (2) or more participants (at the same dose level) report Severe Nonserious AEs 
considered related to the study intervention by the investigator.
3.
If one or more infusion AEs of severe intensity considered related to the study 
intervention by the investigator occurs in 2 or more participants.
4.
An increase aPTT ˃ 4.0-fold versus baseline as confirmed after repeat measurement in 2 
or more participants. aPTT values from the central laboratory for safety will be used for 
this rule and aPTT measured at the Screening Visit should be used as baseline value.
5.
An increase PT ˃ 1.5-fold versus baseline as confirmed after repeat measurement in 2 or 
more participants. PT values from the central laboratory for safety will be used for this 
rule and PT measured at the Screening Visit should be used as baseline value.
Participants who receive intradialytic heparin will likely have an increased 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 aPTT 
will be the first timepoint used to assess aPTT stopping criteria for participants who receive 
intradialytic heparin. Heparin dosed at the time of dialysis should not interfere with aPTT at 
this 12-hour post-dose timepoint (heparin t1/2 is ~1hr). All other aPTT at safety labs 
throughout the course of the study will be drawn pre-dialysis and in the absence of heparin.
These criterion for aPTT (˃ 4.0-fold in 2 or more participants) was based upon that aPTT 
prolongations greater than 3-fold have been observed in severe FXI-deficient populations 
[Asakai, R., et al 1991].  Using the same aPTT assay which was used by the central 
laboratory for PD 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 MK-2060-001, it appears that higher doses of 
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MK-2060 provide similar inhibition as the severe FXI-deficient phenotype, evidenced by 
MK-2060-associated increases in aPTT (local lab) up to 3.9-fold at the highest dose in MK-
2060-001 (120 mg administered subcutaneously).  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 criterion based upon an 
aPTT is >4-fold after repeat measurement in 2 or more participants.
The safety of participants will be assessed on an ongoing basis, and while conditions that 
could warrant stopping dosing are not limited to those noted above, these criteria are meant 
to pre-specify circumstances under which the study may be stopped to review the available 
safety data.  Importantly, if any criterion listed above occurs, further dosing will be stopped 
and review of available safety data by the investigator and Sponsor will be required prior to 
continuing the study, which might include modification of safety monitoring procedures.
6.7
Intervention After the End of the Study
There is no study-specified intervention after the end of the study.
6.8
Clinical Supplies Disclosure
This study is blinded but supplies are provided as open label; therefore, an unblinded 
pharmacist or qualified study-site personnel will be used to blind supplies. Study intervention
identity (name, strength, or potency) is included in the label text; random code/disclosure 
envelopes or lists are not provided.
The emergency unblinding call center will use the intervention randomization 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.
See Section 8.1.10 for a description of the method of unblinding a participant during the 
study, should such action be warranted.
6.9
Standard Policies
Not applicable.
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL
7.1
Discontinuation of Study Intervention
In clinical studies with a single intervention, discontinuation of study intervention can only 
occur before the intervention. Therefore, participants who receive a single-dose intervention 
cannot discontinue study intervention.
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7.2
Participant Withdrawal From the Study
A participant must be withdrawn from the study if the participant or participant’s legally 
acceptable representative withdraws consent from the study.
If a participant withdraws from the study, they will no longer receive study intervention or be 
followed at scheduled protocol visits.
Specific details regarding procedures to be performed at the time of withdrawal from the 
study, as well as specific details regarding withdrawal from FBR, are outlined in Section 
8.1.9. The procedures to be performed should a participant repeatedly fail to return for 
scheduled visits and/or if the study site is unable to contact the participant are outlined in
Section 7.3.
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.
8
STUDY ASSESSMENTS AND PROCEDURES
•
Study procedures and their timing are summarized in the SoA.
•
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.
•
The investigator is responsible for ensuring that procedures are conducted by 
appropriately qualified (by education, training, and experience) staff. Delegation of 
study-site personnel responsibilities will be documented in the Investigator Trial File 
Binder (or equivalent).
•
All study-related medical decisions must be made by an investigator who is a qualified 
physician.
•
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
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•
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of ICF may be used for screening or baseline purposes 
provided the procedures meet the protocol-specified criteria and were performed within 
the time frame defined in the SoA.
•
Additional evaluations/testing may be deemed necessary by the investigator and or the 
Sponsor for reasons related to participant safety. In some cases, such evaluation/testing 
may be potentially sensitive in nature (eg, HIV, hepatitis C), and thus local regulations 
may require that additional informed consent be obtained from the participant. In these 
cases, such evaluations/testing will be performed in accordance with those regulations.
•
The maximum amount of blood collected from each participant over the duration of the 
study will not exceed 340.8 mL (Appendix 8).
•
Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples.
8.1
Administrative and General Procedures
8.1.1
Informed Consent
The investigator or medically qualified designee (consistent with local requirements) must 
obtain documented informed consent from each potential participant (or their legally 
acceptable representative) prior to participating in this clinical study or FBR. If there are 
changes to the participant’s status during the study (eg, health or age of majority 
requirements), the investigator or medically qualified designee must ensure the appropriate 
documented informed consent is in place.
8.1.1.1
General Informed Consent
Informed consent given by the participant or their legally acceptable representative must be 
documented on a consent form. The form must include the study protocol number, study 
protocol title, dated signature, and agreement of the participant (or his/her legally acceptable 
representative) and of the person conducting the consent discussion.
A copy of the signed and dated informed consent form should be given to the participant (or 
their legally acceptable representative) before participation in the study.
The initial ICF, any subsequent revised ICF, and any written information provided to the 
participant must receive the IRB/IEC’s approval/favorable opinion in advance of use. The 
participant or his/her legally acceptable representative should be informed in a timely manner 
if new information becomes available that may be relevant to the participant’s willingness to 
continue participation in the study. The communication of this information will be provided 
and documented via a revised consent form or addendum to the original consent form that 
captures the participant’s or the participant’s legally acceptable representative’s dated 
signature.
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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.
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 and record prior 
medication taken by the participant basically within 2 weeks before Screening 1 (the details 
are defined in the data entry guidelines).
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8.1.5.2
Concomitant Medications
The investigator or qualified designee will record medication, if any, taken by the participant 
during the study.
8.1.6
Assignment of Screening Number
All consented participants will be given a unique screening number that will be used to 
identify the participant for all procedures that occur before randomization. Each participant 
will be assigned only 1 screening number. Screening numbers must not be reused for 
different participants.
Any individual who is screened multiple times will retain the original screening number 
assigned at the initial Screening Visit. Specific details on the screening/rescreening visit 
requirements are in Section 8.11.1. Pre-trial screening logs may be collected for review by 
the Sponsor. If applicable, any information that would make the participant identifiable will 
be removed.
8.1.7
Assignment of Randomization Number
All eligible participants will be randomly allocated and will receive a randomization number. 
The randomization number identifies the participant for all procedures occurring after 
randomization. Once a randomization number is assigned to a participant, it can never be 
reassigned to another participant.
A single participant cannot be assigned more than 1 randomization number.
8.1.8
Study Intervention Administration
Study intervention will be administered by the investigator and/or appropriately qualified 
designee according to the specifications within the pharmacy manual.
8.1.8.1
Timing of Dose Administration
After the Day 1 predose procedures have been completed and it is confirmed that the 
participant meets eligibility, the participant will be assigned a unique randomization number 
by the participant registration center.
The participant will be administered MK-2060 or placebo as an IV infusion. The time of 
initiating IV infusion will be designated as time “0” and the exact time (start and end) of 
administration will be recorded. MK-2060 or placebo will be given 30 minutes after the 
initiation of dialysis and administered via the post-dialyzer line (V side) over approximately 
60 minutes. Infusion time may increase or pause, and restart based upon on tolerability.
Blood samples at Day 1 postdose to Day 2 will be collected in the opposite arm or back of 
the hand from the dialysis vascular access site.
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8.1.9
Discontinuation and Withdrawal
The investigator or study coordinator must notify the Sponsor when a participant has been 
discontinued/withdrawn from the study. If a participant discontinues for any reason at any 
time during the course of the study, the participant may be asked to return to the clinic (or be 
contacted) for a poststudy visit as per the number of days described in Section 8.11.3 to have 
the applicable procedures conducted. However, the investigator may decide to perform the 
poststudy procedures at the time of discontinuation or as soon as possible after 
discontinuation. If the poststudy visit occurs prior to the safety follow-up time frame as 
specified in Section 8.4.1, the investigator should perform a follow-up telephone call at the 
end of the follow-up period (Section 8.4.1) to confirm if any AEs have occurred since the 
poststudy clinic visit. Any AEs that are present at the time of discontinuation/withdrawal 
should be followed in accordance with the safety requirements outlined in Section 8.4.
8.1.9.1
Withdrawal From Future Biomedical Research
Participants may withdraw their consent for FBR. Participants may withdraw consent at any 
time by contacting the study investigator. If medical records for the study are still available, 
the investigator will contact the Sponsor using the designated mailbox 
(clinical.specimen.management@MSD.com). Subsequently, the participant’s consent for 
FBR will be withdrawn. A letter will be sent from the Sponsor to the investigator confirming 
the withdrawal. It is the responsibility of the investigator to inform the participant of 
completion of withdrawal. Any analyses in progress at the time of request for withdrawal or 
already performed before the request being received by the Sponsor will continue to be used 
as part of the overall research study data and results. No new analyses would be generated 
after the request is received.
If the medical records for the study are no longer available (eg, if the investigator is no longer 
required by regulatory authorities to retain the study records) or the specimens have been 
completely anonymized, there will no longer be a link between the participant’s personal 
information and their specimens. In this situation, the request for specimen withdrawal 
cannot be processed.
