A Double-blind, Randomized, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-1654 in Pre-Term and Full-Term Infants
Phase: PHASE1
Conditions: Respiratory Tract Infection, Respiratory Syncytial Virus
Sponsor: Merck Sharp & Dohme LLC

Official Protocol Title: 
NCT number: 
NCT03524118 
Document Date: 
30-Jul-2020
A Double-blind, Randomized, Placebo-controlled, Single 
Ascending Dose Study to Evaluate the Safety, Tolerability, and 
Pharmacokinetics of MK-1654 in Pre-Term and Full-Term Infants

PRODUCT: MK-1654 
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30-JUL-2020
Title Page
THIS PROTOCOL AMENDMENT AND ALL OF THE INFORMATION RELATING 
TO IT ARE CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK 
SHARP & DOHME CORP., A SUBSIDIARY OF MERCK & CO., INC., NJ, U.S.A. 
(MSD).
Protocol Title: A Double-blind, Randomized, Placebo-controlled, Single Ascending Dose 
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-1654 in Pre-Term 
and Full-Term Infants
Protocol Number: 002-04 
Compound Number: MK-1654
Sponsor Name:
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
(hereafter referred to as the Sponsor or MSD)
Legal Registered Address:
One Merck Drive
P.O. Box 100
Whitehouse Station, New Jersey, 08889-0100, U.S.A.
Regulatory Agency Identifying Number(s):
IND
130,097
EudraCT
2017-005062-21
Approval Date: 30 July 2020
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Sponsor Signatory
Typed Name:
Title:
Date
Protocol-specific Sponsor contact information can be found in the Investigator Study
File Binder (or equivalent).
Investigator Signatory
I agree to conduct this clinical study in accordance with the design outlined in this protocol 
and to abide by all provisions of this protocol.
Typed Name:
Title:
Date
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DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
Amendment 4
30-JUL-2020
The purpose of Amendment 04 is:

to modify the blood collection schedule for Panels D and E to add 
a Day 545 post-dose blood draw for ADA and SNA collection for 
participants enrolled in Panels D and E prior to Amendment 04 
who choose to participate in the modified blood collection 
schedule and Panel D and E participants enrolled under 
Amendment 04. The SAE follow-up period for these participants 
has been extended to Day 545 accordingly;

to discontinue the collection of microsample blood for ADA for all 
Panels; 

to discontinue the collection of microsample blood for PK for 
Panels D and E; 

to document 100 mg as the selected dose for Panels D and E;

to allow the oral polio vaccine to be administered concomitantly 
with MK-1654
Amendment 3
18-DEC-2019
The purpose of Amendment 03 was to remove the restrictions for the 
administration of rotavirus vaccine.
Amendment 2
12-DEC-2018
The purpose of Amendment 02 was to ensure that all instances of hives or 
welts are evaluated to ensure consistent follow-up of potential allergic 
reactions.
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Document
Date of Issue
Overall Rationale
Amendment 1
27-JUL-2018
The purpose of Amendment 01 was to extend the scope and duration of 
post-dose safety monitoring to support the safety evaluation of MK-1654.
Original Protocol
16-FEB-2018
Not applicable
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PROTOCOL AMENDMENT SUMMARY OF CHANGES
Amendment: 002-04
Overall Rationale for the Amendments:
To modify the blood collection schedule for Panels D and E to add a Day 545 post-dose blood draw for ADA and SNA collection for 
participants enrolled in Panels D and E prior to Amendment 04 who choose to participate in the modified blood collection schedule
and Panel D and E participants enrolled under Amendment 04. The SAE follow-up period for these participants has been extended to 
Day 545 accordingly; to discontinue the collection of microsample blood for ADA for all Panels; to discontinue the collection of 
microsample blood for PK for Panels D and E; to document 100 mg as the selected dose for Panels D and E; to allow the oral polio 
vaccine to be administered concomitantly with MK-1654.
Summary of Changes Table:
Section # and Name
Description of Change 
Brief Rationale 
Section 1.1 Synopsis
Section 4.1 Overall Design
Section 4.3.3 Rationale for 
Dose Interval and Study 
Design
Section 6.3.1 Intervention 
Assignment

Removed the word “optional.”

Panel D is now an established study Panel.
Section 1.1 Synopsis
Section 1.2 Schema
Section 1.3.2 SoA for 
Panels D2 and E2
Section 3 Hypothesis, 

Updated text to describe additional 
study visit at Day 545 to collect ADA 
and SNA blood samples, for 
participants in Panels D and E prior to 
Amendment 04 who choose to
participate in the modified blood 
collection schedule and for newly 

To characterize ADA and SNA beyond one-year
post-dose.
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Section # and Name
Description of Change 
Brief Rationale 
Objectives, and Endpoints
Section 4.2.1.1 Safety 
Endpoints
Section 8.1.9 
Discontinuation and 
Withdrawal
Section 8.3.4 Safety Follow-
up Telephone Calls
Section 8.4.1 Time Period 
and Frequency for 
Collecting AE, SAE, and 
Other Reportable Safety 
Event Information
Section 8.13.3 Discontinued 
Participants Continuing to be 
Monitored in the Study and 
Post-study Visit
Section 9.1 Statistical 
Analysis Plan Summary
Section 9.4.1 Safety 
Endpoints
Section 9.4.2 
Pharmacokinetic Endpoints
Section 9.4.3 Other 
Endpoints
enrolled Panels D and E participants 
under Amendment 04. 

The SAE follow-up period for 
participants in Panels D2 and E2 has 
been extended to Day 545 accordingly.

A new SoA, Section 1.3.2, was created 
to provide a new blood sampling 
schedule (Group 3) for participants 
enrolled in Panels D and E prior to 
Amendment 04 who choose to 
participate in the modified blood 
collection schedule and for all Panels 
D and E participants enrolled under 
Amendment 04. This new SoA 
includes a Day 545 visit (Visit 8).

The objectives and endpoints were 
updated accordingly to distinguish the 
time points for Panels A, B, and C, and 
Panels D and E.

Modifications were made to the blood sampling 
schedule for Panels D and E to include the 
timepoints of greatest interest for each assay and to 
extend ADA and SNA testing to 18 months 
(Visit 8, Day 545).

To provide time point clarifications.
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Section # and Name
Description of Change 
Brief Rationale 
Section 1.1 Synopsis
Updated estimated study duration from 
approximately 2 years to approximately 
4 years.
Updated the approximate length of time 
Panel D2 and E2 participants will be in the 
study.
Time adjustment due to enrollment delays and the 
addition of a Day 545 post-dose visit for participants in 
Panels D2 and E2.
Section 1.1 Synopsis
Section 1.2 Schema
Section 4.1 Overall Design
Section 4.3.2 Maximum 
Dose/Exposure for This 
Study
Section 4.3.3 Rationale for
Dose Interval and Study 
Design
Section 6.1 Study 
Intervention(s) Administered
Section 6.2.1 Dose 
Preparation
Section 6.3.1 Intervention 
Assignment
Section 8.1.8 Study 
Intervention Administration
Section 9.1 Statistical 
Analysis Plan Summary
Changed the dose for Panels D and E from 
“up to 100 mg” to “100 mg.”
Per siDMC, the 100 mg dose was selected for Panels D
and E.
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Section # and Name
Description of Change 
Brief Rationale 
Section 1.1 Synopsis
Section 6.1 Study 
Intervention
Section 6.2.1 Dose 
Preparation
Section 8.1.8 Study 
Intervention Administration
Added the following dosing instructions:
Panels D and E: 100-mg dose - 1 mL split 
into 2 IM injections
o
0.5 mL administered in the right 
thigh
o
0.5 mL administered in the left 
thigh
To clarify the selected dose volume and administration.
Section 1.3 Schedule of 
Activities (SoA)
Section 3 Hypothesis, 
Objectives, and Endpoints
Section 4.1 Overall Design
Section 4.2.1.2.2 Blood 
Microsampling Assay
Section 8.7.2 Blood 
Microsampling for ADAs
Section 9.4.3 Other
Endpoints
The collection of microsample blood for 
ADA was removed.
Text was added to clarify that microsample 
blood for MK-1654 pharmacokinetics will 
only be collected from infants in Panels, 
A, B, and C.
Section 8.7.2 was removed.
The study will no longer collect microsample blood for 
ADA for infants in ALL panels, as the microsample 
ADA assay is not technically feasible. 
Microsample blood for MK-1654 PK will not be 
collected for infants in Panels D and E, as sufficient 
data are available based on microsamples already 
collected in the study.
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Section # and Name
Description of Change 
Brief Rationale 
Section 1.3.1 SoA for Panels 
A, B, C, D1 and E1
Section 1.3.2 SoA for Panels 
D2 and E2
The weekly RSV surveillance telephone 
calls should be made through 1 week after 
the site-designated RSV season end date.
The participant’s legally acceptable 
representative will no longer be instructed 
to return the Electronic Diary Card Device
after Day 30 via mail.
To clarify the duration of RSV surveillance telephone 
calls.
To allow individuals to return the device in ways other 
than via mail (eg, in person if they live close to the 
site).
Section 2 Introduction
Updated background information on the 
burden of RSV infection in infants.
Updates are based on a systematic review and 
modeling study of RSV in children under 5 years of 
age published in The Lancet.
Section 2.1 Study Rationale
Removed references to targeted trough 
drug level.
The objective is no longer only to achieve the 
preclinical target.
Section 2.2.3 Completed 
Clinical Studies
Updated section header from “Ongoing 
Clinical Studies” to “Completed Clinical 
Studies.”
Changed “Most AEs have been mild” to 
“Most AEs have been transient and mild to 
moderate in intensity.”
The language was updated for alignment with final 
study data.
Section 4.1 Overall Design
Section 8 Study Assessments 
and Procedures
Updated total blood volume drawn per 
participant.
The blood sampling volume was adjusted. Blood 
volume updates are based on the discontinuation of the 
ADA microsample blood collection for Panels A-C,
and modification of the blood collection for Panels D 
and E (discontinuation of PK and ADA microsamples; 
creation of new blood collection schedule, including 
addition of Day 545 blood draw).
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Section # and Name
Description of Change 
Brief Rationale 
Section 4.1 Overall Design
Section 4.2.1.2 
Pharmacokinetic Endpoints
Section 6.3.1 Intervention 
Assignment
Revised text to indicate that only 
participants enrolled prior to Amendment 
04 will be assigned to 1 of 4 blood 
sampling schedules. 
Added text to indicate that Panel D and E 
participants enrolled under Amendment 04 
will be assigned to a separate blood 
sampling schedule. Panel D and E 
participants enrolled prior to Amendment 
04 will have the option of transitioning to 
this blood sampling schedule (D2/E2) or 
remaining on their current schedule 
(D1/E1).
Blood sampling groups were clarified based on the 
new blood sampling schedules for Panels D and E.
Section 4.2.1.5 Future 
Biomedical Research
Section 8.1.1.2 Consent and 
Collection of Specimens for 
Future Biomedical Research
Section 8.11 Biomarkers
Section 10.6 Appendix 6: 
Collection and Management 
of Specimens for Future 
Biomedical Research
Removed the word “substudy” from the 
description of future biomedical research.
Future biomedical research is not a separate substudy.
Section 4.3.3 Rationale for 
Dose Interval and Study 
Design
Corrected the expected number of Panel D 
participants.
Updates match the number stated in other sections. 
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Section # and Name
Description of Change 
Brief Rationale 
Section 5.2 Exclusion 
Criteria
Section 6.5 Concomitant 
Therapy
Removed restrictions pertaining to 
concomitant oral rotavirus (Section 5.2) 
and oral polio vaccines (Sections 5.2 and 
6.5).
Oral rotavirus and oral polio vaccine may be 
administered concomitantly with MK-1654 without 
interference expected and do not require additional 
injections for the participant. 
This amendment removes the restriction on oral polio 
vaccine.
The restriction on oral rotavirus vaccine was removed 
with the previous amendment (AM03); however, 
exclusion criterion 19 was not updated, so this change 
is being made to align the exclusion criterion with what 
is stated in Section 6.5.
Section 8.6.1 Blood 
Collection for MK-1654 
Pharmacokinetics
Removed the following sentence: 
“Leftover specimens will be stored after 
the study for future research for all 
participants whose legally acceptable 
representative provides informed consent.”
This information is also provided in Section 8.9 Future 
Biomedical Research Sample Collection.
8.9 Future Biomedical 
Research Sample Collection
Updated language to clarify the types of
specimens to be collected for Future 
Biomedical Research.
The language in this section was updated to clarify the 
types of specimens to be collected.
Various Sections
Added editorial clarifications.
To improve the clarity of the protocol instructions.
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Table of Contents
DOCUMENT HISTORY ........................................................................................................3
PROTOCOL AMENDMENT SUMMARY OF CHANGES...............................................5
1.
PROTOCOL SUMMARY ............................................................................................19
Synopsis.................................................................................................................19
Schema ..................................................................................................................24
Schedule of Activities (SoA)................................................................................25
SoA for Panels A, B, C, D1, and E1............................................................25
SoA for Panels D2 and E2 ...........................................................................33
2.
INTRODUCTION..........................................................................................................37
Study Rationale....................................................................................................38
Background ..........................................................................................................38
Pharmaceutical and Therapeutic Background .............................................39
Preclinical and Clinical Studies ...................................................................39
Completed Clinical Studies..........................................................................39
Information on Other Study-related Therapy ..............................................39
Benefit/Risk Assessment......................................................................................39
3.
HYPOTHESIS, OBJECTIVES, AND ENDPOINTS .................................................40
4.
STUDY DESIGN............................................................................................................41
Overall Design......................................................................................................41
Scientific Rationale for Study Design.................................................................43
Rationale for Endpoints ...............................................................................44
Safety Endpoints................................................................................44
Pharmacokinetic Endpoints ...............................................................45
Serum PK of MK-1654............................................................45
Blood Microsampling Assay....................................................46
MK-1654 PK and Infant Body Weight....................................46
Pharmacodynamic Endpoints.............................................................46
Anti-drug Antibodies to MK-1654 ..........................................46
RSV SNAs ...............................................................................46
Other Exploratory Endpoints.............................................................46
Acute Respiratory Infection Incidence ....................................47
Future Biomedical Research..............................................................47
Rationale for the Use of Comparator/Placebo .............................................47
Justification for Dose...........................................................................................48
Starting Dose for This Study........................................................................48
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Maximum Dose/Exposure for This Study ...................................................48
Rationale for Dose Interval and Study Design ............................................49
Beginning and End of Study Definition .............................................................49
Clinical Criteria for Early Study Termination .............................................49
Clinical Criteria for Study Pause .................................................................49
5.
STUDY POPULATION ................................................................................................50
Inclusion Criteria.................................................................................................50
Exclusion Criteria................................................................................................51
Lifestyle Considerations......................................................................................53
Screen Failures.....................................................................................................53
Participant Replacement Strategy......................................................................53
6.
STUDY INTERVENTION............................................................................................53
Study Intervention(s) Administered...................................................................53
Medical Devices...........................................................................................55
Preparation/Handling/Storage/Accountability .................................................55
Dose Preparation..........................................................................................55
Handling, Storage, and Accountability........................................................55
Measures to Minimize Bias: Randomization and Blinding..............................56
Intervention Assignment..............................................................................56
Stratification.................................................................................................56
Blinding........................................................................................................57
Study Intervention Compliance..........................................................................57
Concomitant Therapy..........................................................................................57
Rescue Medications and Supportive Care ...................................................58
Dose Modification (Escalation)...........................................................................58
Intervention After the End of the Study............................................................59
Clinical Supplies Disclosure................................................................................59
Standard Policies..................................................................................................60
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL............................................................................................................60
Discontinuation of Study Intervention...............................................................60
Participant Withdrawal From the Study...........................................................60
Lost to Follow-up .................................................................................................61
8.
STUDY ASSESSMENTS AND PROCEDURES........................................................61
Administrative and General Procedures ...........................................................62
Informed Consent.........................................................................................62
General Informed Consent.................................................................62
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Consent and Collection of Specimens for Future Biomedical 
Research.............................................................................................63
Inclusion/Exclusion Criteria ........................................................................63
Participant Identification Card.....................................................................63
Medical History ...........................................................................................63
Prior and Concomitant Medications Review...............................................63
Prior Medications...............................................................................63
Concomitant Medications..................................................................64
Assignment of Screening Number...............................................................64
Assignment of Treatment/Randomization Number.....................................64
Study Intervention Administration ..............................................................64
Timing of Dose Administration.........................................................65
Diary Card..........................................................................................65
Discontinuation and Withdrawal .................................................................65
Withdrawal From Future Biomedical Research ................................66
Participant Blinding/Unblinding..................................................................66
Domiciling ...................................................................................................67
Calibration of Equipment.............................................................................67
Efficacy/Immunogenicity Assessments ..............................................................67
Safety Assessments...............................................................................................67
Physical Examinations.................................................................................68
Vital Signs....................................................................................................68
Systemic and Local Injection Reaction Assessment....................................69
Safety Follow-up Telephone Calls...............................................................69
Clinical Safety Laboratory Assessments .....................................................70
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other 
Reportable Safety Events ....................................................................................70
Time Period and Frequency for Collecting AE, SAE, and Other 
Reportable Safety Event Information ..........................................................71
Method of Detecting AEs, SAEs, and Other Reportable Safety Events......72
Follow-up of AE, SAE, and Other Reportable Safety Event Information...73
Regulatory Reporting Requirements for SAE .............................................73
Pregnancy and Exposure During Breastfeeding ..........................................73
Disease-related Events and/or Disease-related Outcomes Not Qualifying 
as AEs or SAEs............................................................................................73
Events of Clinical Interest (ECIs)................................................................73
Treatment of Overdose........................................................................................74
Pharmacokinetics.................................................................................................74
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Blood Collection for MK-1654 Pharmacokinetics ......................................74
Blood Microsampling for MK-1654 Pharmacokinetics ..............................74
Pharmacodynamics..............................................................................................74
Blood Collection for ADAs and RSV Neutralizing Assay..........................75
Acute Respiratory Infection Determination......................................................75
RSV Season Definition................................................................................75
RSV Surveillance Weekly Telephone Calls ................................................76
Legally Acceptable Representative-reported Respiratory Symptoms .........76
Unscheduled Visit for RSV Assessment......................................................76
Nasal Swab for Respiratory Virus Infection Determination........................77
Future Biomedical Research Sample Collection...............................................78
Planned Genetic Analysis Sample Collection....................................................78
Biomarkers ...........................................................................................................78
Medical Resource Utilization and Health Economics.......................................78
Visit Requirements...............................................................................................78
Screening......................................................................................................78
Intervention Period.......................................................................................78
Discontinued Participants Continuing to be Monitored in the Study and 
Post-study Visit............................................................................................79
9.
STATISTICAL ANALYSIS PLAN .............................................................................79
Statistical Analysis Plan Summary.....................................................................79
Responsibility for Analyses/In-house Blinding .................................................82
Hypotheses/Estimation ........................................................................................82
Analysis Endpoints...............................................................................................82
Safety Endpoints..........................................................................................82
Pharmacokinetic Endpoints .........................................................................83
Other Endpoints ...........................................................................................83
Analysis Populations............................................................................................84
PK Analysis Populations..............................................................................84
Safety Analysis Populations ........................................................................84
Statistical Methods...............................................................................................84
Statistical Methods for Pharmacokinetic Analyses......................................84
Statistical Methods for Safety Analyses ......................................................86
Interim Analyses ..................................................................................................87
Multiplicity ...........................................................................................................87
Sample Size and Power Calculations .................................................................87
Sample Size and Power for Safety Analyses ...............................................87
Sample Size and Power for Pharmacokinetic Analyses ..............................88
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Subgroup Analyses...............................................................................................88
Compliance (Medication Adherence).................................................................88
Extent of Exposure...............................................................................................88
10. SUPPORTING DOCUMENTATION AND OPERATIONAL
CONSIDERATIONS.....................................................................................................89
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations........89
Code of Conduct for Clinical Trials.............................................................89
Financial Disclosure.....................................................................................91
Data Protection.............................................................................................91
Confidentiality of Data ......................................................................92
Confidentiality of Participant Records...............................................92
Confidentiality of IRB/IEC Information............................................92
Committees Structure...................................................................................92
Internal Data Monitoring Committee.................................................92
Publication Policy........................................................................................93
Compliance with Study Registration and Results Posting Requirements ...93
Compliance with Law, Audit, and Debarment ............................................94
Data Quality Assurance ...............................................................................94
Source Documents .......................................................................................95
Study and Site Closure.................................................................................95
Appendix 2: Clinical Laboratory Tests..............................................................96
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting...............................................................97
Definition of AE ..........................................................................................97
Definition of SAE ........................................................................................98
Additional Events Reported.........................................................................99
Recording AE and SAE ...............................................................................99
Reporting of AEs, SAEs, and Other Reportable Safety Events to the 
Sponsor ......................................................................................................103
Appendix 4: Medical Device Incidents: Definition and Procedures for 
Recording, Evaluating, Follow-up, and Reporting.........................................105
Appendix 5: Contraceptive Guidance and Pregnancy Testing......................106
Appendix 6: Collection and Management of Specimens for Future 
Biomedical Research..........................................................................................107
Appendix 7: Country-specific Requirements..................................................112
Appendix 8: Abbreviations ...............................................................................113
11. REFERENCES.............................................................................................................115
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LIST OF TABLES
Table 1
Study Interventions....................................................................................54
Table 2
Reporting Time Periods and Time Frames for Adverse Events and 
Other Reportable Safety Events ...............................................................72
Table 3
95% CIs for Varying Standard Deviations and GM C150days with 27 
Evaluable  Participants on MK-1654 in Panels B, D, and E....................88
Table 4
Protocol-required Screening Laboratory Assessments..............................96
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LIST OF FIGURES
Figure 1
Dose Escalation Diagram...........................................................................24
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1. PROTOCOL SUMMARY
Synopsis
Protocol Title: A Double-blind, Randomized, Placebo-controlled, Single Ascending Dose 
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MK-1654 in Pre-Term 
and Full-Term Infants
Short Title: Phase 1b Study of MK-1654 Safety and PK in Pre-Term and Full-Term Infants
Acronym: Not applicable
Hypotheses, Objectives, and Endpoints:
The following objectives and endpoints will be evaluated in healthy pre-term and full-term 
infants receiving a single ascending dose of MK-1654 or placebo intramuscularly. No formal 
hypotheses will be tested in the study.
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Primary Objectives
Primary Endpoints
- To evaluate the safety and tolerability of 
MK-1654 through Days 365 (Panels A 
through C, D1, and E1) and Day 545 (Panels 
D2 and E2)
- Solicited injection site adverse events (AEs) 
Day 1 through Day 5 post-dose
- Solicited systemic AEs Day 1 through 
Day 5 post-dose
- Serious adverse events (SAEs) from Day 1 
through Days 365 (Panels A through C, D1, 
and E1) and Day 545 (Panels D2 and E2) 
post-dose
Secondary Objectives
Secondary Endpoints
- To estimate the serum pharmacokinetic 
(PK) profile of MK-1654 on Days 7, 14, 90, 
150, and 365 (Panels A through C, D1, and 
E1) and Days 7, 150, and 365 (Panels D2 and 
E2)
- For Panels A through C, D1, and E1: the 
MK-1654 PK variables AUC0-inf, Cmax, Tmax, 
t1/2, and concentration (C7days, C14days, 
C90days, C150days, and C365days)
- For Panels D2 and E2: the MK-1654 PK 
variables AUC0-inf, Cmax, Tmax, t1/2, and 
concentration (C7days, C150days, and 
C365days)
- To describe the incidence of anti-drug 
antibodies (ADAs) to MK-1654 on Days 14, 
90, 150, and 365 (Panels A through C, D1,
and E1) and Days 150, 365, and 545 (Panels 
D2 and E2)
- For Panels A through C, D1, and E1: titer 
of ADAs to MK-1654 on Days 14, 90, 150, 
and 365
- For Panels D2 and E2: titer of ADAs to 
MK-1654 on Days 150, 365, and 545
087XXP

