A Randomized, Double-Blind, Placebo-Controlled, Multiple Rising Dose Clinical Trial to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-6194 in Participants With Moderate to Severe Atopic Dermatitis
Phase: PHASE1
Conditions: Dermatitis, Atopic
Sponsor: Merck Sharp & Dohme LLC

Official Protocol Title: 
NCT number: 
NCT05450198 
Document Date: 
12-Dec-2022
A Randomized, Double-Blind, Placebo-Controlled, Multiple 
Rising Dose Clinical Trial to Investigate Safety, Tolerability, 
Pharmacokinetics, and Pharmacodynamics of MK-6194 in 
Participants with Moderate to Severe Atopic Dermatitis

PRODUCT: MK-6194  
1
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Title Page
THIS PROTOCOL AMENDMENT AND ALL OF THE INFORMATION RELATING 
TO IT ARE CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK 
SHARP & DOHME LLC, RAHWAY, NJ, USA (MSD).
Protocol Title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Rising Dose 
Clinical Trial to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics 
of MK-6194 in Participants with Moderate to Severe Atopic Dermatitis
This protocol amendment is applicable only to the United States.
Protocol Number: 008-04
Compound Number: MK-6194
Sponsor Name:
Merck Sharp & Dohme LLC
(hereafter called the Sponsor or MSD)
Legal Registered Address:
126 East Lincoln Avenue
P.O. Box 2000
Rahway, NJ 07065 USA
Regulatory Agency Identifying Number(s):
EudraCT
2022-001011-12
IND
142873
Approval Date: 12 December 2022
08QVCJ

PRODUCT: MK-6194  
2
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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
08QVCJ

PRODUCT: MK-6194  
3
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
MK-6194-008-04
12-DEC-2022
This is the second US country specific amendment and includes the following 
modifications: 1) inclusion of monthly pregnancy testing from Day 85 through the 
end of the study, 2) clarification of subject and cohort stopping rules, and 3)
clarification of requirements for initiation of the expansion panels.
MK-6194-008-03
26-SEP-2022
Canada added as a country.
MK-6194-008-02
07-JUL-2022
Belgium, Bulgaria, Romania, and Spain specific amendment to clarify a newly 
added test.
MK-6194-008-01
06-JUL-2022
This US country specific amendment modifies dose escalations to occur based on 
the review of safety data through at least one week following the final 
administered dose of MK-6194/placebo in the preceding dose escalation panel.
Additional minor changes in this protocol amendment include an update of data 
from ongoing clinical studies through 01-JUL-2022, an updated study diagram to 
reflect the revised dose escalation criteria and clarify the study design, and 
clarification of screening testing.  
Original Protocol
02-MAY-2022
Not applicable
08QVCJ

	
 	



	
 
	

  


	
	
,-.,- 
3&'-2'&),-.,-*
1!*#)*+!/(1+	

!!((	
 +(2!(1!/%%3,/'(+((1!*)('%>
7 (1%0*)!,'0(!+(,/(!)0;7 1+ +#**%!!(+ (1!*)!,'0(!+(,(1(*)!'!!+!'1+()(/
	
+*!)/)!((1!/%+(#0-+( 5.!'(7=".'1!#%!/'(-(!+67
7
=7 '%)/0 )!@#)!!(+(((!!8*+*!%+71!(!(/(1!!8*+*!%++(!-%#(!+!%!-!%+ /)31'1(1!
*)('%+*!'/! +/!(0)!-!3 /)!@#%),)!(!)+!%!-!%*))0!+'%( *!% 1+$!!'*%!(!71+
'%)/'(+'%#!(1+!!(('%)/0(1((1!!'+(+!!8*+*!%+$+!#**))0
!+'%(+/!(0( !8*!)!'!(,)!(!))!@#%+!%!-!%")(1!)(1$+!+*!'/'%%0!!%5.!'(
77
!'+!,),+,/8*+!%+67
CCI
49&-

PRODUCT: MK-6194  
5
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Summary of Changes Table:
Section # and Name
Description of Change 
Brief Rationale 
1.3 Schedule of 
Activities
Pregnancy testing has been added 
on Day 113 and Day 141. 
The change was incorporated to increase the number of pregnancy 
tests to a monthly cadence after Day 85 through the end of the study.
4.1.2 Decision 
Regarding Dosing of 
Expansion Panels
The requirements for expansion 
panel dosing have been clarified 
to be based on safety review from 
a primary escalation panel at an 
equal or greater dose.
Clarification was made regarding data requirements for dosing the
expansion panels.
6.6.1 Stopping Rules 
Subject and cohort level stopping 
rules have been clarified.
Clarification was added to provide more explicit instructions 
regarding stopping rules. Please refer to point #2 in the Overall 
Rationale for Amendments above.
7.1 Discontinuation of 
Study Intervention
The criterion governing subject 
level discontinuation from dosing 
has been further clarified.
Clarification was added to provide more explicit instructions 
regarding subject level stopping rules. Please refer to point #2 in the 
Overall Rationale for Amendment above.
8.4 Adverse Events, 
Serious Adverse Events, 
and Other Reportable 
Safety Events and 
10.3.2 Definition of AE
Administrative changes
Revisions were made for alignment with the Merck Early Stage 
Development non-oncology protocol template standard language.
08QVCJ

PRODUCT: MK-6194  
6
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Table of Contents
DOCUMENT HISTORY ........................................................................................................3
PROTOCOL AMENDMENT SUMMARY OF CHANGES...............................................4
1
PROTOCOL SUMMARY ............................................................................................13
1.1
Synopsis.................................................................................................................13
1.2
Schema ..................................................................................................................16
1.3
Schedule of Activities...........................................................................................18
2
INTRODUCTION..........................................................................................................22
2.1
Study Rationale....................................................................................................22
2.2
Background ..........................................................................................................22
2.2.1
Pharmaceutical and Therapeutic Background .............................................23
2.2.2
Preclinical and Clinical Studies ...................................................................23
2.2.3
Ongoing Clinical Studies.............................................................................25
2.3
Benefit/Risk Assessment......................................................................................28
3
HYPOTHESES, OBJECTIVES, AND ENDPOINTS................................................28
4
STUDY DESIGN............................................................................................................30
4.1
Overall Design......................................................................................................30
4.1.1
Decisions Regarding Dose Escalation .........................................................31
4.1.2
Decision Regarding Dosing of Expansion Panels .......................................31
4.2
Scientific Rationale for Study Design.................................................................32
4.2.1
Rationale for Endpoints ...............................................................................32
4.2.1.1
Safety Endpoints................................................................................32
4.2.1.2
Pharmacokinetic Endpoints ...............................................................33
4.2.1.3
Pharmacodynamic Endpoints.............................................................33
4.2.1.4
Efficacy Endpoints.............................................................................33
4.2.1.5
Planned Exploratory Biomarker Research.........................................34
4.2.1.5.1
Planned Exploratory Biomarker Research...............................34
4.2.1.5.2
Planned Genetic Analysis ........................................................35
4.2.1.6
Future Biomedical Research..............................................................35
4.2.2
Rationale for the Use of Comparator/Placebo .............................................35
4.3
Justification for Dose...........................................................................................36
4.3.1
Starting Dose for This Study........................................................................36
4.3.2
Maximum Dose/Exposure for This Study ...................................................37
4.3.3
Rationale for Dose Interval and Study Design ............................................38
4.4
Beginning and End-of-Study Definition ............................................................38
4.4.1
Clinical Criteria for Early Study Termination .............................................39
08QVCJ

PRODUCT: MK-6194  
7
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
5
STUDY POPULATION ................................................................................................39
5.1
Inclusion Criteria.................................................................................................40
5.2
Exclusion Criteria................................................................................................42
5.3
Lifestyle Considerations......................................................................................45
5.3.1
Meals and Dietary Restrictions....................................................................45
5.3.1.1
Diet Restrictions.................................................................................45
5.3.1.2
Fruit Juice Restrictions ......................................................................45
5.3.2
Caffeine, Alcohol, and Tobacco Restrictions ..............................................45
5.3.2.1
Caffeine Restrictions..........................................................................45
5.3.2.2
Alcohol Restrictions...........................................................................45
5.3.2.3
Tobacco Restrictions..........................................................................46
5.3.3
Activity Restrictions ....................................................................................46
5.4
Screen Failures.....................................................................................................46
5.5
Participant Replacement Strategy......................................................................46
6
STUDY INTERVENTION............................................................................................46
6.1
Study Intervention(s) Administered...................................................................46
6.2
Preparation/Handling/Storage/Accountability .................................................49
6.2.1
Dose Preparation..........................................................................................49
6.2.2
Handling, Storage, and Accountability........................................................49
6.3
Measures to Minimize Bias: Randomization and Blinding..............................50
6.3.1
Intervention Assignment..............................................................................50
6.3.2
Stratification.................................................................................................50
6.3.3
Blinding........................................................................................................50
6.4
Study Intervention Compliance..........................................................................51
6.5
Concomitant Therapy..........................................................................................51
6.5.1
Rescue Medications and Supportive Care ...................................................53
6.6
Dose Modification (Escalation/Titration/Other)...............................................53
6.6.1
Stopping Rules.............................................................................................54
6.7
Intervention After the End of the Study............................................................56
6.8
Clinical Supplies Disclosure................................................................................56
6.9
Standard Policies..................................................................................................56
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL............................................................................................................57
7.1
Discontinuation of Study Intervention...............................................................57
7.2
Participant Withdrawal From the Study...........................................................58
7.3
Lost to Follow-up .................................................................................................58
8
STUDY ASSESSMENTS AND PROCEDURES........................................................59
8.1
Administrative and General Procedures ...........................................................59
08QVCJ

PRODUCT: MK-6194  
8
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
8.1.1
Informed Consent.........................................................................................59
8.1.1.1
General Informed Consent.................................................................60
8.1.1.2
Consent and Collection of Specimens for Future Biomedical 
Research.............................................................................................60
8.1.2
Inclusion/Exclusion Criteria ........................................................................60
8.1.3
Participant Identification Card.....................................................................60
8.1.4
Medical History ...........................................................................................61
8.1.5
Prior and Concomitant Medications Review...............................................61
8.1.5.1
Prior Medications...............................................................................61
8.1.5.2
Concomitant Medications..................................................................61
8.1.6
Assignment of Screening Number...............................................................61
8.1.7
Assignment of Treatment/Randomization Number.....................................61
8.1.8
Study Intervention Administration ..............................................................62
8.1.8.1
Timing of Dose Administration.........................................................62
8.1.9
Discontinuation and Withdrawal .................................................................62
8.1.9.1
Withdrawal From Future Biomedical Research ................................62
8.1.10
Participant Blinding/Unblinding..................................................................62
8.1.11
Domiciling ...................................................................................................63
8.1.12
Calibration of Equipment.............................................................................63
8.2
Efficacy/Disease Activity Assessments...............................................................63
8.2.1
Skin Biopsy and Dermatologic Photography...............................................63
8.3
Safety Assessments...............................................................................................64
8.3.1
Physical Examinations.................................................................................64
8.3.2
Injection Reactions.......................................................................................64
8.3.2.1
Injection Reaction Assessment ..........................................................64
8.3.2.2
Management of Injection Reactions ..................................................65
8.3.3
Vital Signs....................................................................................................65
8.3.3.1
Resting Vital Signs ............................................................................66
8.3.4
Electrocardiograms ......................................................................................66
8.3.5
Clinical Safety Laboratory Assessments .....................................................68
8.3.6
Pregnancy Testing........................................................................................68
8.3.7
Photograph of Rash......................................................................................69
8.4
Adverse Events, Serious Adverse Events, and Other Reportable Safety 
Events....................................................................................................................69
8.4.1
Time Period and Frequency for Collecting AE, SAE, and Other 
Reportable Safety Event Information ..........................................................69
8.4.2
Method of Detecting AEs, SAEs, and Other Reportable Safety Events......71
8.4.3
Follow-up of AE, SAE, and Other Reportable Safety Event Information...71
8.4.4
Regulatory Reporting Requirements for SAE .............................................71
08QVCJ

PRODUCT: MK-6194  
9
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
8.4.5
Pregnancy and Exposure During Breastfeeding ..........................................72
8.4.6
Disease-related Events and/or Disease-related Outcomes Not Qualifying 
as AEs or SAEs............................................................................................72
8.4.7
Events of Clinical Interest............................................................................72
8.5
Treatment of Overdose........................................................................................73
8.6
Pharmacokinetics.................................................................................................73
8.6.1
Blood Collection for Serum MK-6194 ........................................................73
8.7
Pharmacodynamics..............................................................................................74
8.8
Biomarkers ...........................................................................................................74
8.8.1
Planned Genetic Analysis Sample Collection..............................................74
8.8.2
Exploratory Biomarkers...............................................................................74
8.8.3
Immunogenicity Assessments......................................................................74
8.9
Future Biomedical Research Sample Collection...............................................74
8.10
Visit Requirements...............................................................................................75
8.10.1
Screening......................................................................................................75
8.10.2
Treatment Period Visit.................................................................................75
8.10.3
Participants Discontinued From Study Intervention but Continuing to be 
Monitored in the Study ................................................................................75
8.10.4
Poststudy Visit .............................................................................................75
8.10.5
Critical Procedures Based on Study Objectives: Timing of Procedure.......75
8.10.6
Study Design/Dosing/Procedures Modifications Permitted Within 
Protocol Parameters .....................................................................................76
9
STATISTICAL ANALYSIS PLAN .............................................................................78
9.1
Statistical Analysis Plan Summary.....................................................................78
9.2
Responsibility for Analyses.................................................................................78
9.3
Hypotheses/Estimation ........................................................................................79
9.4
Analysis Endpoints...............................................................................................79
9.5
Analysis Populations............................................................................................79
9.6
Statistical Methods...............................................................................................80
9.7
Interim Analyses ..................................................................................................81
9.8
Multiplicity ...........................................................................................................82
9.9
Sample Size and Power Calculations .................................................................82
10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS.....................................................................................................83
10.1
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations........83
10.1.1
Code of Conduct for Clinical Trials.............................................................83
10.1.2
Financial Disclosure.....................................................................................85
10.1.3
Data Protection.............................................................................................86
10.1.3.1
Confidentiality of Data ......................................................................86
08QVCJ

PRODUCT: MK-6194  
10
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.1.3.2
Confidentiality of Participant Records...............................................86
10.1.3.3
Confidentiality of IRB/IEC Information............................................86
10.1.4
Committees Structure...................................................................................87
10.1.5
Publication Policy........................................................................................87
10.1.6
Compliance with Study Registration and Results Posting Requirements ...87
10.1.7
Compliance with Law, Audit, and Debarment ............................................87
10.1.8
Data Quality Assurance ...............................................................................88
10.1.9
Source Documents .......................................................................................89
10.1.10
Study and Site Closure.................................................................................89
10.2
Appendix 2: Clinical Laboratory Tests..............................................................90
10.3
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting...............................................................92
10.3.1
Definitions of Medication Error, Misuse, and Abuse..................................92
10.3.2
Definition of AE ..........................................................................................92
10.3.3
Definition of SAE ........................................................................................93
10.3.4
Additional Events Reported.........................................................................94
10.3.5
Recording AE and SAE ...............................................................................95
10.3.6
Reporting of AEs, SAEs, and Other Reportable Safety Events to the 
Sponsor ........................................................................................................98
10.4
Appendix 4: Medical Device and Drug-device Combination Products: 
Product Quality Complaints/Malfunctions: Definitions, Recording, and 
Follow-up ............................................................................................................100
10.5
Appendix 5: Contraceptive Guidance..............................................................101
10.5.1
Definitions..................................................................................................101
10.5.2
Contraception Requirements......................................................................103
10.6
Appendix 6: Collection and Management of Specimens for Future 
Biomedical Research..........................................................................................104
10.7
Appendix 7: Country-specific Requirements..................................................109
10.8
Appendix 8: Blood Volume Table ....................................................................110
10.9
Appendix 9: 12-Lead Electrocardiogram Abnormality Criteria ..................111
10.10 Appendix 10: Algorithm for Assessing Out of Range Laboratory Values ...113
10.11 Appendix 11: Guideline for the Diagnosis of Atopic Dermatitis...................114
10.12 Appendix 12: Clinical Outcome Assessment Measures..................................115
10.12.1
Eczema Area and Severity Index (EASI) ..................................................115
10.12.2
Peak Pruritus Numerical Rating Score ......................................................116
10.12.3
Validated Investigator’s Global Assessment for Atopic Dermatitis..........117
10.13 Appendix 13: Abbreviations .............................................................................118
11
REFERENCES.............................................................................................................123
08QVCJ

PRODUCT: MK-6194  
11
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
LIST OF TABLES
Table 1
Planned Doses Scheme ..............................................................................16
Table 2
Study Interventions....................................................................................47
Table 3
Sample Allocation Schedule......................................................................50
Table 4
Reporting Time Periods and Time Frames for Adverse Events and 
Other Reportable Safety Events.................................................................70
Table 5
Pharmacokinetic (Blood/Urine) Collection Windows...............................76
Table 6
Probability of Success for Posterior Probability by True Fold Change.....82
Table 7
Protocol-required Safety Laboratory Assessments....................................90
08QVCJ

PRODUCT: MK-6194  
12
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
LIST OF FIGURES
Figure 1
Study Diagram ...........................................................................................17
08QVCJ

	
 	

=

	
 
	

  

:

	
::
0-'+**
&''('
  !"#$%!&%"%'!$()%%!"#%(*%!+,+!
%'%)%(-!+(,(!./!(0"%!)$%(0"1)'2!('+"1)'0'+
/	
)('*(+3(1!)(!(.!-!)!(*'!)((+
)'&
 #%(*%!+,+!.(#0/	
)('*(+3(1(*'!)((+
(&'-0, 
0+')**! /H(3*! -.-.+'-*
E0*(1!+!+)!%,!3(1$?!'(-!+(1!$?!'(-!+*(+($%!7
1++(#0+($!'#'(!#%(*)('*(+3(1!)(!(+!-!)!(*'!)((+7
$?!'(-!+
*(+
))0
J
!-%#(!(1!+/!(0(%!)$%(0/
	
*)('*(+ 3(1(*'
!)((+"/%%3,#%(*%!+!
+#$'#(!#++()(7
J
+"+'(#(/)+,#!(
+
.!')0
J
'1)'(!) !+!)#/)	

*)('*(+3(1 (*'!)((+
/%%3,#%(*%!+!+#$'#(!#+
+()(7
J
CCI
49&-

	
 	



	
 
	

  

$?!'(-!+
*(+
J
'1)'(!) !)!,#%()0'!%%
*1)'0'+/	

*)('*(+3(1(*'!)((+
/%%3,#%(*%!+!+#$'#(!#+
+()(7
J
E0*(1!++>(%!)(!#%(*%!+!
+#$'#(!#++()(/


J
#*1!(0*,/)!,+
3&*-
.(#01+!
1+!
))0#)*+!
)!(!(
'(
(*'!)((+
*#%(
(!(>#%(*)('*(+3(1!)(!(+!-!)!(*'
!)((+
.(#00*!
(!)-!(%
(!)-!(!%
.!@#!(%
1++#%(+(! +(#07
0*!/()%
%'!$
.(#0&%,
#$%!$%
&%,%!+
)('*(+).#$?!'(+
-!+(,()
.*+)
+((!#)(/.(#0
CCI
CCI
49&-

	
 	

;

	
 
	

  

1,/&'2&(+-*
<*(: *)('*(+3%%$!%%'(!A) !7
#)(/
)('*(
'1*)('*(3%%*)('*(!(1!+(#0/)**)8(!%0
/)
(1!(!(1!*)('*(*)-!+'#!(!/)!'+!((1)#,1(1!
/%'('(7/(!)+')!!,*1+!/**)8(!%0
CCI
CCI
CCI
49&-

	
 	



	
 
	

  

1.0'3&--(	',,*
8!'#(-!-!)+,1(((!!