8.1.10
Participant Blinding/Unblinding
STUDY INTERVENTION IDENTIFICATION INFORMATION IS TO BE UNMASKED 
ONLY IF NECESSARY FOR THE WELFARE OF THE PARTICIPANT. EVERY 
EFFORT SHOULD BE MADE NOT TO UNBLIND.
For emergency situations where the investigator or medically qualified designee (consistent 
with local requirements) needs to identify the intervention used by a participant and/or the 
dosage administered, he/she will contact the emergency unblinding call center by telephone 
and make a request for emergency unblinding. As requested by the investigator or medically 
qualified designee, the emergency unblinding call center will provide the information to 
him/her promptly and report unblinding to the Sponsor. Before 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
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of the AEs observed, the relation to study intervention, the reason thereof, etc, in the medical 
record. If it is not possible to record this assessment in the medical record before the 
unblinding, the unblinding should not be delayed.
If 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.
At the end of the study, random code/disclosure envelopes or lists and unblinding logs are to 
be returned to the Sponsor or designee.
8.1.11
Domiciling
Participants will report to the CRU the day before the scheduled day of administration of the 
study intervention or the scheduled day of administration of the study intervention at the 
discretion of the investigator. Participants will remain in the CRU until the 
-hour, postdose 
procedures (completion of dialysis on Day
 have been performed (Day 
. At the discretion 
of the investigator, participants may be requested to remain in the CRU longer.
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 study, 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 required to avoid scheduling any non-urgent/elective surgical or 
dental procedures, and to avoid strenuous physical activity and contact sport activities 
for the duration of the trial.

Participants will be provided with an identification card, which identify them as 
participants in an anti-coagulant research study and, in the event of an emergency, will 
serve to notify healthcare providers that they might be at risk for provoked bleeding.

If aPTT values are > 3-fold above baseline, or PT values are > 1.5-fold above baseline 
(at any time point), participants will be asked to remain in the clinic for at least
hours, 
and until aPTT and/or PT values are no longer increasing (upon retest), at the discretion 
of the investigator. aPTT and PT values from the central laboratory for safety will be 
used and aPTT and PT measured at the Screening Visit should be used as baseline value.
CC
I
C
CI
CC
I
CCI
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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.
8.2
Efficacy Assessments
There are no efficacy assessments in this study.
8.3
Safety Assessments
Details regarding specific safety procedures/assessments to be performed in this study are 
provided. The total amount of blood to be drawn over the course of the study (from prestudy 
to poststudy visits), including approximate blood volumes drawn by visit and by sample type
per participant, can be found in Appendix 2.
Planned time points for all safety assessments are provided in the SoA.
8.3.1
Physical Examinations
A physical examination will be conducted by an investigator per institutional standard. 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses.
8.3.2
Management of Infusion Reaction During and Post-dose
As outlined in the IB, the risk of infusion reactions to MK-2060 is considered low since the 
molecule contains primarily human sequences. However, infusion reactions may be 
observed. Since the purpose of the study is to characterize the safety profile of MK-2060, no 
prophylactic pre-medications to reduce the risk of infusion reactions will be given prior to 
MK-2060 administration.
In rare instances, systemic infusion reactions are severe and may have a fatal outcome. It is 
likely that most infusion reactions will occur within the first 30 to 60 minutes of 
administration, though they may be observed up to 24 to 30 hours postdose. An anaphylactic 
reaction is a severe type of infusion reaction that is characterized by cutaneous and mucosal 
symptoms, such as generalized hives, pruritis or flushing, swollen lip-tongue-uvula and 
angioedema, accompanied by respiratory compromise (bronchospasm, stridor or hoarseness) 
and/or changes in blood pressure (hypotension). Severe infusion reactions, including 
cytokine release syndrome and hypersensitivity reactions must be promptly treated with 
interruption 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.
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8.3.2.1
Local Infusion Reaction Assessment
A local infusion site examination will be obtained as outlined in Section 1.3 and will include 
an assessment of any pain, tenderness, erythema/redness and induration/swelling.  These 
events will be evaluated based upon the system outlined in the guidance for the industry 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials [Food and Drug Administration. Sep-2007.] in Table 4. A local 
infusion reaction must be assessed and managed promptly per site procedure.
Participants who call the CRU to report an infusion site reaction within 7 days postdose may 
be asked to return to the CRU as soon as possible for an additional local infusion site reaction 
assessment.
Table 4
Local Infusion Reaction Assessment
Local Site 
Reaction
Mild
Moderate
Severe
Potentially Life
Threatening
Pain
Does not 
interfere with 
activity
Repeated use of non-
narcotic pain reliever 
> 24 hr or interferes 
with activity
Any use of narcotic 
pain reliever or 
prevents daily 
activity
Emergency room (ER) 
visit or hospitalization
Tenderness
Mild discomfort 
to touch
Discomfort with 
movement
Significant 
discomfort at rest
ER visit or 
hospitalization
Erythema/
Redness
2.5-5 cm
5.1 – 10 cm
> 10 cm
Necrosis or exfoliative 
dermatitis 
Induration/
Swelling
2.5 – 5 cm and 
does not 
interfere with 
activity
5.1 – 10 cm or 
interferes with activity
> 10 cm or prevents 
daily activity
Necrosis
8.3.2.2
Systemic Infusion Reaction Assessment
Participants will be monitored during the administration of MK-2060/placebo for 48 hours 
postdose at CRU after the initiation of administration.  During this time, signs and symptoms 
of a systemic 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.  Infusion 
reactions must be assessed and managed promptly.
8.3.3
Assessment of Time to Hemostasis
Assessment of time to adequate hemostasis will be conducted at the conclusion of each onsite 
dialysis session. Procedure for assessment of time to hemostasis will be provided in the
Operations Manual. Baseline time to hemostasis will be established by the assessments 
performed during the screening period (mean of two assessments at Screening 1 and 2).
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8.3.4
Height and Weight
Height and weight will be measured and recorded. Hight and body weight will be obtained 
with the participant’s shoes off and jacket or coat removed.
BMI
BMI equals a person’s weight in kilograms divided by height in meters squared 
(BMI=kg/m2). BMI will be rounded to the nearest whole number according to the standard 
convention of 0.1 to 0.4 round down and 0.5 to 0.9 round up.
Dry weight (body weight after HD or HDF) should be used for BMI calculations.
8.3.5
Resting Vital Signs
Blood Pressure and Pulse Rate
BP and PR measurements will be assessed with a completely automated device. Manual 
techniques will be used only if an automated device is not available. The correct size of the 
BP cuff and the correct positioning on the participant is essential to increase the accuracy of 
BP measurements.
Participants should be resting in a semi-recumbent or supine position for at least 10 minutes 
prior to having BP and PR measurements obtained. The same position must be used for all 
measurements for each individual participant.
The predose (baseline) BP and PR will be triplicate measurements, obtained at least 1 to 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). Screening and postdose BP and PR measurements 
will be single measurements.
Respiratory Rate and Body Temperature
RR and body temperature will be single measurement per timepoint at all timepoints. The 
same method must be used for all measurements for each individual participant.
8.3.6
Electrocardiograms
Twelve (12)-lead ECG will be obtained and reviewed by an investigator or medically 
qualified designee as outlined in the SoA. The HR will be calculated and PR, QRS, QT, and 
QTc intervals will be measured, and then these will be recorded. The correction formula to 
be used for QTc is Fridericia.
Special care must be taken for proper lead placement by qualified personnel. Skin should be 
clean and dry before lead placement. Participants may need to be shaved to ensure proper 
lead placement. Participants assigned female sex at birth may need to remove interfering 
garments.
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If repeat ECGs are required, the clinical site will decide whether to leave the electrodes in 
place or mark the position of the electrodes for subsequent ECGs. To mark the position of the 
electrodes, 12-lead electrode sites will be marked on the skin of each participant with an 
ECG skin-marker pen to ensure reproducible electrode placement.
Participants should be resting in the semi-recumbent or supine position for at least 
10 minutes before each ECG measurement. The same position must be used for all 
measurements for each individual participant.
Predose (baseline) ECGs will be obtained in triplicate at least 1 to 2 minutes apart within 3 
hours before dosing. The median of these measurements will be used as the baseline to 
calculate change from baseline for safety evaluations (and for rechecks, if needed). Screening 
and all postdose ECG measurements will be a single measurement.
8.3.7
Clinical Safety Laboratory Assessments
Refer to Appendix 2 for the list of clinical laboratory tests to be performed and to the SoA for 
the timing and frequency.
•
The investigator or medically qualified designee (consistent with local requirements) 
must review the laboratory report, document this review, and record any clinically 
relevant changes occurring during the study in the AE section of the CRF. The laboratory 
reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless 
judged by the investigator to be more severe than expected for the participant’s condition.
•
All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA.
•
If laboratory values from nonprotocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in study participant management or are 
considered clinically significant by the investigator (eg, SAE or AE or dose 
modification), then the results must be recorded in the appropriate CRF (eg, SLAB).
•
For any laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 150 days after the dose of study intervention, every 
attempt should be made to perform repeat assessments until the values return to normal or 
baseline or if a new baseline is established as determined by the investigator.
8.3.8
Photograph of Rash
Photographs of the rash are highly recommended to be taken immediately, along with any 
additional information that may assist the investigator to evaluate the skin reaction, skin 
eruption or rash occurrence in determining etiology and drug relationship.
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8.4
Adverse Events, Serious Adverse Events, and Other Reportable Safety Events
The definitions of an AE or SAE, as well as the method of recording, evaluating, and 
assessing causality of AE and SAE and the procedures for completing and transmitting AE, 
SAE, and other reportable safety event reports can be found in Appendix 3.