PRODUCT: MK-1654 
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30-JUL-2020
Overall Design:
Study Phase
Phase 1/Phase 2
Primary Purpose
Prevention
Indication
Prevention of lower respiratory tract infections (LRI) and 
hospitalizations caused by respiratory syncytial virus (RSV) 
A and B strains in infants born at 29 weeks gestational age
or older and of up to 8 months chronological age.
Population
Healthy pre-term infants (born at 29 to 35 weeks gestational 
age) and healthy full-term infants (born at over 35 weeks 
gestational age). All participants will have chronological 
age of 2 weeks to 8 months. 
Study Type
Interventional
Intervention Model
Single Group
This is a multi-site single ascending dose study.
Type of Control
Placebo
Study Blinding
Double-blind
Estimated Duration of Study
The Sponsor estimates that the study will require 
approximately 4 years from the time that written informed 
consent is provided for the first participant until the last 
participant’s last study-related telephone call or visit.
For purposes of analysis and reporting, the overall study 
ends when the Sponsor receives the last serology assay 
result.
Number of Participants:
Approximately 180 participants will be randomized such that a sufficient number of
evaluable participants in each panel complete the study, as described in Section 9.9.
087XXP

PRODUCT: MK-1654 
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PROTOCOL/AMENDMENT NO.: 002-04 
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30-JUL-2020
Intervention Groups and Duration:
Intervention 
Groups
Panel
Drug
Dose 
Strength
Dose 
Frequency
Route of 
Admin.
Regimen
Panel A
(Pre-term infants)
MK-
1654
20 mg
Once
IM
Single 0.2 mL
injection on Day 1
Placeboa
NA
Panel B
(Pre-term infants)
MK-
1654
50 mg
Once
IM
Single 0.5 mL 
injection on Day 1
Placeboa
NA
Panel C
(Pre-term infants)
MK-
1654
75 mg
Once
IM
0.75 mL dose 
divided into 
0.5 mL (in the right 
thigh) + 0.25 mL 
(in the left thigh)
injections on Day 1
Placeboa
NA
Panel D
(Pre-term infants)
MK-
1654
100 mg
Once
IM
1 mL dose (divided 
into 0.5 mL in the 
right thigh + 0.5 
mL in the left 
thigh) injections on 
Day 1
Placeboa
NA
Panel E
(Full-term infants)
MK-
1654
100 mg
Once
IM
1 mL dose (divided 
into 0.5 mL in the 
right thigh + 0.5 
mL in the left 
thigh) injections on 
Day 1
Placeboa
NA
IM=intramuscular; NA=not applicable.
a Placebo product is 0.9% sodium chloride, USP sterile saline.
Total 
Number
6 intervention arms (5 active, 1 placebo)
Duration of 
Participation
Each participant will participate in the study for approximately 365 days or 
545 days (depending on Panel) from the time the participant’s legally 
acceptable representative signs the Informed Consent Form (ICF) through the 
final contact. After a screening phase of up to 2 weeks, each participant will 
receive the assigned intervention on Day 1. After the intervention, participants 
in Panels A, B, C, D1, and E1 will be followed through Day 365, and 
participants in Panels D2 and E2 will be followed through Day 545.
087XXP

PRODUCT: MK-1654 
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PROTOCOL/AMENDMENT NO.: 002-04 
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30-JUL-2020
Study Governance Committees:
Steering Committee
No
Executive Oversight Committee
No
Data Monitoring Committee
Yes
Clinical Adjudication Committee
No
Study governance considerations are outlined in Appendix 1.
Study Accepts Healthy Volunteers: Yes
A list of abbreviations used in this document can be found in Appendix 8.
087XXP

PRODUCT: MK-1654 
24
PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Schema
The study design is depicted in Figure 1.
Figure 1
Dose Escalation Diagram
IM = Intramuscularly, N = total number of participants enrolled in the panel, siDMC = standing Internal Data Monitoring Committee
Participants in Panels D and E will be separated into two groups to distinguish participation, dependent on time of enrollment and consent.
*D1 and E1: Participants enrolled in Panels D and E prior to Amendment 04 choosing not to participate in the modified schedule will follow the D1 and E1 SoA.
**D2 and E2: Participants enrolled in Panels D and E prior to Amendment 04 choosing to participate in the modified schedule will follow the D2 and E2 SoA. 
Participants enrolled in Panels D and E under amendment 04 must follow the D2 and E2 SoA. 
087XXP

PRODUCT: MK-1654 
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PROTOCOL/AMENDMENT NO.: 002-04 
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30-JUL-2020
Schedule of Activities (SoA)
SoA for Panels A, B, C, D1, and E1
Study Period
Screening
Intervention 
(Panel A, B, C, D1, 
E1)
Follow-up
(365 days post dose)
Notes: 
Participants enrolled in 
Panels D and E prior to 
Amendment 04 choosing not 
to participate in the modified 
schedule will follow the D1 
and E1 SoA (See Section 4.1).
Visit Number/Title Screening
1
TC
TC
2
3
4
TC
5
6
TC
TC
7
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1 
Pre-
dose
1 
Dose
1 Post-
dose
1 
Post-
dose 
pm
2
3 +1 7 +2 14
±2
31 ±3 90 
±5
150 
±5
210
±5
270
±5
365 
±7
per 
investigator 
discretion
Administrative Procedures
Informed Consent
X
Informed Consent 
for Future 
Biomedical Research
X
Inclusion/Exclusion 
Criteria
X
X
Prior to randomization on 
Day 1, confirm that the 
participant continues to meet 
eligibility criteria.
Participant 
Identification Card
X
Medical History
X
X
Record on the Medical History 
eCRF any condition not 
already recorded at the 
screening baseline medical 
history or as AEs (on the AEs
eCRF).
087XXP

PRODUCT: MK-1654 
26
PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Study Period
Screening
Intervention 
(Panel A, B, C, D1, 
E1)
Follow-up
(365 days post dose)
Notes: 
Participants enrolled in 
Panels D and E prior to 
Amendment 04 choosing not 
to participate in the modified 
schedule will follow the D1 
and E1 SoA (See Section 4.1).
Visit Number/Title Screening
1
TC
TC
2
3
4
TC
5
6
TC
TC
7
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1 
Pre-
dose
1 
Dose
1 Post-
dose
1 
Post-
dose 
pm
2
3 +1 7 +2 14
±2
31 ±3 90 
±5
150 
±5
210
±5
270
±5
365 
±7
per 
investigator 
discretion
Prior/Concomitant 
Medication Review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
All concomitant medications 
taken on Days 1 through 30 
will be recorded; only 
concomitant medications 
related to a respiratory event or
SAE will be recorded from 
Day 31 through Day 365. 
Intervention
Randomization
X
Randomization (allocation) 
number is assigned at the time 
of study intervention
administration. Participants 
will be assigned by IRT to 1 of 
4 different blood sampling
schedules (1a, 1b, 2a, or 2b).
MK-1654 or Placebo 
Administration
X
Refer to Section 6.1 Study 
Intervention Administration 
and Section 6.6 Dose 
Modification (Escalation) for 
details.
Electronic Diary 
Card Device Given 
to and Collected 
from Participant’s 
Legally Acceptable 
Representative
X
Participant’s legally acceptable 
representative will be 
instructed to return the device 
after Day 30.
087XXP