((),((!!

%'%?#'(((!!

.(#0,-!)'!'+!)(+)!#(%!**!8 7
1.0((+*)0?'1-&* 
%+(/$$)!-(++**!8=7
:;
(),
1!+(#0!+,+!*'(!$%!  ,#)!7
CCI
49&-

	
 	

:

	
 
	

  

CCI
49&-

	
 	



	
 
	

  

:8
().1'2(3*
1.0&'.
(&--
-&3-'-
'*4
*1.0
'*
().1.0
:
=
:A
;;
;B
8<
98 AE
E:
=A
B;
BB
::8
:;E
:9:
:<B
.,-*&3&'(.1&*
/)!+!(
M
.!'7;7"777
/)!+!(/)&
M
.!'7;7"777
)('*()
M
.!'777=
'%#+A8'%#+)(!)
M
M
.!'7;7";7"77
!-!3/A(.')!!,"%0
+*!'/'')(!)3%%$!)!-!3!(
*)!+!*))() (
!'%E+()0
M
.!'77
))A'((!'(!-!3
MM
.!';7"7;"77;
++,!(/.')!!,#$!)
M
.!'77
++,!(/)!(!(A
 (#$!)
M
.!';7;"77:
20&'(.1&*
#%%*10+'%!8(
M
M
M
.!'77=7
0(*)!+!
E!,1(
M
.!'77=7
F!,1(
M
M
.!'77=7
G.5E"&6
M
M M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
.!'77=7=7
0+";"	"
=";:":;>3(1
=1*)!+!7;1*+(+!
G.5&0!*!)(#)!6
M
M M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
.!'77=7=7
0+";"	"
=";:":;>3(1
=1*)!+!7;1*+(+!
%!C
M
M M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
.!'77=7
"**!8	
0>)!+!1)*+(+!
%%(1!)0+>!C!+#)!!(
)*%'(!(0*)!+! 0
1*+(+!"+,%!!+#)!!((%%
(1!)(!*(+
'%?!'(+(!)!'(++!++!(
M M
M
M
M
M
M
M
M
M
M
M
M
M
M
M
.!'77=7
0+";"	"
=";:":;>*)!+!
7;1*+(+!
CCI
49&-

PRODUCT: MK-6194  
19
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Study Period:
Screening
Intervention
Post-
study
Notes
Scheduled Day
1
8
15
22
29
36
43 57
71
85
92
99
113
127
141
169
AE/SAE review including assessment for 
systemic injection reaction
X---------------------------------------------------------------------------------------------------X
Sec 8.4, 10.3
Laboratory Procedures
Serum FSH - (WONCBP only)
X
Sec. Appendix2, Appendix 5
Serum or urine β-hCG pregnancy test 
(WOCBP only)
X
X
X
X
X
X
X
X
X
X
X
Sec 8.3.6, Appendix 2
Day 1 predose serum pregnancy test may 
be obtained within 72 hours of dosing.
HIV, hepatitis B and C screen (per site 
SOP)
X
Sec. 8.3.5, Appendix 2
Purified protein derivation (PPD) test or
QuantiFERON®-TB Gold test (per site 
SOP)
X
Sec 5.1, 5.2, Appendix 2
To assess IC/EC, performed at local or 
central lab
Urine Drug Screen (UDS)
X
X
Sec. 8.3.5, 8.10.5, Appendix 2
Mandatory at Screening and predose 
Day 1; any additional UDS are conducted 
per site SOP
Alcohol test
X
X
Mandatory at Screening; any additional 
tests are conducted per site SOP
Section 8.10.5, Appendix 2
Hematology (Including CBC)
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.5, Appendix 2
Days 1, 15, 29, 43, 57, 71 and 85: at 
predose
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.5, Appendix 2
Days 1, 15, 29, 43, 57, 71 and 85: at 
predose
Chemistry
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
Sec. 8.3.5, Appendix 2
Days 1, 15, 29, 43, 57, 71 and 85: at 
predose
Coagulation tests (PT/INR, aPTT)
X
Sec. 8.3.6, Appendix 2
Pharmacokinetics
Blood for MK-6194 Assayb
X X
X
X
X
X
X
X
X
Sec 8.9
Days 1 and 29: predose, and 12h postdose.
Days 15, 43, 85: predose
Pharmacodynamics / Biomarker
Blood for ADAb
X
X
X
X
Sec 8.9
Days 1, 15 and 85 at predose
08QVCJ

	
 	



	
 
	

  

1.0&'.
(&--
-&3-'-
'*4
*1.0
'*
().1.0
:
=
:A
;;
;B
8<
98 AE
E:
=A
B;
BB
::8
:;E
:9:
:<B
CCI
49&-

	
 	



	
 
	

  

1.0&'.
(&--
-&3-'-
'*4
*1.0
'*
().1.0
:
=
:A
;;
;B
8<
98 AE
E:
=A
B;
BB
::8
:;E
:9:
:<B
CCI
49&-

	
 	



	
 
	

  

;

	

;:
1.0'-
E##(#!+!+!)!+#%(+" *)(/)0+/#'(%)+#//'!(#$!)+/
)!,+(1($0(*)*!)%0)!+()'(,#!)!+*+!+"'#+!+),,!R%+"7C7
7"!(%S7	
+-!%#(!(1(+!%!'(-!%0!8*+)!,#%()0 '!%%+"
3(1#('(-(,'0((8'#!'!%%'#(!)*)(+71+ !'1+//!)+#@#!
**)(#(0()!$%'!(1!0+)!,#%(!#!)!+*+!+/*(!(+3(13!),!/
#(#!+!+!7(*'!)((++#(#! +!+!)!3(1+,/'(#!(
!'%!!/)31'1*#$%+1!'%'%()%+1-!+#,,!+(! +,/'('%'%!//''0
/$+!()!(!(7
1!*))0$?!'(-!/(1+*)('% 3%%$! ('1)'(!) !(1!+/!(0 (%!)$%(0/
	
/%%3,#%(*%!+!+


;;
5(>&'1-.
!/!)((1!&/)!(%!$'2,)#/)(	
7
'-2'&	-(22((0'2 4<:B9! - 4;4,1- -'+(&,*
(*'!)((++'1)'"*)#)('"/%()0+2+!+!3(1!+((!
*)!-%!'!/T!-!%*!'#()!+R,".77"!(%S7)0+2+!-!)!
*)#)(#+)!1%%)2/!(#)!+/(1!+!+!7-)!(0/'#+%!'1++1-!$!!
*)*+!"'%#,!*!)%$))!)0+/#'(",!!('/'()+"1'!%%+2!3!#!
0+)!,#%("%(!)!+2')$!"!-)!(%(),,!)+//%(7(*'
!)((+(0*'%%0/%%3+'1)'")!%*+,'#)+!-!)(1+(0!)+7(!(+3(1
!)(!(+!-!)!!)((+))!%0*)-!3(1#(()!(!(7!+*(!(1! -%$%(0/
##%()0(1!)*!+ (()!(*(!(+3(1(*'!)((+"+#'1+#*%#$"5
'%%( 
U (,+(6" (*'% )%9+ ()%2#$" '%%
( =" (*'!)((+'(#!+($!+!+!3(1+,/'( #!(!'%!!7
F1%!%!,$%,'(1!)*0/)(1!()!(!(/(*'!)((+"VT/*(!(+
+'(#! #*%#$ ()!(!(/(!)0!) R.%-!)$!),"977"!(%S"31'10)!+#%(
#!(!'%!!7
#*%#$+++'(!3(1  1,1!)/)!@#!'0/!0!+)!)+ 5+#'1+ /!'(#+
'?#'(-(+6 !- *+)++" 31%! +0+(!'9#+!(1!()!(!(/(*'
!)((+)!++'(!3(1')!+!)+2/?)-!)+!')-+'#%)!-!(+ 
CCI
49&-

	
 	

=

	
 
	

  

''!)R.,1"977S71!)!/)!"-!%()!(!(/)(*'!)((+(1(//!)+$(1
+,/'( '%'%$!!/( 1+''!*($%!+/!(0*)/%!+#),!(%0!!!7
%'%!//''0/%3+!(*'!)((+1+$!!+13*)!-#+%0RE+!1"7
E7"!(%		S7!2() 1!)*!#('+*)(!)+1*3(1%%%01+ !-!%*!*!,0%(!
)!'$(1#5=;67!'!$!)"*)!%)0(/)(1!) 1+!
$(*'!)((+5
=;6 !+()(!+,/'('%'%$!!/(/
=;-!)+#+*%'!$"(1(*!)++(!#*(=3!!2+/(!)()!(!(1''%#!71!+!(
)!*#$%'%0-%$%!$#()!(0!(*#$%+1!7
1!+!+#**)(,('(!(1(	
0*)(+,/'(*!)++(!('%'%
$!!/(,-#%+ 3(1(*'!)((+71!)!/)!"(1!*))0+!')0
$?!'(-!+")!+*!'(-!%0" /(1+ #%(*%!+! 1+!$ +(#0)!(!(!)!(1!+/!(0
(%!)$%(0"*)/%! )!,!8*+*)/%!/%%3, #%(*%!+!+/	

,*)('*(+ 3(1!)(!(+!-!)!(*'!)((+7 8*%)()0$?!'(-!+3%%
++!++31!(1!)	
*)(+'%'%$!!/((*)('*(+ 3(1(*'!)((+7
2!(,!(1!)"(1!+!)!+#%(+3%%!(!)!31!(1!) /#)(1!) -!+(,(/	
 
(*'!)((++3))(!!/(-!1+!'%'%()%+7
;;:
)&,(1(-.
)&+1( 5(>&'1-.
#(#!/%()0+!+!+)!+#%(/)+)#*(!#!1!+(++
**)*)(!#!'(-(0"/(!)-!$0!//7)!,+((!#(!/%()0*)'!++!+
$0-)!(0/!'1++(1(+#**)!++(1! '(-(0/!// R%( "7;S7
8*+/)!,+#+,)!*!(! +()(/%3+!+/1++13
*)!%)0!-!'!/ '%'%!//''0+%%*)//''!*(()%+*)('*(+ 3(1
-)!(0/#(#! +!+!+"'%#,."<"'1)' CGER+(!%"7"!(%

SRE)(!"7"!(%=SRE!"97"!(%SR)!(1"97"!(%SR+! 3?,"
7"!(%;SR+! 3?,"7"!(%	SR.#"7"!(%S7
	
3++'-!)!$01!)*!#('+"'756"31'13+'@#)!$0
(1!.*+)*)%7)!-#+((1!'@#+("	
3+)!/!))!(+7
;;;
&(-(-.	-(1.*
!/!)((1!&/)!(%!*)!'%'%'%'%/)(	
7
CCI
CCI
49&-

	
 	



	
 
	

  

CCI
49&-

	
 	

;

	
 
	

  

CCI
49&-

	
 	



	
 
	

  

CCI
49&-

	
 	

:

	
 
	

  

1!+(($%!'#(!#++%!+*1% ')++%%*!%+((!5!%+
631'1 : -#%+/
 1-!!-!%*!/!+*1%7





CCI
CCI
49&-

	
 	



	
 
	

  

;8
5-2*>****,-
('($!,#)(!!(1(*)('*(+'%'%+(#!+3%%)!'(%0$!!/(/)
()!(!(#),*)('*("+'%'%+(#!+)!!+,!(*)-!/)($#(
(1!+/!(0!//!'(-!!++/-!+(,(%!'!7
(%!(%+)!,),+*!'/'$!!/(+)+2+/)*)('*(+*)('*(,(1+
'%'%+(#00$!/#(1!''*0,&/)!'+!('#!(+7
8

!5#	
?! 

E0*(1!+!+)!%,!3(1$?!'(-!+(1!$?!'(-!+*(+($%!7
1++(#0+($!'#'(!#%(*)('*(+3(1!)(!(+!-!)!(*'!)((+7
$?!'(-!+
*(+
))0
J
!-%#(!(1!+/!(0(%!)$%(0/
	
*)('*(+ 3(1(*'
!)((+"/%%3,#%(*%!+!
+#$'#(!#++()(7
J
+"+'(#(/)+,#!(
+
.!')0
J
'1)'(!) !+!)#/)	

*)('*(+3(1(*'!)((+
/%%3,#%(*%!+!+#$'#(!#+
+()(7
J
CCI
CCI
49&-

	
 	

	

	
 
	

  

$?!'(-!+
*(+
J
'1)'(!) !)!,#%()0'!%%
*1)'0'+/	

*)('*(+3(1(*'!)((+
/%%3,#%(*%!+!+#$'#(!#+
+()(7
J
J
#*1!(0*,/)!,+
!)()0A8*%)()0
J
!+#)!+/)!(!(!+*+!
J
++!++!!),,$)2!)+/(*'
!)((++!+!'(-(07
J
!(/0%!'#%)5,!'"A)
*)(!'6$)2!)+(1(0$!
'(-!/'%'%)!+*+!A)!++('!"
*1)'0''(-(0A)(1!
!'1+/'(/	
7
J
&%A)+2$*+0$)2!)
*)!(!)+(1(0'%#!$#()!(
%(!(""*)(!$+!
%0+!+7
CCI
CCI
49&-

	
 	

=

	
 
	

  

$?!'(-!+
*(+
J
'1)'(!) !#,!'(0/
	
*)('*(+ 3(1(*'!)((+
/%%3,#%(*%!+!+#$'#(!#+
+()(
J
((!)+
J
!8*%)!(1!)!%(+1*$!(3!!
,!!('-)()!+*+!(
	
+()()!%(((1!
)!')!"*1)'0'+"
'%'%(7
J
C!)%!,!!('-)(
++'(("*1)'0'+"
'%'%('%%!'(!(1++(#0
J
 !8*%)!(1!)!%(+1*$!(3!!
,!!('-)()!+*+!((1!
()!(!(5+6+(!)!"
!'1++/+!+!7G)(')++
(1!1#,!!0$!%0 !/)
++'(3(1'%'%('%%!'(!
(1!+(#07
J
C!)%!,!!('-)(
++'(('%'%('%%!'(!
(1++(#07
9


9:
3&*-
CCI
49&-

	
 	

=

	
 
	

  

.*!'/'*)'!#)!+($!*!)/)!#),(1!+(#0"'%#, *)!+')$!(!+
++'(!-+(33+")!#(%!.!'(7= /(1!.7 !(%+/!'1*)'!#)!
)!*)-!.!'(7
9::
(*'-*&.-'**('-
+!+'%(/)!%(!%&>1!*)('*(+!%3%%$!+!3(1
	
7;,A*%'!$'!!-!)03!!2+7+!!+'%(!'++(!%&3%%$!
!/(!))!-!3/+/!(0("'%#,-!)+!!-!(+"*10+'%!8("-(%+,+"
?!'(+(!)!'(+"%$)()0(!+(+C+ /)*)('*(+(1)#,1(%!+(!
3!!2/%%3,(1!/%+!/	
A*%'!$

!-!3/(3%%$!/#)(1!)+#**%!!(!3(1
+/!(0(/)

+!+'%(/)!%&(!%>





+!!+'%($+!(1!+/!(0()!-!3#(%!$-! ++#**)(!$0>
9:;
(*'-&.-'*-'2C+-*'--*
1!+/!(0()!@#)!/)+,/!8*+*!%+((1!+!+!3%%$!%!++(1
(1()!@#)!/)+!!+'%(7
CCI
CCI
CCI
CCI
CCI
49&-

	
 	

=

	
 
	

  

8*+*!%+ ""0((!+,/%%3,)!-!3/+/!(0(/)

*)('*(+/)*))0!+'%(*!%(!@#%),)!(!)+! (1(1-!$!!
()!/):0+/%%3,(1!/)+(+!5067
8*+*!%+"0!)%% #*(*)('*(+!'1*!%78*+
*!%+3%%$!+(!)!+!+(1()!(1!+!5)%3!)6(1(1!+!(1!
'))!+*,!+'%(*!%7
9;
(-2('-2'&1.0*-
-#%+ 3(1#(#!+!+!)!(1!(!!)!'*!(+/	
7 .(#0,
	
*)('*(+3(1(*'!)((+ +')('%!8(+(!*(!/!(1!*'(/
	
+/!(0"*1)'0'!+#)!+**#%(3(1
#(#!+!+!7 (!(+3(1(*'!)((+1-!%)!0$!!+13(!8*!)!'!
'%'%$!!/(/)$+!(1!)*0 *#$%+1!+(#0 RE+!1"7E7"!(%		S +
3!%%+*#$%'%0-%$%! *)!%)01+!$()!%!+!$0!2() 1!)*!#('+7
8*+#)!+('*(!(1!*)*+! +!),!)!$!%3(1+!(1(3!)!'1!-!
3!%%(%!)(!7%+! (),3(1*)!+*!'/!+(**,)#%!+3%%$!
*%!!(!7#)(1!))!"(1!(/*)('*(+(1!!8*+*!%+3%%*!)(
(1!**)(#(0( )!')!/#%%0-!+(,(!31!(1!)	
'*)-!!,/#%
'%'%$!!/((-#%+ 3(1(*'!)((+