Adverse events, SAEs, and other reportable safety events will be reported by the participant 
(or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized 
representative).
The investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE as well as other reportable safety events. 
Investigators need to document if an SAE was associated with a medication error, misuse, or 
abuse. Investigators remain responsible for following up AEs, SAEs, and other reportable 
safety events for outcome according to Section 8.4.3.
The investigator, who is a qualified physician, will assess events that meet the definition of 
an AE or SAE as well as other reportable safety events with respect to seriousness, 
intensity/toxicity and causality.
8.4.1
Time Period and Frequency for Collecting AE, SAE, and Other Reportable 
Safety Event Information
AEs, SAEs, and other reportable safety events that occur after the participant provides 
documented informed consent, but before intervention randomization, must be reported by 
the investigator under any of the following circumstances:
•
if the participant is receiving placebo run-in or other run-in treatment,
•
if the event causes the participant to be excluded from the study,
•
if it is the result of a protocol-specified intervention, including, but not limited to washout 
or discontinuation of usual therapy, diet, placebo, or a procedure.
From the time of intervention randomization through 164 days after cessation of intervention, 
all AEs, SAEs and other reportable safety events must be reported by the investigator.
Additionally, any SAE brought to the attention of an investigator any time outside the period 
specified in the previous paragraph also must be reported immediately to the Sponsor if the 
event is considered related to study intervention.
Investigators are not obligated to actively seek AEs or SAEs or other reportable safety events 
in former study participants. However, if the investigator learns of any SAE, including a 
death, at any time after a participant has been discharged from the study, and the investigator 
considers the event to be reasonably related to the study intervention or study participation, 
the investigator must promptly notify the Sponsor.
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All initial and follow-up AEs, SAEs, and other reportable safety events will be recorded and 
reported to the Sponsor or designee within the time frames as indicated in Table 5.
Exception: A positive pregnancy test at the time of initial screening is not a reportable event 
unless the participant has received study intervention.
Table 5
Reporting Time Periods and Time Frames for Adverse Events and Other 
Reportable Safety Events
Type of 
Event
Reporting Time Period:
Consent to 
Randomization/ 
Allocation
Reporting Time 
Period:
Randomization/ 
Allocation through 
Protocol-specified 
Follow-up Period
Reporting Time 
Period:
After the 
Protocol-specified 
Follow-up Period
Time Frame to 
Report Event and 
Follow-up 
Information to 
Sponsor:
NSAE
Report if:
- due to protocol-
specified intervention
- causes exclusion
- participant is receiving 
placebo run-in or other 
run-in treatment
Report all
Not required
Per data entry 
guidelines
SAE
Report if:
- due to protocol-
specified intervention
- causes exclusion
- participant is receiving 
placebo run-in or other 
run-in treatment
Report all
Report if:
- drug/vaccine 
related.
(Follow ongoing to 
outcome)
Within 24 hours of 
learning of event
Pregnancy/
Lactation 
Exposure
Report if:
- participant has been 
exposed to any protocol-
specified intervention 
(eg, procedure, washout 
or run-in treatment 
including placebo run-in)
Exception: A positive 
pregnancy test at the time 
of initial screening is not 
a reportable event.
Report all
Previously reported 
– Follow to 
completion/
termination; report 
outcome
Within 24 hours of 
learning of event
ECI (require 
regulatory 
reporting)
Report if:
- due to intervention
- causes exclusion
Report
- potential DILI
- require regulatory 
reporting
Not required
Within 24 hours of 
learning of event
ECI (do not 
require 
regulatory 
reporting)
Report if:
- due to intervention
- causes exclusion
Report
- non-DILI ECIs 
and those not 
requiring regulatory 
reporting
Not required
Within 5 calendar 
days of learning of 
event
Cancer
Report if:
- due to intervention
- causes exclusion
Report all
Not required
Within 5 calendar 
days of learning of 
event
(unless serious)
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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:
Overdose
Report if:
- receiving placebo run-in 
or other run-in 
medication 
Report all
Not required
Within 24 hours of 
learning of event
DILI=drug-induced liver injury; ECI=event of clinical interest; NSAE=nonserious adverse event; SAE=serious adverse 
event.
8.4.2
Method of Detecting AEs, SAEs, and Other Reportable Safety Events
Care will be taken not to introduce bias when detecting AEs and/or SAEs and other 
reportable safety events. Open-ended and nonleading verbal questioning of the participant is 
the preferred method to inquire about AE occurrence.
8.4.3
Follow-up of AE, SAE, and Other Reportable Safety Event Information
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs, SAEs, and other reportable safety events,
including pregnancy and exposure during breastfeeding, ECIs, cancer, and overdose will be 
followed until resolution, stabilization, until the event is otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.3). In addition, the investigator will 
make every attempt to follow all nonserious AEs that occur in randomized participants for 
outcome. Further information on follow-up procedures is given in Appendix 3.
8.4.4
Regulatory Reporting Requirements for SAE
Prompt notification (within 24 hours) by the investigator to the Sponsor of SAE is essential 
so that legal obligations and ethical responsibilities towards the safety of participants and the 
safety of a study intervention under clinical investigation are met.
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements and global laws and 
regulations relating to safety reporting to regulatory authorities, IRB/IECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and Sponsor policy and forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAE) from the Sponsor will file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements.
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8.4.5
Pregnancy and Exposure During Breastfeeding
Information in this section is not applicable since participants are participants capable of 
producing ejaculate whose partner’s pregnancy/lactation information is not required.
8.4.6
Disease-related Events and/or Disease-related Outcomes Not Qualifying as 
AEs or SAEs
Not applicable.
8.4.7
Events of Clinical Interest
Selected serious and nonserious AEs are also known as ECIs and must be reported to the 
Sponsor.
Events of clinical interest for this study include:
1. An overdose of Sponsor's product, as defined in Section 8.5.
2. Potential DILI events defined as an elevated AST or ALT laboratory value that is greater 
than or equal to 3X the ULN and an elevated total bilirubin laboratory value that is 
greater than or equal to 2X the ULN and, at the same time, an alkaline phosphatase 
laboratory value that is less than 2X the ULN, as determined by way of protocol-
specified laboratory testing or unscheduled laboratory testing.*
*Note: These criteria are based on available regulatory guidance documents. The purpose 
of the criteria is to specify a threshold of abnormal hepatic tests that may require an 
additional evaluation for an underlying etiology. The study-site guidance for assessment 
and follow up of these criteria can be found in the Investigator Study File Binder (or 
equivalent).
It may also be appropriate to conduct additional evaluation for an underlying etiology in the 
setting of abnormalities of liver blood tests including AST, ALT, bilirubin, and alkaline 
phosphatase that do not meet the criteria noted above. In these cases, the decision to proceed 
with additional evaluation will be made through consultation between the study investigators 
and the Sponsor Clinical Director. However, abnormalities of liver blood tests that do not 
meet the criteria noted above are not ECIs for this study.
8.5
Treatment of Overdose
For purposes of this study, an overdose will be defined as any dose of any drug administered 
as part of the study exceeding the dose prescribed by the protocol. It is up to the investigator 
or the reporting physician to decide whether a dose is to be considered an overdose, in 
consultation with the Sponsor.
Sponsor does not recommend specific treatment for an overdose. Decisions regarding dose 
interruptions or modifications will be made by the investigator in consultation with the 
Sponsor Clinical Director based on the clinical evaluation of the participant.
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8.6
Pharmacokinetics
The decision as to which plasma samples collected will be measured for evaluation of PK or 
PK-Pharmacodynamics will be collaboratively determined by the Sponsor. If indicated, these 
samples may also be measured and/or pooled for assay in an exploratory manner for 
metabolites and/or additional pharmacodynamic markers. Blood samples collected may be 
stored and further analysis may be performed, if required.
8.6.1
Blood Collection for Plasma MK-2060 and ADA
Sample collection, storage, and shipment instructions for plasma samples will be provided in 
the Study Operations Manual.
8.7
Pharmacodynamics
Sample collection, storage, and shipment instructions for PD samples (aPTT/PT/FXI activity) 
will be provided in the Study Operations Manual. They will be performed at a central vendor 
for PD. The PD data for statistical analysis and potential modeling work will be based on the 
information from the central vendor for PD. Blood samples collected may be stored and 
further analysis may be performed, if required.
aPTT and PT at screening, predose, and postdose specified in the SoA will be performed by 
the central laboratory for safety to monitor safety as defined in Section 8.3.7.
8.8
Biomarkers
Collection of samples for other biomarker research is also part of this study. The following 
samples for biomarker research will be collected from all participants as specified in the 
SoA:
•
Blood for Genetic Analysis
8.8.1
Planned Genetic Analysis Sample Collection
The planned genetic analysis sample should be drawn for planned analysis of the association 
between genetic variants in DNA and drug response. This sample will not be collected at the 
site if there is either a local law or regulation prohibiting collection, or if the IRB/IEC does 
not approve the collection of the sample for these purposes. If the sample is collected, 
leftover extracted DNA will be stored for 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.
The planned genetic analysis sample should be obtained predose on Day 1 but may be 
collected at the next scheduled blood draw, if needed. Sample collection, storage, and 
shipment instructions for planned genetic analysis samples will be in the 
Operations/Laboratory Manual.
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8.9
Future Biomedical Research Sample Collection
If the participant provides documented informed consent for FBR, the following specimens 
will be obtained as part of FBR:
•
Leftover DNA for future research
8.10
Medical Resource Utilization and Health Economics
Medical Resource Utilization and Health Economics are not evaluated in this study.
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
Before intervention randomization, potential participants will be evaluated to determine that 
they fulfill the entry requirements as set forth in Section 5.