PRODUCT: MK-1654 
27
PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Study Period
Screening
Intervention 
(Panel A, B, C, D1, 
E1)
Follow-up
(365 days post dose)
Notes: 
Participants enrolled in 
Panels D and E prior to 
Amendment 04 choosing not 
to participate in the modified 
schedule will follow the D1 
and E1 SoA (See Section 4.1).
Visit Number/Title Screening
1
TC
TC
2
3
4
TC
5
6
TC
TC
7
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1 
Pre-
dose
1 
Dose
1 Post-
dose
1 
Post-
dose 
pm
2
3 +1 7 +2 14
±2
31 ±3 90 
±5
150 
±5
210
±5
270
±5
365 
±7
per 
investigator 
discretion
Safety Procedures
Full Physical 
Examination 
including Weight
and Length
X
X
Weight and Length
X
X
X
X
X
Directed Physical 
Examination
X
X
Symptom-directed physical 
examination, as deemed 
necessary by the investigator.
Systemic and Local 
Treatment Reaction 
Assessment
X
X
X
X
X
Participants will be monitored 
at the study site for 2 hours
post-dose on Day 1 and have 
safety monitoring visits on 
Days 3 and 7.
Vital Signs
X
X
X
X
X
X
X
X
X
X
Repeat vital signs at 1- and 2-
hours post-dose for all 
participants. Refer to Section 
8.3.2 Vital Signs for details.
Hematology and 
Chemistry
X
Refer to Sec 10.2 Appendix 2: 
Clinical Laboratory Tests for 
details.
087XXP

PRODUCT: MK-1654 
28
PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Study Period
Screening
Intervention 
(Panel A, B, C, D1, 
E1)
Follow-up
(365 days post dose)
Notes: 
Participants enrolled in 
Panels D and E prior to 
Amendment 04 choosing not 
to participate in the modified 
schedule will follow the D1 
and E1 SoA (See Section 4.1).
Visit Number/Title Screening
1
TC
TC
2
3
4
TC
5
6
TC
TC
7
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1 
Pre-
dose
1 
Dose
1 Post-
dose
1 
Post-
dose 
pm
2
3 +1 7 +2 14
±2
31 ±3 90 
±5
150 
±5
210
±5
270
±5
365 
±7
per 
investigator 
discretion
AE/SAE Review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
All AEs through Day 14; 
solicited AEs of allergic 
reactions (hives or welts, lip 
swelling, wheezing, and 
difficulty breathing) through 
Day 30; respiratory AEs (see 
row below) and SAEs through 
Day 365.
Respiratory Virus Assessments
Respiratory AEs
Collection
Per criteria in Section 8.8.2
Observed/reported symptoms 
of respiratory infection will be 
collected as respiratory AEs on 
the AEs eCRF. If the 
symptoms meet the criteria for 
acute respiratory infection 
(ARI; see Section 8.8.2), 
participants will be evaluated 
at the earliest available 
unscheduled visit.
087XXP

PRODUCT: MK-1654 
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PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Study Period
Screening
Intervention 
(Panel A, B, C, D1, 
E1)
Follow-up
(365 days post dose)
Notes: 
Participants enrolled in 
Panels D and E prior to 
Amendment 04 choosing not 
to participate in the modified 
schedule will follow the D1 
and E1 SoA (See Section 4.1).
Visit Number/Title Screening
1
TC
TC
2
3
4
TC
5
6
TC
TC
7
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1 
Pre-
dose
1 
Dose
1 Post-
dose
1 
Post-
dose 
pm
2
3 +1 7 +2 14
±2
31 ±3 90 
±5
150 
±5
210
±5
270
±5
365 
±7
per 
investigator 
discretion
RSV Surveillance 
Weekly Telephone 
Calls
Weekly RSV surveillance TC
through 1 week after site designated 
RSV season end date
RSV weekly surveillance starts 
on Day 14 until Sponsor deems 
that RSV season has ended. 
From Day 14, sites will 
conduct weekly surveillance 
calls to the legally acceptable 
representative to determine if 
any respiratory symptoms have
occurred in the previous week.
If the symptoms meet the 
criteria for ARI (see 
Section 8.8.2), participants will 
be evaluated at the earliest 
available RSV assessment 
visit, within 10 days after 
symptom onset.
087XXP

PRODUCT: MK-1654 
30
PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Study Period
Screening
Intervention 
(Panel A, B, C, D1, 
E1)
Follow-up
(365 days post dose)
Notes: 
Participants enrolled in 
Panels D and E prior to 
Amendment 04 choosing not 
to participate in the modified 
schedule will follow the D1 
and E1 SoA (See Section 4.1).
Visit Number/Title Screening
1
TC
TC
2
3
4
TC
5
6
TC
TC
7
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1 
Pre-
dose
1 
Dose
1 Post-
dose
1 
Post-
dose 
pm
2
3 +1 7 +2 14
±2
31 ±3 90 
±5
150 
±5
210
±5
270
±5
365 
±7
per 
investigator 
discretion
Nasal Mucosal 
Sample for 
Respiratory Virus 
RT-PCR
Per criteria in Section 8.8.5
X
If ARI symptoms are 
confirmed, nasal swab will be 
obtained (see Section 8.8.5 and 
the operations/laboratory 
manual).
Pharmacokinetics/Pharmacodynamics/Biomarkers
Different PK and microsample 
blood draw schedules reduce 
the number of blood samples 
required of each individual 
participant. 
Schedule 1a:
Schedule 1a Blood 
for MK-1654 PK
X
X
X
X
Schedule 1a Blood 
for ADAs
X
X
X
Schedule 1a Blood 
for RSV SNA
X
X
Schedule 1a 
Microsample Blood 
for MK-1654 PK
X
X
As of Amendment 04, 
microsample blood for PK will 
no longer be collected from 
Panel D1 and E1 infants.
087XXP

PRODUCT: MK-1654 
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PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Study Period
Screening
Intervention 
(Panel A, B, C, D1, 
E1)
Follow-up
(365 days post dose)
Notes: 
Participants enrolled in 
Panels D and E prior to 
Amendment 04 choosing not 
to participate in the modified 
schedule will follow the D1 
and E1 SoA (See Section 4.1).
Visit Number/Title Screening
1
TC
TC
2
3
4
TC
5
6
TC
TC
7
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1 
Pre-
dose
1 
Dose
1 Post-
dose
1 
Post-
dose 
pm
2
3 +1 7 +2 14
±2
31 ±3 90 
±5
150 
±5
210
±5
270
±5
365 
±7
per 
investigator 
discretion
Schedule 1b:
Schedule 1b Blood 
for MK-1654 PK
X
X
X
X
Schedule 1b Blood 
for ADAs
X
X
X
Schedule 1b Blood 
for RSV SNA
X
X
Schedule 1b 
Microsample Blood 
for MK-1654 PK
X
X
As of Amendment 04, 
microsample blood for PK will 
no longer be collected from 
Panel D1 and E1 infants.
Schedule 2a:
Schedule 2a Blood 
for MK-1654 PK 
X
X
X
X
Schedule 2a Blood 
for ADAs
X
X
X
X
Schedule 2a Blood 
for RSV SNA
X
X
X
Schedule 2a 
Microsample Blood 
for MK-1654 PK
X
X
As of Amendment 04, 
microsample blood for PK will 
no longer be collected from 
Panel D1 and E1 infants.
087XXP

PRODUCT: MK-1654 
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PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Study Period
Screening
Intervention 
(Panel A, B, C, D1, 
E1)
Follow-up
(365 days post dose)
Notes: 
Participants enrolled in 
Panels D and E prior to 
Amendment 04 choosing not 
to participate in the modified 
schedule will follow the D1 
and E1 SoA (See Section 4.1).
Visit Number/Title Screening
1
TC
TC
2
3
4
TC
5
6
TC
TC
7
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1 
Pre-
dose
1 
Dose
1 Post-
dose
1 
Post-
dose 
pm
2
3 +1 7 +2 14
±2
31 ±3 90 
±5
150 
±5
210
±5
270
±5
365 
±7
per 
investigator 
discretion
Schedule 2b:
Schedule 2b Blood 
for MK-1654 PK 
X
X
X
X
Schedule 2b Blood 
for ADAs
X
X
X
X
Schedule 2b Blood 
for RSV SNA
X
X
X
Schedule 2b 
Microsample Blood 
for MK-1654 PK
X
X
As of Amendment 04, 
microsample blood for PK will 
no longer be collected from 
Panel D1 and E1 infants.
ADAs=anti-drug antibodies; AEs=adverse events; ARI=acute respiratory infection; eCRF=electronic case report form; IRT=Interactive Response Technology; 
PK=pharmacokinetics; Post-dose pm=in the evening of Day 1 post-dose; RSV=respiratory syncytial virus; RT-PCR=reverse transcription polymerase chain reaction; 
SAEs=serious adverse events; SNA=serum neutralizing antibodies; TC=telephone call; UNSCH=unscheduled visit.
087XXP

PRODUCT: MK-1654 
33
PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
SoA for Panels D2 and E2
Study Period
Screening Intervention 
(Panel D2, E2)
Follow-up
(545 days post dose)
Notes:
Participants enrolled in Panels D and E 
prior to Amendment 04 choosing to 
participate in the modified schedule will 
follow the D2 and E2 SoA. 
Participants enrolled in Panels D and E 
under Amendment 04 must follow the D2 
and E2 SoA. 
See Section 4.1
Visit Number/Title
Screening
1
TC
T
C
2
3
4
TC
5
6
TC TC
7
8
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1
Pre-
dose
1 
Dose
1 
Post-
dose
1 
Post-
dose 
pm
2
3 
+1
7 
+2
14
±2
31 
±3
90
±5
150
±5
210
±5
270
±5
365 
±7
545
±10
per 
investigator 
discretion
Administrative Procedures
Informed Consent
X
Informed Consent 
Addendum
                                                                        X
For participants enrolled in Panels D & E 
prior to Amendment 04 who choose to 
participate in the modified schedule, obtain 
consent with the Informed Consent 
Addendum.
Informed Consent for 
Future Biomedical 
Research
X
Inclusion/Exclusion 
Criteria
X
X
Prior to randomization on Day 1, confirm 
that the participant continues to meet 
eligibility criteria.
Participant Identification 
Card
X
Medical History
X
X
Record on the Medical History eCRF any 
condition not already recorded at the 
screening baseline medical history or as AEs 
(on the AEs eCRF).
087XXP

PRODUCT: MK-1654 
34
PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Study Period
Screening Intervention 
(Panel D2, E2)
Follow-up
(545 days post dose)
Notes:
Participants enrolled in Panels D and E 
prior to Amendment 04 choosing to 
participate in the modified schedule will 
follow the D2 and E2 SoA. 
Participants enrolled in Panels D and E 
under Amendment 04 must follow the D2 
and E2 SoA. 
See Section 4.1
Visit Number/Title
Screening
1
TC
T
C
2
3
4
TC
5
6
TC TC
7
8
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1
Pre-
dose
1 
Dose
1 
Post-
dose
1 
Post-
dose 
pm
2
3 
+1
7 
+2
14
±2
31 
±3
90
±5
150
±5
210
±5
270
±5
365 
±7
545
±10
per 
investigator 
discretion
Prior/Concomitant 
Medication Review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
All concomitant medications taken on 
Days 1 through 30 will be recorded; only 
concomitant medications related to a 
respiratory event or SAE will be recorded 
from Day 31 through Day 545. 
Intervention 
Randomization
X
Randomization (allocation) number is 
assigned at the time of study intervention 
administration.
MK-1654 or Placebo 
Administration
X
Refer to Section 6.1 Study Intervention 
Administration and Section 6.6 Dose 
Modification (Escalation) for details.
Electronic Diary Card 
Device Given to and 
Collected from 
Participant’s Legally 
Acceptable 
Representative
X
Participant’s legally acceptable 
representative will be instructed to return the 
device after Day 30.
Safety Procedures
Full Physical 
Examination including 
Weight and Length
X
X
Weight and Length
X
X
X
X
Directed Physical 
Examination
X
X
Symptom-directed physical examination, 
as deemed necessary by the investigator.
087XXP

PRODUCT: MK-1654 
35
PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Study Period
Screening Intervention 
(Panel D2, E2)
Follow-up
(545 days post dose)
Notes:
Participants enrolled in Panels D and E 
prior to Amendment 04 choosing to 
participate in the modified schedule will 
follow the D2 and E2 SoA. 
Participants enrolled in Panels D and E 
under Amendment 04 must follow the D2 
and E2 SoA. 
See Section 4.1
Visit Number/Title
Screening
1
TC
T
C
2
3
4
TC
5
6
TC TC
7
8
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1
Pre-
dose
1 
Dose
1 
Post-
dose
1 
Post-
dose 
pm
2
3 
+1
7 
+2
14
±2
31 
±3
90
±5
150
±5
210
±5
270
±5
365 
±7
545
±10
per 
investigator 
discretion
Systemic and Local 
Treatment Reaction 
Assessment
X
X
X
X
X
Participants will be monitored at the study 
site for 2 hours post-dose on Day 1 and have 
safety monitoring visits on Days 3 and 7.
Vital Signs
X
X
X
X
X
X
X
X
X
X
X
Repeat vital signs at 1- and 2-hours post-dose 
for all participants in panels. Refer to Section 
8.3.2 Vital Signs for details.
Hematology and 
Chemistry
X
Refer to Sec 10.2
Appendix 2: Clinical 
Laboratory Tests for details.
AE/SAE Review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
All AEs through Day 14; solicited AEs of 
allergic reactions (hives or welts, lip 
swelling, wheezing, and difficulty breathing) 
through Day 30; respiratory AEs through 
Day 365 (see row below), and SAEs through 
Day 545. 
Respiratory Virus Assessments
Respiratory AEs 
Collection
Per criteria in Section 8.8.2
Per 
criteria in 
Section 
8.8.2
Observed/reported symptoms of respiratory 
infection will be collected as respiratory AEs 
on the AEs eCRF. If the symptoms meet the 
criteria for acute respiratory infection (ARI; 
see Section 8.8.2), participants will be 
evaluated at the earliest available 
unscheduled visit.
087XXP