9;:
'-2'&-.+'-*
9;::
20-.+'-*
(+('*(!(1(+()(/	
-!)(1!*)*+!+!),!3%%$!
,!!)%%03!%%(%!)(!*)('*(+ 3(1(*'!)((+ $+!*)!'%'%+/!(0
(8'%,'% (!+(,'0%,#+2!0 7 1!+('-!)+!/,+
')++%% /(1!+!+(#!+)!'#(!#+"'%#,?!'(+(!)!'(+"31'1)!
()$%! )!-!)+$%!71!(1!)($%!-!)+!/,)!*)(!')++%%+(#!+ +
%!+*1%3(1#(!-!'!/!+*1%'!),?#)07(%%0"(1)!!
*)('*(+ %+)!*)(!0+*!"31'13+ (++'(!3(1'1,!+
*10+'%!8()!+%-!3(1#((!)-!(7
CCI
CCI
CCI
49&-

	
 	

==

	
 
	

  

,-#%+3(1(*'!)((+"%!+*1%/(!''*!+')!+!
+!)#,%!-!%+"31'1'$!/##*(*!)'!(/*(!(+71!)!/)!"$+!(1!
*)!'%'%'%'%+/!(0*)/%!+"**)*)(!+/!(0!*(+1-!$!! ')*)(!
'%#,(),/)'%'%+'%#,*10+'%!8( +#**%!!(!$0
(),!(!!-%#(/ ?!'(+(!)!'(+" ++!++!(/)!+(,-(%+,+5&"E"&"
6"%!C" %$)()0+/!(0(!+(+5+!)#'1!+()0"1!(%,0'%#,&
3(1//!)!(% (++!++/)!+*1%" #)%0++67./!(0(/)!'1+,
*!% 3%%$!')!/#%%0)!-!3! $!/)!!+'%(((1!!8(1,1!)+!7
9;:;
)&,('>-(-.+'-*
9;:8
)&,('.0-,(-.+'-*
F1%!$%3%%$!'%%!'(!/)#*1!(0*'%0+!+/')'#%(,)!,/)!@#!'0
$+%#(!'!%%'#(+(!-%#(!	
*1)'0'!//!'(#!)#%(*%!+!
'(+7
9;:9
22((0-.+'-*
1! /%%3,'%'%!*(+ 1-!$!!'1+!+!8*%)()0!*(+/)(1++(#0>
CCI
CCI
CCI
49&-

	
 	

=

	
 
	

  

9;:A
--.C+'&'&0 5',&>&*&()
9;:A:
--.C+'&'&05',&>&*&()
1!!'1+/'(/0!3(1!)*!#('++('*%!(!%0#!)+(#'1
)!+($!%!)!)!,),13$!+((%!-!),!!3)#,+()!(,*(!(+71#+"(
/#(#)!*(!(+"(+*)(((-!+(,(!(1!!(!)(+/)!+*+!))!++('!(
(1!()!(!(++(!)!"+3!%%+!(!)(+/+(1!'#)+!/#)'%'%
+(#!+71!+!!//)(+0!(/0-!%*)!'(-!A*1)'0'$)2!)+
,!!)(!/)((1(0$!((!),#!+,%!,!('$((1!)*!+7
!(/0-!%$)2!)+"$+*!'!+5!," $%'*!(+"(++#!(!)%63%%$!
'%%!'(!(+#**)(%0+!+/'!%%#%)'*!(+5!,""*)(!"""!($%(!+6
(1!)')'#%(,%!'#%!+7-!+(,(+0'%#!"$#()!(%(!(>
&%A++#!*)(!%0+!+
++#!A)$%+*%!+/)(1++(#00#!),*)(!$+!$)2!)%0+!+
#+,-)!(0/*%(/)+(1('#%'%#!"$#()!(%(!(P#++0+5!,"
.6%@#'1)(,)*10A+++*!'()!()0"'0(!()0"#1+('1!+()07
1!+! **)'1!+0$!#+!(@#(/0+%#$%!"'!%% A)(++#!$+!%0(!+(
/#)(1!)!%#'(!(1!)*0!'1+/'(A)++!+++!+!)!%(!*)!(!)+7)
#1+('1!'%%0+!+/)(+*(%'(!8('!%%#%)+()$#(0
%+$!'%#!7))!%(/*)(!!8*)!++()!+*+!((1!)*00$!*!)/)!
(!(/0-!%*)!'(-!$)2!)+(1('#%*(!(+!%!'(/)(1!)*071+
)!+!)'13#%+!)-!(!-!%*+#'1++0+/)/#(#)!'%'%#+!7
CCI
49&-

PRODUCT: MK-6194  
35
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Blood/Tissue RNA analyses
Both genome-wide and targeted RNA-based expression profiling and sequencing in blood 
and/or tissue may be performed to define gene signatures that correlate with clinical response 
to treatment with therapy. Specific gene sets may be evaluated, and new signatures may be 
identified. Individual genes may also be evaluated (eg, IL-2. MicroRNA profiling may also 
be pursued as well as exosomal profiling).
4.2.1.5.2
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.
4.2.1.6
Future Biomedical Research
The Sponsor will conduct FBR on specimens for which consent was provided during this 
study. This research may include genetic analyses (DNA), gene expression profiling (RNA), 
proteomics, metabolomics (serum, plasma), and/or the measurement of other analytes, 
depending on which specimens are consented for FBR.
Such research is for biomarker testing to address emergent questions not described elsewhere 
in the protocol and will only be conducted on specimens from appropriately consented 
participants. The objective of collecting/retaining specimens for FBR is to explore and 
identify biomarkers that inform the scientific understanding of diseases and/or their 
therapeutic treatments. The overarching goal is to use such information to develop safer, 
more effective drugs/vaccines, and/or to ensure that participants receive the correct dose of 
the correct drug/vaccine at the correct time. The details of FBR research are presented in
Appendix 6.
4.2.2
Rationale for the Use of Comparator/Placebo
Placebo will be used in this study to allow for an appropriate assessment of the safety data of 
MK-6194 and to maintain study blinding to reduce bias.
08QVCJ

	
 	

=

	
 
	

  

98
#1*2('-2'&'*
CCI
49&-

	
 	

=:

	
 
	

  

CCI
49&-

	
 	

=

	
 
	

  

988
'-2'&'*-&3-.1.0*-
+,)!,!/HF//!/)+ /3+,!!)%%03!%%(%!)(!
)!+#%(!*)!/!)!(%)!,!8*+(1(3++#+(!*)('*(+ 3(1#(#!
+!+!R("7"!(%S"R'1"7"!(%S7





,!(1!)"(1+(+#**)(+(1(
1!!8*+*!%+5!%63%%!)%%#*(
*!)*!% 0+!
#*(
"($((%((3
!+(+#**)(/#)(1!)
!-!%*!(/	
7(+!8*!'(!(1(!%3%%$!+!(



%!'()'!*(#),'%'%+(#!+3(1	
+(3))(!7#!((1!
*10+%,0/(1!(!+(!+$%$))!)"(1!!8*+#)!(%),!*)(!(1!)*!#('+$+!
#,%$+'//%+(1!+!!+(0*'%%0%(!71#+"(+!+((!(1((1!
((%''!()(/#,%$#%++!')!(!+!!+T/(1(/#+!)#
R%-!#"[7"!(%;S7#)(1!))!"(1!-,%!8*+#)!(#,%$#%++
!+((!($!T/(1(/#+!!R#"7B7"!(%		S R.1!)3" 977"!(%
		S7#!(%(!)+2/),!(8'(0+#//'!(!8*+#)!(!?'#%(!"%),!
*)(!(1!)*!#('+)!(++'(!3(1!$)0/!(%)+2(/!%!*)(!)+7
99
5----.-.4'241.02-'-
1!-!)%%+(#0$!,+31!(1!/)+(*)('*(5)(1!)%!,%%0''!*($%!)!*)!+!((-!6
*)-!+'#!(!/)!'+!(71!-!)%%+(#0!+31!(1!%+(*)('*(
'*%!(!+(1!%+(+(#0)!%(!'('("3(1)3+'+!(")+%+((/%%3#*5!"(1!
*)('*(+#$%!($!'('(!$0(1!-!+(,()67
CCI
CCI
CCI
CCI
CCI
CCI
49&-

PRODUCT: MK-6194  
39
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
For purposes of analysis and reporting, the overall study ends when the Sponsor receives the 
last laboratory result or at the time of final contact with the last participant, whichever comes 
last.
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
The clinical study may be terminated early if the extent (incidence and/or severity) of 
emerging effects/clinical endpoints is such that the risk/benefit ratio to the study population 
as a whole is unacceptable. In addition, further recruitment in the study or at (a) particular 
study site(s) may be stopped due to insufficient compliance with the protocol, GCP, and/or 
other applicable regulatory requirements, procedure-related problems or the number of 
discontinuations for administrative reasons is too high.
A primary objective of this early Phase 1 study is to identify the maximum 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), our studies include 
people of varying age, race, ethnicity, and sex. The collection and use of these demographic 
data are to follow all local laws and guidelines in keeping with the needs for participant 
08QVCJ

	
 	




	
 
	

  

'/!(%(031%!+#**)(,(1!+(#0/(1!+!+!"(+)!%(!/'()+"(1!
#!)-!+(,(7
)+*!'(-!**)-%/*)('%!-(+()!')#(!(!)%%!(')(!)"%+
23+*)('%3-!)+)!8!*(+"+(*!)((!7
A:
-(1*'-	&&
*)('*(3%%$!!%,$%!/)'%#+(1! +(#0/(1!*)('*( !!(+%%/(1!
/%%3,')(!)>

0+'2&(+--.**	)&(&*(*
7E+'%'%,++/(*'!)((+5+!/!$0(1!')(!)/E/
?2P**!86/)(%!+((1+*))((1!.')!!,-+(+!(!)!$0
*)('*((!)-!3()!-!3*(!(I+!'%1+()0'/)(/,++
(1)#,1*10+'%!8($0-!+(,()7
7)('*(I++!+!+/(%!+(!)(!+!-!)(0 ((1!&+!%!50*)!+!6G+(
+!/! $0 (1!/%%3,5+!!.!'(7**!86>

7+'+!)!($!'(!/)+0+(!'()!(!()*1((1!)*07
CCI
CCI
49&-

PRODUCT: MK-6194  
41
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
6.   Have a Body Mass Index (BMI) ≥18 and ≤38 kg/m2. BMI = weight (kg)/height (m)2 at 
the prestudy (screening) visit. See Section 8.3 for criteria on rounding to the nearest 
whole number. 
Demographics
7.   Is male or female, from ≥18 years to ≤75 years of age inclusive, at the time of providing
informed consent.
Female Participants
8.   A female participant is eligible to participate if she is not pregnant or breastfeeding, and 
at least one of the following conditions applies: 
•
Not a WOCBP
OR
•
A WOCBP and:
-
Uses a contraceptive method that is highly effective (with a failure rate of <1% 
per year), or be abstinent from heterosexual intercourse as their preferred and 
usual lifestyle (abstinent on a long-term and persistent basis), as described in 
Appendix 5 during the intervention period and for at least ~84 days after the last 
dose of study intervention. The investigator should evaluate the potential for 
contraceptive method failure (ie, noncompliance, recently initiated) in relationship 
to the first dose of study intervention. Contraceptive use by women should be 
consistent with local regulations regarding the methods of contraception for those 
participating in clinical studies.
-
Has a negative highly sensitive pregnancy test (urine or serum as required by
local regulations) before the first dose of study intervention. If a urine test cannot 
be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is 
required. In such cases, the participant must be excluded from participation if the 
serum pregnancy result is positive. Additional requirements for pregnancy testing 
during and after study intervention are in Section 8.3.6.
-
Abstains from breastfeeding during the study intervention period and for at least 
84 days after study intervention MK-6194.
-
Medical history, menstrual history, and recent sexual activity has been reviewed 
by the investigator to decrease the risk for inclusion of a woman with an early 
undetected pregnancy.
08QVCJ

PRODUCT: MK-6194  
42
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Informed Consent
9.   The participant (or legally acceptable representative) has provided documented informed 
consent/assent for the study. Skin biopsy is optional for Panels A-C and it is required for 
Panels D, E and F.
10. The participant may also provide consent/assent for FBR. However, the participant may 
participate in the study without participating in FBR.
Additional Categories
11. Participant is eligible according to the following TB screening criteria:
•
No evidence of active TB, latent TB, or inadequately treated TB as evidenced by one
of the following:
•
Negative QuantiFERON test or equivalent assay at screening or within 90 days prior 
to randomization date, OR
•
History of fully treated active or latent TB according to local standard of care. 
Investigator must verify adequate previous anti-TB treatment and provide 
documentation; these participants do not require QuantiFERON testing.
5.2
Exclusion Criteria
The participant must be excluded from the study if the participant meets any of the following 
criteria:
Medical Conditions
1.   Has known systemic hypersensitivity to the MK-6194 drug substance or other IL-2 based 
therapy, its inactive ingredients or the placebo. 
2.   Has a concurrent significant skin disease other than atopic dermatitis (such as psoriasis), 
a concurrent clinically significant disease or clinically relevant laboratory abnormalities, 
or a history of any illness or medical condition that, in the opinion of the study 
investigator or sponsor, might confound the results of the study or poses an additional 
risk to the patient by their participation in the study.
3.   Within 6 months prior to Screening, any significant organ dysfunction that is unstable or 
inadequately treated, including cardiac (see below), renal, liver, central nervous system, 
pulmonary, vascular, gastrointestinal, endocrine, psychiatric, ophthalmologic, or 
metabolic conditions or clinically significant laboratory abnormalities that place the 
patient at unacceptable risk for participation in a trial of an immunomodulatory therapy in 
the judgment of the investigator and sponsor.
4.   Mentally or legally incapacitated, has significant emotional problems at the time of 
prestudy (screening) visit or expected during the conduct of the study or has a history of 
08QVCJ

	
 	


=

	
 
	

  

'%'%%0+,/'(*+0'1()'+)!)/(1!%+(; 0!)+7)('*(+311-!1
+(#(%!*)!++0$!!)%%!(1!+(#0((1!+')!(/(1!-!+(,()7
;7E+()0/''!)5%,'067
8'!*(+>56!@#(!%0()!(!!%(#++2')')')'
+(#/(1!'!)-8)P56(1!)%,'!+(1(1-!$!!+#''!++/#%%0()!(!3(1
**)*)(!/%%3#*(1!)!/)!#%2!%0()!'#)/)(1!#)(/(1!+(#0"(1!
*/(1!-!+(,()3(1,)!!!(/(1!.*+)5!,"%,'!+(1(1-!
$!!+#''!++/#%%0()!(!X 0!)+*))((1!+')!!,-+(67
7E+()0/0')%/)'("',!+(-!1!)(/%#)!5!3B)2E!)(++'(
RBES%++=)
6"#'()%%!))10(1+"')')!-+'#%) ("+()2!"
#'()%%!10*!)(!+")#'()%%!$!(!+3(1(1+/.')!!,7
:7 E+0'%'%%0+,/'(%$)()0$)%(0"31'1"(1!*/(1!
-!+(,()"*)!+!(++/!(0''!)((1!*)('*("3%%*)!-!((1!*)('*( /)
'*%!(,(1!+(#0)3%%(!)/!)!3(1(1!(!)*)!((/(1!+(#0)!+#%(+
J
7E+1+()0/!)(!(+!-!)! *#%)0/#'((!+( $)%(0"31'1"(1!
*/(1!-!+(,()"*)!+!(++/!(0''!)((1!*)('*(7
	7E+1+()0/),)(++#!%%,)/(7
7 E+1+()0/+0*(('1!)*!+ +(!)3(13!!2+/) (")0
1+()0/++!(!1!)*!++*%!8"++!(!1!)*!+ +(!)"*1(1%' +(!)")
. +(!)7
7 E+'(-!'%'%%0+,/'(/!'(")0/!'()!@#),1+*(% ()
()!(!(3(1()-!#+(/!'(-!+#*(3!!2+*))(0-+(")0
/!'()!@#),)%(/!'(-!(1!)*0#*(3!!2+*))(0-+(7
7 E+1+()0/+,/'(#%(*%!A)+!-!)!%%!),!+5!,")#,"%(!8%%!),06 ) 1+
1*10%'(')!'()+,/'((%!)$%(05!"+0+(!'%%!),')!'(6(
*)!+')*()*)!+')*()#,+)/7 )('*(+311-!1+()0/+!-!)!
%%!),!+(1((*)!+!(+/!(0''!)((1!*)('*(0 $!!)%%!(1!
+(#0((1!+')!(/(1!-!+(,()7
=7 E+*+(-! (!+(5+6 /)E&+,"1!*((+($!+)EG")1+*+(-!E&'$
3(1 !,(-!E&+$ +!)%,!+7

7 E+ (!)%+(#(/$%5**)8(!%0;63(1 
 3!!2+*))((1!
*)!+(#05+')!!,6-+(7
;7 E+1?)+#),!)03(1=(1+*))((1!*)!+(#05+')!!,6-+()1+
?)+#),!)0*%!#),(1!+(#07
CCI
49&-

	
 	



	
 
	

  

&'&	'-(',-
)&+0
:7 E+1 *))()!(!(3(1)!'$()/!(1!)*0"'%#,
	
 5+!!.!'(7;6
7 +#$%!()!/)/)()!(!(3(1(*'%5!8'!*(*)-!%3A!# *(!'0
(*'%')('+(!)+ 3(110)')(+!7;T')!()'%!'!(!
7T')! //!)!+)!+'#!(1!)*06*))(3!!2)+0+(!'(1!)*05'%#,
#+#**)!++-!,!(+"$%,'+"')('+(!)+")*1((1!)*06/)(*'
!)((+#),(1!!()!()%7!/!)(.!'(7;/)(1!)(%%3!!'(7
	7 +#$%!()!/)/))('*(!+(1!#+!/0(1!)!'( 5+!!.!'(7;6"
'%#,*)!+')*(*)!+')*()#,+)1!)$%)!!!+$!,,
**)8(!%03!!2+5);1%/%-!+6*))(+()(/(1!(%+!/+(#0
(!)-!("(1)#,1#((1!+(#0"#(%(1!*+(+(#0-+(71!)!0$!'!)(
!'(+(1()!*!)((!5+!!.!'(7;67
7 E+)!'!-!%-!)((!#(!-)#+-''!3(1
 3!!2+*))((1!.')!!,-+(
)(!+()!'!-!%-!)((!#(!-)#+-''(#),(1!'#)+!/(1!+(#0
/)3!!2+/(!)(1!%+(+!/+(#0)#,7
7 +'#))!(%00'1)'+0+(!'5)%)()-!#+6(/!'(-!(1!)*0/)
'1)'/!'(5+#'1+*!#'0+(+"'0(!,%-)#+"1!)*!+ +(!)")(0*'%
0'$'(!)67
7 +'#))!(%0)!'!-,%0*1'0(!!*%!(,(1!)*07
&'&	'-(1&&-	-(1.0C+&-(
=7 +(1!)-!+(,(%+(#03(1
 3!!2+5); 1%/%-!+"31'1!-!)+,)!(!)6
*))((1!*)!+(#05+')!!,6-+(71!333%%$!!)-!/)(1!(!/(1!
%+(-+((1!*)!-#++(#07
(!>
J
)('*(+ $+!)-(%+(#!+)(!)-!(%)!,+()0+(#!+0$!
'%#!(1!+(#07
-'*(****,-*