Screening 1 should occur within 28 days prior to intervention randomization. Screening 2 
should occur within 5 to 8 days prior to intervention randomization. Screening 2 should 
occur after review of all data from Screening 1. Dialysis should be done at Screenings 1 and
2.
Participants may be rescreened after consultation with the Sponsor. Rescreening should 
include all screening procedures (except for blood collection for FSH if a postmenopausal 
state was confirmed by FSH test) listed in the SoA, including consent review. Rescreen 
procedures cannot be conducted the day prior to intervention randomization.
8.11.2
Treatment Period
Refer to the SoA (Section 1.3), and Administrative and General Procedures (Section 8.1).
8.11.3
Poststudy
Participants will be required to return to clinic 150 (±7) days after the dose of study 
intervention for the poststudy visit.
8.11.4
Phone Call Follow-up
A phone call follow-up or on-site follow-up (dialysis day) will be performed 164 (±7) days 
after the dose of study intervention.  The follow-up will facilitate the collection of relevant 
safety information.  The participants will be interviewed to obtained information relating to 
AEs and SAEs since the poststudy clinic visit.  All safety information described by the 
participants must be documented in the source documents and be reviewed by the 
investigator.
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If the follow-up occurs less than 164 days after the dose of study intervention, a subsequent 
follow-up should be made at 164 (+7) days post the dose of study intervention to determine if 
any AEs have occurred since 1st follow-up. 
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.  
8.11.5
Critical Procedures Based on Study Objectives: Timing of Procedure
For this study, the blood sample for MK-2060 is the critical procedure.
At any postdose time point, the blood sample for MK-2060 needs to be collected as close to 
the exact time point as possible. All other procedures should be completed as close to the 
prescribed/scheduled time as possible. Study procedures can be performed before or after the 
prescribed/scheduled time.
The order of priority can be changed during the study with joint agreement of the investigator 
and the Sponsor Clinical Director.
Any nonscheduled procedures required for urgent evaluation of safety concerns take 
precedence over all routine scheduled procedures.
The following variance in procedure collection times will be permitted.
•
Blood collection for PK, PD, ADA, laboratory safety tests, including aPTT/PT, and 
genetic analysis as outlined in Table 6.
Table 6
Blood Collection Windows
Collection Time
Collection Window
Predose
Within 3 hrs prior to the initiation of dialysis
1 hr
Immediately prior to the end of IV infusion (i.e. no more than 5 min before
anticipated time of the end of IV infusion)
12 hrs
±15 min
24 hrs
±1 hr
48 hrs
± 1 hr and prior to the initiation of dialysis
52 hrs
Post dialysis
96 hrs
± 2 hrs and prior to the initiation of dialysis. If this prescribed time is not 
dialysis day, +1 day and prior to the initiation of dialysis.
168 hrs
± 2 hrs and prior to the initiation of dialysis. Blood samples for PK and PD 
will be also collected at post dialysis.
Day 12
±1 day and within 12 hrs prior to the initiation of dialysis
Days 15 and 22
±2 days and within 12 hrs prior to the initiation of dialysis
Day 29
±3 days and within 12 hrs prior to the initiation of dialysis. Blood samples for 
PK and PD will be also collected at post dialysis.
Days 60 and 90
±5 days and within 12 hrs prior to the initiation of dialysis
Day 120
±7 days and within 12 hrs prior to the initiation of dialysis.  Blood samples for 
PK and PD will be also collected at post dialysis.
Day 150
±7 days and within 12 hrs prior to the initiation of dialysis
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•
Safety evaluations for PE, systemic infusion reaction assessment, VS and 12-lead ECG as 
outlined in Table 7.
Table 7
Safety Evaluations Windows
Evaluation Time
Evaluation Window
Predose
Within 3 hrs prior to the initiation of dialysis
15 and 30 min
1 and 2 hrs
±15 min
3.5 hrs
±15 min
8 hrs
±15 min
12 hrs
±30 min
24 hrs
±1 hr
48 hrs
± 2 hrs and prior to the initiation of dialysis
96 hrs
± 2 hrs and prior to the initiation of dialysis. If this prescribed time
is not dialysis day,  +1 day and prior to the initiation of dialysis.
168 hrs
± 2 hrs and prior to the initiation of dialysis
Day 12
±1 day and within 12 hrs prior to the initiation of dialysis
Days 15 and 22
±2 days and within 12 hrs prior to the initiation of dialysis
Day 29
±3 days and within 12 hrs prior to the initiation of dialysis
Days 60 and 90
±5 days and within 12 hrs prior to the initiation of dialysis
Days 120 and 150
±7 days and within 12 hrs prior to the initiation of dialysis
•
Assessment of time to adequate hemostasis: After dialysis catheters are removed from the 
dialysis access site.
•
Hemoccult Test: within 2 days of specified timepoint.
8.11.6
Study Design/Dosing/Procedures Modifications Permitted Within Protocol 
Parameters
This is a Phase 1 assessment of MK-2060 in humans, and the PK, pharmacodynamic, and 
safety profiles of the compound are still being elucidated. This protocol is written with some 
flexibility to accommodate the inherent dynamic nature of Phase 1 clinical studies. 
Modifications to the dose, dosing regimen, and/or clinical or laboratory procedures currently 
outlined may be required to achieve the scientific goals of the study 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.
•
Addition of PK pause
•
Instructions to take study intervention with or without food or drink may be modified 
based on newly available data
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•
Modification of the PK/pharmacodynamic sample processing and shipping details based 
on newly available data
The PK/pharmacodynamic sampling scheme currently outlined in the protocol may be 
modified during the study based on newly available PK or pharmacodynamic data (eg, to 
obtain data closer to the time of peak plasma concentrations). If indicated, these collected 
samples may also be assayed in an exploratory manner for metabolites and/or additional 
pharmacodynamic markers.
Up to additional 50 mL of blood may be drawn for safety, PK, and/or pharmacodynamic 
analyses. The total blood volume withdrawn from any single participant will not exceed the 
maximum allowable volume during his/her participation in the entire study (Appendix 8).
The timing of procedures for assessment of safety procedures (eg, vital signs, ECG, safety 
laboratory tests, etc) may be modified during the study based on newly available data. 
Additional laboratory safety tests may be added to blood samples previously drawn to obtain 
additional safety information. These changes will not increase the number of study 
procedures for a given participant during his/her participation in the entire study.
It is understood that the current study may use some or none of the alterations described 
above. Any alteration made to this protocol to meet the study objectives must be detailed by 
the Sponsor in a letter to the Study File and forwarded to the investigator for retention. The 
letter may be forwarded to the IRB/IEC at the discretion of the investigator.
9
STATISTICAL ANALYSIS PLAN
9.1
Statistical Analysis Plan Summary
This section contains a summary of the statistical analyses for this trial. Full detail can be 
found in the subsequent sections. 
Safety
AEs will be tabulated by treatment group. Summary statistics and plots will be generated for 
raw laboratory safety tests, ECGs, and vital sign 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
Individual values will be listed for each PK parameter and appropriate non-model based 
descriptive statistics will be provided: N (number of participants 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
Individual aPTT fold-change from baseline values will be natural log-transformed and 
evaluated with a linear mixed effect model containing fixed effects for treatment, 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 difference (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 time and 
the GMR (MK-2060 fold-change from baseline/placebo fold-change from baseline) by dose 
and time.
The proportion of participants with a fold-increase in aPTT 168 hours after a single dose of at 
least 1.5 will be tabulated.
Sample Size and Power Calculations
The total participants of approximately 16 (MK-2060=approximately 
 
placebo=approximately
is considered to be adequate to address the primary objective 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 Clinical Biostatistics Department in collaboration with the Quantitative 
Pharmacology and Pharmacometrics Department and Translational Pharmacology 
Department of the Sponsor.
If, after the study has begun, changes are made to the statistical analysis plan stated below, 
then these deviations to the plan will be listed, along with an explanation as to why they 
occurred, in the Clinical Study Report.
9.3
Hypotheses/Estimation
Objectives of the study are stated in the Section 3.
9.4
Analysis Endpoints
Primary Endpoints
1.
AEs
Secondary Endpoints
1.
Pharmacokinetics: Plasma AUC0-inf, AUC0-last, AUC0-168, Cmax, C168, Tmax, Tlast, 
t1/2, CL and Vz
2.
Pharmacodynamics: aPTT (fold change from baseline)
CCI
CC
I
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Exploratory Endpoints
1.
Factor XI activity (fold change from baseline)
2.
Prothrombin time (fold change from baseline)
3.
Time to hemostasis
4.
ADA
For change from baseline, the baseline is defined as the panel-specific pre-dose value.
9.5
Analysis Populations
The following populations are defined for the analysis and reporting of data. All participants 
will be reported, and their data analyzed, according to the treatment(s) they actually received. 
All Participants as Treated (APaT): The All Participants as Treated Population consists of all 
participants who received at least one dose of treatment. This population will be used for 
assessments of safety.
Per-Protocol (PP): The Per-Protocol Population consists of the set of data generated by the 
subset of participants 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 major protocol deviations. Major protocol deviations will be 
identified to the extent possible prior to unblinding by individuals responsible for data 
collection, and its analysis and interpretation. Any participants 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 participants 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
AEs will be tabulated by treatment. Summary statistics and plots will be generated for raw 
laboratory safety tests, ECGs, and vital sign 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
Values will be listed for each PK parameter and appropriate non-model based descriptive 
statistics will be provided: N (number of participants with non-missing data), arithmetic 
mean, standard deviation, arithmetic percent CV (calculated as 100 x standard 
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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).