PRODUCT: MK-1654 
36
PROTOCOL/AMENDMENT NO.: 002-04 
MK-1654-002-04 FINAL PROTOCOL
30-JUL-2020
Study Period
Screening Intervention 
(Panel D2, E2)
Follow-up
(545 days post dose)
Notes:
Participants enrolled in Panels D and E 
prior to Amendment 04 choosing to 
participate in the modified schedule will 
follow the D2 and E2 SoA. 
Participants enrolled in Panels D and E 
under Amendment 04 must follow the D2 
and E2 SoA. 
See Section 4.1
Visit Number/Title
Screening
1
TC
T
C
2
3
4
TC
5
6
TC TC
7
8
UNSCH
Scheduled Day and 
Window (days):
Up to 14 
prior to 
Day 1
1
Pre-
dose
1 
Dose
1 
Post-
dose
1 
Post-
dose 
pm
2
3 
+1
7 
+2
14
±2
31 
±3
90
±5
150
±5
210
±5
270
±5
365 
±7
545
±10
per 
investigator 
discretion
RSV Surveillance 
Weekly Telephone Calls
Weekly RSV surveillance TC 
through 1 week after site 
designated RSV season end 
date
RSV weekly surveillance starts on Day 14 
until Sponsor deems that RSV season has 
ended. From Day 14, sites will conduct 
weekly surveillance calls to the legally 
acceptable representative to determine if any 
respiratory symptoms have occurred in the 
previous week. If the symptoms meet the 
criteria for ARI (see Section 8.8.2), 
participants will be evaluated at the earliest 
available RSV assessment visit, within 10 
days after symptom onset.
Nasal Mucosal Sample 
for Respiratory Virus 
RT-PCR
Per criteria in Section 8.8.5
X
If ARI symptoms are confirmed, nasal swab 
will be obtained (see Section 8.8.5 and the 
operations/laboratory manual).
Pharmacokinetics/Pharmacodynamics/Biomarkers
Schedule 3 Blood for 
MK-1654 PK 
X
X
X
X
Schedule 3 Blood for 
ADAs
X
X
X
X
Schedule 3 Blood for 
RSV SNA
X
X
X
X
ADAs=anti-drug antibodies; AEs=adverse events; ARI=acute respiratory infection; eCRF=electronic case report form; IRT=Interactive Response Technology; 
PK=pharmacokinetics; Post-dose pm=in the evening of Day 1 post-dose; RSV=respiratory syncytial virus; RT-PCR=reverse transcription polymerase chain reaction; 
SAEs=serious adverse events; SNA=serum neutralizing antibodies; TC=telephone call; UNSCH=unscheduled visit.
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2. INTRODUCTION
Burden of RSV Infection in Infants 
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis, lower 
respiratory tract infections (LRI), and hospitalization in infants. An estimated 74,000 to 
126,000 infant hospitalizations in the United States result from RSV each year, representing
an annual rate of 25 to 40 per 1000 infants [Hall, C. B., et al 2013] [Shay, D. K., et al 1999] 
[Holman, R. C., et al 2004]. RSV infection has been associated with 43% to 74% of
bronchiolitis and 19% to 54% of pneumonia cases in hospitalized children [Shay, D. K., et al 
1999]. In 2015, RSV was estimated to have caused 28% of acute LRIs and 2.7 to 3.8 million 
hospitalizations globally in children under 5 years of age. Almost half of the hospitalizations 
(45%) occurred in infants younger than 6 months. Mortality from RSV infection was
significant, with an estimated 94,600 to 149,400 childhood deaths worldwide [Shi, T., et al 
2015]. The overwhelming majority of RSV-associated deaths occur in developing countries. 
In contrast, in the United States, the death rate in infants due to RSV is low, likely due to 
quality supportive care [Nair, H., et al 2010].
Beyond hospitalization and death, RSV infection is a significant driver of outpatient health 
care utilization in infants, leads to the development of some chronic respiratory illnesses, and 
results in workdays missed by caregivers [Bourgeois, F. T., et al 2009]. An estimated 2.2% 
(1.7 million visits) of all United States primary care visits of children ≤5 years old in 2000 
were due to RSV infection. Pre-term infants with RSV averaged 12.4 physician office visits
for any cause and 5 visits for respiratory causes during their first 2 years of life, whereas
children without RSV averaged 9.4 visits for any cause and 2.9 visits for respiratory causes
during their first 2 years of life [Diez-Domingo, J., et al 2014]. Compared to influenza, 
children with RSV were more likely to receive intensive medical care, medications, including 
antibiotics, and radiologic studies [Bourgeois, F. T., et al 2009]. Children previously infected 
with RSV also have a higher risk of developing some chronic conditions, including allergic 
rhino-conjunctivitis [Diez-Domingo, J., et al 2014], recurrent wheezing, and asthma [Polack 
F. P. 2015]. Taken together, these data highlight the burden of RSV for infants, caregivers, 
and healthcare providers and systems. 
Pre-term infants, and those with underlying medical conditions, are pre-disposed to severe 
RSV infection. A prophylactic monoclonal antibody (mAb) targeting the RSV fusion (F) 
protein, palivizumab (SynagisTM, MedImmune), is approved for the prevention of serious 
lower respiratory tract disease caused by RSV in children at high risk for RSV disease [U.S.
Prescribing Information 2009] [American Academy of Pediatrics Committee on Infectious 
Diseases 2014]. However, the majority of infants hospitalized with RSV infection have no 
predisposing risk factors and are otherwise healthy (only a younger age and prematurity have 
been independently associated with RSV illness requiring hospitalization) [Hall, C. B., et al 
2009]. The infant population in which palivizumab is recommended has narrowed 
considerably due to limited clinical benefit and high cost [American Academy of Pediatrics 
Committee on Infectious Diseases 2014]; monthly dosing to cover the entire RSV season 
also limits the wide application of palivizumab. Therefore, there is a need for prophylaxis to 
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prevent RSV infection and related complications in infants not recommended to receive 
palivizumab, which represents the overwhelming majority of healthy pre-term and full-term 
infants. 
Passive immunization with a neutralizing mAb against the RSV F protein, ie, palivizumab, is 
a proven prophylaxis approach in infants. This approach provides near-immediate protection 
at birth [American Academy of Pediatrics Committee on Infectious Diseases 2014] and 
accommodates the immature immune system and high safety requisites of this infant 
population [Acosta, P. L., et al 2015] [David Snydman (Tufts) 2013]. Similarly, MK-1654 is 
also a neutralizing mAb against RSV, with additional attributes to facilitate its application as 
an RSV prophylactic for infants currently not receiving palivizumab, as outlined in 
Section 2.1. 
Study Rationale
This study is being conducted to assess the safety, tolerability, and serum PK following 
administration of MK-1654 IM to healthy pre-term and full-term infants. The main objective 
is to identify a well-tolerated dose in infants that is expected to provide high protection 
against RSV through 5 months post-injection. 
Similar to the completed Phase 1a study in healthy adult participants (P001), this study is 
randomized, placebo-controlled, double-blind, and uses a single ascending dose design. 
Information on the safety and PK of MK-1654 in pre-term and full-term infants will further 
facilitate dose selection and clinical development in the target infant population. 
The study will enroll healthy pre-term infants born at 29 to 35 weeks gestational age and 
healthy infants born at over 35 weeks gestational age (throughout this protocol, defined as 
“full-term” in order to distinguish from the pre-term infant population, acknowledging that 
this differs from accepted definitions of full-term infants). All participants will have 
chronological age between 2 weeks and 8 months at the time of consent, consistent with the 
peak age of hospitalization for RSV (2-3 months chronological age) and increased risk for 
RSV infection in infants. The full-term infants will be the final cohort within the study, after 
dose escalation and confirmation of short-term safety in pre-term infants.
RSV prophylaxis is currently unavailable for most infants. Palivizumab is approved in the 
United States, the European Union, and more than 80 countries globally for RSV prophylaxis 
in infants at high risk for RSV disease. However, the American Academy of Pediatrics 
recommends limiting use of palivizumab for infants born <29 weeks gestation and infants 
with certain chronic illnesses such as congenital heart disease or chronic lung disease, due to 
its modest efficacy, high cost, and the need for 5 separate monthly injections [American 
Academy of Pediatrics Committee on Infectious Diseases 2014] [Joffe, S., et al 1999].
Background
Refer to the IB for detailed background information on MK-1654.
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Pharmaceutical and Therapeutic Background
MK-1654 is a fully human mAb targeting the RSV F protein, which the virus utilizes to enter 
host cells and fuse infected cells with adjacent cells, spreading by forming syncytia. The 
F protein is considered a key antigen for protective immunity, based on natural immunity 
studies and active and passive vaccine approaches (ie, palivizumab) [American Academy of 
Pediatrics Committee on Infectious Diseases 2014] [Graham, B. S., et al 2015]. MK-1654 
binds to the F protein and neutralizes RSV infection of cells in vitro and reduces viral load in 
the nose and lungs of cotton rats infected with RSV A or B when administered 
prophylactically [Wyde PR, Moore DK, Hepburn T, Silverman CL, Porter TG, Gross M, 
1995]. Compared to palivizumab, MK-1654 exhibits greater potency both in vitro and in the 
preclinical cotton-rat model (see IB). Mutations in the Fc region of MK-1654 result in an 
extended half-life such that PK modeling suggests that a single dose of MK-1654 will sustain 
therapeutic levels for 5 months in the majority of infants entering their first RSV season (see 
IB for details).
Preclinical and Clinical Studies
Refer to the IB for preclinical information on MK-1654.
Completed Clinical Studies
The FIH study, P001, was a 1-year, randomized, placebo-controlled, double-blind, single 
ascending dose study to assess the safety, tolerability, and PK of MK-1654 administered as a 
single IM (100, 300 mg) or IV (300, 1000, 3000 mg) dose to healthy adult participants. One 
hundred and fifty-two healthy male and female (non-child bearing potential) participants 
aged 19 to 59 years were enrolled (enrollment completed FEB-2018). Preliminary results 
from this study were used to confirm that the safety and PK profile and dose levels of MK-
1654 in healthy adults warranted initiating this Phase 1b study in healthy pre-term and full-
term infants. No acute safety reactions to MK-1654 were noted through completion of the 
highest dose (3000 mg IV) in Study P001. Most AEs were transient and considered mild to 
moderate in intensity by the investigator. No MK-1654-related SAEs were reported. See the 
IB for additional information.
Information on Other Study-related Therapy
Not applicable.
Benefit/Risk Assessment
It cannot be guaranteed that participants in clinical studies will directly benefit from 
intervention during participation, as clinical studies are designed to provide information 
about the safety and effectiveness of an investigational medicine.
Additional details regarding specific benefits and risks for participants participating in this 
clinical study may be found in the accompanying IB and ICF documents.
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3. HYPOTHESIS, OBJECTIVES, AND ENDPOINTS
The following objectives and endpoints will be evaluated in healthy pre-term and full-term 
infants receiving a single ascending dose of MK-1654 or placebo intramuscularly. No formal 
hypotheses will be tested in the study.
Objectives
Endpoints
Primary
•
To evaluate the safety and tolerability of 
MK-1654 through Day 365 (Panels A
through C, D1, and E1) and Day 545 
(Panels D2 and E2)
•
Solicited injection site adverse events 
(AEs) Day 1 through Day 5 post-dose
•
Solicited systemic AEs Day 1 through 
Day 5 post-dose
•
Serious adverse events (SAEs) from 
Day 1 through Day 365 (Panels A
through C, D1, and E1) and Day 545 
(Panels D2 and E2) post-dose
Secondary
•
To estimate the serum pharmacokinetic 
(PK) profile of MK-1654 on Days 7, 14, 
90, 150, and 365 (Panels A through C, 
D1, and E1) and Days 7, 150, and 365 
(Panels D2 and E2)
•
For Panels A through C, D1, and E1: the 
MK-1654 PK variables AUC0-inf, Cmax, 
Tmax, t1/2, and concentration (C7days, 
C14days, C90days, C150days, and 
C365days)
•
For Panels D2 and E2: the MK-1654 PK 
variables AUC0-inf, Cmax, Tmax, t1/2, and 
concentration (C7days, C150days, and 
C365days)
•
To describe the incidence of anti-drug 
antibodies (ADAs) to MK-1654 on 
Days 14, 90, 150, and 365 (Panels A
through C, D1, and E1) and Days 150, 
365, and 545 (Panels D2 and E2)
•
For Panels A through C, D1, and E1: titer 
of ADAs to MK-1654 on Days 14, 90, 
150, and 365
•
For Panels D2 and E2: titer of ADAs to 
MK-1654 on Days 150, 365, and 545
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Objectives
Endpoints
Tertiary/Exploratory
•
To describe any associations between 
ADA titer and PK, safety, and RSV 
serum neutralizing antibody titer
•
Associations between ADA titer, PK 
parameters, safety endpoints, and RSV 
serum neutralizing antibody titer
•
To evaluate the effect of MK-1654 on 
RSV serum neutralizing antibody titers
on Days 150 and 365 (Panels A through 
C, D1, and E1) and Days 150, 365, and 
545 (Panels D2 and E2) after a single IM 
dose of MK-1654
•
RSV serum neutralizing antibody titers
•
To evaluate the PK profile of MK-1654 
in blood microsamples (Panels A through 
C)
•
Blood microsample PK profile after a 
single IM dose of MK-1654 (Panels A
through C)
•
To estimate the PK profile of MK-1654 
in different segments of the target 
population with respect to body weight
•
Associations between PK parameters and 
body weight
•
To describe the incidence of viral acute 
respiratory infection (ARI) in the study, 
as determined by reverse transcription 
polymerase chain reaction (RT-PCR) 
detection and presence of symptoms, 
including RSV-associated outpatient 
lower respiratory tract infection (LRI) or 
hospitalization
•
RSV, influenza, and human 
metapneumovirus (hMPV) in nasal swab 
in infants with symptoms consistent with 
respiratory infection
•
RSV-associated ARI 
•
RSV-associated LRI
•
RSV-associated hospitalization
•
RSV-associated medically attended LRI 
(including office or clinic visit, 
emergency department, urgent care, or 
hospitalizations) 
4. STUDY DESIGN
Overall Design
This is a randomized, placebo-controlled, single ascending dose, multi-site, double-blind, 
safety, tolerability, and PK study of MK-1654 in healthy pre-term and full-term infants.
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Approximately 180 healthy male and female infants will be enrolled in the study, including 
140 pre-term (born at 29 to 35 weeks gestational age) and 40 full-term (born at over 
35 weeks gestational age) infants. All participants will have chronological age of 2 weeks to 
8 months. 
Pre-term infants will be enrolled worldwide and allocated to 1 of 4 dose escalation panels 
(Panel A, B, C, or D). Within each sequential dose escalation panel, participants will be 
randomized by IRT in a 4:1 ratio (active:placebo) to receive one of the following active 
doses or placebo: 
•
Panel A: 20 mg, 
•
Panel B: 50 mg, 
•
Panel C: 75 mg, or 
•
Panel D: 100 mg. 
Panel A will enroll a total of 10 participants (8 active, 2 placebo) at the lowest dose level; 
Panel B will enroll a total of 40 participants (32 active, 8 placebo) at 50 mg; Panel C will 
enroll 50 participants (40 active, 10 placebo) at 75 mg to cover the expected target clinical 
dose; and Panel D will enroll 40 participants (32 active, 8 placebo) to receive 100 mg, the 
highest possible dose. Available safety, tolerability, and PK data from Panels A, B, and C 
will be analyzed to inform the final dose level and allocation of participants in Panel D per 
Sponsor siDMC Meeting decision, as detailed in Section 6.6. Treatment 
allocation/randomization of pre-term infants in Panels B, C, and D will be stratified by 
weight using IRT, as described in Section 6.3.2.
Full-term infants will be enrolled worldwide into Panel E. Within this panel, participants will 
be randomized by IRT in a 4:1 ratio (active:placebo) to receive either the following active 
dose or placebo: 
•
Panel E: 100 mg
Panel E will enroll 40 participants (32 active, 8 placebo) at 100 mg, the highest possible 
dose. The dose level in Panel E will be determined as in Panel D per Sponsor siDMC.
All participants will receive the assigned study intervention (MK-1654 or placebo [0.9% 
sodium chloride, USP sterile saline]) administered via IM injection(s) on Day 1. Participants
in panels A and B will receive study intervention administered as a single IM injection, as 
specified in the pharmacy manual. Participants in panels C, D, and E will receive 1 dose of 
study intervention divided and administered as 2 IM injections, as specified in the pharmacy 
manual and Section 8.1.8.
After randomization to MK-1654 or placebo within a panel, participants enrolled prior to 
Amendment 04 will also be randomized by IRT to 1 of 4 different blood sampling schedules 
(Group 1a, Group 1b, Group 2a, or Group 2b). These differ in the schedule of venous and
microsampling, as outlined in SoA 1.3.1 and the operations/laboratory manual. This 
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approach provides sufficient safety and PK data to support dose escalation decisions and to 
meet study objectives while minimizing the number of blood draws and total blood volume 
drawn from each participant at each visit and during the study overall. The approximate total 
blood volume drawn per participant is approximately 9.0 mL, as detailed in the 
operations/laboratory manual.
As of Amendment 04, 2 SoAs have been created for participants in Panels D and E to 
distinguish their participation in the modified schedule, as follows:

Panels D1 and E1 (Section 1.3.1):
o
Participants enrolled in Panels D and E prior to Amendment 04 choosing not 
to participate in the modified schedule will follow the Panels D1 and E1 SoA.