7 E+H'(!)-%X
:+!'5%!+6)X
+!'5/!%!+6#*'/)(
)!'1!'2(+')!!,)()!+!05!6"1+1+()0/)+2/'()+/)
)+!+!(!+5!,"1!)(/%#)!A')0*(10)/%01+()0/%,H
+0)!6"1+#'))!'(!10*2%!)10*,!+!")+(2,''((
!'(+(1(*)%,(1!HAH'(!)-%7
CCI
49&-

PRODUCT: MK-6194  
45
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Other Exclusions
25. Under the age of legal consent.
26. Is unwilling to comply with the study restrictions (see Section 5.3).
27. A regular user of any illicit drugs except cannabis, or has a history of drug (including 
alcohol) abuse within approximately 1 year. Participants must have a negative UDS, with 
the exception of cannabis or a medicine for which there is a current prescription from a 
licensed medical provider, prior to randomization.
28. 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.
29. 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
Dietary restrictions are not required.
5.3.1.2
Fruit Juice Restrictions
Fruit juice restrictions are not required.
5.3.2
Caffeine, Alcohol, and Tobacco Restrictions
5.3.2.1
Caffeine Restrictions
Participants will be instructed to avoid the ingestion of caffeine for at least 30 minutes before 
scheduled ECGs, HR, and BP procedures/assessments.
5.3.2.2
Alcohol Restrictions
Participants will be counseled as needed to limit alcohol use to ≤1 standard drink per day or 
less than approximately 7 standard drinks per week in females, and ≤2 standard drinks per 
day or less than approximately 14 standard drinks per week in males, on average. One 
standard drink is defined as any beverage containing 14 g of pure alcohol or as defined by 
local guidelines. 
08QVCJ

PRODUCT: MK-6194  
46
PROTOCOL/AMENDMENT NO.: 008-04
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
5.3.2.3
Tobacco Restrictions
Participants will be instructed to avoid the ingestion of nicotine-containing products for at 
least 30 minutes before scheduled ECGs, HR, and BP procedures/assessments. For all time 
during the study, tobacco restriction is not required.
5.3.3
Activity Restrictions
Participants will avoid unaccustomed strenuous physical activity (ie, weightlifting, running, 
bicycling, etc) from the prestudy (screening) visit until administration of the initial dose of 
study intervention, throughout the study and until the poststudy visit.
5.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomized in the study. A minimal set of screen-failure information 
may be included, as outlined in the eCRF entry guidelines. Minimal information may include 
demography, screen-failure details, eligibility criteria, and any AEs or SAEs meeting 
reporting requirements.
5.5
Participant Replacement Strategy
If a participant discontinues from study intervention or withdraws from the study, a 
replacement participant may be enrolled if deemed appropriate by the investigator and 
Sponsor. The replacement participant will generally receive the same intervention or 
intervention sequence (as appropriate) as the participant being replaced. The replacement 
participant will be assigned a unique treatment/randomization number.
6
STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
Clinical supplies (MK-6194 or placebo) 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 differences are noted in Appendix 7.
08QVCJ

	
 	


:

	
 
	

  

$%!
.(#0(!)-!(+
CCI
49&-

	
 	




	
 
	

  

CCI
49&-

PRODUCT:  MK-6194  
49
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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.
MK-6194 sterile solution will be prepared and/or dosed per the instructions outlined in the 
Pharmacy Manual.
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.
08QVCJ

	
	

;

	


	

  

<8
*1&*'-,D5*-.',D'--.5-.-
<8:
-&3-'-**-,-
)('*(+3%%$!++,!)%0''),('*#(!),!!)(!%%'(
+'1!#%!7
+*%!%%'(+'1!#%!+*)-!$%!=7
@3L'!!-!)03!!2+
 1!+#,,!+(!+!+ 0$!?#+(!33)$+!!-%#(/+/!(0"(%!)$%(0""A)
*1)'0'($+!)-!3(1*)!-#+%0+(!)+!+7
$ !%+ "  0!)%%#*(*)('*(+7
<8;
&2('-
+()(/'($+!,!"+!8")(1!)'1)'(!)+('+3%%$!#+!(1++(#07
<88
5-.-
#$%!$%,(!'1@#!3%%$!#+!7	
 *%'!$3%%$!*)!*)!A)
+*!+!$%!/+1$0#$%!*1)'+()@#%/!+(#0+(!*!)+!%7
1!*)('*("(1!-!+(,()".*+)*!)+!%)!%!,(!5+631)!-%-!
(1!+(#0(!)-!( +()()'%'%!-%#(/(1!*)('*(+)!#3)!/
(1!(!)-!(++,!(+7
CCI
49&-

	
	

;

	


	

  

<9
1.0-&3-'-	',+-(
(!))#*(+/) (1!*)('%+*!'/!()!(!( *%)!@#)!'+#%(($!(3!!(1!
-!+(,()(1!.*+)3)((!'#!((/(1!'%%$)(-!!'+
*)('*(,!!(7
F1!(1!-#%+!/)*)('*(+*)!*)!/)$#%2+#**%0"(1!*)!*)(/
(1!+!3%%$!'/)!$0+!'!$!)/(1!+(#0+(! +(//7
F1!*)('*(+)!+!((1!+(!"(1!03%%)!'!-!+(#0(!)-!()!'(%0/)(1!
-!+(,())!+,!!"#!)!'%+#*!)-+71!(!(!/!'1+!
+(!)!(1!'%'3%%$!)!')!(1!+#)'!'#!(+)!')!(1!7
1!+!/+(#0(!)-!(+(#0*)('*(!(/'(3%%$!'/)!((1!
(!/+,$0!$!)/(1!+(#0+(!+(//(1!)(1(1!*!)++(!),(1!
+(#0(!)-!(7
<A
	'-(',-
)&+0
CCI
49&-

	
	

;

	


	

  

?((-1.-*
J
1!)!)!-%$%!((1!''#))!(#+!/	
(+*'(#!
)!+*+!+/%%3,-''(7 1!)!/)!"'')'!3(1 %'%-''(
+()+"(+)!'!!(1((1!*)('*(I+ -''($!$)#,1(#*((!
''),(%'%-''(+()+7
J
))0)$+(!)+!+/(1!..G-''(0$!+(!)!
(1)#,1#((1!+(#07
J
'(-(!-''!+5+#'1+'(-(!/%#! -''!+6+1#%$!+(!)!
''),(%'%-''(+()+31!!-!)!'%%0**)*)(!7
J
-!)((!#(!-''!+5'%#,"$#((%(!(-)'!%%""G"
G"0!%%3/!-!)"0)%(0*1"&C"+%%*8")(-)#+6)!*)1$(!
3(1
3!!2+/+')!!,"(1)#,1#((1!+(#0"/) 3!!2+/(!)(1!%+(+!/
+(#0)#,7
CCI
49&-

	
	

;=

	


	

  

<A:
*(1.('-*-.1++'&3	&
*(1
&,-2'&'+(&,*
1++'&3	&2'&-H('-('-
!/!)(.!'(7=7 5?!'(!'(+67
<+3%%$!+(//!3(1!'%%0()!*!)+!%3(1**)*)(!''!++(/#%%+!)-'!
'#(!')!1+*(%+(/'%((!)*+((#(/!'%(!)-!(7
<<
'*'.2('- $*('-
&'-)&%
%%+!!+'%(!'++3%%$!!?(%0$0(1!-!+(,()(1!.*+)7
!$!)+/(1!.*+)+/!(0)!-!3(!3%%'%#!>(1!()%'%'%)!'()"()%
'%'%+'!(+("+!)%!-!%'%'%)!'()()%$+((+('7 (%.*+)
((!!!+0'%#!(1!.."..%!")!+!)'1++'(!*1)'%,+(71!
.*+)+/!(0)!-!3(!3%%$(*#(/)(1!-!+(,())!,),-!+(,()+
!-%#(/+/!(0(%!)$%(0/)(1!*)!-#++,*!)-!+(,()+I
)!'!((+!!+'%(!(1!!8(*!%7
CCI
49&-

	
	

;

	


	

  

/"+?#,!$0(1!.*+)-!+(,()"(1!+/!(0(%!)$%(0((?#+(/0
+!!+'%("(1!+!3%%($!')!+!+*%!7+(!"*)('*(+0>
J
!'!-!(1!+!+!%!-!%(/#)(1!)!8*%)!+/!(0(%!)$%(0((1(%!-!%"
J
!'!-!%3!)+!/(1!+(#0(!)-!(53(1)3(1#(/6"
J
!'!-!(1!+!)%3!)+!+-!+!")
J
+,0$!+(**!7
)('*(+'(#(')(!))!#(%!.!'(:7
)%%!(+,/(1!!8*+!%+")0$!)!#'!)''!%%!((1!
+')!(/(1!.*+)7
<<:
'++-1*
1!/%%3,+(**,)#%!+3%%$!#+!#),(1!'#'(/(1++(#07
/0/(1!$!%3+(**,)#%!+)!!("(1!+(#03%%$!*#+!"/#)(1!)+,
3%%''#)#(%(1!.*+)1+)!-!3!(1!((%(0/(-%$%!7'(#!(1!+(#0
5?(,)!!!(3(1(1!.*+)-!+(,()6"+#$+((%!!(3%%$!
+#$((!/)**)-%7
CCI
CCI
49&-

	
	

;;

	


	

  

/0/(1!$!%3+(**,)#%!+)!!("+#$+!@#!(1,1!)+!+3%%$!%3!)!$+!
?(,)!!!(/(1!.*+)-!+(,())!)/)(1!+(#0('(#!7
CCI
49&-

	
	

;

	


	

  

<E
-&3-'-2&)-.'2)1.0
1!)!++(#0+*!'/!(!)-!( /(!)(1!!/(1!+(#07
<=
	-(1++**('*1&
1!!!),!'0#$%,'%%'!(!)3%%#+!(1!(!)-!( %%'(A) (
+'1!#%!/)(1!+(#0(#$%*)('*(+( #+2 +(#0(!)-!( !((07 1!
!!),!'0#$%,'%%'!(!)+1#%%0$!#+!'+!+/!!),!'05+!!.!'(
77671!.*+)3%%(*)-!)'!A+'%+#)!!-!%*!+)%+(+3(1(1!
'%'%+#**%!+7
1++(#0 +$%!"$#(+#**%!+)!*)-!*!%$!%P(1!)!/)!"#$%!
*1)'+()@#%/!+(#0+(!*!)+!%3%%$!#+!($%+#**%!+7.(#0(!)-!(
!((05!"+()!,(1")*(!'06+'%#!(1!%$!%(!8(P)'!A+'%+#)!
!-!%*!+)%+(+)!(*)-!7
<B
-.&.'(*
(**%'$%!7
CCI
49&-

PRODUCT:  MK-6194  
57
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL
7.1
Discontinuation of Study Intervention
Discontinuation of study intervention does not represent withdrawal from the study. As 
certain data on clinical events beyond study intervention discontinuation may be important to 
the study, they must be collected through the participant’s last scheduled follow-up, even if 
the participant has discontinued study intervention. Therefore, all participants who 
discontinue study intervention before completion of the protocol-specified treatment period 
will still continue to participate in the study as specified in Section 1.3 and Section 8.1.9, or 
if available, a PCL. 
Participants may discontinue study intervention at any time for any reason or be discontinued 
from the study intervention at the discretion of the investigator should any untoward effect 
occur. In addition, a participant may be discontinued from study intervention by the 
investigator or the Sponsor if study intervention is inappropriate, the study plan is violated, or 
for administrative and/or other safety reasons. Specific details regarding procedures to be 
performed at study intervention discontinuation are provided in Section 8.1.9.
A participant must be discontinued from study intervention, but continue to be monitored in 
the study, for any of the following reasons:
•
The participant or participant’s legally acceptable representative requests to discontinue 
study intervention.
•
Participants who receive a systemic rescue treatment or phototherapy
Note: Participants who use topical corticosteroids prior to Week 6 will be permitted to 
continue in the study.
•
The participant’s treatment assignment has been unblinded by the investigator, MSD 
subsidiary, or through the emergency unblinding call center.
•
The participant missed four doses of study intervention within the first eight weeks of the 
study.
•
The participant has a Grade 3 or higher AE (Grade 2 or higher for the system-organ class 
of Cardiac Disorders) considered related to study intervention. 
•
The participant has a medical condition or personal circumstance which, in the opinion of 
the investigator and/or Sponsor, placed the participant at unnecessary risk from continued 
administration of study intervention.
•
The participant has a positive UDS, except for cannabis, at any time during the course of 
the study. The drug screen can be confirmed by a recheck at the discretion of the 
investigator after discussion with the Sponsor.
08QVCJ

PRODUCT:  MK-6194  
58
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Note: participants may be allowed to continue the study intervention with a positive UDS 
due to the use of specific medications (see Section 6.5) if they have an active prescription 
from a licensed health care provider and the Investigator and Sponsor both agree that the 
participant may continue to participate in the study.
•
The participant meets at least one study specific stopping criterion as listed in Section 
6.6.1 
Discontinuation from study intervention is “permanent.” Once a participant is discontinued
from study intervention, they shall not be allowed to restart study intervention.
7.2
Participant Withdrawal From the Study
Participants may withdraw from the study at any time for any reason. If a participant 
withdraws from the study, they will no longer receive study intervention or be followed at 
scheduled protocol visits.
A participant must be withdrawn from the study if:
•
The participant or participant’s legally acceptable representative withdraws consent from 
the study.
Specific details regarding procedures to be performed at the time of withdrawal from the 
study, as well as specific details regarding withdrawal from 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.
•
Note: A participant is not considered lost to follow-up until the last scheduled visit for the 
individual participant. The missing data for the participant will be managed via the 
prespecified statistical data handling and analysis guidelines.
08QVCJ

PRODUCT:  MK-6194  
59
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
8
STUDY ASSESSMENTS AND PROCEDURES
•
Study procedures and their timing are summarized in the SoA.
•
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.
•
The investigator is responsible for ensuring that procedures are conducted by 
appropriately qualified (by education, training, and experience) staff. Delegation of 
study-site personnel responsibilities will be documented in the Investigator Trial File 
Binder (or equivalent).
•
All study-related medical decisions must be made by an investigator who is a qualified 
physician.
•
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
•
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of ICF may be used for screening or baseline purposes 
provided the procedure met the protocol-specified criteria and were performed within the 
time frame defined in the SoA.
•
Additional evaluations/testing may be deemed necessary by the investigator and or the 
Sponsor for reasons related to participant safety. In some cases, such evaluation/testing 
may be potentially sensitive in nature (eg, HIV, hepatitis C), and thus local regulations 
may require that additional informed consent be obtained from the participant. In these 
cases, such evaluations/testing will be performed in accordance with those regulations.
The maximum amount of blood collected from each participant over the duration of the study
will not exceed ~524 mL (Appendix 8 OR operations/laboratory manual).
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with 
the samples.
8.1
Administrative and General Procedures
8.1.1
Informed Consent
The investigator or medically qualified designee (consistent with local requirements) must 
obtain documented informed consent from each potential participant (or their legally 
acceptable representative) prior to participating in this clinical study or FBR. If there are 
changes to the participant’s status during the study (eg, health or age of majority 
requirements), the investigator or medically qualified designee must ensure the appropriate 
documented informed consent is in place.
08QVCJ

PRODUCT:  MK-6194  
60
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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.
If the investigator recommends continuation of study intervention beyond disease 
progression, the participant or their legally acceptable representative will be asked to provide 
documented informed consent.
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 
08QVCJ

PRODUCT:  MK-6194  
61
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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, including any 
protocol-specified washout requirement, and record prior medication taken by the participant 
within 10 weeks before first dose of study intervention.
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 participant 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.
8.1.7
Assignment of Treatment/Randomization Number
All eligible participants will be randomly allocated and will receive a 
treatment/randomization number. The treatment/randomization number identifies the 
participant for all procedures occurring after treatment randomization. Once a 
treatment/randomization number is assigned to a participant, it can never be reassigned to 
another participant.
A single participant cannot be assigned more than 1 treatment/randomization number.
08QVCJ

PRODUCT:  MK-6194  
62
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
8.1.8
Study Intervention Administration
Study intervention(s) will be administered by the investigator and/or study staff according to 
the specifications within the pharmacy manual.
8.1.8.1
Timing of Dose Administration
All doses of study intervention will be given in the morning at approximately the same time.
8.1.9
Discontinuation and Withdrawal
The investigator or study coordinator must notify the Sponsor when a participant has been 
discontinued/withdrawn from the study and/or intervention. If a participant discontinues for 
any reason at any time during the course of the study and/or intervention, 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 8.10.4  to have the applicable procedures conducted. However, the 
investigator may decide to perform the poststudy procedures at the time of discontinuation or 
as soon as possible after discontinuation. If the poststudy visit occurs prior to the safety 
follow-up time frame as specified in Section 8.4.1, 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.
08QVCJ

PRODUCT:  MK-6194  
63
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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 toxicity 
grade 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.
8.1.11
Domiciling
Not applicable for this study.
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/Disease Activity Assessments
There are no direct efficacy assessments in this study; surrogate markers of efficacy are 
outlined in Section 8.7.
8.2.1
Skin Biopsy and Dermatologic Photography
To participate in the skin biopsy and dermatologic photography, to capture lesions of interest 
or importance, the participant must be willing to give written consent for these specific 
procedures. Skin biopsies and/or photography must not be obtained on participants who 
refuse consent for biopsies and/or photography. A participant may be exempted from 
08QVCJ

	
	



	


	

  