Pharmacodynamics
Individual aPTT fold-change from baseline values will be natural log-transformed and 
evaluated with a linear mixed effect model containing fixed effects for treatment, 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 difference (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 time and 
the GMR (MK-2060 fold-change from baseline/placebo fold-change from baseline) by dose 
and time.
The proportion of participants with a fold-increase in aPTT 168 hours after a single dose of at 
least 
will be tabulated.
Summary statistics will be provided for PD endpoints by time.
The relationship between plasma concentrations and aPTT, FXI activity, and PT may be 
explored graphically.
ADA
The number of participants with positive / negative antibody drug response to antibodies to 
MK-2060 will be summarized. Frequency counts for the maximum antibody titer for 
participants classified as positive will also be reported.
9.7
Interim Analyses
No formal interim analysis is planned.
9.8
Multiplicity
Since there are no pre-specified hypotheses, no adjustments for multiplicity are needed.
9.9
Sample Size and Power Calculations
The total participants of approximately 16 (MK-2060=approximately 
, 
placebo=approximately 
is considered to be adequate to address the primary objective of 
the study. 
CC
I
C
CI
CCI
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10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS
10.1
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1
Code of Conduct for Clinical Trials
Merck Sharp & Dohme LLC, Rahway, NJ, USA (MSD)
Code of Conduct for Interventional Clinical Trials
I.
Introduction
A.
Purpose
Merck Sharp & Dohme LLC, Rahway, NJ, USA (MSD), through its subsidiaries, conducts clinical trials 
worldwide to evaluate the safety and effectiveness of our products. As such, we are committed to designing, 
planning, conducting, analyzing, and reporting these trials in compliance with the highest ethical and scientific 
standards. Protection of participants in clinical trials is the overriding concern in the design and conduct of clinical 
trials. In all cases, MSD clinical trials will be conducted in compliance with MSD’s global standards, local and/or 
national regulations (including all applicable data protection laws and regulations), and International Council for 
Harmonisation Good Clinical Practice (ICH-GCP) E6 and ICH General Considerations for Clinical Studies E8, 
and in accordance with the ethical principles that have their origin in the Declaration of Helsinki. 
B.
Scope
Highest ethical and scientific standards shall be endorsed for all clinical interventional investigations sponsored by 
MSD irrespective of the party (parties) employed for their execution (e.g., contract research organizations, 
collaborative research efforts). This Code is not intended to apply to trials that are observational in nature, or 
which are retrospective. Further, this Code does not apply to investigator-initiated trials, which are not under the 
full control of MSD.
II.
Scientific Issues
A.
Trial Conduct
1.
Trial Design
Except for pilot or estimation trials, clinical trial protocols will be hypothesis-driven to assess safety, efficacy 
and/or pharmacokinetic or pharmacodynamic indices of MSD or comparator products. Alternatively, MSD 
may conduct outcomes research trials, trials to assess or validate various endpoint measures, or trials to 
determine patient preferences, etc. 
The design (i.e., participant population, duration, statistical power) must be adequate to address the specific 
purpose of the trial and shall respect the data protection rights of all participants, trial site staff and, where 
applicable, third parties. Input may be considered from a broad range of stakeholders, including patient 
advocacy groups/patients representing the trial population, caregivers, and healthcare providers to ensure 
operational feasibility. Trial design also includes proactive identification of critical to quality factors utilizing 
a risk-based approach.  Plans are then developed to assess and mitigate risks to those factors as appropriate 
during the trial.  All trial protocols are and will be assessed for the need and capability to enroll 
underrepresented groups. Participants must meet protocol entry criteria to be enrolled in the trial.
2.
Site Selection
MSD’s clinical trials are conducted globally in many different countries and in diverse populations, including 
people of varying age, race, ethnicity, gender, and accounting for other potential disease related factors. MSD 
selects investigative sites based on medical expertise, access to appropriate participants, adequacy of facilities 
and staff, previous performance in clinical trials, as well as budgetary considerations. Prior to trial initiation, 
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sites are evaluated by MSD personnel (or individuals acting on behalf of MSD) to assess the ability to 
successfully conduct the trial.  Individuals involved in trial conduct receive  training commensurate with their 
role prior to their becoming involved in the trial.
Where appropriate, and in accordance with regulatory authority guidance, MSD will make concerted efforts 
to raise awareness of clinical trial opportunities in various communities. MSD will seek to engage 
underrepresented groups and those disproportionately impacted by the disease under study. MSD will 
support clinical trial investigators to enroll underrepresented groups and expand access to those who will 
ultimately use the products under investigation.
3.
Site Monitoring/Scientific Integrity
Investigative trial sites are monitored to assess compliance with the trial protocol and Good Clinical Practice 
(GCP). MSD reviews clinical data for accuracy, completeness, and consistency. Data are verified versus 
source documentation according to standard operating procedures. Per MSD policies and procedures, if 
potential fraud, scientific/research misconduct, privacy incidents/breaches or Clinical Trial-related 
Significant Quality Issues are reported, such matters are investigated. When necessary, appropriate corrective 
and/or preventative actions are defined and regulatory authorities and/or ethics review committees are 
notified. 
B.
Publication and Authorship
Regardless of trial outcome, MSD commits to publish the primary and secondary results of its registered trials of 
marketed products in which treatment is assigned, according to the pre-specified plans for data analysis. To the 
extent scientifically appropriate, MSD seeks to publish the results of other analyses it conducts that are important 
to patients, physicians, and payers. Some early phase or pilot trials are intended to be hypothesis-generating rather 
than hypothesis testing; in such cases, publication of results may not be appropriate since the trial may be 
underpowered and the analyses complicated by statistical issues such as multiplicity.
MSD’s policy on authorship is consistent with the recommendations published by the International Committee of 
Medical Journal Editors (ICMJE). In summary, authorship should reflect significant contribution to the design and 
conduct of the trial, performance or interpretation of the analysis, and/or writing of the manuscript. All named 
authors must be able to defend the trial results and conclusions. MSD funding of a trial will be acknowledged in 
publications. 
III. Participant Protection
A.
Regulatory Authority and Ethics Committee Review (Institutional Review Board [IRB]/Independent Ethics 
Committee [IEC])
All protocols and protocol amendments will be submitted by MSD for regulatory authority 
acceptance/authorization prior to implementation of the trial or amendment, in compliance with local and/or 
national regulations.
The protocol, protocol amendment(s), informed consent form, investigator’s brochure, and other relevant trial 
documents must be reviewed and approved by an IRB/IEC before being implemented at each site, in compliance 
with local and/or national regulations and ICH Guidelines. Changes to the protocol that are required urgently to 
eliminate an immediate hazard and to protect participant safety may be enacted in anticipation of ethics committee 
approval. MSD will inform regulatory authorities of such new measures to protect participant safety, in 
compliance with local and/or national regulations. 
B.
Safety
The guiding principle in decision-making in clinical trials is that participant welfare is of primary importance. 
Potential participants will be informed of the risks and benefits of, as well as alternatives to, trial participation. At 
a minimum, trial designs will take into account the local standard of care. 
All participation in MSD clinical trials is voluntary. Participants enter the trial only after informed consent is 
obtained. Trial designs include procedures and systems for the identification, monitoring and reporting of safety 
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concerns.  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.
During trial planning, the need for an independent Data Monitoring Committee (DMC) is assessed.  DMC review 
of data accumulated during the conduct of the trial is integral to the well-being of trial participants.
C.
Confidentiality
MSD is committed to safeguarding participant confidentiality, to the greatest extent possible, as well as all 
applicable data protection rights. Unless required by law, only the investigator, Sponsor (or individuals acting on 
behalf of MSD), ethics committee, and/or regulatory authorities will have access to confidential medical records 
that might identify the participant by name. 
D.
Genomic Research
Genomic research will only be conducted in accordance with a protocol and informed consent authorized by an 
ethics committee.
E.
Trial Results
At the time of providing informed consent and in accordance with local laws and regulations, participants should 
be informed about the plans for availability of trial results.
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 medical record review and medical evaluation to identify potentially eligible participants.
B.
Clinical Research Funding
Informed consent forms will disclose that the trial is sponsored by MSD, and that the investigator or sponsoring 
institution is being paid or provided a grant for performing the trial. However, the local ethics committee may 
wish to alter the wording of the disclosure statement to be consistent with financial practices at that institution. As 
noted above, all publications resulting from MSD trials will indicate MSD as a source of funding.
C.
Funding for Travel and Other Requests
Funding of travel by investigators and support staff (e.g., to scientific meetings, investigator meetings, etc.) will be 
consistent with local guidelines and practices. 
V.
Investigator Commitment
Investigators will be expected to review MSD’s Code of Conduct as an appendix to the trial protocol, and in signing the 
protocol, agree to support these ethical and scientific standards.
10.1.2
Financial Disclosure
Financial disclosure requirements are outlined in the US Food and Drug Administration 
Regulations, Financial Disclosure by Clinical Investigators (21 CFR Part 54). It is the 
Sponsor’s responsibility to determine, based on these regulations, whether a request for 
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financial disclosure information is required. It is the investigator’s/subinvestigator’s 
responsibility to comply with any such request.
The investigator/subinvestigator(s) agree, if requested by the Sponsor in accordance with 21 
CFR Part 54, to provide his/her financial interests in and/or arrangements with the Sponsor to 
allow for the submission of complete and accurate certification and disclosure statements. 
The investigator/subinvestigator(s) further agree to provide this information on a 
Certification/Disclosure Form, frequently known as a financial disclosure form, provided by 
the Sponsor. The investigator/subinvestigator(s) also consent to the transmission of this 
information to the Sponsor in the United States for these purposes. This may involve the 
transmission of information to countries that do not have laws protecting personal data.
10.1.3
Data Protection
The Sponsor will conduct this study in compliance with all applicable data protection 
regulations.