Panels D2 and E2 (Section 1.3.2):
o
Participants enrolled in Panels D and E prior to Amendment 04 choosing to 
participate in the modified schedule will follow the Panels D2 and E2 SoA 
(Group 3).
o
Participants enrolled in Panels D and E under Amendment 04 must follow the 
Panels D2 and E2 SoA.
See the Dose Escalation Diagram in Figure 1 and the dose escalation procedures and decision 
criteria in Section 6.6 Dose Modification (Escalation) and Section 4.4.2 Clinical Criteria for 
Study Pause.
Specific procedures to be performed during the study, as well as their prescribed times and 
associated visit windows, are outlined in the SoA in Section 1.3. Details of each procedure 
are provided in Section 8.
In addition to the interim safety and PK assessments for dose escalation decisions between 
panels, an interim safety and PK analysis will also be performed when the PK data are 
available for all evaluable pre-term infant participants in Panels A and B and at least 10 
pre-term infant participants in Panel C through Day 150 and will include available safety and 
PK data from Panels D and E , as described in Section 9.7. The study will be complete once 
all participants have completed their final safety visit.
Scientific Rationale for Study Design
Rationale for selection of the primary safety endpoint and of the secondary and tertiary PK, 
pharmacodynamic, and other exploratory endpoints in this study is discussed below. See 
Section 4.3.3 and the IB for additional details on the scientific rationale for the study design.
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Rationale for Endpoints
Safety Endpoints
As this is an early clinical investigation of MK-1654, safety and tolerability of MK-1654 will 
be the primary endpoints and will be carefully monitored. AEs, systemic and local injection 
reaction assessments, physical examinations, and VS will be assessed during the intervention 
and follow-up periods, with assessment collection times optimized based on the expected PK 
properties of MK-1654 in infants and the typical timing of reactions to mAbs. All AEs will 
be assessed for intensity.
Participants will be observed at the study site for 2 hours post-dose for safety monitoring for 
any immediate AEs, then will return to the study site for visits and for safety and PK 
assessments as set out in Section 1.3 SoA. In addition, on the evening of Day 1 and on Days
2, 31, 210 (7 months) and 270 (9 months), participants will receive safety follow-up 
telephone calls for review of concomitant medications and any AEs/SAEs specified in 
Section 8.3.4. Instructions for supportive care are outlined in Section 6.5.1. Temperature and 
AEs will also be documented on a validated diary card administered via handheld electronic 
device, with entries reviewed with the legally acceptable representative during the follow-up 
safety visit on Days 7 and 14 and telephone call on Day 31.
The safety follow-up period will be 365 days post-dose for Panels A through C, D1, and E1
and 545 days post-dose for Panels D2 and E2. The safety parameters for this study will 
include the proportion of participants with the following: 
Elevated temperature (≥102.2°F [39.0°C] rectal or ≥101.7°F [38.7°C] axillary 
equivalent) from Day 1 through Day 5 post-dose; 
Solicited systemic treatment reaction AEs (irritability, drowsiness, fever, and appetite 
lost) from Day 1 through Day 5 post-dose;
Solicited local injection reaction AEs (redness/erythema, swelling, and 
pain/tenderness) reported using the electronic diary card from Day 1 through Day 5
post-dose; 
Solicited AEs of allergic reactions (hives or welts, lip swelling, wheezing, and 
difficulty breathing) from Day 1 through Day 30 post-dose;
Respiratory AEs from Day 1 post-dose through Day 365 post-dose;
Any other unsolicited non-serious AEs occurring from Day 1 through Day 14 post-
dose;
SAEs throughout the study duration (from the time the consent form is signed 
through Day 365 (Panels A through C, D1, and E1)/Day 545 (Panels D2 and E2)
post-dose and/or completion of the participant’s participation in the study; for 
complete details on SAE data collection, refer to Section 10.3.4).
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As with all biologic medications, MK-1654 carries a risk of acute systemic reactions upon 
exposure. These reactions can be categorized as common acute systemic injection reactions, 
acute hypersensitivity reactions, and high cytokine release reactions. For other biologic 
medications, these reactions have been best described in adults. In adults, common acute
systemic injection reactions are usually mild, and may manifest with rigors, back pain, 
abdominal pain, nausea, vomiting, diarrhea, dyspnea, flushing, pruritus, and changes in heart 
rate or blood pressure. Acute hypersensitivity reactions typically occur after repeated 
exposures but can occur with the first dose. In addition to signs similar to common acute 
systemic injection reactions, participants may develop urticaria, wheezing, coughing, facial 
swelling, angioedema, and more significant changes in VS. Following initial exposure or re-
exposure to palivizumab, cases of anaphylaxis and anaphylactic shock, including fatal cases, 
have been reported. An anaphylactic reaction is a severe type of acute systemic injection 
reaction characterized by cutaneous and mucosal symptoms such as generalized hives, 
pruritus or flushing, swollen lips-tongue-uvula and angioedema, accompanied by respiratory 
compromise (bronchospasm, stridor, or hoarseness) and/or changes in blood pressure 
(hypotension), per the 2006 Sampson criteria for anaphylaxis (Grade 4 reaction) [Sampson, 
H. A., et al 2006].
The risk of any of these acute systemic injection reactions to the MK-1654 antibody is 
considered very low as it contains only human elements. The MK-1654 antibody has no 
endogenous target in humans. In the P001 clinical study, in which MK-1654 was
administered both IM and IV, no acute safety reactions to MK-1654 were noted in healthy 
adult participants up to a dose of 3000 mg IV, as described in Section 2.2.3. Administration 
of a single IM dose of MK-1654 in this study further reduces the risk of hypersensitivity 
reactions that were seen with re-exposure to palivizumab after multiple monthly doses. 
Nevertheless, given potential safety risks, participants will be closely monitored post-dose 
with a scheduled onsite safety observation period. Study staff will monitor participants 
through 2 hours post-dose for local and systemic symptoms of reactogenicity to MK-1654 
with VS, plus physical examination as needed. 
Pharmacokinetic Endpoints
As part of the allocation number assignment and blood sampling groups, participants
enrolled prior to Amendment 04 will be assigned by IRT to 1 of 4 different blood sampling
schedules (Group 1a, 1b, 2a, or 2b). Participants who enroll in Panels D and E under 
Amendment 04 will be assigned to a separate blood sampling group (Group 3). Blood 
sampling groups describe the time points at which participants are to have blood drawn, as
scheduled in the SoA and outlined in the operations/laboratory manual, for the following 
PK/PD assays.
Serum PK of MK-1654
The PK of MK-1654 will be measured as described in Section 1.3 to define Cmax, the 
distribution of the mAb, and the PK profile when administered IM. PK will be measured 
using a validated bioanalytical assay throughout the entire 1-year study period to determine 
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the half-life of the molecule, which will support PK projections for subsequent clinical 
development in the target infant population. 
Blood Microsampling Assay
The blood microsampling PK profile after a single IM dose of MK-1654 will be evaluated. 
This will support development of a validated whole blood microsampling assay for MK-1654 
PK, with the intent that blood volumes required for these tests would be reduced in future 
studies. 
MK-1654 PK and Infant Body Weight
The PK profile of MK-1654 will be estimated in different segments of the infant population 
with respect to body weight. This will help to further characterize MK-1654 PK and further 
inform dose selection in the target infant population. Treatment allocation/randomization of 
pre-term infants in Panels B, C, and D will be stratified by weight using IRT, as described in
Section 6.3.2.
Pharmacodynamic Endpoints
The following exploratory endpoints will be evaluated to characterize the pharmacodynamics 
of a single IM dose of MK-1654.
Anti-drug Antibodies to MK-1654
The presence and titer of ADAs will be measured. ADAs can develop to biologics like 
MK-1654 and may be either clinically inconsequential or change the drug PK and/or 
efficacy. Moreover, ADAs may lead to loss of drug efficacy and/or AEs. Therefore, ADA 
titers will be analyzed for association with PK and safety events and, as applicable, for 
associations with RSV SNA titers, as described below. 
RSV SNAs
This study will also evaluate the effect of single ascending doses of MK-1654 on RSV SNA. 
In this assay, serial dilutions of the participant’s serum will be used to inhibit the entry of 
RSV into target cells in vitro. Total RSV serum neutralizing activity could be influenced by 
environmental exposure to RSV in addition to the presence of MK-1654. Moreover, the 
activity of MK-1654 may be inhibited by the presence of ADAs. Therefore, unexpected 
changes in RSV SNA titers will be examined for associations with respiratory infection and 
ADA titer. 
Other Exploratory Endpoints
The following additional exploratory endpoint will be evaluated.
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Acute Respiratory Infection Incidence
The incidence of viral ARI in the study will be explored, as determined by presence of 
symptoms (as listed in Section 8.8.2) and RT-PCR detection. This will serve to describe the 
incidence of ARI, including RSV, influenza, and hMPV infection, and help to determine the 
infectious cause of the ARI and estimate the relative proportion of RSV A and B infections in 
the target infant population. The procedures for respiratory virus infection determination are 
detailed in Section 8.8. Note that this study is not powered to show an effect of MK-1654 on 
the incidence of LRI or hospitalizations caused by RSV. 
Future Biomedical Research
The Sponsor will conduct future biomedical research on specimens for which consent was 
provided during this study. This research may include genetic analyses (deoxyribonucleic 
acid [DNA]), gene expression profiling (ribonucleic acid [RNA]), proteomics, metabolomics 
(serum, plasma) and/or the measurement of other analytes, depending on which specimens 
are consented for future biomedical research.
Such research is for biomarker testing to address emergent questions not described elsewhere 
in the protocol (as part of the main study) and will only be conducted on specimens from 
appropriately consented participants. The objective of collecting/retaining specimens for 
future biomedical research is to explore and identify biomarkers that inform the scientific 
understanding of diseases and/or their therapeutic treatments. The overarching goal is to use 
such information to develop safer, more effective drugs/vaccines, and/or to ensure that 
participants receive the correct dose of the correct drug/vaccine at the correct time. The 
details of this future biomedical research are presented in Appendix 6: Collection and 
Management of Specimens for Future Biomedical Research.
Rationale for the Use of Comparator/Placebo
The primary goal of the study is to evaluate the safety and tolerability of MK-1654 in the 
target infant population. A placebo-controlled study will allow for an unbiased assessment of 
safety and tolerability of MK-1654. Secondary and exploratory outcomes are also supported 
by the use of placebo, including the identification of ADAs, which should only be observed 
in participants receiving MK-1654, and the effect of MK-1654 on RSV serum neutralizing 
activity, which could be influenced by environmental exposure to RSV, making a placebo 
arm a key negative control. Lastly, as participants are healthy infants of at least 29 weeks 
gestational age and not recommended to receive palivizumab (the only approved RSV 
prophylactic), an active comparator is not possible. Sterile 0.9% saline has been chosen as 
the placebo as the goal of the study is to test the relative safety and tolerability of the 
MK-1654 investigational product.
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Justification for Dose
Starting Dose for This Study
The starting IM dose in this study is 20 mg (refer to the IB for discussion of the starting IM 
dose and safety margin in humans). The MK-1654 molecule is considered to be of low risk to 
human participants as a fully human mAb with linear PK in non-human primates and no 
endogenous target in humans. It is expected to have no biologic effect in the absence of RSV 
infection. The safety of MK-1654 administration to humans is supported by the results from 
preclinical toxicology, tissue cross-reactivity, and cytokine release studies (refer to the IB for 
additional details). It is also supported by preliminary clinical findings from the FIH study in 
healthy adult participants, in which MK-1654 was tested up to an IM dose of 300 mg and up 
to an IV dose of 3000 mg, as described in Section 2.2.3.
Maximum Dose/Exposure for This Study
The maximum dose of MK-1654 in this study (100 mg) was chosen to meet or exceed the 
anticipated clinical dose of MK-1654, which will be determined after an analysis of the 
safety, tolerability, and PK from this study and prior to initiation of subsequent clinical 
studies in infants. This maximum dose is supported by safety margins provided by both the 
pre-clinical safety and P001 FIH studies of MK-1654. For comparison of the projected 
exposures in infants at MK-1654 doses at or exceeding 100 mg with those observed in the rat 
repeated-dose toxicity study and projected in the P001 FIH study, see the IB. 
Prior clinical evaluation in adults and infants of similar mAbs targeting the RSV F protein 
also supports the maximum dose in this study. The projected exposures for MK-1654 in 
infants after administration of the proposed doses in this study are based on preclinical 
studies of MK-1654 as well as extensive modeling with the clinical benchmark, 
motavizumab-YTE; see the IB for details.
MK-1654 has a similar target, mechanism of action, and safety and PK profile to those of 
MedImmune’s marketed agent, palivizumab, which is indicated for infants at high risk of 
RSV disease. Both mAbs are directed against a foreign target acting via the established 
mechanism of binding to the RSV F protein to prevent viral cell entry [American Academy 
of Pediatrics Committee on Infectious Diseases 2014]. MedImmune has also tested another 
mAb with a similar mechanism of action, motavizumab, in a Phase 3 randomized, double-
blind, placebo-controlled study in infants [O'Brien, K. L., et al 2015]. A version of 
motavizumab with YTE mutations (similar to MK-1654) tested in a Phase 1 study in healthy 
adults showed a comparable safety and tolerability profile to that of the parental mAb, 
motavizumab, along with an extended half-life after IV dosing up to 30 mg/kg [Robbie, G. J., 
et al 2013]. MedImmune has also recently completed a FIH study of another RSV F protein-
specific mAb with YTE mutations, MEDI8897, in healthy adult participants. In this study, 
MEDI8897 administered up to an IM dose of 300 mg and up to an IV dose of 3000 mg had a 
safety profile similar to that of placebo [Griffin MP, Khan AA, Esser MT, Jensen K, Takas 
T, Kankam MK 2016].
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Rationale for Dose Interval and Study Design
The dosing regimen was determined based on the known pharmacology of similar mAbs, the 
dose-linear PK profile and extended half-life of MK-1654 in non-human primates and PK 
profile of MK-1654 in healthy adults, the preclinical safety margins for MK-1654, and 
inclusion of extensive safety monitoring in the present study. Safety assessment studies, 
ancillary pharmacology studies, and the ongoing FIH study with MK-1654 provide no 
contraindications to the initiation of clinical studies of MK-1654 administered via the IM 
route in infants. No dose-limiting toxicities were observed in the GLP repeat-dose toxicity 
study in rats, and substantial preclinical safety margins were obtained over initial human 
doses.
This study will have up to 5 sequential dose escalation panels and enroll approximately
180 participants (approximately 144 receiving MK-1654 and 36 receiving placebo). The 
rationale for Panel D in 40 participants (32 active and 8 placebo) is to gain additional 
experience at MK-1654 100 mg.
Beginning and End of Study Definition
The overall study begins when written informed consent is provided for the first participant. 
The overall study ends when the last participant completes the last study-related telephone-
call or visit, withdraws from the study, or is lost to follow-up (ie, the participant is unable to 
be contacted by the investigator).
For purposes of analysis and reporting, the overall study ends when the Sponsor receives the 
last serology assay result.
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, Good Clinical 
Practice (GCP) and/or other applicable regulatory requirements, and/or procedure-related 
problems and/or if the number of discontinuations for administrative reasons is too high.
Clinical Criteria for Study Pause
During the study, if any of the following events occur, the study will be paused to further 
dosing:

One treatment-related SAE.