*)('*((1!$*+!+((1!+')!(/(1!-!+(,()+(%%*)('*(!!%+
"&)/(1!()%7)('*((1!$0*1(,)*10+*(%7
!(%!+()#'(/)+2$*+0!)(%,'*1(,)*103%%$!*)-!(1!
.(#0*!)(+A$)()0#%7
=8
20****,-*
!(%+)!,),+*!'/'+/!(0*)'!#)!+A++!++!(+($!*!)/)!(1++(#0)!
*)-!71!((%#(/$%A(++#!($!)3A'%%!'(!-!)(1!'#)+!/(1!+(#0
5/)*)!+(#0(*+(+(#0-+(+6"'%#,**)8(!$%A(++#!-%#!+
)3A'%%!'(!$0-+($0+*%!(0*!*!)*)('*("'$!/# **!87
%!(! *(+/)%%+/!(0++!++!(+)!*)-!(1!.7
=8:
)0*(C,-'-*
'*%!(!*10+'%!8(3%%$!'#'(!$0-!+(,())!'%%0@#%/!
!+,!!5'++(!(3(1%'%)!@#)!!(+6*!)+((#(%+()7E!,1(3!,1(
3%%%+$!!+#)!)!')!7
-!+(,()++1#%*0+*!'%((!(('%'%+,+)!%(!(*)!-#++!)#+
%%!++!+7
5
&!@#%+*!)+Q+3!,1(2%,)+-!$01!,1(!(!)++@#)!
5&L2,A67& 3%%$!)#!((1!!)!+(31%!#$!)''),((1!+()
'-!(/7 (7
)#37; (7	)##*7
&03!,1(1!,1(3%%$!$(!3(1(1!*)('*(I++1!+//?'2!()'(
)!-!7
=8;
-H('-('-*
CCI
49&-

	
	

;

	


	

  

=88
?-*
J
!*!)(#)!"E""&3%%$!++!++!7 1!+!!(1#+($!#+!/)%%
!+#)!!(+/)!'1-#%*)('*(7
J
&*#%+!!+#)!!(+3%%$!++!++!+!)!'#$!(*+( 3(1
'*%!(!%0#((!!-'!7#%(!'1@#!+3%%$!#+!%0/#((!
!-'!+(-%$%!7
J
&*#%+!!+#)!!(++1#%$!*)!'!!$0(%!+( #(!+/)!+(/)(1!
*)('*( @#!(+!((,3(1#(+()'(+7
J
G.+($!(2!$!/)!$%'%%!'(/)%$)()0(!+(+7
CCI
49&-

PRODUCT:  MK-6194  
66
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
8.3.3.1
Resting Vital Signs
Vital Sign Measurements (Heart Rate and Blood Pressure)
Participants should be resting in a quiet setting without distractions in a semirecumbent or 
supine position for at least 10 minutes before having VS measurements obtained. 
Semirecumbent VS will include HR, systolic and diastolic BP, RR, and BT at timepoints 
indicated in the SoA. The correct size of the BP cuff and the correct positioning on the 
participants' arm is essential to increase the accuracy of BP measurements.
The screening, predose (baseline) HR and BP will be a single measurement within 3 hours of 
dosing MK-6194/placebo. Postdose VS measurements will be single measurements.
Body Temperature
BT will be measured. The same method must be used for all measurements for each 
individual participant and should be the same for all participants.
8.3.4
Electrocardiograms
•
All ECGs will be obtained and reviewed by an investigator or medically qualified 
designee (consistent with local requirements) as outlined in the SoA (see Section 1.3) 
using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, 
and QTc intervals. Refer to Appendix 9 for evaluation and potentially significant 
findings.
•
Day 1 Predose ECGs will be obtained in triplicate at least 1to 2 minutes apart within 
3 hours prior to dosing MK-6194/placebo.  In addition, Day 1 12 hour ECG will be 
measured in triplicate. All other post-dose ECG measurements will be single 
measurements (Refer to Section 1.3).
•
Special care must be taken for proper lead placement by qualified personnel. Skin should 
be clean and dry before lead placement. Participants may need to be shaved to ensure 
proper lead placement. Female participants may need to remove interfering garments.
•
Participants should be resting in the semirecumbent position for at least 10 minutes 
before each ECG measurement.
•
The correction formula to be used for QTc is Fridericia.
•
If repeat ECGs are required, the clinical site will decide whether to leave the electrodes in 
place or mark the position of the electrodes for subsequent ECGs. To mark the position of 
the electrodes, 12-lead electrode sites will be marked on the skin of each participant with 
an ECG skin-marker pen to ensure reproducible electrode placement.
08QVCJ

PRODUCT:  MK-6194  
67
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
For Single ECG Measurement:
•
During each treatment period, if a participant demonstrates an increase in QTc interval 
≥60 msec compared with predose baseline measurement, the ECG will be repeated twice 
within 5 minutes. The median value of the QTc interval from the 3 ECGs will represent 
the value at that time point. If the median QTc interval increase from baseline for any 
postdose time point is ≥60 msec, the participant will continue to be monitored by repeat 
12-lead ECGs every 15 minutes for at least 1 hour or until the QTc is within 60 msec of 
baseline. If prolongation of the QTc interval ≥60 msec persists, a consultation with a 
study cardiologist may be appropriate and the Sponsor should be notified.
•
During each treatment period, if a participant demonstrates a QTc interval ≥500 msec on 
a postdose ECG, the ECG will be repeated twice within 5 minutes. The median value of 
the QTc interval from the 3 ECGs will represent the value at that time point. If the 
median QTc interval is ≥500 msec, the Sponsor should be notified and the ECGs should 
be reviewed by a cardiologist. The participant should be telemetry monitored (until the 
QTc is <500 msec) or should be considered for transfer to a location where closer 
monitoring and definitive care (eg, a CCU or ICU) is available.
For Triplicate ECG Measurements:
•
At each time point when triplicate ECGs are required, 3 individual ECG tracings should 
be obtained at least 1-2 minutes apart. The full set of triplicates should be completed in 
no more than 6 minutes.
•
Before each treatment administration on Day 1, predose ECGs will be obtained in 
triplicate approximately 1 to 2 minutes apart within 3 hours before dosing MK-
6194/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).
•
During each treatment administration, if a participant demonstrates a median increase in 
QTc interval ≥60 msec compared to the median predose baseline measurement, the 
participant will continue to be monitored by at least single repeat 12-lead ECGs every 
15 minutes for at least 1 hour or until the QTc is within 60 msec of baseline. If 
prolongation of the QTc interval ≥60 msec persists, a consultation with a cardiologist 
may be appropriate and the Sponsor should be notified.
•
During each treatment period, if the median QTc interval is ≥500 msec for postdose 
measurements, the Sponsor should be notified and the ECGs should be reviewed by a 
cardiologist. The participant should be telemetry monitored (until the QTc is <500 msec) 
or should be considered for transfer to a location where closer monitoring and definitive 
care (eg, a CCU or ICU) is available.
If the participant has unstable hemodynamics, or has any clinically significant dysrhythmias 
noted on telemetry, the participant should be immediately transferred to an acute care setting 
for definitive therapy.
08QVCJ

PRODUCT:  MK-6194  
68
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
If prolongation of the QTc is noted, concomitant medications that prolong QTc should be 
held until the QTc is within 60 msec of baseline and the QTc is <500 msec.
A cardiologist will be consulted by the investigator as needed to review ECG tracings with 
significant abnormalities.
8.3.5
Clinical Safety Laboratory Assessments
Refer to Appendix 2 for the list of clinical laboratory tests to be performed and to the SoA for 
the timing and frequency.
•
The investigator or medically qualified designee (consistent with local requirements) 
must review the laboratory report, document this review, and record any clinically 
relevant changes occurring during the study in the AE section of the CRF. The laboratory 
reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless 
judged by the investigator to be more severe than expected for the participant’s condition.
•
All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA.
•
If laboratory values from nonprotocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in study participant management or are 
considered clinically significant by the investigator (eg, SAE or AE or dose 
modification), then the results must be recorded in the appropriate CRF (eg, SLAB).
•
For any laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 84 days after the last dose of study intervention, every 
attempt should be made to perform repeat assessments until the values return to normal or 
baseline or if a new baseline is established as determined by the investigator.
8.3.6
Pregnancy Testing
•
Pregnancy testing:
-
Pregnancy testing requirements for study inclusion are described in Section 5.1.
-
Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at timepoints indicated in the SoA during/after intervention.
-
Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at the end of relevant systemic exposure.
-
Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the investigator or required by local regulation, to establish the absence 
of pregnancy at any time during the subject's participation in the study.
08QVCJ

	
	

	

	


	

  

=9
.3&*3-*!&'1*.3&*3-*! -.)&+'&/203-*
1!!/(+/)."+3!%%+(1!!(1/)!'),"!-%#(,"
++!++,'#+%(0/.(1!*)'!#)!+/)'*%!(,()+((,"
."(1!))!*)($%!+/!(0!-!()!*)(+'$!/#**!8=7
-!)+!!-!(+".+"(1!))!*)($%!+/!(0!-!(+3%%$!)!*)(!$0(1!*)('*(
5)"31!**)*)(!"$0')!,-!)"+#)),(!")(1!*)('*(Q+%!,%%0#(1) !
)!*)!+!((-!67
1!-!+(,() 0!+,!!+)!)!+*+$%!/)!(!'(,"'#!(,")!*)(,
!-!(+(1(!!((1!!/(/) .+3!%%+(1!))!*)($%!+/!(0!-!(+7
-!+(,()+!!('#!(/.3+++'(!3(1!'(!)))"+#+!")
$#+!7
-!+(,()+)!)!+*+$%!/)/%%3,#*+".+"(1!))!*)($%!+/!(0
!-!(+/)#('!''),(.!'(7
7=7 1!-!+(,()"31+@#%/!*10+'"
3%%++!++!-!(+(1(!!((1!!/(/).+3!%%+(1!))!*)($%!+/!(0
!-!(+3(1)!+*!'((+!)#+!++"(!+(0A(8'(0'#+%(07
=9:

,&'.-.&61-(02'&	'(-!! -.)&+'&/
203--2'&,'-
+".+"(1!))!*)($%!+/!(0!-!(+(1(''#)/(!)(1!*)('*(*)-!+
'#!(!/)!'+!("$#($!/)!(!)-!( %%'(A) ("#+($!
)!*)(!$0(1!-!+(,() #!) 0/(1!/%%3,')'#+('!+>
J
/(1!*)('*(+)!'!-,*%'!$)#)(1!))#()!(!("
J
/(1!!-!('#+!+(1!*)('*(($!!8'%#!/)(1!+(#0"
J
/(+(1!)!+#%(/*)('%+*!'/!(!)-!("'%#," $#((%(!(3+1#(
)+'(#(/#+#%(1!)*0"!("*%'!$")*)'!#)!7
)(1!(!/(!)-!( ) ((1)#,1V
 0+/(!)'!++(/
(!)-!("%%+".+(1!))!*)($%!+/!(0!-!(+#+($!)!*)(!$0(1!
-!+(,()7
(%%0"0.$)#,1(((1!((!(/-!+(,()0(!#(+!(1!*!)
+*!'/!(1!*)!-#+*),)*1%+#+($!)!*)(!!(!%0((1!.*+)/(1!
!-!(+ '+!)!)!%(!(+(#0(!)-!(7
CCI
49&-

PRODUCT:  MK-6194  
70
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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.
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 4.
Exception: A positive pregnancy test at the time of initial screening is not a reportable event 
unless the participant has received study intervention.
Table 4
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
08QVCJ

PRODUCT:  MK-6194  
71
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Type of Event
Reporting Time 
Period:
Consent to 
Randomization/ 
Allocation
Reporting Time 
Period:
Randomization/ 
Allocation through 
Protocol-specified 
Follow-up Period
Reporting Time 
Period:
After the Protocol-
specified Follow-up 
Period
Time Frame to 
Report Event and 
Follow-up 
Information to 
Sponsor:
ECI (require 
regulatory 
reporting)
Report if:
- due to intervention
- causes exclusion
Report
- potential DILI
- require regulatory 
reporting
Not required
Within 24 hours of 
learning of event
ECI (do not 
require 
regulatory 
reporting)
Report if:
- due to intervention
- causes exclusion
Report
- non-DILI ECIs and 
those not requiring 
regulatory reporting
Not required
Within 5 calendar 
days of learning of 
event
Cancer
Report if:
- due to intervention
- causes exclusion
Report all
Not required
Within 5 calendar 
days of learning of 
event
(unless serious)
Overdose
Report if:
- receiving placebo 
run-in or other run-
in medication 
Report all
Not required
Within 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.
08QVCJ

	
	

:

	


	

  

-!+(,()+/!(0)!*)(+#+($!*)!*)!/).<.+ ''),(%'%)!,#%()0
)!@#)!!(+.*+)*%'0/)3)!(-!+(,()++!'!++)07
-!+(,()31)!'!-!+-!+(,()+/!(0)!*)(!+')$,.)(1!)
+*!'/'+/!(0/)(5!,"+#)0)%+(,/.6/)(1!.*+)3%%/%!(
%,3(1(1!& 3%%(/0(1!&A"/**)*)(!''),(%'%)!@#)!!(+7
=9A
&--(0-.C+'*1&1&-5&*2.-
%(1#,1*)!,'0/(!8*+#)!#),$)!+(/!!,)!('+!)!+"0
*)!,'0)/(!8*+#)!#),$)!+(/!!,*)('*(5+*(!#+%0)!*)(!(
(1!-!+(,())(1!)!+,!!6(1(''#)+#),(1!+(#0)!)!*)($%!((1!.*+)7
%%)!*)(!*)!,'!+#+($!/%%3!((1!'*%!(A(!)(/(1!*)!,'07
0*)!,'0'*%'(3%%$!)!*)(! +).7
1!!'%)!+5!8*%!>(!)%1!%(1)/!(%+!+!6/)!%!'(-!(!)(/
*)!,'03%%$!)!*)(!+).7)!(%(!+(,+13,/!(#+3%%$!$)
3(1+!-!)!$)%(!+A',!(%%!+(1(%!+(!%!'(-!(!)(/
*)!,'03%%$!)!*)(!+./)(1!/!(#+7
)!,'0#('!+/!'(*'*)!,'0"+*(!#+$)("++!$)("$!,
10(/)%!"$%,1(!-#"/!(%!(1"()#(!)!!(1"+')),!"+(%%$)(1
#+($!)!*)(!++!)#+!-!(+5*)((!'%-!(+67/(1!*)!,'0'(#!+(
(!)"(1!#('!51!%(1//(6#+(%+$!)!*)(!7
=9<
**4&.3-*-.'&**4&.1(',*'G120-*
*'&*
+!+!)!%(!!-!(+A)+!+!)!%(!#('!+(@#%/0,++).+)!
(**%'$%!((1++(#07
CCI
49&-

	
	

:=

	


	

  

=A

&,-'23&.'*
)*#)*+!+/(1++(#0"-!)+!3%%$!!/!+0+!/0)#,+(!)!
+*)(/(1!+(#0!8'!!,(1!+!*)!+')$!$0(1!*)('%7(+#*((1!-!+(,()
)(1!)!*)(,*10+'(!'!31!(1!)+!+($!'+!)!-!)+!"
'+#%((3(1(1!.*+)7
.*+)!+()!'!+*!'/'()!(!(/)-!)+!7!'++)!,),+!
(!))#*(+)/'(+3%%$!!$0(1!-!+(,()'+#%((3(1(1!
.*+)%'%)!'()$+!(1!'%'%!-%#(/(1!*)('*(7
=<
)&,('>-(*
1!!'++(31'1+!)# +*%!+'%%!'(!3%%$!!+#)! /)!-%#(/
A*1)'0'+3%%$!'%%$)(-!%0!(!)!$0(1!.*+)5!,"+*%!+(
%3!)+!+0($!!+#)! /+*%!+(1,1!)+!+)!-!%#!(!'($%!)#,
''!()(+67/'(!"(1!+!+*%!+0%+$!!+#)! A)*%!/)++0
!8*%)()0!)/)!($%(!+A)(%*1)'0')2!)+7
=<:
5''.	'('-2'&&1, 4<:B9
.*%!'%%!'("+(),!"+1*!(+()#'(+/)+!)# +*%!+3%%$!*)-!
(1!.(#0 *!)(+ #%7
CCI
49&-

PRODUCT:  MK-6194  
74
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
8.7
Pharmacodynamics
Please refer to Section 4.2.1.4 Pharmacodynamic Endpoints for details. Sample collection, 
storage, and shipment instructions for pharmacodynamic samples will be in Study Operations 
Manual.
8.8
Biomarkers
Collection of samples for other biomarker research is also part of this study. The following 
samples for biomarker research are required and will be collected from all participants as 
specified in the SoA:
•
Blood for Planned Genetic Analysis
•
Blood for Serum Biomarkers
•
Blood for Paxgene RNA Biomarkers
•
Blood for Paxgene DNA Biomarkers
•
Blood for PBMC Biomarkers
•
Skin Biopsy for Biomarkers
8.8.1
Planned Genetic Analysis Sample Collection
8.8.2
Exploratory Biomarkers
To further inform on MK-6194 pharmacodynamics and/or mechanism of action under 
multiple dose conditions the following biospecimens to support exploratory analyses of 
cellular components (eg, protein, RNA, DNA) and other circulating molecules will be 
collected from all participants in this study as specified in the SoA. Sample collection, 
storage, and shipment instructions for the exploratory biomarker specimens will be provided 
in the Study Operations/Laboratory Manual. 
8.8.3
Immunogenicity Assessments
Samples for ADA will be collected prior to administration of MK-6194 on each scheduled 
day of study intervention and at other specific timepoints as specified in the SoA. Detected 
ADA titers will be confirmed. Assaying to detect neutralizing antibodies may be performed.
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
•
Leftover main study serum from MK-6194 assay stored for future research
08QVCJ

PRODUCT:  MK-6194  
75
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
•
Leftover main study serum from ADA assay stored for future research
•
Leftover samples listed in Section 8.8 Biomarkers (including any extracted material from 
samples)
8.10
Visit Requirements
Visit requirements are outlined in Section 1.3. Specific procedure-related details are provided 
in Section 8.
8.10.1
Screening
Approximately 4 weeks before intervention randomization, potential participants will be 
evaluated to determine that they fulfill the entry requirements as set forth in Section 5.
Participants may be rescreened after consultation with the Sponsor. Rescreening should 
include all screening procedures listed in the SoA, including consent review. Rescreen 
procedures cannot be conducted the day prior to intervention randomization if there are Day
1 procedures planned per protocol.
8.10.2
Treatment Period Visit
Refer to the SoA (Section 1.3) and Administrative and General Procedures (Section 8.1).
8.10.3
Participants Discontinued From Study Intervention but Continuing to be 
Monitored in the Study
At any point if a participant discontinues from treatment but continues to be monitored in the 
study, all or a subset of study procedures specified in the SoA may be completed at the 
discretion of the investigator and with Sponsor agreement. The subset of study procedures 
completed will be communicated in a PCL.
8.10.4
Poststudy Visit
Participants will be required to return to clinic approximately 84 days after the last dose of 
study intervention for the poststudy visit. If the poststudy visit occurs less than 84 days after 
the last dose of study intervention, a subsequent follow-up telephone call should be made at 
84 days post the last dose of study intervention to determine if any AEs have occurred since 
the poststudy clinic visit.
8.10.5
Critical Procedures Based on Study Objectives: Timing of Procedure
For this study, the blood sample for MK-6194 is the critical procedure.
At any postdose time point, the blood sample for MK-6194 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.
08QVCJ