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names 
or any information that would make the participant identifiable will not be transferred.
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
10.1.3.1
Confidentiality of Data
By signing this protocol, the investigator affirms to the Sponsor that information furnished to 
the investigator by the Sponsor will be maintained in confidence, and such information will 
be divulged to the IRB, IEC, or similar or expert committee; affiliated institution and 
employees, only under an appropriate understanding of confidentiality with such board or 
committee, affiliated institution and employees. Data generated by this study will be 
considered confidential by the investigator, except to the extent that it is included in a 
publication as provided in the Publications section of this protocol.
10.1.3.2
Confidentiality of Participant Records
By signing this protocol, the investigator agrees that the Sponsor (or Sponsor representative), 
IRB/IEC, or regulatory authority representatives may consult and/or copy study documents to 
verify worksheet/CRF data. By signing the consent form, the participant agrees to this 
process. If study documents will be photocopied during the process of verifying 
worksheet/CRF information, the participant will be identified by unique code only; full 
names/initials will be masked before transmission to the Sponsor.
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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
Publication Policy
The results of this study may be published or presented at scientific meetings. The Sponsor 
will comply with the requirements for publication of study results. In accordance with 
standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement.
If publication activity is not directed by the Sponsor, the investigator agrees to submit all 
manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect 
proprietary information and to provide comments.
Authorship will be determined by mutual agreement and in line with ICMJE authorship 
requirements.
10.1.5
Compliance with Study Registration and Results Posting Requirements
Under the terms of the FDAAA of 2007 and the EMA clinical trial Directive 2001/20/EC, the 
Sponsor of the study is solely responsible for determining whether the study and its results 
are subject to the requirements for submission to http://www.clinicaltrials.gov, 
www.clinicaltrialsregister.eu or other local registries. MSD, as Sponsor of this study, will 
review this protocol and submit the information necessary to fulfill these requirements. MSD 
entries are not limited to FDAAA or the EMA clinical trials directive mandated trials. 
Information posted will allow participants to identify potentially appropriate studies for their 
disease conditions and pursue participation by calling a central contact number for further 
information on appropriate study locations and study-site contact information.
By signing this protocol, the investigator acknowledges that the statutory obligations under 
FDAAA, the EMA clinical trials directive, or other locally mandated registries are that of the 
Sponsor and agrees not to submit any information about this study or its results to those 
registries.
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10.1.6
Compliance with Law, Audit, and Debarment
By signing this protocol, the investigator agrees to conduct the study in an efficient and 
diligent manner and in conformance with this protocol; generally accepted standards of GCP
(eg, ICH GCP: Consolidated Guideline and other generally accepted standards of GCP); and 
all applicable federal, state and local laws, rules and regulations relating to the conduct of the 
clinical study.
The Code of Conduct, a collection of goals and considerations that govern the ethical and 
scientific conduct of clinical investigations sponsored by MSD, is provided in this appendix 
under the Code of Conduct for Clinical Trials.
The investigator agrees not to seek reimbursement from participants, their insurance 
providers, or from government programs for procedures included as part of the study 
reimbursed to the investigator by the Sponsor.
The investigator will promptly inform the Sponsor of any regulatory authority inspection 
conducted for this study.
The investigator agrees to provide the Sponsor with relevant information from inspection 
observations/findings to allow the Sponsor to assist in responding to any citations resulting 
from regulatory authority inspection and will provide the Sponsor with a copy of the 
proposed response for consultation before submission to the regulatory authority. 
Persons debarred from conducting or working on clinical studies by any court or regulatory 
authority will not be allowed to conduct or work on this Sponsor’s studies. The investigator 
will immediately disclose in writing to the Sponsor if any person who is involved in 
conducting the study is debarred or if any proceeding for debarment is pending or, to the best 
of the investigator’s knowledge, threatened. 
For investigators located in countries with serious breach reporting requirements, investigator 
will promptly report to the Sponsor any serious breach or suspected serious breach that 
occurs in compliance with those requirements.  Unless more specifically defined in the 
applicable requirements, a serious breach is any breach of the applicable clinical trial 
regulation or of the clinical trial protocol which is likely to affect to a significant degree: (i) 
the safety or rights of a trial participant, or (ii) the reliability and robustness of the data 
generated in the clinical trial.
10.1.7
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.
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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.
10.1.8
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.
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10.1.9
Study and Site Closure
The Sponsor or its designee may stop the study or study-site participation in the study for 
medical, safety, regulatory, administrative, or other reasons consistent with applicable laws, 
regulations, and GCP.
In the event the Sponsor prematurely terminates a particular study site, the Sponsor or 
designee will promptly notify that study site’s IRB/IEC as specified by applicable regulatory 
requirement(s).
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10.2
Appendix 2: Clinical Laboratory Tests
•
The tests detailed in Table 8 will be performed by the central laboratory for safety tests.
•
Local laboratory results are only required in the event that the central laboratory for 
safety results is not available in time for study intervention administration. If a local 
sample is required, it is important that the sample for central analysis is obtained at the 
same time. Additionally, if the local laboratory results are used to make a study
intervention decision, the results must be entered into the CRF.
•
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
BUN
Potassium
AST/SGOT
Total and direct 
bilirubin
Albumin
Bicarbonate
Chloride
Phosphorous
Creatinine
Sodium
ALT/SGPT
Total Protein
Glucose (fasting)
Calcium
Alkaline phosphatase
Other
•
aPTT and PT
•
•
Hemoccult Test
Other Screening 
Tests
•
FSH (as needed)
•
Saliva drug screen
•
Serology (HIV antigen and antibody, hepatitis B surface antigen, and 
hepatitis C virus antibody)
•
All study-required laboratory assessments will be performed by a central 
laboratory for safety, with the exception of saliva drug screen.
Note: Before blood drawing for glucose, participants will fast from all food and drinks, 
except water and non-caffeinated tea, for at least 8 hours.
The investigator must document their review of each laboratory safety report.
CCI
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10.3
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1
Definitions of Medication Error, Misuse, and Abuse
Medication Error
This is an unintended failure in the drug treatment process that leads to or has the potential to 
lead to harm to the patient.
Misuse
This refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the terms of the product information.
Abuse
This corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product for a perceived psychological or physiological reward or desired non-therapeutic 
effect.
10.3.2
Definition of AE
AE definition
•
An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of study intervention, whether or not considered related to the 
study intervention.
•
Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study intervention.
•
Note: For purposes of AE definition, study intervention includes any pharmaceutical 
product, biological product, vaccine, diagnostic agent, medical device, combination 
product, or protocol specified procedure whether investigational or marketed (including 
placebo, active comparator product, or run-in intervention), manufactured by, licensed 
by, provided by, or distributed by the Sponsor for human use in this study.
Events meeting the AE definition
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the investigator.
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•
Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.
•
For all reports of overdose (whether accidental or intentional) with an associated AE, the 
AE term should reflect the clinical symptoms or abnormal test result. An overdose 
without any associated clinical symptoms or abnormal laboratory results is reported using 
the terminology “accidental or intentional overdose without adverse effect.”
•
Any new cancer or progression of existing cancer.
Events NOT meeting the AE definition
•
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.
•
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
•
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
•
Surgical procedure(s) planned prior to informed consent to treat a preexisting condition 
that has not worsened.
•
Refer to Section 8.4.6 for protocol-specific exceptions.
10.3.3
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met.
An SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
•
The term “life-threatening” in the definition of “serious” refers to an event in which
the participant was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe.
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c.
Requires inpatient hospitalization or prolongation of existing hospitalization
•
Hospitalization is defined as an inpatient admission, regardless of length of stay, even 
if the hospitalization is a precautionary measure for continued observation. (Note: 
Hospitalization for an elective procedure to treat a preexisting condition that has not 
worsened is not an SAE.) A preexisting condition is a clinical condition that is 
diagnosed prior to the use of an MSD product and is documented in the participant’s 
medical history.
d.
Results in persistent or significant disability/incapacity
•
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.
•
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (eg, sprained ankle) that may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
•
In offspring of participant taking the product regardless of time to diagnosis.
f.
Other important medical events
•
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that may 
not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 1 
of the other outcomes listed in the above definition. These events should usually be 
considered serious.
•
Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse.
10.3.4
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
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10.3.5
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 
number, will be blinded on the copies of the medical records before submission to the 
Sponsor.
•
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of intensity
•
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, not when it is rated as severe.
•
The investigator will make an assessment of intensity for each AE and SAE (and other 
reportable safety event) reported during the study and assign it to 1 of the following
categories:
- Mild: An event that is easily tolerated by the participant, causing minimal discomfort, 
and not interfering with everyday activities (for pediatric studies, awareness of 
symptoms, but easily tolerated).
- Moderate: An event that causes sufficient discomfort to interfere with normal 
everyday activities (for pediatric studies, definitely acting like something is wrong).
- Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. Severe is a category used for rating the 
intensity of an event; and both AE and SAE can be assessed as severe (for pediatric 
studies, extremely distressed or unable to do usual activities).
Assessment of causality
•
Did the study intervention product cause the AE?
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•
The determination of the likelihood that the study intervention caused the AE will be 
provided by an investigator who is a qualified physician. The investigator’s signed/dated 
initials on the source document or worksheet that supports the causality noted on the AE 
form, ensures that a medically qualified assessment of causality was done. This initialed 
document must be retained for the required regulatory time frame. The criteria below are 
intended as reference guidelines to assist the investigator in assessing the likelihood of a 
relationship between the test product and the AE based upon the available information.