Two or more treatment-related severe AEs (Grade 3 or higher) for 2 days or greater 
duration, as defined in the diary card, within the same dose panel. 
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AEs will be assessed for intensity as described in Section 10.3.4.
In the event of any of the above occurrences, a meeting to review available safety data by the 
investigator and Sponsor will be required for approval of further dosing.
5. STUDY POPULATION
Healthy male and female participants who are pre-term infants (born at 29 to 35 weeks 
gestational age) or full-term infants (born at over 35 weeks gestational age), all of whom 
have chronological age of 2 weeks to 8 months, will be enrolled in this study.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Type of Participant and Disease Characteristics
1. Be healthy (based on screening safety laboratory, medical history, and physical 
examination results) participants.
Demographics
Participant is Male or Female.
Participant is a pre-term infant (born at 29 weeks to 35 weeks gestational age) or a 
full-term infant (born at over 35 weeks gestational age), as confirmed in medical 
records.
Participant has chronological age of 2 weeks to 8 months at the time of signing the 
informed consent.
Participant weighs at least 2 kg at the time of screening.
Informed Consent
The participant’s legally acceptable representative provides written informed consent 
for the study. The participant’s legally acceptable representative may also provide 
consent for future biomedical research. However, the participant may participate in 
the main study without participating in future biomedical research.
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Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
Has been recommended to receive palivizumab per local standard of care.
Has one or more documented out-of-range safety laboratory results, adjusted for age, 
at the time of screening†:
a.
Serum Creatinine >2.0 X upper limit of normal (ULN) for age [Unbound 
Medicine 2018]
b. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.0 X 
ULN [Unbound Medicine 2018]
c.
Hemoglobin <9.0 g/dL
d. WBC count <4000 cells/mm3
e.
Platelets <120,000/mm3
† Retest is allowed at the discretion of the study investigator.
Has a known hypersensitivity to any component of the RSV mAb.
Has a history of congenital or acquired immunodeficiency (eg, splenomegaly).
Has documented HIV infection.
Has documented hepatitis B (HBsAg+) or hepatitis C (HCV RNA+) infection.
Has known history of functional or anatomic asplenia.
Has a recent (within 14 days prior to screening) diagnosis of failure to thrive.
Has known or history of a coagulation disorder contraindicating IM injection.
Has received or is expected to receive blood products (except irradiated platelets)
within 3 months prior to enrollment.
Has prior known documented RSV infection.
Has hemodynamically significant congenital heart disease.
Note: Participants with asymptomatic patent ductus arteriosus, foramen ovale, and 
atrial septal defect are allowed for enrollment. 
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Has chronic lung disease of prematurity requiring ongoing medical therapy.
Has a history or current evidence of any condition, therapy, lab abnormality or other 
circumstance that, in the opinion of the investigator, might expose the participant to 
undue risk by participating in the study, confound the results of the study, or interfere 
with the participant’s participation for the full duration of the study.
Has any history of malignancy prior to randomization.
If any of the following Medical Conditions criteria apply, the Day 1 Visit may be 
rescheduled for a time when these criteria are not met:
Has had a recent febrile illness (rectal temperature 38.1°C [100.5°F] or higher or 
axillary temperature 37.8°C [100.0°F] or higher) within 72 hours pre-dose
Is not up-to-date on required vaccinations per local pediatric vaccine schedule at time 
of screening.
Has received inactivated or component vaccines (eg, influenza, hepatitis B) less than 
14 days pre-dose.
Has received live, attenuated, non-study licensed pediatric vaccines (eg, Bacillus 
Calmette–Guérin vaccine), except for oral rotavirus and oral polio vaccine, less than 
30 days pre-dose.
Prior/Concomitant Therapy
Prior administration of any vaccine or mAb for the prevention of RSV.
Prior/Concurrent Clinical Study Experience
Is currently participating in or has participated in an interventional clinical study with 
an investigational compound or device at any time prior to first dose administration or 
while participating in this current study. Participants enrolled in observational studies 
may be included and will be reviewed on a case-by-case basis for approval by the 
Sponsor.
Has enrolled previously in the current study and been discontinued.
Participant’s mother participated in RSV vaccine clinical study while pregnant and 
participant is 3 months or less in chronological age. 
Diagnostic Assessments
Not applicable.
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Other Exclusions 
Is unable to provide blood sample at screening.
Cannot be adequately followed for safety according to the protocol plan.
Has a parent/legal guardian/legally acceptable representative who is unlikely to 
adhere to study procedures, keep appointments, or is planning to relocate during the 
study.
Has any other reason that in the opinion of the investigator may interfere with the
evaluation required by the study.
28. 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.
Lifestyle Considerations
No restrictions are required.
Screen Failures
Screen failures are defined as participants whose legally acceptable representative provides
consent to participate in the clinical study, but are not subsequently randomized in the study. 
A minimal set of screen failure information is required to ensure transparent reporting of 
screen failure participants to meet the Consolidated Standards of Reporting Trials 
(CONSORT) publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
AEs or SAEs meeting reporting requirements as outlined in the data entry guidelines.
Participant Replacement Strategy
A participant who withdraws from the study will not be replaced.
6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
Clinical supplies (study intervention(s) provided by the Sponsor) will be packaged to support 
enrollment. Clinical supplies will be affixed with a clinical label in accordance with 
regulatory requirements.
Study Intervention(s) Administered
The study interventions to be used in this study are outlined in Table 1.
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Table 1
Study Interventions
Arm 
Name
Arm Type
Intervention 
Name
Type
Dose 
Formulation
Unit Dose 
Strength(s)
Dosage 
Levels
Route of 
Administration
Regimen
Use
IMP/
NIMP
Sourcing
MK-1654
Experimental
Active
Biological/Vaccine
Vial
100 mg/mL
20 mg
50 mg, 
75 mg, 
100 mg
IM
Single 0.2 mL,
Single 0.5 mL,
0.75 mL (0.5 mL in the 
right thigh + 0.25 mL in 
the left thigh), 
1 mL (0.5 mL in the 
right thigh + 0.5 mL in 
the left thigh)
Experimental
IMP
Sponsor
Placebo
Placebo 
Comparator
Placebo
Other
Vial
Not 
applicable
Not 
applicable
IM
Same as MK-1654 
regimen
Placebo
NIMP
Sponsor or 
site
Placebo=Sterile saline 0.9% sodium chloride injection, USP provided by either the Sponsor or the site. Equivalent volumes of saline will be used to correspond with the respective dose level.
IM=intramuscular; IMP=investigational medicinal product; NIMP=non-investigational medicinal product; USP=United States Pharmacopeia.
All supplies indicated in Table 1 will be provided per the “Sourcing” column depending upon local country operational requirements. 
Every attempt should be made to source these supplies from a single lot/batch number.
Refer to Section 8.1.8 for details regarding administration of the study intervention.
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Medical Devices
Not applicable for this study.
Preparation/Handling/Storage/Accountability
Dose Preparation
Specific calculations or evaluations required to be performed in order 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 provided in Section 4.3. 
MK-1654 and placebo (0.9% sodium chloride, USP sterile saline) will be prepared by an 
unblinded pharmacist or medically qualified study personnel (see Section 6.3.3). The 
syringe(s) for IM injection(s) should be prepared shortly before administration, whenever 
possible, per the instructions, including for syringe stability and storage conditions.
The assigned study intervention (MK-1654 or placebo) will be administered via IM (vastus 
lateralis) injection on Day 1 to all participants as determined by the Panel:

Panel A: 20-mg dose – 0.2 mL single IM injection

Panel B: 50-mg dose – 0.5 mL single IM injection

Panel C: 75-mg dose – 0.75 mL split into 2 IM injections
o
0.5 mL administered in right thigh
o
0.25 mL administered in left thigh

Panels D and E: 100-mg dose - 1 mL split into 2 IM injections
o
0.5 mL administered in right thigh
o
0.5 mL administered in left thigh
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.
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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.
Measures to Minimize Bias: Randomization and Blinding
Intervention Assignment
Intervention allocation/randomization will occur centrally using an IRT system. There are 6 
study intervention arms. Participants will be assigned randomly in a 4:1 ratio to 20 mg 
MK-1654 or placebo, 50 mg MK-1654 or placebo, 75 mg MK-1654 or placebo, or, 100 mg 
MK-1654 or placebo in panels A, B, C, and D, respectively, or 100 mg MK-1654 or placebo 
in panel E. Nested in the randomization to MK-1654 or placebo within Panels A through C, 
D1, and E1, participants will also be randomized by IRT to 1 of 4 different blood sampling
schedules (Group 1a, Group 1b, Group 2a, or Group 2b). All participants in Panels D2 and 
E2 will follow the same blood sampling schedule (Group 3).
Stratification
Treatment allocation/randomization of pre-term infants in Panels B, C, and D will be 
stratified by weight. 
In Panels B and D, at least 12.5% of participants enrolled will be small pre-term infants 
(weigh 2 to 5 kg [inclusive] at randomization), and up to 87.5% of participants enrolled will 
be large pre-term infants (weigh more than 5 kg at randomization). 
In Panel C, at least 10% of participants enrolled will be small pre-term infants (weigh 2 to 
5 kg [inclusive] at randomization), and up to 90% of participants enrolled will be large pre-
term infants (weigh more than 5 kg at randomization).
Treatment allocation/randomization of pre-term infants in Panel A will not be stratified by 
weight, due to the small number of participants in this lowest-dose panel. Safety and PK 
evaluation in small infants will be sufficient based on the number of small pre-term infants in 
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Panels B, C, and D, so stratification of treatment allocation/randomization of full-term 
infants in Panel E will not be necessary.
Blinding
A double-blinding technique will be used. MK-1654 and placebo will be prepared and
administered in a blinded fashion by an unblinded pharmacist or medically qualified study 
personnel not otherwise involved in the conduct of the study. Unblinded study personnel 
should not have contact with participants for any study-related procedures/assessments post-
dose, including all safety follow-up procedures. The participant’s legally acceptable 
representative and the investigator(s) will be unaware of the study intervention assignments. 
See Section 8.1.10 for a description of the method of unblinding a participant during the 
study, should such action be warranted.
Study Intervention Compliance
Study interventions will be prepared and administered as described in Section 6.2.1 and 
Section 6.3.3 and stored, handled, and documented as described in Section 6.2.2. 
Study intervention information, such as Component Identification Number, dose panel, and 
time of administration, must be recorded on the appropriate electronic case report form 
(eCRF) as outlined in the Data Entry Guidelines.
Concomitant Therapy
Administration of non-study licensed pediatric vaccines [eg, influenza, hepatitis B, 
diphtheria, tetanus, and pertussis vaccine(s)] will be permitted during this study provided the 
following conditions are met:
Inactivated or component vaccines (eg, influenza, hepatitis B) should not be 
administered less than 14 days pre- or post-dose.
Live, attenuated, non-study licensed pediatric vaccines (eg, Bacillus Calmette–Guérin 
vaccine) should not be administered less than 30 days pre- or post-dose.
No prior administration of any vaccine or mAb for the prevention of RSV.
Oral rotavirus and oral polio vaccine may be administered without any exclusionary 
windows around MK-1654.
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed 
during the time periods specified by this protocol for that medication or vaccination. If there 
is a clinical indication for any medication or vaccination specifically prohibited, 
discontinuation from study therapy may be required. The investigator should discuss any 
questions regarding this with the Sponsor Clinical Director. The final decision on any 
supportive therapy or vaccination rests with the investigator and/or the participant's primary 
physician. However, the decision to continue the participant in the study requires the mutual 
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agreement of the investigator, the Sponsor, and the participant’s legally acceptable 
representative.
Any concurrent medication or medical treatment must be recorded on the appropriate eCRF.
Paracetamol/acetaminophen may be used for minor ailments without prior consultation with 
the Sponsor.
Rescue Medications and Supportive Care
As outlined in the IB and Section 4.2.1.1, the risk of acute systemic or local injection 
reactions to MK-1654 is considered low. However, acute systemic or local injection reactions 
may be observed. As the purpose of the study is to characterize the safety profile of 
MK-1654, no prophylactic pre-medications to reduce the risk of injection reactions will be 
given prior to MK-1654 administration. 
All participants will be observed for 2 hours post-dose for acute reactions to MK-1654 and 
evaluated for systemic and local injection reactions. Severe injection reactions, including 
cytokine release syndrome and hypersensitivity reactions, must be promptly treated with 
medical management, appropriate monitoring, and life-saving measures. Appropriate 
resuscitation equipment and a physician/designee and/or study staff will be readily available 
during the period of drug administration through the 2-hour post-dose onsite safety 
observation period. Less severe injection reactions may respond to medical management. 
Acetaminophen may be administered per investigator discretion without prior consultation 
with the Sponsor.
Participants who experience injection reactions, including hypersensitivity reactions, in 
conjunction with the study intervention should receive appropriate supportive care measures 
as deemed necessary by the treating physician. Investigators should strongly consider 
hospitalization for any severe systemic reaction or any life-threatening reactions. Participants 
should be carefully observed until complete resolution of all signs and symptoms, if a 
reaction occurs. Any AEs will be reported according to the guidelines in Section 8.4 and 
Section 10.3 (Appendix 3).
Dose Modification (Escalation)
Each panel will enroll 4 participants (study-wide, not per site) with review of safety through 
Day 3 before additional participants can be dosed within the panel, except in Panel D and E if 
the dose level is not escalated from Panel C. The site lead investigator(s) at the respective 
site(s) and Sponsor will assess the first 2 participants for safety through Day 3 prior to dosing 
the next 2 participants. The site lead or sub-investigator(s) at the respective site(s) and 
Sponsor will then assess the next 2 participants for safety through Day 3 prior to dosing
additional participants in the panel. An IRT hold will prevent enrollment/randomization of 
additional participants study-wide until this is achieved; when this hold is lifted, 
enrollment/randomization and dosing of the remaining participants in the panel may proceed 
(study-wide). This is to allow for identification of any potential systemic treatment-related 
AEs that could be observed with dose escalation. If no clinical criteria for study pause in
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Section 4.4.2 are met, further dosing within the panel may proceed. Safety follow-up, as 
scheduled in the SoA, is detailed in Section 4.2.1.1. 
The decision to escalate the dose between Panels A and B and Panels B and C will be made 
based on review of: 1) available safety data through at least Day 14 for at least 50% of 
participants in the previous panel(s); and 2) available PK data from the previous panel(s). 
Ongoing safety monitoring and PK analyses will continue throughout Panels A, B, and C.
The decision to dose escalate between Panels C and D in pre-term infants and between 
Panel C in pre-term infants and Panel E in full-term infants, and on the dose level(s) in 
Panels D and E (up to 100 mg), will be made in an siDMC Meeting based on review of: 
1) available safety data through at least Day 14 from Panels A, B, and C; 2) PK data through 
Day 90 for evaluable participants in Panel A and PK data through Day 30 for at least 50% of 
evaluable participants in Panel B; and 3) available PK data from Panel C. Note that Panels D 
and E may initiate prior to completion of Panel C. 
The siDMC will hold a meeting after Panel C for the decision to escalate the dose in
Panels D and E. 
If, as judged by the Sponsor, the safety, tolerability, and PK data do not justify dose 
escalation, the dose will not be increased as planned. Instead, participants may:
•
Receive the same dose level to further explore safety and tolerability at that level,
•
Receive a lower dose of the study intervention,
•
Receive the same or lower dose, or
•
Dosing may be stopped.
Clinical criteria for study pause are specified in Section 4.4.2.
Intervention After the End of the Study
There is no study-specified intervention following the end of the study.
Clinical Supplies Disclosure
The emergency unblinding call center will use the randomization schedule for the study to 
unblind participants and to unmask study intervention identity. The emergency unblinding 
call center should only be used in cases of emergency (see Section 8.1.10). In the event that 
the emergency unblinding call center is not available for a given site in this study, the central 
electronic intervention allocation/randomization system (IRT) should be used to unblind 
participants and to unmask study intervention identity. The Sponsor will not provide random 
code/disclosure envelopes or lists with the clinical supplies. See Section 8.1.10 for a 
description of the method of unblinding a participant during the study, should such action be 
warranted.
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Standard Policies
Not applicable for this study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL
Discontinuation of Study Intervention
Discontinuation of study intervention does not represent withdrawal from the study.
As certain data on clinical events beyond study intervention discontinuation may be 
important to the study, they must be collected through the participant’s last scheduled follow-
up, even if the participant has discontinued study intervention. Therefore, all participants 
who discontinue study intervention prior to completion of the protocol-specified intervention
period will still continue to participate in the study as specified in the SoA and 
Section 8.13.3.
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 8.13.3.
A participant must be discontinued from study intervention but continue to be monitored in 
the study for any of the following reasons:
•
The participant’s legally acceptable representative requests to discontinue study 
intervention.