	
	

:

	


	

  

1!)!)/*))(0'$!'1,!#),(1!+(#03(1?(,)!!!(/(1!-!+(,()
(1!.*+)%'%)!'()7
0+'1!#%!*)'!#)!+)!@#)!/)#),!(!-%#(/+/!(0''!)+(2!
*)!'!!'!-!)%%)#(!+'1!#%!*)'!#)!+7
1!/%%3,-)'!*)'!#)!'%%!'((!+3%%$!*!)((!7
J
A*1)'0' %%!'(+#(%!$%!;
=:@<
1.0*-'*-&'(.1&*'.2('-*&,.")-&''('
&,&*
1++1+!++!++!(/	
 1#+"(1!"*1)'0'"
+/!(0*)/%!+/(1!'*#)! +(%%$!,!%#'(!71+*)('%+3)((!3(1+!
/%!8$%(0(''(!(1!1!)!(0'(#)!/1+!'%'%+(#!+7
CCI
49&-

PRODUCT:  MK-6194  
77
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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 total biweekly dose may not 
exceed those currently outlined in the protocol.
•
Repeat of or decrease in the dose of the study intervention administered in any given 
period/panel
•
Interchange of doses between panels
•
Entire panel(s) may be omitted
•
Decrease in the duration of study intervention administration (eg, number of doses)
•
Adjustment of the dosing interval (eg, q3w, but not to be more frequent than q2w)
•
Remove a planned PK pause if agreed by Sponsor and investigator if no further 
increases in total daily dose
•
Addition of study pause
•
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.
08QVCJ

	
	

:

	


	

  

B



	
B:
*(-0**-1,,&0
20
'!'!/-!)+!!8*!)!'!+3%%$!!+')*(-!%0+#) !7.#)0+((+('+
*%(+3%%$!,!!)(!/)(1!'1,!/)$+!%!-%#!+!(1!)$!'*#(!),%
+'%!5)3'1,!/)$+!%!6)(1!%,+'%!$'2()+/)!/))!*)(,
5*!)'!('1,!/)$+!%!6(1!'!'!/+ +'(#(/+,#!(
+"+!!!'%'%%0**)*)(!7
B;
*+'-*/02'&-0**
1!+((+('%%0++/(1!($(!/)(1++(#03%%$!'#'(!$0")#!)(1!
)!'(#+*'!+/" (1!)%0%'%!-!%*!(.((+('+!*)(!('%%$)(
CCI
49&-

	
	

:	

	


	

  

3(1 (1!H#(((-!1)'%,01)'!()'+!*)(!()+%(%
!'! !*)(!(/(1!.*+)7
/"/(!)(1!+(#01+$!,#"'1,!+)!!((1!+((+('%%0++*%+((!$!%3"
(1!(1!+!!-(+((1!*%3%%$!%+(!"%,3(1!8*%(+(310(1!0
''#))!"(1!%'%.(#0!*)(7
B8
0+')***,'-
B9
-0**-.+'-*
&,&0-.+'-*
./!(0>+7
('-.&0-.+'-*
1)'0'>#*1!(0*,/)!,+
C+'&'&0-.+'-*
BA
-0**'+1'-*
1!/%%3,**#%(+)!!/!/)(1!%0++)!*)(,/((1++(#07%%
*)('*(+3%%$!)!*)(!"(1!)(%0 !"''),((1!()!(!(5+6(1!0
)!'!-!7
CCI
CCI
CCI
CCI
49&-

	
	



	


	

  

B<
*()'.*
&,&0-0**
20 '!'!/-!)+!!8*!)!'!+3%%$!!+')*(-!%0+#) !7.#)0
+((+('+*%(+3%%$!,!!)(!/)(1!'1,!/)$+!%!-%#!+!(1!)$!'*#(!
),%+'%!5)3'1,!/)$+!%!6)(1!%,+'%!$'2()+/)!/)
)!*)(,5*!)'!('1,!/)$+!%!6(1!'!'!/+ +'(#!/+,
#!(+"+!!!'%'%%0**)*)(!7
('-.&0-0**
CCI
CCI
49&-

	
	



	


	

  

C+'&'&0-0**
BE
-&,-0**
#),(1!%/!*)(/(1!()%"!+')*(-!+#)0%!-!%)!+#%(+5"
*1)'0'+"$)2!)+A)+/!(06 3%%$!*)!*)!+!!! (+#**)(!'+
2,!!(,++#'1++!!+'%(!!(,+71!,,)!,(! +#)!+3%%$!
*)!+!(!%0/)!'1+!%!-!%+**)*)(!7

'1,!/)
CCI
CCI
CCI
49&-

	
	



	


	

  

$+!%!.3%%$!*)-!((1!(!)%0++ (3!!2 $+!(1!-%$%(0/
(1!((1!)'%'% !+#)!+ 0%+$!+#) !((1!(!)(!*(+7
B=
1+(0
?#+(!(/)#%(*%'(0+!!!+'!+/!(0+(1!*))0!*(%0!
10*(1!+++/)+!')0!*(3%%$!(!+(!7
BB
,+D-.'F&	(1'-*
GL'!//'!(/-)(PL*+(!))*)$$%(0P.L+()!-(7
.%,+'%!5+6Ld%,5Ge67
CCI
49&-

PRODUCT:  MK-6194  
83
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS
10.1
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1
Code of Conduct for Clinical Trials
Merck Sharp & Dohme LLC, Rahway, NJ, USA (MSD)
Code of Conduct for Interventional Clinical Trials
I. Introduction
A. Purpose
MSD, through its subsidiaries, conducts clinical trials worldwide to evaluate the safety and effectiveness of our 
products. As such, we are committed to designing, implementing, conducting, analyzing, and reporting these trials 
in compliance with the highest ethical and scientific standards. Protection of participants in clinical trials is the 
overriding concern in the design and conduct of clinical trials. In all cases, MSD clinical trials will be conducted 
in compliance with local and/or national regulations (including all applicable data protection laws and
regulations), and International Council for Harmonisation Good Clinical Practice (ICH-GCP), and also in 
accordance with the ethical principles that have their origin in the Declaration of Helsinki.
B. Scope
Highest ethical and scientific standards shall be endorsed for all clinical interventional investigations sponsored by 
MSD irrespective of the party (parties) employed for their execution (e.g., contract research organizations, 
collaborative research efforts). This Code is not intended to apply to trials that are observational in nature, or 
which are retrospective. Further, this Code does not apply to investigator-initiated trials, which are not under the 
full control of MSD.
II. Scientific Issues
A. Trial Conduct
1. Trial Design
Except for pilot or estimation trials, clinical trial protocols will be hypothesis-driven to assess safety, efficacy 
and/or pharmacokinetic or pharmacodynamic indices of MSD or comparator products. Alternatively, MSD 
may conduct outcomes research trials, trials to assess or validate various endpoint measures, or trials to 
determine patient preferences, etc.
The design (i.e., participant population, duration, statistical power) must be adequate to address the specific 
purpose of the trial and shall respect the data protection rights of all participants, trial site staff and, where 
applicable, third parties. All trial protocols are and will be assessed for the need and capability to enroll 
underrepresented groups. Participants must meet protocol entry criteria to be enrolled in the trial. 
2. Site Selection
MSD’s clinical trials are conducted globally in many different countries and in diverse populations, including 
people of varying age, race, ethnicity, gender, and accounting for other potential disease related factors. MSD 
selects investigative sites based on medical expertise, access to appropriate participants, adequacy of facilities 
and staff, previous performance in clinical trials, as well as budgetary considerations. Prior to trial initiation, 
sites are evaluated by MSD personnel (or individuals acting on behalf of MSD) to assess the ability to 
successfully conduct the trial.
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 
08QVCJ

PRODUCT:  MK-6194  
84
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
underrepresented groups and those disproportionately impacted by the disease under study. MSD will support 
clinical trial investigators to enroll underrepresented groups and expand access to those who will ultimately 
use the products under investigation.
3. Site Monitoring/Scientific Integrity
Investigative trial sites are monitored to assess compliance with the trial protocol and Good Clinical Practice 
(GCP). MSD reviews clinical data for accuracy, completeness, and consistency. Data are verified versus 
source documentation according to standard operating procedures. Per MSD policies and procedures, if
potential fraud, scientific/research misconduct, privacy incidents/breaches or Clinical Trial-related 
Significant Quality Issues are reported, such matters are investigated. When necessary, appropriate corrective 
and/or preventative actions are defined and regulatory authorities and/or ethics review committees are 
notified.
B. Publication and Authorship
Regardless of trial outcome, MSD commits to publish the primary and secondary results of its registered trials of 
marketed products in which treatment is assigned, according to the pre-specified plans for data analysis. To the 
extent scientifically appropriate, MSD seeks to publish the results of other analyses it conducts that are important 
to patients, physicians, and payers. Some early phase or pilot trials are intended to be hypothesis-generating rather 
than hypothesis testing; in such cases, publication of results may not be appropriate since the trial may be 
underpowered and the analyses complicated by statistical issues such as multiplicity.
MSD’s policy on authorship is consistent with the recommendations published by the International Committee of 
Medical Journal Editors (ICMJE). In summary, authorship should reflect significant contribution to the design and 
conduct of the trial, performance or interpretation of the analysis, and/or writing of the manuscript. All named 
authors must be able to defend the trial results and conclusions. MSD funding of a trial will be acknowledged in 
publications.
III. Participant Protection
A. Regulatory Authority and Ethics Committee Review (Institutional Review Board [IRB]/Independent Ethics 
Committee [IEC])
All protocols and protocol amendments will be submitted by MSD for regulatory authority 
acceptance/authorization prior to implementation of the trial or amendment, in compliance with local and/or 
national regulations.
The protocol, protocol amendment(s), informed consent form, investigator’s brochure, and other relevant trial 
documents must be reviewed and approved by an IRB/IEC before being implemented at each site, in compliance 
with local and/or national regulations. Changes to the protocol that are required urgently to eliminate an 
immediate hazard and to protect participant safety may be enacted in anticipation of ethics committee approval. 
MSD will inform regulatory authorities of such new measures to protect participant safety, in compliance with 
local and/or national regulations.
B. Safety
The guiding principle in decision-making in clinical trials is that participant welfare is of primary importance. 
Potential participants will be informed of the risks and benefits of, as well as alternatives to, trial participation. At 
a minimum, trial designs will take into account the local standard of care.
All participation in MSD clinical trials is voluntary. Participants enter the trial only after informed consent is 
obtained. Participants may withdraw from an MSD trial at any time, without any influence on their access to, or 
receipt of, medical care that may otherwise be available to them.
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 
08QVCJ

PRODUCT:  MK-6194  
85
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
behalf of MSD), ethics committee, and/or regulatory authorities will have access to confidential medical records 
that might identify the participant by name.
D. Genomic Research
Genomic research will only be conducted in accordance with a protocol and informed consent authorized by an 
ethics committee.
IV. Financial Considerations
A. Payments to Investigators
Clinical trials are time- and labor-intensive. It is MSD’s policy to compensate investigators (or the sponsoring 
institution) in a fair manner for the work performed in support of MSD trials. MSD does not pay incentives to 
enroll participants in its trials. However, when enrollment is particularly challenging, additional payments may be 
made to compensate for the time spent in extra recruiting efforts.
MSD does not pay for participant referrals. However, MSD may compensate referring physicians for time spent 
on chart review and medical evaluation to identify potentially eligible participants.
B. Clinical Research Funding
Informed consent forms will disclose that the trial is sponsored by MSD, and that the investigator or sponsoring 
institution is being paid or provided a grant for performing the trial. However, the local ethics committee may 
wish to alter the wording of the disclosure statement to be consistent with financial practices at that institution. As 
noted above, all publications resulting from MSD trials will indicate MSD as a source of funding.
C. Funding for Travel and Other Requests
Funding of travel by investigators and support staff (e.g., to scientific meetings, investigator meetings, etc.) will be 
consistent with local guidelines and practices.
V. Investigator Commitment
Investigators will be expected to review MSD’s Code of Conduct as an appendix to the trial protocol, and in signing the 
protocol, agree to support these ethical and scientific standards.
10.1.2
Financial Disclosure
Financial disclosure requirements are outlined in the US Food and Drug Administration 
Regulations, Financial Disclosure by Clinical Investigators (21 CFR Part 54). It is the 
Sponsor’s responsibility to determine, based on these regulations, whether a request for 
financial disclosure information is required. It is the investigator’s/subinvestigator’s 
responsibility to comply with any such request.
The investigator/subinvestigator(s) agree, if requested by the Sponsor in accordance with 21 
CFR Part 54, to provide his/her financial interests in and/or arrangements with the Sponsor to 
allow for the submission of complete and accurate certification and disclosure statements. 
The investigator/subinvestigator(s) further agree to provide this information on a 
Certification/Disclosure Form, frequently known as a financial disclosure form, provided by 
the Sponsor. The investigator/subinvestigator(s) also consent to the transmission of this 
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.
08QVCJ

PRODUCT:  MK-6194  
86
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.1.3
Data Protection
The Sponsor will conduct this study in compliance with all applicable data protection 
regulations.
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names 
or any information that would make the participant identifiable will not be transferred.
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
10.1.3.1
Confidentiality of Data
By signing this protocol, the investigator affirms to the Sponsor that information furnished to 
the investigator by the Sponsor will be maintained in confidence, and such information will 
be divulged to the IRB, IEC, or similar or expert committee; affiliated institution and 
employees, only under an appropriate understanding of confidentiality with such board or 
committee, affiliated institution and employees. Data generated by this study will be 
considered confidential by the investigator, except to the extent that it is included in a 
publication as provided in the Publications section of this protocol.
10.1.3.2
Confidentiality of Participant Records
By signing this protocol, the investigator agrees that the Sponsor (or Sponsor representative), 
IRB/IEC, or regulatory authority representatives may consult and/or copy study documents to 
verify worksheet/CRF data. By signing the consent form, the participant agrees to this 
process. If study documents will be photocopied during the process of verifying 
worksheet/CRF information, the participant will be identified by unique code only; full 
names/initials will be masked before transmission to the Sponsor.
By signing this protocol, the investigator agrees to treat all participant data used and 
disclosed in connection with this study in accordance with all applicable privacy laws, rules 
and regulations.
10.1.3.3
Confidentiality of IRB/IEC Information
The Sponsor is required to record the name and address of each IRB/IEC that reviews and 
approves this study. The Sponsor is also required to document that each IRB/IEC meets 
regulatory and ICH GCP requirements by requesting and maintaining records of the names 
and qualifications of the IRB/IEC members and to make these records available for 
regulatory agency review upon request by those agencies.
08QVCJ

PRODUCT:  MK-6194  
87
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.1.4
Committees Structure
This section is not applicable as there are no study governance committees. 
10.1.5
Publication Policy
The results of this study may be published or presented at scientific meetings. The Sponsor 
will comply with the requirements for publication of study results. In accordance with 
standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement.
If publication activity is not directed by the Sponsor, the investigator agrees to submit all 
manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect 
proprietary information and to provide comments.
Authorship will be determined by mutual agreement and in line with ICMJE authorship 
requirements.
10.1.6
Compliance with Study Registration and Results Posting Requirements
Under the terms of the FDAAA of 2007 and the EMA clinical trial Directive 2001/20/EC, the 
Sponsor of the study is solely responsible for determining whether the study and its results 
are subject to the requirements for submission to http://www.clinicaltrials.gov, 
www.clinicaltrialsregister.eu or other local registries. MSD, as Sponsor of this study, will 
review this protocol and submit the information necessary to fulfill these requirements. MSD 
entries are not limited to FDAAA or the EMA clinical trials directive mandated trials. 
Information posted will allow participants to identify potentially appropriate studies for their 
disease conditions and pursue participation by calling a central contact number for further 
information on appropriate study locations and study-site contact information.
By signing this protocol, the investigator acknowledges that the statutory obligations under 
FDAAA, the EMA clinical trials directive, or other locally mandated registries are that of the 
Sponsor and agrees not to submit any information about this study or its results to those 
registries.
10.1.7
Compliance with Law, Audit, and Debarment
By signing this protocol, the investigator agrees to conduct the study in an efficient and 
diligent manner and in conformance with this protocol; generally accepted standards of GCP
(eg, ICH GCP: Consolidated Guideline and other generally accepted standards of GCP); and 
all applicable federal, state and local laws, rules and regulations relating to the conduct of the 
clinical study.
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.
08QVCJ

PRODUCT:  MK-6194  
88
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
The investigator agrees not to seek reimbursement from participants, their insurance 
providers, or from government programs for procedures included as part of the study 
reimbursed to the investigator by the Sponsor.
The investigator will promptly inform the Sponsor of any regulatory authority inspection 
conducted for this study.
The investigator agrees to provide the Sponsor with relevant information from inspection 
observations/findings to allow the Sponsor to assist in responding to any citations resulting 
from regulatory authority inspection and will provide the Sponsor with a copy of the 
proposed response for consultation before submission to the regulatory authority. 
Persons debarred from conducting or working on clinical studies by any court or regulatory 
authority will not be allowed to conduct or work on this Sponsor’s studies. The investigator 
will immediately disclose in writing to the Sponsor if any person who is involved in 
conducting the study is debarred or if any proceeding for debarment is pending or, to the best 
of the investigator’s knowledge, threatened.
10.1.8
Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The investigator 
or qualified designee is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF.
Detailed information regarding Data Management procedures for this protocol will be 
provided separately.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.
Study documentation will be promptly and fully disclosed to the Sponsor by the investigator 
upon request and also shall be made available at the study site upon request for inspection, 
copying, review, and audit at reasonable times by representatives of the Sponsor or any 
regulatory authorities. The investigator agrees to promptly take any reasonable steps that are 
requested by the Sponsor or any regulatory authorities as a result of an audit or inspection to 
cure deficiencies in the study documentation and worksheets/CRFs.
The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data.
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 
08QVCJ