•
The following components are to be used to assess the relationship between the 
study intervention and the AE; the greater the correlation with the components and 
their respective elements (in number and/or intensity), the more likely the study 
intervention caused the AE:
- Exposure: Is there evidence that the participant was actually exposed to the study 
intervention such as: reliable history, acceptable compliance assessment (pill count, 
diary, etc), expected pharmacologic effect, or measurement of drug/metabolite in 
bodily specimen?
- Time Course: Did the AE follow in a reasonable temporal sequence from 
administration of the study intervention? Is the time of onset of the AE compatible 
with a drug-induced effect (applies to studies with investigational medicinal 
product)?
- Likely Cause: Is the AE not reasonably explained by another etiology such as 
underlying disease, other drug(s)/vaccine(s), or other host or environmental factors.
- Dechallenge: Was the study intervention discontinued or dose/exposure/frequency 
reduced?
◦
If yes, did the AE resolve or improve?
◦
If yes, this is a positive dechallenge.
◦
If no, this is a negative dechallenge.
(Note: This criterion is not applicable if: (1) the AE resulted in death or permanent 
disability; (2) the AE resolved/improved despite continuation of the study 
intervention; (3) the study is a single-dose drug study; or (4) study intervention(s) 
is/are only used 1 time.)
- Rechallenge: Was the participant re-exposed to the study intervention in this study?
◦
If yes, did the AE recur or worsen?
◦
If yes, this is a positive rechallenge.
◦
If no, this is a negative rechallenge.
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(Note: This criterion is not applicable if: (1) the initial AE resulted in death or 
permanent disability, or (2) the study is a single-dose drug study; or (3) study 
intervention(s) is/are used only 1 time.)
NOTE: IF A RECHALLENGE IS PLANNED FOR AN AE THAT WAS SERIOUS AND 
MAY HAVE BEEN CAUSED BY THE STUDY INTERVENTTION, OR IF RE-
EXPOSURE TO THE STUDY INTERVENTION POSES ADDITIONAL POTENTIAL 
SIGNIFICANT RISK TO THE PARTICIPANT THEN THE RECHALLENGE MUST BE 
APPROVED IN ADVANCE BY THE SPONSOR CLINICAL DIRECTOR, AND IF 
REQUIRED, THE IRB/IEC.
•
Consistency with study intervention profile: Is the clinical/pathological presentation of 
the AE consistent with previous knowledge regarding the study intervention or drug class 
pharmacology or toxicology?
•
The assessment of relationship will be reported on the CRFs/worksheets by an 
investigator who is a qualified physician according to their best clinical judgment, 
including consideration of the above elements.
•
Use the following scale of criteria as guidance (not all criteria must be present to be 
indicative of a study intervention relationship).
- Yes, there is a reasonable possibility of study intervention relationship:
◦
There is evidence of exposure to the study intervention. The temporal sequence 
of the AE onset relative to the administration of the study intervention is 
reasonable. The AE is more likely explained by the study intervention than by 
another cause.
- No, there is not a reasonable possibility of study intervention relationship:
◦
Participant did not receive the study intervention OR temporal sequence of the 
AE onset relative to administration of the study intervention is not reasonable 
OR the AE is more likely explained by another cause than the study 
intervention. (Also entered for a participant with overdose without an associated 
AE.)
•
The investigator must review and provide an assessment of causality for each AE/SAE 
and document this in the medical notes.
•
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 their opinion of causality in light of follow-up information 
and send an SAE follow-up report with the updated causality assessment.
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•
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.
10.3.6
Reporting of AEs, SAEs, and Other Reportable Safety Events to the Sponsor
AE, SAE, and other reportable safety event reporting to Sponsor via electronic data 
collection tool
•
The primary mechanism for reporting to the Sponsor will be the EDC tool.
-
Electronic reporting procedures can be found in the EDC data entry guidelines (or 
equivalent).
•
If the electronic system is unavailable for more than 24 hours, then the site will use the 
paper AE Reporting form.
◦
Reference Section 8.4.1 for reporting time requirements.
•
The site will enter the SAE data into the electronic system as soon as it becomes 
available.
•
After the study is completed at a given site, the EDC tool will be taken off-line to prevent 
the entry of new data or changes to existing data.
•
If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the EDC tool has been taken off-line, then the site can 
report this information on a paper SAE form or by telephone (see next section).
•
Contacts for SAE reporting can be found in the Investigator Study File Binder (or 
equivalent).
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SAE reporting to the Sponsor via paper CRF
•
If the EDC tool is not operational, facsimile transmission or secure e-mail of the SAE 
paper CRF is the preferred method to transmit this information to the Sponsor.
•
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service.
•
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames.
•
Contacts and instructions for SAE reporting and paper reporting procedures can be found 
in the Investigator Study File Binder (or equivalent).
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10.4
Appendix 4: Medical Device and Drug-device Combination Products: Product 
Quality Complaints/Malfunctions: Definitions, Recording, and Follow-up
Not applicable.
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10.5
Appendix 5: Contraceptive Guidance
10.5.1
Definitions
Women of Nonchildbearing Potential (WONCBP)
Women in the following categories are considered WONCBP:
•
Premenopausal female with 1 of the following:
- Documented hysterectomy
- Documented bilateral salpingectomy
- Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than 
the above (eg, Mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview.
•
Postmenopausal female
- A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
◦
A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or HRT. 
However, in the absence of 12 months of amenorrhea, confirmation with two 
FSH measurements in the postmenopausal range is required. 
- Females on HRT and whose menopausal status is in doubt must discontinue HRT to 
allow confirmation of postmenopausal status before study enrollment.
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10.6
Appendix 6: Collection and Management of Specimens for Future Biomedical 
Research
1. Definitions
a. Biomarker: A biological molecule found in blood, other body fluids, or tissues that is
a sign of a normal or abnormal process or of a condition or disease. A biomarker may
be used to see how well the body responds to a treatment for a disease or condition.1
b. Pharmacogenomics: The investigation of variations of DNA and RNA characteristics 
as related to drug/vaccine response.2
c. Pharmacogenetics: A subset of pharmacogenomics, pharmacogenetics is the influence 
of variations in DNA sequence on drug/vaccine response.2
d. DNA: Deoxyribonucleic acid.
e. RNA: Ribonucleic acid.
2. Scope of Future Biomedical Research3, 4
The specimens consented and/or collected in this study as outlined in Section 8.9 will be 
used in various experiments to understand:

The biology of how drugs/vaccines work

Biomarkers responsible for how a drug/vaccine enters and is removed by the body

Other pathways with which drugs/vaccines may interact

The biology of disease
The specimen(s) may be used for future assay development and/or drug/vaccine 
development.
It is now well recognized that information obtained from studying and testing clinical 
specimens offers unique opportunities to enhance our understanding of how individuals 
respond to drugs/vaccines, enhance our understanding of human disease and ultimately 
improve public health through development of novel treatments targeted to populations 
with the greatest need. All specimens will be used by the Sponsor or those working for or 
with the Sponsor.
3. Summary of Procedures for Future Biomedical Research3, 4
a. Participants for Enrollment
All participants enrolled in the clinical study will be considered for enrollment in 
future biomedical research.
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b. Informed Consent
Informed consent for specimens (ie, DNA, RNA, protein, etc) will be obtained during 
screening for protocol enrollment from all participants or legal guardians, at a study 
visit by the investigator or his or her designate. Informed consent for future 
biomedical research should be presented to the participants on the visit designated in 
the SoA. If delayed, present consent at next possible Participant Visit. Consent forms 
signed by the participant will be kept at the clinical study site under secure storage for 
regulatory reasons.
A template of each study site’s approved informed consent will be stored in the 
Sponsor’s clinical document repository.
c. eCRF Documentation for Future Biomedical Research Specimens
Documentation of participant consent for future biomedical research will be captured 
in the eCRFs. Any specimens for which such an informed consent cannot be verified 
will be destroyed.
d. Future Biomedical Research Specimen(s)
Collection of specimens for future biomedical research will be performed as outlined 
in the SoA. In general, if additional blood specimens are being collected for future 
biomedical research, these will usually be obtained at a time when the participant is 
having blood drawn for other study purposes.
4. Confidential Participant Information for Future Biomedical Research3, 4
In order to optimize the research that can be conducted with future biomedical research
specimens, it is critical to link participants' clinical information with future test results. In 
fact, little or no research can be conducted without connecting the clinical study data to 
the specimen. The clinical data allow specific analyses to be conducted. Knowing 
participant characteristics like sex, age, medical history and intervention outcomes are 
critical to understanding clinical context of analytical results.
To maintain privacy of information collected from specimens obtained for future 
biomedical research, the Sponsor has developed secure policies and procedures. All 
specimens will be single-coded per ICH E15 guidelines as described below.
At the clinical study site, unique codes will be placed on the future biomedical research
specimens. This code is a random number which does not contain any personally 
identifying information embedded within it. The link (or key) between participant 
identifiers and this unique code will be held at the study site. No personal identifiers will 
appear on the specimen tube.
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5. Biorepository Specimen Usage3, 4
Specimens obtained for the Sponsor will be used for analyses using good scientific 
practices. Analyses using the future biomedical research specimens may be performed by 
the Sponsor, or an additional third party (eg, a university investigator) designated by the 
Sponsor. The investigator conducting the analysis will follow the Sponsor’s privacy and 
confidentiality requirements. Any contracted third party analyses will conform to the 
specific scope of analysis outlined in future biomedical research protocol and consent. 
Future biomedical research specimens remaining with the third party after specific 
analysis is performed will be reported to the Sponsor.