For participants who are discontinued from study intervention but continue to be 
monitored in the study, all visits and procedures, as outlined in the SoA, should be 
completed.
Discontinuation from study intervention is “permanent.” Once a participant is discontinued, 
he/she shall not be allowed to restart study intervention.
Participant Withdrawal From the Study
A participant must be withdrawn from the study if the participant’s legally acceptable 
representative withdraws consent from the study.
If a participant withdraws from the study, they will no longer receive study intervention or be 
followed at scheduled protocol visits.
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Specific details regarding procedures to be performed at the time of withdrawal from the 
study, as well as specific details regarding withdrawal from future biomedical research, are 
outlined in Section 8.1.9. The procedures to be performed should a participant repeatedly fail 
to return for scheduled visits and/or if the study site is unable to contact the participant are 
outlined in Section 7.3.
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’s legally acceptable representative and 
reschedule the missed visit. If the participant’s legally acceptable representative is 
contacted, the participant’s legally acceptable representative 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’s legally acceptable representative at each missed visit (eg, telephone calls 
and/or a certified letter to the legally acceptable representative’s last known mailing 
address or locally equivalent methods). These contact attempts should be documented in 
the participant’s medical record.
•
Note: A participant is not considered lost to follow-up until the last scheduled visit for the 
individual participant. The missing data for the participant will be managed via the 
prespecified statistical data handling and analysis guidelines.
8. STUDY ASSESSMENTS AND PROCEDURES
•
Study procedures and their timing are summarized in the SoA.
•
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.
•
The investigator is responsible for ensuring that procedures are conducted by 
appropriately qualified (by education, training, and experience) staff. Delegation of study 
site personnel responsibilities will be documented in the Investigator Trial File Binder (or 
equivalent).
•
All study-related medical decisions must be made by an investigator who is a qualified 
physician.
•
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
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•
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of ICF may be utilized for screening or baseline 
purposes provided the procedure met the protocol-specified criteria and were performed 
within the time frame defined in the SoA.
•
Additional evaluations/testing may be deemed necessary by the investigator and or the 
Sponsor for reasons related to participant safety. In some cases, such evaluation/testing 
may be potentially sensitive in nature (eg, HIV, Hepatitis C), and thus local regulations 
may require that additional informed consent be obtained from the participant’s legally 
acceptable representative. In these cases, such evaluations/testing will be performed in 
accordance with those regulations.
The approximate total blood volume drawn per participant is approximately 9.0 mL, as 
detailed in the operations/laboratory manual. The maximum amount of blood collected from 
each participant over the duration of the study, including for any extra assessments that may 
be required, will be in accordance with regulatory guidelines for pediatric studies and 
recommended maximum blood draw volumes [Jack, R. 2001]. Repeat or unscheduled 
samples may be taken for safety reasons or for technical issues with the samples.
Administrative and General Procedures
Informed Consent
The investigator or medically qualified designee (consistent with local requirements) must 
obtain documented consent from each potential participant’s legally acceptable 
representative prior to participating in a clinical study or future biomedical research. If there 
are changes to the participant’s status during the study (eg, health or age of majority 
requirements), the investigator or medically qualified designee must ensure the appropriate 
consent is in place.
General Informed Consent
Consent must be documented on the consent form by the dated signature of the participant’s 
legally acceptable representative along with the dated signature of the person conducting the 
consent discussion.
A copy of the signed and dated consent form should be given to the participant’s legally 
acceptable representative before the individual’s participation in the study.
The initial ICF, any subsequent revised written ICF, and any written information provided to 
the participant’s legally acceptable representative must receive the Institutional Review 
Board/Independent Ethics Committee’s (IRB/IEC’s) approval/favorable opinion in advance 
of use. The participant’s legally acceptable representative should be informed in a timely 
manner if new information becomes available that may be relevant to the willingness for the 
participant to continue participation in the study. The communication of this information will 
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be provided and documented via a revised consent form or addendum to the original consent 
form that captures the dated signature of the participant’s legally acceptable representative.
Specifics about a study and the study population will be added to the consent form template 
at the protocol level.
The informed consent will adhere to IRB/IEC requirements, applicable laws and regulations, 
and Sponsor requirements.
Consent and Collection of Specimens for Future Biomedical Research
The investigator or medically qualified designee will explain the future biomedical research 
consent to the participant’s legally acceptable representative, answer all of his/her questions, 
and obtain written informed consent before performing any procedure related to future 
biomedical research. A copy of the informed consent will be given to the participant’s legally 
acceptable representative.
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.
Participant Identification Card
The legally acceptable representative for each participant will be given a participant 
identification card identifying the individual as a participant 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 legally 
acceptable representative for each participant with a participant identification card 
immediately after written informed consent is provided. At the time of intervention
allocation/randomization, site personnel will add the intervention/randomization number to 
the participant identification card.
The participant identification card also contains contact information for the emergency 
unblinding call center so that a healthcare provider can obtain information about study 
intervention in emergency situations where the investigator is not available.
Medical History
A medical history will be obtained by the investigator or qualified designee.
Prior and Concomitant Medications Review
Prior Medications
The investigator or qualified designee will review prior medication/vaccination use and 
record prior medication taken by the participant to assess inclusion and exclusion criteria 
including time windows for medication/vaccination use.
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Concomitant Medications
The investigator or qualified designee will record medication, if any, taken by the participant 
during the study.
Any concurrent medication or medical treatment must be recorded on the appropriate eCRF. 
On the day of dosing, it is important to record the use of any analgesic or antipyretic use on 
the electronic diary card and appropriate eCRF.
If a medical condition required the use of immunoglobulins, blood, or blood products during 
a participant’s participation in this study, one of the individuals listed on the Sponsor Contact 
Information page must be notified as soon as possible and any such use must be documented 
on the appropriate eCRF.
Assignment of Screening Number
All consented participants will be given a unique screening number that will be used to 
identify the participant for all procedures that occur prior to randomization. Each participant 
will be assigned only 1 screening number. Screening numbers must not be re-used for 
different participants.
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 provided in Section 8.13.1.
Assignment of Treatment/Randomization Number
All eligible participants will be randomly allocated and will receive a 
treatment/randomization number. The treatment/randomization number identifies the 
participant for all procedures occurring after treatment allocation/randomization. Once a 
treatment/randomization number is assigned to a participant, it can never be re-assigned to 
another participant.
A single participant cannot be assigned more than 1 treatment/randomization number.
Study Intervention Administration
Unblinded study personnel not otherwise involved in the conduct of the study will prepare 
and administer the study intervention. Study intervention should be prepared by and 
administered by an unblinded pharmacist or appropriately qualified members of the study 
personnel (eg, physician, nurse, physician’s assistant, nurse practitioner, pharmacist, or 
medical assistant) as allowed by local/state, country, and institutional guidance and described 
in Section 6.2, Section 6.3.3, and the pharmacy manual.
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The assigned study intervention (MK-1654 or placebo) will be administered via IM (vastus 
lateralis) injection on Day 1 to all participants as defined by the Panel: 
•
Panel A: 20-mg dose – 0.2 mL single IM injection
•
Panel B: 50-mg dose – 0.5 mL single IM injection
•
Panel C: 75-mg dose – 0.75 mL split into 2 IM injections
o
0.5 mL administered in right thigh
o
0.25 mL administered in left thigh
•
Panels D and E: 100-mg dose - 1 mL split into 2 IM injections
o
0.5 mL administered in the right thigh
o
0.5 mL administered in the left thigh
Timing of Dose Administration
Study intervention is given on the day of treatment allocation/randomization or as close as 
possible to the date on which the participant is allocated/assigned.
MK-1654 or placebo, as randomly assigned, will be administered to each participant at the 
study site on Day 1, as set out in the SoA and specified in Section 6.2.1, Section 8.1.8, and 
the Pharmacy Manual. 
See Section 6.5 on the timing of study intervention administration with regard to concomitant 
therapy.
Participants will be observed for 2 hours immediately post-dose for safety monitoring by the 
blinded investigator and/or study staff, as described in the SoA and Section 4.2.1.1.
Diary Card
Each participant’s legally acceptable representative will be provided an electronic diary card 
on a handheld electronic device to help in identifying any systemic or local injection 
reactions. The electronic diary card and use of the handheld electronic device will be 
reviewed with the participant’s legally acceptable representative at the study site, as indicated 
in the SoA.
Discontinuation and Withdrawal
Participants who discontinue study intervention prior to completion of the intervention period
should be encouraged to continue to be followed for all remaining study visits.
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When a participant withdraws from participation in the study, all applicable activities 
scheduled for the final study visit should be performed (at the time of withdrawal). Any AEs
that are present at the time of withdrawal should be followed in accordance with the safety 
requirements outlined in Section 8.4. Participants who discontinue ≥2 weeks after last blood 
draw will complete the Day 365 (Panels A through C, D1, and E1) or Day 545 (Panels D2
and E2) visit blood collection, regardless of their assigned blood sampling schedule group. 
Withdrawal From Future Biomedical Research
Consent for future biomedical research may be withdrawn by the participant’s legally 
acceptable representative. Consent may be withdrawn by the legally acceptable 
representative at any time by contacting the principal investigator for the main study. If 
medical records for the main study are still available, the investigator will contact the 
Sponsor using the designated mailbox (clinical.specimen.management@merck.com). 
Subsequently, the participant's consent for future biomedical research will be withdrawn. A 
letter will be sent from the Sponsor to the investigator confirming the withdrawal. It is the 
responsibility of the investigator to inform the participant’s legally acceptable representative
of completion of withdrawal. Any analyses in progress at the time of request for withdrawal 
or already performed prior to the request being received by the Sponsor will continue to be 
used as part of the overall research study data and results. No new analyses would be 
generated after the request is received.
In the event that the medical records for the main study are no longer available (eg, if the 
investigator is no longer required by regulatory authorities to retain the main study records) 
or the specimens have been completely anonymized, there will no longer be a link between 
the participant’s personal information and their specimens. In this situation, the request for 
specimen withdrawal cannot be processed. 
Participant Blinding/Unblinding
STUDY INTERVENTION IDENTIFICATION INFORMATION IS TO BE UNMASKED 
ONLY IF NECESSARY FOR THE WELFARE OF THE PARTICIPANT. EVERY 
EFFORT SHOULD BE MADE NOT TO UNBLIND.
For emergency situations where the investigator or medically qualified designee (consistent 
with local requirements) needs to identify the intervention used by a participant and/or the 
dosage administered, he/she will contact the emergency unblinding call center by telephone 
and make a request for emergency unblinding. As requested by the investigator or medically 
qualified designee, the emergency unblinding call center will provide the information to 
him/her promptly and report unblinding to the Sponsor. Prior to contacting the emergency 
unblinding call center to request unblinding of a participant’s intervention assignment, the 
investigator who is a qualified physician should make reasonable attempts to enter the 
intensity grade of the AEs observed, the relation to study intervention, the reason thereof, 
etc., in the medical chart. If it is not possible to record this assessment in the chart prior to the 
unblinding, the unblinding should not be delayed.
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In the event that unblinding has occurred, the circumstances around the unblinding (eg, date, 
reason, and person performing the unblinding) must be documented promptly, and the 
Sponsor Clinical Director notified as soon as possible.
Once an emergency unblinding has taken place, the investigator, site personnel, and Sponsor 
personnel may be unblinded so that the appropriate follow-up medical care can be provided 
to the participant.
Participants whose treatment assignment has been unblinded by the investigator or medically 
qualified designee and/or nonstudy treating physician should continue to be monitored in the 
study.
Additionally, the investigator or medically qualified designee must go into the IRT system 
and perform the unblind in the IRT system to update drug disposition. In the event that the 
emergency unblinding call center is not available for a given site in this study, the IRT 
system should be used for emergency unblinding in the event that this is required for 
participant safety.
At the end of the study, random code/disclosure envelopes or lists and unblinding logs are to 
be returned to the Sponsor or designee.
Domiciling
Not applicable for this study.
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 is reliable and/or reproducible. 
Documentation of equipment calibration must be retained as source documentation at the 
study site.
Efficacy/Immunogenicity Assessments
There are no direct efficacy assessments in this study; surrogate markers of efficacy are 
outlined in Section 8.8.
Safety Assessments
Details regarding specific safety procedures/assessments to be performed in this study are 
provided below. The total amount of blood to be drawn over the course of the study (from 
pre-study to post-study visits), including approximate blood volumes drawn by visit and by 
sample type per participant, are detailed in the operations/laboratory manual.
Planned time points for all safety assessments are provided in the SoA.
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Physical Examinations
A complete physical examination will be conducted by an investigator or medically qualified 
designee (consistent with local requirements) as per institutional standard. Body weight and 
length will also be measured and recorded.
A brief directed physical examination will be conducted by an investigator or medically 
qualified designee (consistent with local requirements) per institutional standard based upon 
any emergent symptoms at the discretion of the investigator.
Investigators should pay special attention to clinical signs related to previous serious 
illnesses.
Vital Signs
•
Body temperature, heart rate, and respiratory rate will be assessed.
•
Temperature and respiratory rate will be measured and recorded as single measurements. 
The same method must be used for all measurements for each individual participant and 
should be the same for all participants.
•
Rectal or axillary temperature will be taken by study staff pre- and post-dose as set out in 
the SoA. Participants who have febrile illness (rectal temperature ≥38.1°C [100.5°F] or 
axillary temperature ≥37.8°C [100.0°F]) within 72 hours pre-dose must be rescheduled. 
•
Rectal is the preferred method of obtaining participant’s temperature. Axillary 
(underarm) is an acceptable method. Temperature readings must be recorded on the 
electronic diary card. Temperature readings should be taken at approximately the same 
time each day. Use of temporal or tympanic thermometers to collect temperature for this 
study is prohibited.
•
The participant’s legally acceptable representative will be asked to record a temperature 
reading on the electronic diary card from Day 1 through Day 5 post-dose. Temperature 
measurement must be recorded in the electronic diary card if fever is suspected during 
Day 6 through Day 14 post-dose.
•
Heart rate will be measured with a completely automated device. Manual techniques will 
be used only if an automated device is not available. Heart rate measurements should be 
preceded by at least 5 minutes of rest for the participant in a quiet setting without 
distractions.
•
All VS measurements, including temperature readings captured on the electronic diary 
card, will be recorded on the appropriate eCRF.
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Systemic and Local Injection Reaction Assessment