PRODUCT:  MK-6194  
89
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
study is being conducted in accordance with the currently approved protocol and any other
study agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including participants’ documented informed consent, pertaining to 
the conduct of this study must be retained by the investigator for 15 years after study 
completion unless local regulations or institutional policies require a longer retention period. 
No records may be destroyed during the retention period without the written approval of the 
Sponsor. No records may be transferred to another location or party without written 
notification to the Sponsor.
10.1.9
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. The investigator/institution should maintain adequate and 
accurate source documents and study records that include all pertinent observations on each 
of the site’s participants. Source documents and data should be attributable, legible, 
contemporaneous, original, accurate, and complete. Changes to source data should be 
traceable, should not obscure the original entry, and should be explained if necessary (eg, via 
an audit trail). Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator/institution may need to request previous medical records or transfer records, 
depending on the study. Also, current medical records must be available.
10.1.10
Study and Site Closure
The Sponsor or its designee may stop the study or study-site participation in the study for 
medical, safety, regulatory, administrative, or other reasons consistent with applicable laws, 
regulations, and GCP.
In the event the Sponsor prematurely terminates a particular study site, the Sponsor or 
designee will promptly notify that study site’s IRB/IEC as specified by applicable regulatory 
requirement(s).
08QVCJ

PRODUCT:  MK-6194  
90
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.2
Appendix 2: Clinical Laboratory Tests
•
The tests detailed in Table 7 will be performed by the central laboratory.
•
Local laboratory results are only required in the event that the central laboratory results 
are not available in time for either study intervention administration and/or response 
evaluation. 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 either a study intervention decision or response evaluation, 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 7
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 bilirubin 
(and direct 
bilirubin, if total 
bilirubin is 
above the ULN)
Albumin
Bicarbonate
Chloride
Phosphorous
Creatinine
Sodium
ALT/SGPT
Total Protein
Glucose 
Calcium
Alkaline 
phosphatase
LDH
Immunoglobulin E 
(IgE)
CRP
Routine 
Urinalysis
•
Specific gravity
•
pH, glucose, protein, blood, ketones, [bilirubin, urobilinogen, nitrite, 
leukocyte esterase] by dipstick
•
Microscopic examination (if blood or protein is abnormal)
Pregnancy 
Testing
•
Highly sensitive serum or urine hCG pregnancy test (as needed for WOCBP)
08QVCJ

PRODUCT:  MK-6194  
91
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Laboratory 
Assessments
Parameters
Other Screening 
Tests
•
Coagulation: PT and INR, aPTT
•
FSH (as needed in WONCBP only)
•
Urine drug screen (to include at minimum: amphetamines, barbiturates, 
cocaine, opiates, cannabinoids and benzodiazepines) 
•
Alcohol test
•
Serology (HIV antibody, HBsAg, HBsAb, HBcAb, and hepatitis C virus 
antibody) per site SOP
•
Purified protein derivation (PPD test or QuantiFERON®-TB Gold test
•
All study-required laboratory assessments will be performed by a central 
laboratory, except pregnancy tests, TB test, Urine Drug Screen (UDS), and 
alcohol test, which may be performed centrally or locally.
ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; FSH=follicle-stimulating 
hormone; [HBsAg=hepatitis B surface antigen]; hCG=human chorionic gonadotropin; [HIV=human immunodeficiency 
virus]; MCH=mean corpuscular hemoglobin; MCV=mean corpuscular volume; RBC=red blood cell; SGOT=serum 
glutamic-oxaloacetic transaminase; SGPT=serum glutamic-pyruvic transaminase; ULN=upper limit of normal; 
WBC=white blood cell; WOCBP=women of childbearing potential; WONCBP=women of nonchildbearing potential
The investigator (or medically qualified designee) must document their review of each 
laboratory safety report.
08QVCJ

PRODUCT:  MK-6194  
92
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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 (also referred to as Sponsor’s 
product) includes any pharmaceutical product, biological product, vaccine, diagnostic 
agent, medical device, combination product, or protocol specified procedure whether 
investigational or marketed (including placebo, active comparator product, or run-in 
intervention), manufactured by, licensed by, provided by, or distributed by the Sponsor 
for human use in this study.
Events meeting the AE definition
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the investigator.
08QVCJ

PRODUCT:  MK-6194  
93
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
•
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.
08QVCJ

PRODUCT:  MK-6194  
94
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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
08QVCJ

PRODUCT:  MK-6194  
95
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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 /toxicity
•
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, not when it is rated as severe.
•
The investigator will make an assessment of intensity for each AE and SAE (and other 
reportable safety event) according to the NCI CTCAE, version 5.0 (27 November 2017) . 
Any AE that changes CTCAE grade over the course of a given episode will have each 
change of grade recorded on the AE CRFs/worksheets.
- Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated.
- Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental ADL.
- Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care ADL.
- Grade 4: Life threatening consequences; urgent intervention indicated.
- Grade 5: Death related to AE.
08QVCJ

PRODUCT:  MK-6194  
96
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Assessment of causality
•
Did the Sponsor’s product cause the AE?
•
The determination of the likelihood that the Sponsor’s product caused the AE will be 
provided by an investigator who is a qualified physician. The investigator’s signed/dated 
initials on the source document or worksheet that supports the causality noted on the AE 
form, ensures that a medically qualified assessment of causality was done. This initialed 
document must be retained for the required regulatory time frame. The criteria below are 
intended as reference guidelines to assist the investigator in assessing the likelihood of a 
relationship between the test product and the AE based upon the available information.
•
The following components are to be used to assess the relationship between the 
Sponsor’s product and the AE; the greater the correlation with the components and 
their respective elements (in number and/or intensity), the more likely the Sponsor’s 
product caused the AE:
- Exposure: Is there evidence that the participant was actually exposed to the 
Sponsor’s product such as: reliable history, acceptable compliance assessment (pill 
count, diary, etc), expected pharmacologic effect, or measurement of 
drug/metabolite in bodily specimen?
- Time Course: Did the AE follow in a reasonable temporal sequence from 
administration of the Sponsor’s product? Is the time of onset of the AE compatible 
with a drug-induced effect (applies to studies with investigational medicinal 
product)?
- Likely Cause: Is the AE not reasonably explained by another etiology such as 
underlying disease, other drug(s)/vaccine(s), or other host or environmental factors.
- Dechallenge: Was the Sponsor’s product discontinued or dose/exposure/frequency 
reduced?
◦
If yes, did the AE resolve or improve?
◦
If yes, this is a positive dechallenge.
◦
If no, this is a negative dechallenge.
(Note: This criterion is not applicable if: (1) the AE resulted in death or permanent 
disability; (2) the AE resolved/improved despite continuation of the Sponsor’s 
product; (3) the study is a single-dose drug study; or (4) Sponsor’s product(s) is/are 
only used 1 time.)
- Rechallenge: Was the participant re-exposed to the Sponsor’s product in this study?
◦
If yes, did the AE recur or worsen?
08QVCJ

PRODUCT:  MK-6194  
97
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
◦
If yes, this is a positive rechallenge.
◦
If no, this is a negative rechallenge.
(Note: This criterion is not applicable if: (1) the initial AE resulted in death or 
permanent disability, or (2) the study is a single-dose drug study; or (3) Sponsor’s 
product(s) is/are used only 1 time.)
NOTE: IF A RECHALLENGE IS PLANNED FOR AN AE THAT WAS SERIOUS AND 
MAY HAVE BEEN CAUSED BY THE SPONSOR’S PRODUCT, OR IF RE-EXPOSURE 
TO THE SPONSOR’S PRODUCT POSES ADDITIONAL POTENTIAL SIGNIFICANT 
RISK TO THE PARTICIPANT THEN THE RECHALLENGE MUST BE APPROVED IN 
ADVANCE BY THE SPONSOR CLINICAL DIRECTOR, AND IF REQUIRED, THE 
IRB/IEC.
•
Consistency with study intervention profile: Is the clinical/pathological presentation of 
the AE consistent with previous knowledge regarding the Sponsor’s product or drug class 
pharmacology or toxicology?
•
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 Sponsor’s product relationship).
- Yes, there is a reasonable possibility of Sponsor’s product relationship:
◦
There is evidence of exposure to the Sponsor’s product. The temporal sequence 
of the AE onset relative to the administration of the Sponsor’s product is 
reasonable. The AE is more likely explained by the Sponsor’s product than by 
another cause.
- No, there is not a reasonable possibility of Sponsor’s product relationship:
◦
Participant did not receive the Sponsor’s product OR temporal sequence of the 
AE onset relative to administration of the Sponsor’s product is not reasonable 
OR the AE is more likely explained by another cause than the Sponsor’s 
product. (Also entered for a participant with overdose without an associated 
AE.)
•
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.
08QVCJ

PRODUCT:  MK-6194  
98
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
•
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.
•
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).
08QVCJ

PRODUCT:  MK-6194  
99
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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).
08QVCJ

PRODUCT:  MK-6194  
100
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.4
Appendix 4: Medical Device and Drug-device Combination Products: Product 
Quality Complaints/Malfunctions: Definitions, Recording, and Follow-up
Not applicable.
08QVCJ

PRODUCT:  MK-6194  
101
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.5
Appendix 5: Contraceptive Guidance
10.5.1
Definitions
Women of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below):
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
•
Premenarchal
•
Premenopausal female with 1 of the following:
- Documented hysterectomy
- Documented bilateral salpingectomy
- Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than the 
above (eg, Mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.
•
Postmenopausal female
- A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.
◦
A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or HRT. 
However, in the absence of 12 months of amenorrhea, confirmation with two 
FSH measurements in the postmenopausal range is required.
Females on HRT and whose menopausal status is in doubt will be required to use one of the 
non-hormonal highly effective contraception methods if they wish to continue their HRT 
during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment.
08QVCJ

PRODUCT:  MK-6194  
102
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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.
08QVCJ

PRODUCT:  MK-6194  
103
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.5.2
Contraception Requirements
Contraceptives allowed during the study includea:
Highly Effective Contraceptive Methods That Have Low User Dependencyb
Failure rate of <1% per year when used consistently and correctly.
•
Progestogen-only subdermal contraceptive implantc,d
•
IUSc,e
•
Non-hormonal IUD
•
Bilateral tubal occlusion
•
Azoospermic partner (vasectomized or secondary to medical cause)
This is a highly effective contraception method provided that the partner is the sole male sexual partner of 
the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. A spermatogenesis cycle is approximately 90 days.
Note: Documentation of azoospermia for a male participant can come from the site personnel’s review of 
the participant’s medical records, medical examination, or medical history interview. 
Highly Effective Contraceptive Methods That Are User Dependentb
Failure rate of <1% per year when used consistently and correctly.
•
Combined (estrogen- and progestogen- containing) hormonal contraceptionc,d
- Oral
- Intravaginal
- Transdermal
- Injectable
•
Progestogen-only hormonal contraceptionc,d
- Oral
- Injectable
Sexual Abstinence
•
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the participant.
a   Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for participants of clinical studies.
b   Typical use failure rates are higher than perfect-use failure rates (ie, when used consistently and correctly).
c   Male condoms must be used in addition to female participant hormonal contraception.
d   If locally required, in accordance with CTFG guidelines, acceptable hormonal contraceptives are limited to 
those which inhibit ovulation.
e   IUS is a progestin releasing IUD.
Note: The following are not acceptable methods of contraception:
-  Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus 
interruptus), spermicides only, and LAM.
-  Male condom with cap, diaphragm, or sponge with spermicide.
-  Male and female condom should not be used together (due to risk of failure with friction).
08QVCJ

PRODUCT:  MK-6194  
104
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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.
08QVCJ

PRODUCT:  MK-6194  
105
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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.
08QVCJ

PRODUCT:  MK-6194  
106
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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 
08QVCJ

PRODUCT:  MK-6194  
107
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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.
08QVCJ

PRODUCT:  MK-6194  
108
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
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/
08QVCJ

PRODUCT:  MK-6194  
109
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.7
Appendix 7: Country-specific Requirements
Not Applicable.
08QVCJ

	
	



	


	

  

CCI
49&-

PRODUCT:  MK-6194  
111
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.9
Appendix 9: 12-Lead Electrocardiogram Abnormality Criteria
Screen Failure Criteria
Potentially Significant 
Postrandomization Findings 
(clarification on action to 
take)
RHYTHM
Sinus Tachycardia
110 bpm
HR >110 bpm and HR 
increase of ≥25 bpm from 
baseline
Sinus Bradycardia
<40 bpm
HR <40 bpm and HR 
decrease of ≥5 bpm from 
baseline
Sinus Pause/Arrest
>2.0 seconds
>2.0 seconds
Atrial Premature Complex
1 beat
3 beats
Ventricular Premature 
Complex
All
3 beats
Ectopic Atrial Rhythm 
None
None
Junctional Rhythm
Junctional Rhythm with 
HR <40 bpm
Junctional Rhythm with HR 
<40 bpm
Idioventricular Rhythm
All
All
Atrial Fibrillation
All
All
Atrial Flutter
All
All
Supraventricular 
Tachycardia
All
All
Ventricular Tachycardia
All
All
AXIS
Left Axis Deviation
RBBB With LAHB
New Onset LAHB
Right Axis Deviation
RBBB With LPHB
New Onset LPHB
CONDUCTION
1st Degree AV Block
PR 230 ms
PR 230 ms + Increase of 15 
ms; or PR Increase of >25%
2nd Degree AV Block
Mobitz Type II
Mobitz Type II
3rd Degree AV Block
All
All
LBBB
All
All
RBBB
RBBB With LAHB/LPHB 
as Defined Above
New Onset RBBB (Not 
Including Rate-related)
ICRBBB (QRS <120 ms)
No Exclusion
Nothing
Short PR/Preexcitation 
Syndrome
Delta Wave + PR <120 ms
Delta Wave + PR <120 ms
Other Intra-Ventricular 
Conduction Delay
QRS 130 ms
QRS 130 ms + Increase of 
10 ms
08QVCJ

PRODUCT:  MK-6194  
112
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
Screen Failure Criteria
Potentially Significant 
Postrandomization Findings 
(clarification on action to 
take)
QTc (B or F)
Male
QTc 470 ms
QTc 500 ms or Increase of 
60 ms From Baseline
Female
QTc 480 ms
QTc 500 ms or Increase of 
60 ms From Baseline
HYPERTROPHY
Atrial Abnormalities
Definite Evidence of P 
Mitrale or P Pulmonale
Definite Evidence of P 
Mitrale or P Pulmonale
Ventricular Abnormalities
Voltage Criteria for LVH 
Plus Strain Pattern
Voltage Criteria for LVH Plus 
Strain Pattern
MYOCARDIAL INFARCTION
Acute or Recent
All
All
Old
All
All
ST/T MORPHOLOGY
ST Elevation Suggestive of 
Myocardial Injury 
In 2 or more contiguous 
leads
In 2 or more contiguous leads
ST Depression Suggestive 
of Myocardial Ischaemia 
In 2 or more contiguous
leads
In 2 or more contiguous leads
T-wave Inversions 
Suggestive of Myocardial 
Ischaemia 
In 2 or more contiguous 
leads
In 2 or more contiguous leads
Non-specific ST-T Changes 
(In 2 or More Leads)
No exclusion
In 2 or more contiguous leads
PACEMAKER
All
All
AV=atrioventricular; bpm=beats per minute; HR=heart rate: ICRBBB=incomplete right bundle branch block; 
LAHB=left anterior hemiblock; LPHB=left posterior hemiblock; LVH=left ventricular hypertrophy; mm=millimeter; 
ms=milliseconds, PR=pulse rate; QTcB=QT correction using Bazett’s formula; QTcF=QT correction using Fredericia 
formula; RBBB=right bundle branch block; ST/T=ST-segment/T wave.
Baseline is defined as Predose Day 1
08QVCJ

PRODUCT:  MK-6194  
113
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.10 Appendix 10: Algorithm for Assessing Out of Range Laboratory Values
For all laboratory values obtained at prestudy (screening) visit and/or predose evaluation:
A. If all protocol-specified laboratory values are normal, the participant may enter the study.
B. If a protocol specified laboratory value is outside of the parameter(s) outlined in the 
inclusion/exclusion criteria (including a repeat if performed), the participant will be 
excluded from the study.
C. If ≥1 protocol-specified laboratory value not specified in the inclusion/exclusion criteria 
is outside the normal range, the following choices are available:
a.   The participant may be excluded from the study;
b.   The participant may be included in the study if the abnormal value(s) is NCS (the 
investigator must annotate the laboratory value “NCS” on the laboratory safety test 
source document).
c.   The participant may be included in the study if the abnormality is consistent with a 
pre-existing medical condition which is not excluded per protocol (eg, elevated 
eosinophil count in a participant with asthma or seasonal allergies), the medical 
condition should be annotated on the laboratory report.
OR
a.   The abnormal test may be repeated (refer items a. and b. below for continuation of 
algorithm for repeated values).
•
If the repeat test value is within the normal range, the participant may enter the 
study.
•
If the repeat test value is still abnormal, the study investigator will evaluate the 
potential participant with a complete history and physical examination, looking 
especially for diseases that could result in the abnormal laboratory value in 
question. If such diseases can be ruled out, and if the abnormal laboratory value is 
not clinically relevant, then the participant may enter the study.
D. If there is any clinical uncertainty regarding the significance of an abnormal value, the 
participant will be excluded from the study.
08QVCJ

PRODUCT:  MK-6194  
114
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
10.11 Appendix 11: Guideline for the Diagnosis of Atopic Dermatitis
The information below outlines examples of clinical outcome assessment measures to be 
used in this trial.  Trial-specific source documents will be provided to sites.     
Screening
Hanifin and Rajka Criteria for Atopic Dermatitis
[Williams, H.C., Textbook:  Atopic Dermatitis: The Epidemiology, Causes and Prevention of Atopic 
Eczema, Cambridge University Press, 2000]
08QVCJ

	
	

;

	


	

  

:@:; ++-.C:;	-(1(',****,-*1&*
:@:;:
(D,&-.3&0-.C$%
CCI
49&-

	
	



	


	

  

CCI
49&-

	
	

:

	


	

  

CCI
49&-

	
	



	


	

  

:@:8 ++-.C :8//&3'-*
//&3'-
C+-..
&,

( )#,($!+

$+)*("+()$#("!($%+"!8')!(

-!)+!!-!(

$+%#(!!+*1%'#(

%!()+/!)+!

'(-(!*)(%(1)$*%+(

-!)+!)!'(
.
+*)((!()+/!)+!
<
)!#!)(1!'#)-!
</
)!#!)(1!'#)-!/)(/(0
<%+(
)!#!)(1!'#)-!/)(%+(
&C
$'%%!%!((!C#!)
&.
$%)#,+')!!
&
$0++!8
&
$%*)!++#)!
&.
$0+#)/'!)!
&
&0(!*!)(#)!
&
*%!(!$%'#(
<
)'')!#(

'/!'!(!)-%
A
'%!)'!
8
8#*%+''!()(
)
')!(!
)%
')!(!'%!)'!