6. Withdrawal From Future Biomedical Research3, 4
Participants may withdraw their consent for FBR and ask that their biospecimens not be 
used for FBR. Participants may withdraw consent at any time by contacting the study 
investigator. If medical records for the study are still available, the investigator will 
contact the Sponsor using the designated mailbox 
(clinical.specimen.management@MSD.com). Subsequently, the participant's specimens 
will be flagged in the biorepository and restricted to study use only. If specimens were 
collected from study participants specifically for FBR, these specimens will be removed 
from the biorepository and destroyed. Documentation will be sent to the investigator 
confirming withdrawal and/or destruction, if applicable. It is the responsibility of the 
investigator to inform the participant of completion of the withdrawal and/or destruction, 
if applicable. Any analyses in progress at the time of request for withdrawal/destruction 
or already performed before the request being received by the Sponsor will continue to be 
used as part of the overall research study data and results. No new analyses would be 
generated after the request is received.
If the medical records for the study are no longer available (eg, if the investigator is no 
longer required by regulatory authorities to retain the study records) or the specimens 
have been completely anonymized, there will no longer be a link between the 
participant’s personal information and their specimens. In this situation, the request for 
withdrawal of consent and/or destruction cannot be processed.
7. Retention of Specimens3, 4
Future biomedical research specimens will be stored in the biorepository for potential 
analysis for up to 20 years from the end of the study. Specimens may be stored for longer 
if a regulatory or governmental authority has active questions that are being answered. In 
this special circumstance, specimens will be stored until these questions have been 
adequately addressed.
Specimens from the study site will be shipped to a central laboratory and then shipped to 
the Sponsor-designated biorepository. If a central laboratory is not utilized in a particular
study, the study site will ship directly to the Sponsor-designated biorepository. The 
specimens will be stored under strict supervision in a limited access facility which 
operates to assure the integrity of the specimens. Specimens will be destroyed according 
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to Sponsor policies and procedures and this destruction will be documented in the 
biorepository database.
8. Data Security3, 4
Databases containing specimen information and test results are accessible only to the 
authorized Sponsor representatives and the designated study administrator research 
personnel and/or collaborators. Database user authentication is highly secure, and is 
accomplished using network security policies and practices based on international 
standards to protect against unauthorized access.
9. Reporting of Future Biomedical Research Data to Participants3, 4
No information obtained from exploratory laboratory studies will be reported to the 
participant, family, or physicians. Principle reasons not to inform or return results to the 
participant include: lack of relevance to participant health, limitations of predictive 
capability, and concerns regarding misinterpretation.
If important research findings are discovered, the Sponsor may publish results, present 
results in national meetings, and make results accessible on a public website in order to
rapidly report this information to doctors and participants. Participants will not be 
identified by name in any published reports about this study or in any other scientific 
publication or presentation.
10. Future Biomedical Research Study Population3, 4
Every effort will be made to recruit all participants diagnosed and treated on Sponsor 
clinical studies for future biomedical research.
11. Risks Versus Benefits of Future Biomedical Research3, 4
For future biomedical research, risks to the participant have been minimized and are 
described in the future biomedical research informed consent.
The Sponsor has developed strict security, policies, and procedures to address participant 
data privacy concerns. Data privacy risks are largely limited to rare situations involving 
possible breach of confidentiality. In this highly unlikely situation, there is risk that the 
information, like all medical information, may be misused.
12. Questions
Any questions related to the future biomedical research should be emailed directly to 
clinical.specimen.management@MSD.com.
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13. References
1. National Cancer Institute [Internet]: Available from 
https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45618
2. International Council on Harmonisation [Internet]: E15: Definitions for Genomic 
Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample 
Coding Categories. Available from 
http://www.ich.org/products/guidelines/efficacy/efficacy-single/article/definitions-
for-genomic-biomarkers-pharmacogenomics-pharmacogenetics-genomic-data-and-
sample-cod.html 
3. Industry Pharmacogenomics Working Group [Internet]: Understanding the Intent, 
Scope and Public Health Benefits of Exploratory Biomarker Research: A Guide for 
IRBs/IECs and Investigational Site Staff. Available at http://i-pwg.org/ 
4. Industry Pharmacogenomics Working Group [Internet]: Pharmacogenomics 
Informational Brochure for IRBs/IECs and Investigational Site Staff. Available at 
http://i-pwg.org/
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10.7
Appendix 7: Country-specific Requirements
Not applicable.
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10.8
Appendix 8: Blood Volume Table
Prestudy
Treatment 
Periods
Poststudy
Total 
Collections
mL Per 
Collection
Total mL/ 
Test
Safety:
Hematology and Chemistry
2
9
1
12
9.0
108.0
aPTT and PT
1
9
10
1.8
18.0
1
1
2.0
2.0
HIV, hepatitis B and C 
screen
1
1
5.0
5.0
FSH
2
2
2.0
4.0
PK/PD/Biomarker
Blood for Plasma MK-2060
PK and ADA assay
7
1
8
2.7
21.6
Blood for Plasma MK-2060
PK assay only
11
11
1.8
19.8
Blood for aPTT/PT/FXI 
activity
18
1
19
8.1
153.9
Blood for Planned Genetic 
Analysis
1
1
8.5
8.5
Total Blood Volume per Participant a
336.8
Total Blood Volume per Participant (including FSH) a
340.8
a If additional pharmacokinetic/pharmacodynamic and/or safety analysis is necessary, additional blood (no more than 
50 mL in total) may be obtained.
CCI
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10.9
Appendix 9: Abbreviations
Abbreviation
Expanded Term
ADA
anti-drug antibodies
ADME
absorption, distribution, metabolism, and excretion
AE
adverse event 
α-GI
α-Glucosidase Inhibitor
ALT
alanine aminotransferase
APaT
All Participants as Treated
aPTT
activated partial thromboplastin time
ASO
anti-sense oligo
AST
aspartate aminotransferase
ATIII
antithrombin III
AUC
area under the plasma concentration-time curve
AUC0-168
area under the plasma concentration-time curve from time 0 to 168 
hours post-dose
AUC0-inf
area under the plasma concentration-time curve from time 0 to infinity
AUC0-last
area under the plasma concentration-time curve from time 0 to the time 
of the last measurable concentration
AV
arteriovenous
AxMP
auxiliary medicinal product
BMI
body mass index
BP
blood pressure
BUN
blood urea nitrogen
C168
plasma concentration at 168 hours post-dose
CFR
Code of Federal Regulations
Cmax
maximum plasma concentration
CL
clearance
COVID-19
Coronavirus disease caused by sever acute respiratory syndrome 
coronavirus 2
CRF
Case Report Form 
CRU
clinical research unit
CSR
clinical study report
DILI
drug-induced liver injury
DNA
deoxyribonucleic acid 
DPP-4
Dipeptidyl Peptidase-4
ECG
electrocardiogram 
ECI
event of clinical interest
eCRF
electronic Case Report Form
EDC
electronic data collection 
EEA
European Economic Area
EMA
European Medicines Agency
ER
emergency room
ESRD
End-stage renal disease
CCI
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Abbreviation
Expanded Term
FBR
future biomedical research
FDAAA
Food and Drug Administration Amendments Act
FDC
Fixed Dose Combination
FSH
follicle-stimulating hormone 
FSR
First Site Ready
FXa
Factor Xa
FXI
Factor XI
FXIa
Factor XIa
GCP
Good Clinical Practice 
GCV
geometric coefficient of variance
GI
gastrointestinal
GLP-1
glucagon-like peptide-1
HD
hemodialysis
HDF
hemodiafiltration
HIF-PH
hypoxia-inducible factor prolyl-hydroxylase
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
IB
Investigator’s Brochure 
ICF
Informed Consent Form
ICH
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
ICMJE
International Committee of Medical Journal Editors
ID
identification
IEC
Independent Ethics Committee
IgG
immunoglobulin G
IMP
investigational medicinal product
IRB
Institutional Review Board
IV
intravenous
IVIG
intravenous immunoglobulin
mAb
monoclonal antibody
MCH
mean corpuscular hemoglobin
MCV
mean corpuscular volume
NCS
not clinically significant
NIMP
noninvestigational medicinal product
NSAID(s)
non-steroidal anti-inflammatory drug(s)
NOAEL
no observed adverse effect level 
PD
pharmacodynamic(s)
PE
physical examination
PK
pharmacokinetic(s)
PP
per protocol
PR
pulse rate
PT
prothrombin time
CCI
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Abbreviation
Expanded Term
QW
every week
QTc
QT corrected (corrected QT interval)
RBC
red blood cell
RhoGAM
a brand of Rh immunoglobulin
RNA
ribonucleic acid
RR
respiratory rate
SAD
single ascending dose
SAE
serious adverse event 
SC
subcutaneous (ly)
SGOT
serum glutamic oxaloacetic transaminase
SGPT
serum glutamic pyruvic transaminase
SLAB
supplemental laboratory test(s)
SMi
small molecular inhibitor
SoA
schedule of activities
spKt/V
single-pool Kt/V
SUSAR
suspected unexpected serious adverse reaction
Tinf
time at the end of infusion
Tlast
time of last measurable concentration
Tmax
time to maximum observed plasma concentration
t1/2
half life
ULN
upper limit of normal
VS
vital signs
V side
Vein side
Vz
volume of distribution
WBC
white blood cell
PONCBP
participant/participants of nonchildbearing potential
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11
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Factor XI, in Patients with End-Stage Renal Disease on 
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[Ellsworth K. 2018]
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Coagulation by Activated Partial Thromboplastin Time 
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[Moffat, GJ., et al 2014]
Moffat GJ, Retter MW, Kwon G, et al. Placental transfer of a 
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during organogenesis to late gestation. Birth Defects Res B 
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[Nitta K., et al 2019]
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Toseki Igakkai Zasshi. 2019 Dec;52(12):679-754
[Sohn, W., et al 2015]
Sohn W, Lee E, Kankam MK, et al. An open-label study in 
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