+!!*)()

)!'(-!*)(!
<
'%'%)!+!)'1#(
.
#,1.!-!)(0)0
...
%#$.#'!.!-!)(0(,.'%!
.
%'%.(#0!*)(

!)%,0)(!)/)-!)+!-!(+
;7
!)%,0)(!)/)-!)+!-!(+"G!)+;7
G
'!//'!(/-)(

)#,#'!%-!)?#)0

!80)$#'%!''

()!-!3'((!!

8'%#+')(!)
C
!%!'()'),)

!-!(/'%'%(!)!+(
!
!%!'()'+!!*)()
.
! 0!%2!#+)$!(++0

8*+#)!),
CCI
49&-

	
	

	

	


	

  

//&3'-
C+-..
&,

#)*!!'!+,!'0

8!'#(-!-!)+,1(((!!
!+
!%!'()'*(!()!*)(!#('!+
H;
#)H;

!8*+#)!)!+*+!
..
!)%0+(,!!-!%*!(+'!(+(

)#,+()(

)#,+()(!!(+'(

/)%/8!"*)//!$!!
E
/)+(1#
.E
/%%'%!+(#%(,1)!
C
C%'%)'('!
C.
C)#%'0(!%0.(#%(,'()
C
,+()!+*1,!%)!/%#8+!+!
C
,+()(!+(%
C
C$)()0)'('!
C.
C)#%'0(!')*1,!%0.(#%(,'()
CGE
C)/(-!)+#+1+(+!+!
E$
1!,%$
E$'
1!,%$'
E&'$
1!*((+&')!($0
E&+,
1!*((+&+#)/'!(,!
E&+$
1!*((+&+#)/'!($0
E&G
1!*((+&-)#+
1C
1#'1)',()*
EG
1!*((+-)#+
EG
1##!/'!'0-)#+
E
1!)()(!
EH
1!%(1)!%(!@#%(0/%/!
E
1)!)!*%'!!((1!)*0
E..&
E!*('+*!'/'./!(0&)
E
E!(')(
5+6
(!)%0++5+!+6
&
-!+(,()I+&)'1#)!

/)!+!()
E
(!)(%#'% /)E)+( /!'1'%!@#)!!(+/)
1)'!#('%+/)E#<+!
9
(!)(%((!!/!'%9#)%()+

,,
<
(!+-!')!#(

!*!!((1'+((!!
,
#,%$#%
,
#,%$#%
CCI
49&-

	
	



	


	

  

//&3'-
C+-..
&,
,C
#,%$#%C
,C
#,%$#%C
,G
#,%$#%-)$%!
E
#1+('1!+()0

-!+(,(%!'%*)#'(

-!+(,(%!3)#,

(!)(%)% !)(

#!'%,0
)+
#!)!%(!+
&
+((#(%!-!3&)
.
!+*+!-%#()(!).%#)+7 /)#!$+!
(1!)*!#('+

(!)'(-!)!+*+!(!'1%,0

*(1'(1)$'0(*!'*#)*#)
<
()#(!)!!-'!
<.
()#(!)!1)!)!%!+,+0+(!
G
()-!#+
G
-(),+('
G.
(!)'(-!-'!)!+*+!+0+(!
FC
(!)(%F)2,C)#*
F.
(!,)(!3!$)!+*+!+0+(!
95+6
9#+2+!1$()5+6
.
)/+20*!)/)'!+((#+

%'((%!))1!!(1
H
!'!+(!)#,1H#!+()!
E
'((!!10),!+!
G
%-!((!#(!/%#! -''!

%3!)%(/)%
H
%3!)%(/@#(((
$
'%%($0

8#+(!)!+!
!
!'%'()0/)!,#%()0'(-(!+

!+%!+"#*+")#$!%%
G
!+%!+"#*+")#$!%% *%#+-)'!%%

,!(')!+'!,,

!++!,!)
.
')+(!%%(!+($%(0

8#(%!)(!+!

/!8'(0)$$%(0(!)-%
CCI
49&-

	
	



	


	

  

//&3'-
C+-..
&,
M
!(1()!8(!

(%'!)+((#(!
.
('%'%%0+,/'(

!3)#,**%'(
&
!+*1%'$)'1(+
E
1#*)(!+

-!+(,(%!'%*)#'(

(#)%2%%!)

$+!)-!-!)+!!//!'(%!-!%
..
+(!)%(/%()0)#,+
<G&
))3$#%()-%!(&

$?!'(-!)!+*+!

$?!'(-!)!+*+!)(!
.
-!)%%+#)--%
.
+(!/)#%(

-!)(1!'#(!)
&
!)*1!)%$%#'%!)'!%%
&
*%'!$
&
*10+%,'%%0$+!

)('%%)/'(!((!)

10+'%!8(

*1)'2!('

*!)*)('%

*#)/!*)(!!)-(
H
*)#'(@#%(0'*%(

*(!()!*)(!#('!

)(1)$(!
<G
*+)%!e#%()-%!(
HF
!-!)03!!2+
H
@#%(0/%/!
H
!*)(!(/H#(((-!1)'%,01)'!()'+

)!/)'()0'1)''#,1

)$#'%!''
)
)!'!!1+!+!

)!+*)()0)(!
.
.'!(/'-+)0((!!
.
.,%!+'!,+!
.
+!)#+-!)+!!-!(
.
.((+('%%0++%
..G
+!-!)!'#(!)!+*)()0+0)!')-)#+
.
+#$'#(!#+
.
+()!-(
.C
+!)#,%#('8%'!('()++!
CCI
49&-

	
	



	


	

  

//&3'-
C+-..
&,
.C
.!)#,%#('*0)#-'()++!
+
.(,(!)%((),((!!
.&
.#**%!!(%%$)()0(!+(5+6
.
.0+(!'%#*#+!)0(1!(+#+
.
+'1!#%!/'(-(!+
.
.()*!)(,)'!#)!+
+.
+#**%!!(%.((+('%%0++%
.C
+(#%()/(!)/!),!!+
.<.
+#+*!'(!#!8*!'(!+!)#+-!)+!)!'(
.G
+#+(!-)%)!+*+!

10#+'(-(!,#%(!1!2!
&
(#$!)'#%++
'-
'-!(% '!%%+

)!(!(%,$%(0++!++!(5/)6
!//
//!'()'!%%+
8
!(8#*%+''!()(

(),!(!(!)#,+*+(
)!,+
)!,#%()0'!%%+
(A
1%/%/!
<.
#**!))30'#,1+0)!
<
<%'!)(-!'%(+
<
#!8*%!'1)''#,1
<.
#)!)#,+')!!
<
#**!)%(/)%
<
#**!))!+*)()0()'(/!'(
<G&
#()-%!(&
<G
#%()-%!(
G.
G+#%%,.'%!
G
-%#!/+()$#(
G.
-(%+,+
G A
G%#!/+()$#(
F&
31(!$%'!%%
F
F)2)#'(-(0'(-(0*)!(
F&
3A3!/'1%$!),*(!(%
F&
3A3!/'1%$!),*(!(%
[:
 !('1++'(!*)(!2+!
CCI
49&-

PRODUCT:  MK-6194  
123
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
11
REFERENCES
[Allegretti, J., et al 2021]
Allegretti J, Canavan J, Mitsialis V, Hamilton 
M, Carrellas M, Freer K, et al. Low dose IL-2 
for the treatment of moderate to severe 
ulcerative colitis [abstract]. Presented at: 2021 
Crohn's and Colitis Congress; 2021 Jan 21-24; 
[online meeting]. Inflamm Bowel Dis. 
2021;27(suppl 1):S6-7.
[06DTYJ]
[Allegretti, J., et al 2021]
Allegretti J, Canavan J, Mitsialis V, Hamilton 
M, Carrellas M, Freer K, et al. Low dose IL-2 
for the treatment of moderate to severe 
ulcerative colitis [Abstract]. Presented at: 2021 
Crohn’s & Colitis Congress; 2021 Jan 21-24; 
[online meeting]. Inflamm Bowel Dis. 2021 Feb 
1;160(3 suppl):S6-S7.
[07XQK5]
[Beck, L. A., et al 2014]
Beck LA, Thaci D, Hamilton JD, Graham NM, 
Bieber T, Rocklin R, et al. Dupilumab treatment 
in adults with moderate-to-severe atopic 
dermatitis. N Engl J Med. 2014 Jul 
10;371(2):130-9.
[07Z9P9]
[Castela, E., et al 2014]
Castela E, Le Duff F, Butori C, Ticchioni M, 
Hofman P, Bahadoran P, et al. Effects of low-
dose recombinant interleukin 2 to promote T-
regulatory cells in alopecia areata. JAMA 
Dermatol. 2014 Jul;150(7):748-51.
[06DTYM]
[Fanton, C., et al 2020]
Fanton C, Furie R, Dixit N, Haglund C, Lu L, 
Siddhanti S, et al. Selective expansion of 
regulatory T cells in patients with systemic 
lupus erythematosus by a novel IL-2 conjugate, 
NKTR-358. Poster session presented at: 
American College of Rheumatology (ACR) 
Convergence; 2020 Nov 5-9; [online meeting]. 
Abstract no. 1824.
[06DTYR]
08QVCJ

PRODUCT:  MK-6194  
124
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
[Fanton, C., et al 2020]
Fanton C, Furie R, Dixit N, Haglund C, Lu L, 
Siddhanti S, et al. Selective expansion of 
regulatory T cells in patients with systemic 
lupus erythematosus by a novel IL-2 conjugate, 
NKTR-358 [abstract]. Poster session presented 
at: American College of Rheumatology (ACR) 
Convergence; 2020 Nov 5-9; [online meeting]. 
Arthritis Rheumatol. 2020;72(suppl 10).
[07Z67F]
[Guttman-Yassky, E., et al 
2021]
Guttman-Yassky E, Teixeira HD, Simpson EL, 
Papp KA, Pangan AL, Blauvelt A, et al. Once-
daily upadacitinib versus placebo in adolescents 
and adults with moderate-to-severe atopic 
dermatitis (Measure Up 1 and Measure Up 2): 
results from two replicate double-blind, 
randomised controlled phase 3 trials. Lancet. 
2021 Jun 5;397:2151-68. Erratum in: Lancet. 
2021 Jun 5;397:2150.
[07Z9PY]
[Hanifin, J. M., et al 2001]
Hanifin JM, Thurston M, Omoto M, Cherill R, 
Tofte SJ, Graeber M, et al. The eczema area and 
severity index (EASI): assessment of reliability in 
atopic dermatitis. Exp Dermatol 2001;10:11-8.
[03RN4G]
[Hartemann, A., et al 
2013]
Hartemann A, Bensimon G, Payan CA, 
Jacqueminet S, Bourron O, Nicolas N, et al. 
Low-dose interleukin 2 in patients with type 1 
diabetes: a phase 1/2 randomised, double-blind, 
placebo-controlled trial. Lancet Diabetes 
Endocrinol. 2013 Dec;1:295-305.
[06DTZ0]
[He, J., et al 2016]
He J, Zhang X, Wei Y, Sun X, Chen Y, Deng J, 
et al. Low-dose interleukin-2 treatment 
selectively modulates CD4(+) T cell subsets in 
patients with systemic lupus erythematosus. Nat 
Med. 2016 Sep;22(9):991-3. Additional 
material; 2 p.
[07X6X9]
[Hsieh, K. H., et al 1991]
Hsieh KH, Chou CC, Huang SF. Interleukin 2 
therapy in severe atopic dermatitis. J Clin 
Immunol. 1991;11(1):22-8.
[07Z9Q3]
[Klatzmann, D. 2015]
Klatzmann D, Abbas AK. The promise of low-
dose interleukin-2 therapy for autoimmune and 
inflammatory diseases. Nat Rev Immunol. 2015 
May;15:283-94.
[06DTZK]
08QVCJ

PRODUCT:  MK-6194  
125
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
[Kolios, A. G. A., et al 
2021]
Kolios AGA, Tsokos GC, Klatzmann D. 
Interleukin-2 and regulatory T cells in 
rheumatic diseases. Nat Rev Rheumatol. 2021 
Dec;17:749-66.
[07ZX0C]
[Koreth, J., et al 2011]
Koreth J, Matsuoka K, Kim HT, McDonough 
SM, Bindra B, Alyea EP 3rd, et al. Interleukin-
2 and regulatory T cells in graft-versus-host 
disease. N Engl J Med. 2011 Dec 
1;365(22):2055-66.
[06DTZP]
[Kuo, P. Y., et al 1998]
Kuo PY, Sherwood JK, Saltzman WM. Topical 
antibody delivery systems produce sustained 
levels in mucosal tissue and blood. Nat 
Biotechnol. 1998 Feb;16:163-7.
[06G7JM]
[Langan, S. M., et al 
2020]
Langan SM, Irvine AD, Weidinger S. Atopic 
dermatitis. Lancet. 2020 Aug 1;396:345-60.
[07ZWZR]
[Leshem, Y. A., et al 
2015]
Leshem YA, Hajar T, Hanifin JM, Simpson EL. 
What the Eczema Area and Severity Index 
score tells us about the severity of atopic 
dermatitis: an interpretability study. Br J 
Dermatol. 2015;172:1353-7.
[07ZWXJ]
[Moldoveanu, Z., et al 
2005]
Moldoveanu Z, Huang WQ, Kulhavy R, Pate 
MS, Mestecky J. Human male genital tract 
secretions: both mucosal and systemic immune 
compartments contribute to the humoral 
immunity. J Immunol. 2005;175:4127-36.
[06G7K2]
[Renert-Yuval, Y., et al 
2021]
Renert-Yuval Y, Thyssen JP, Bissonnette R, 
Bieber T, Kabashima K, Hijnen D, et al. 
Biomarkers in atopic dermatitis-a review on 
behalf of the International Eczema Council. J 
Allergy Clin Immunol. 2021 Apr;147(4):1174-
90.e1.
[07ZX07]
[Rosenzwajg M, Lorenzon 
R, Cacoub P, Pham HP, 
Pitoiset F, El Soufi K 
2019]
Rosenzwajg M, Lorenzon R, Cacoub P, Pham 
HP, Pitoiset F, El Soufi K, et al. Immunological 
and clinical effects of low-dose interleukin-2 
across 11 autoimmune diseases in a single, open 
clinical trial. Ann Rheum Dis. 2019 
Feb;78(2):209-217.
[06FDX4]
08QVCJ

PRODUCT:  MK-6194  
126
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
[Rosenzwajg, M., et al 
2015]
Rosenzwajg M, Churlaud G, Mallone R, Six A, 
Derian N, Chaara W, et al. Low-dose 
interleukin-2 fosters a dose-dependent 
regulatory T cell tuned milieu in T1D patients. J 
Autoimmun. 2015;58:48-58.
[06DV0D]
[Rosenzwajg, M., et al 
2019]
Rosenzwajg M, Lorenzon R, Cacoub P, Pham 
HP, Pitoiset F, El Soufi K, et al. Immunological 
and clinical effects of low-lose interleukin-2 
across 11 autoimmune diseases in a single, open 
clinical trial. Ann Rheum Dis. 2019;78:209-17.
[06DV0C]
[Saadoun, D., et al 2011]
Saadoun D, Rosenzwajg M, Joly F, Six A, 
Carrat F, Thibault V, et al. Regulatory T-cell 
responses to low-dose interleukin-2 in HCV-
induced vasculitis. N Engl J Med. 2011 Dec 
1;365(22):2067-77. Erratum in: N Engl J Med. 
2014 Feb 20;370(8):786.
[06DV0H]
[Schmitt, J., et al 2007]
Schmitt J, Langan S, Williams HC, on behalf of 
the European Dermato-Epidemiology Network. 
What are the best outcome measurements for 
atopic eczema? A systematic review. J Allergy 
Clin Immunol 2007;120:1389-98.
[03RN50]
[Sherwood, J. K., et al 
1996]
Sherwood JK, Zeitlin L, Chen X, Whaley KJ, 
Cone RA, Saltzman WM. Residence half-life of 
IgG administered topically to the mouse vagina. 
Biol Reprod. 1996;54:264-9.
[06G7JW]
[Silverberg, J. I., et al 
2021]
Silverberg JI, Guttman-Yassky E, Gadkari A, 
Kuznik A, Mallya UG, Mastey V, et al. Real-
world persistence with dupilumab among adults 
with atopic dermatitis. Ann Allergy Asthma 
Immunol. 2021;126:40-5.
[07ZX04]
[Simpson, E. L., et al 
2020]
Simpson EL, Sinclair R, Forman S, Wollenberg 
A, Aschoff R, Cork M, et al. Efficacy and 
safety of abrocitinib in adults and adolescents 
with moderate-to-severe atopic dermatitis 
(JADE MONO-1): a multicentre, double-blind, 
randomised, placebo-controlled, phase 3 trial. 
Lancet. 2020 Jul 25;396:255-66.
[07Z9QB]
08QVCJ

PRODUCT:  MK-6194  
127
PROTOCOL/AMENDMENT NO.:  008-04  
MK-6194-008-04 FINAL PROTOCOL
12-DEC-2022
[Simpson, E., et al 2020]
Simpson E, Bissonnette R, Eichenfield LF, 
Guttman-Yassky E, King B, Silverberg JI, et al. 
The validated Investigator Global Assessment 
for atopic dermatitis (vIGA-AD): the 
development and reliability testing of a novel 
clinical outcome measurement instrument for 
the severity of atopic dermatitis. J Am Acad 
Dermatol. 2020 Sep;83(3):839-46.
[07ZWZL]
[Singh, J. A. 2022]
Singh JA. Risks and Benefits of Janus kinase 
inhibitors in rheumatoid arthritis - past, present, 
and future. N Engl J Med. 2022 Jan 
27;386(4):387-9.
[07ZX0D]
[Tchao, N., et al 2021]
Tchao N, Amouzadeh H, Sarkar N, Chow V, 
Hu X, Kroenke M, et al. Efavaleukin alfa, a 
novel IL-2 mutein, selectively expands 
regulatory T cells in patients with SLE: interim 
results of a phase 1b multiple ascending dose 
study [abstract]. Poster session presented at: 
American College of Rheumatology (ACR) 
Convergence 2021; 2021 Nov 5-9; [online 
meeting]. Arthritis Rheumatol. 2021 Nov 
9;73(suppl 10).
[080B0G]
[Yosipovitch, G., et al 
2019]
Yosipovitch G, Reaney M, Mastey V, Eckert L, 
Abbe A, Nelson L, et al. Peak Pruritus 
Numerical Rating Scale: psychometric 
validation and responder definition for 
assessing itch in moderate-to-severe atopic 
dermatitis. Br J Dermatol. 2019;181:761-9.
[07ZWYQ]
08QVCJ