Participants will be monitored at the study site during dosing as outlined in the SoA for signs 
and symptoms of a systemic injection reaction, including urticaria (hives or welts), lip 
swelling, wheezing, and/or difficulty breathing. If hives or welts occur during the 30 days 
following MK-1654 administration, the participant’s legally acceptable representative should 
contact the site to schedule an appointment with the study site for an evaluation as soon as 
possible, where the study investigator will determine whether the rash represents an 
urticarial-like eruption. The study site will also receive notice if allergic reactions are entered 
in the electronic diary card and should contact the participant's legally acceptable 
representative for an evaluation if hives or welts or other allergic reactions occur during the 
30 days following MK-1654 administration. If a rash is confirmed by the study investigator 
as consistent with urticaria, the investigator may obtain a dermatology consult based on the 
investigator’s discretion. Any systemic injection reactions must be assessed and managed 
promptly, as described in Section 6.5.1. 
During the safety follow-up period (30 days post dosing), surveillance for RSV infection, 
including the common symptoms of difficulty breathing and wheezing, will also be ongoing 
(beginning on Day 14 post dosing) for both respiratory infection and allergic reaction. During 
this time (Days 14-30), clinical judgment will be required to assess the symptoms as part of 
respiratory infection or allergic reaction. Regardless of the diagnosis, the participant should 
be brought in for clinical assessment and further evaluation. 
An examination of the local injection site(s) will also be performed as scheduled in the SoA, 
including an assessment of any pain, tenderness, erythema/redness, and induration/swelling
for each injection site. These events will be evaluated based on the scale outlined in
Section 10.3.4. 
Any subsequent systemic or local injection reaction symptoms will be captured as AEs/SAEs 
during safety monitoring visits and follow-up, as scheduled in the SoA, and at home by the 
participant’s legally acceptable representative on the diary card using the handheld electronic 
device, as described in Section 4.2.1.1.
Any adverse systemic or local injection reaction will be recorded on the appropriate eCRF.
Safety Follow-up Telephone Calls
Safety follow-up telephone calls will be performed at the time points indicated in the SoA. If 
a participant is hospitalized at the time, a safety follow-up call will be performed. Safety calls 
must be performed by appropriately trained study site staff. If the initial call is unsuccessful, 
the study site staff should make a total of 3 attempts for each scheduled safety call. All 
attempts to contact the participant’s legally acceptable representative will be recorded in the 
source documents. The calls will facilitate the collection of relevant safety information. The 
participant’s legally acceptable representative will be interviewed to obtain information 
relating to all AEs through Day 14, solicited AEs of allergic reactions (hives or welts, lip 
swelling, wheezing, and difficulty breathing) through Day 30, respiratory AEs through Day 
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365, and SAEs through Day 365 (Panels A through C, D1, and E1) or Day 545 (Panels D2
and E2). 
In addition, all concomitant medications and vaccinations will be recorded. All safety 
information described by the participant’s legally acceptable representative must be 
documented in the source documents.
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 must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the case report 
form (CRF). The laboratory reports must be filed with the source documents. Clinically 
significant abnormal laboratory findings are those which are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
•
All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the operations/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 5 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.
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Reportable 
Safety Events
The definitions of an AE or SAE, as well as the method of recording, evaluating, and 
assessing causality of AE and SAE and the procedures for completing and transmitting AE, 
SAE, and other reportable safety event reports can be found in Appendix 3.
Adverse events, SAEs, and other reportable safety events will be reported by the participant 
(or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized 
representative).
The investigator, who is a qualified physician, and any designees are responsible for 
detecting, assessing, documenting, and reporting events that meet the definition of an AE or
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SAE, as well as other reportable safety events. Investigators remain responsible for following 
up AE, SAEs, and other reportable safety events for outcome according to Section 8.4.3.
Time Period and Frequency for Collecting AE, SAE, and Other Reportable 
Safety Event Information
All AEs, SAEs, and other reportable safety events that occur after the consent form is signed 
but before allocation/randomization must be reported by the investigator if they cause the 
participant to be excluded from the study or are the result of a protocol-specified 
intervention, including but not limited to washout or discontinuation of usual therapy, diet, 
placebo treatment, or a procedure.
From the time of allocation/randomization through Day 365 (Panels A through C, D1, and 
E1) or Day 545 (Panels D2 and E2) following the administration of study intervention, all 
SAEs and other reportable safety events must be reported by the investigator.
Additionally, any SAE brought to the attention of an investigator at any time outside of the 
time period specified in the previous paragraph, also must be reported immediately to the 
Sponsor if the event is either:
A death that occurs prior to the participant completing the study but outside the time 
period specified in the previous paragraph.
OR
An SAE that is considered by an investigator who is a qualified physician to be study 
intervention-related.
Investigators are not obligated to actively seek AE or SAE or other reportable safety events 
in former study participants. However, if the investigator learns of any SAE, including a 
death, at any time after a participant has been discharged from the study, and he/she 
considers the event to be reasonably related to the study intervention or study participation, 
the investigator must promptly notify the Sponsor.
All initial and follow-up AEs, SAEs, and other reportable safety events will be recorded and 
reported to the Sponsor or designee within the time frames as indicated in Table 2.
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Table 2
Reporting Time Periods and Time Frames for Adverse Events and Other 
Reportable Safety Events
Type of Event
Reporting Time 
Period:
Consent to 
Randomization/ 
Allocation
Reporting Time 
Period:
Randomization/ 
Allocation through 
Protocol-Specified 
Follow-up Period
Reporting Time Period:
After the Protocol Specified 
Follow-up Period
Timeframe to 
Report Event 
and Follow-up 
Information to 
SPONSOR:
Non-Serious Adverse 
Event (NSAE)
Report if:
- due to protocol-
specified 
intervention
- causes exclusion
Report all
Not required
Per data entry 
guidelines
Serious Adverse Event 
(SAE)
Report if:
- due to protocol-
specified 
intervention
- causes exclusion
Report all
Report if:
- drug/vaccine related.
- any death until participant 
completion of study
(Follow ongoing to 
outcome)
Within 
24 hours of 
learning of 
event
Pregnancy/Lactation 
Exposure
Report if:
- due to 
intervention
- causes exclusion
Report all
Previously reported –
Follow to 
completion/termination; 
report outcome
Within 
24 hours of 
learning of 
event
Event of Clinical Interest 
(ECI; require regulatory 
reporting)
Report if:
- due to 
intervention
- causes exclusion
Report
- Potential drug-
induced liver injury 
(DILI)
- Require 
regulatory 
reporting
Not required
Within 
24 hours of 
learning of 
event
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
Overdose
Report if:
- receiving placebo 
run-in or other run-
in medication 
Report all
Not required
Within 
5 calendar 
days of 
learning of 
event
Method of Detecting AEs, SAEs, and Other Reportable Safety Events
Care will be taken not to introduce bias when detecting AE and/or SAE and other reportable 
safety events. Open-ended and nonleading verbal questioning of the participant is the 
preferred method to inquire about AE occurrence.
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Follow-up of AE, SAE, and Other Reportable Safety Event Information
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs, SAEs, and other reportable safety events 
including pregnancy and exposure during breastfeeding, events of clinical interest (ECIs), 
cancer, and overdose will be followed until resolution, stabilization, until the event is 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). In 
addition, the investigator will make every attempt to follow all nonserious AEs that occur in 
randomized participants for outcome. Further information on follow-up procedures is given 
in Appendix 3.
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. All 
AEs will be reported to regulatory authorities, IRB/IECs, and investigators in accordance 
with all applicable global laws and regulations (ie, per ICH Topic E6 (R2) Guidelines for 
Good Clinical Practice [GCP]).
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and Sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAE) from the Sponsor will file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements.
Pregnancy and Exposure During Breastfeeding
Not applicable, as this study is in infants only.
Disease-related Events and/or Disease-related Outcomes Not Qualifying as AEs 
or SAEs
Not applicable for this study.
Events of Clinical Interest (ECIs)
Selected nonserious and SAEs are also known as ECIs and must be reported to the Sponsor.
Events of clinical interest for this study include:
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1. An elevated AST or ALT lab value that is greater than or equal to 3X the upper limit of 
normal and an elevated total bilirubin lab value that is greater than or equal to 2X the 
upper limit of normal and, at the same time, an alkaline phosphatase lab value that is less 
than 2X the upper limit of normal, as determined by way of protocol-specified laboratory 
testing or unscheduled laboratory testing.*
*Note: These criteria are based upon available regulatory guidance documents. The 
purpose of the criteria is to specify a threshold of abnormal hepatic tests that may require 
an additional evaluation for an underlying etiology. The study site guidance for 
assessment and follow-up of these criteria can be found in the Investigator Study File 
Binder (or equivalent).
Treatment of Overdose
In this study, an overdose is any dose higher than the dose level in the assigned panel.
No specific information is available on the treatment of overdose.
Pharmacokinetics
The decision as to which serum samples collected will be assayed for evaluation of 
PK/pharmacodynamics will be collaboratively determined by the Sponsor (eg, samples at 
lower doses may not be assayed if samples at higher doses reveal undetectable drug 
concentrations). If indicated, these samples may also be assayed and/or pooled for assay in an 
exploratory manner for metabolites and/or additional pharmacodynamic markers. See the 
Pharmacokinetics/Pharmacodynamics/Biomarkers schedule in the SoA for the timing of each 
of the 4 blood draw schedules, with detailed instructions and blood volumes to be drawn for 
each PK assay provided in the operations/laboratory manual.
Blood Collection for MK-1654 Pharmacokinetics
Sample collection, storage, and shipment instructions for serum samples are provided in the 
operations/laboratory manual.
Blood Microsampling for MK-1654 Pharmacokinetics
Microsample collection, storage, and shipment instructions for blood microsamples are
provided in the operations/laboratory manual. 
Pharmacodynamics
Sample collection, storage, and shipment instructions for pharmacodynamics samples are 
provided in the operations/laboratory manual. See the Pharmacokinetics/Pharmacodynamics/
Biomarkers schedule in the SoA for the timing of each of the blood draw schedules, with
detailed instructions and blood volumes to be drawn for each pharmacodynamics assay 
provided in the operations/laboratory manual.
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Blood Collection for ADAs and RSV Neutralizing Assay
Sample collection, storage, and shipment instructions for serum samples are provided in the 
operations/laboratory manual.
Acute Respiratory Infection Determination
See the SoA for the timing of respiratory AEs collection and RSV surveillance weekly 
telephone calls for determining the need for an unscheduled RSV assessment visit and nasal 
swab for respiratory virus infection detection.
RSV Season Definition
The Sponsor will define the expected start and end of RSV season for each region 
participating in the study, based on several prior years’ RSV seasons, as determined by 
national surveillance and/or available peer-reviewed literature. Detailed instructions will be 
provided in the operations manual. 
Globally each year, RSV epidemics initiate near the equator, in August and January in the 
Northern and Southern Hemisphere, respectively, then move toward temperate regions. 
Global patterns in monthly RSV activity have been observed and annual average percentage 
of RSV activity calculated for 152 sites globally in an ongoing review of RSV seasonality 
studies and online datasets by the Respiratory Syncytial Virus Consortium in Europe 
(RESCEU) [You, Li 2017].
In the United States, RSV season onset has ranged from late October to late January and 
season offset has ranged from late January to early April in all 10 Department of Health and 
Human Services (HHS) regions, except in Florida, which has an earlier RSV season onset 
and longer duration, as reported by the Centers for Disease Control (CDC) National 
Respiratory and Enteric Virus Surveillance System (NREVSS). During the 2013–14 season, 
similarly to previous national patterns, RSV began circulating nationally in early November 
and ended in late March, with circulation peaking at 24% in late December. The RSV season 
(onset, offset, peak, and duration) is defined nationally, by HHS region, and by state, based 
on CDC analysis of RSV laboratory detections reported to the NREVSS. The CDC and 
World Health Organization define the onset of the RSV season as a 10% threshold of RSV-
positive specimens during 2 consecutive weeks. 
In the European Union, the RSV season is typically November to April with a peak in the 
mid-winter months [European Medicines Agency 2017]. The European influenza 
surveillance system captures RSV detection through the influenza-like illness (ILI) or ARI 
surveillance system from 21 European Union countries, as reported for the 2014-15 season 
by the European Centre for Disease Control (ECDC) [European Center For Disease 
Prevention And Control 2015]. 
In the Southern Hemisphere, the RSV season is generally April to August, starting in 
February in tropical and subtropical regions and then moving south, peaking in July in 
temperate regions. 
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RSV Surveillance Weekly Telephone Calls
During the RSV season, as defined in Section 8.8.1, RSV weekly surveillance starts on 
Day 14 until the Sponsor deems that RSV season is ended. From Day 14, study sites will 
conduct weekly telephone surveillance calls to the legally acceptable representative to 
determine if there have been any changes in the participant’s health and if any health care 
visits have occurred in the last week. If the answer is affirmative, then sites will further 
inquire if any of the following symptoms of ARI have occurred: 
•
Runny or stuffy nose 
•
Cough 
•
Fever/feverishness 
•
Trouble feeding 
•
Noisy breathing (respiratory tract congestion)
•
Difficulty or labored breathing 
•
Wheezing 
•
Chest wall in-drawing 
If any 2 or more of these symptoms have occurred for at least 2 days duration and the 
symptoms are consistent with ARI, or if any of the ARI symptoms are of concern to the 
investigator, regardless of duration, a site visit for RSV assessment should be arranged as 
described in Section 8.8.4.
Legally Acceptable Representative-reported Respiratory Symptoms
In addition to the sites conducting weekly RSV surveillance telephone calls, the legally 
acceptable representatives will be instructed to phone the site to report respiratory symptoms 
that have occurred for at least 2 days duration. If 2 or more respiratory symptoms have 
occurred for at least 2 days duration and the symptoms are consistent with ARI, or if any of 
the ARI symptoms are of concern to the investigator, regardless of duration, a site visit for 
RSV assessment should be arranged as described in Section 8.8.4.
Unscheduled Visit for RSV Assessment
If ARI is suspected (during surveillance and/or symptoms collection), the participant should 
be assessed at the study site as soon as is feasible and no later than 8 days after the legally 
acceptable representative’s initial contact. The unscheduled visit for RSV assessment should 
occur no later than 10 days after symptom onset. ARI is defined as 2 or more of the 
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symptoms listed in Section 8.8.2 having occurred for at least 2 days duration, or if in the 
opinion of the investigator, the symptoms are consistent with ARI, regardless of duration.
A physical exam (including heart rate, respiratory rate, O2%, and temperature) will be 
performed to confirm if any of the following signs and symptoms of lower respiratory tract 
infection (LRI) are present: 
•
Decreased O2 saturation (<95% on room air at sea level or <92% on room air at 
≥1800 meters)
•
Wheezing, chest wall in-drawing, or difficulty breathing
•
Rales and crackles, rhonchi or coarse breath sounds, or decreased breath sounds on 
respiratory exam
RSV-associated LRI is defined as the presence of any of these symptoms, with RSV detected 
by RT-PCR.
RSV-associated outpatient LRI is defined as above, for a participant seen in an outpatient 
clinic/doctor’s office, emergency department, or urgent care center.
Following careful evaluation of signs and symptoms of ARI/LRI, the study investigator 
should determine if further triage or evaluation is needed, consistent with the standard of 
care, and in conjunction with the participant’s primary physician (if applicable).
RSV-associated hospitalization is defined as hospital admission for RSV or new onset of 
respiratory illness during a hospital admission with RSV detected by RT-PCR.
Non-serious respiratory AEs confirmed during the unscheduled visit for RSV assessment will 
be recorded on the AEs eCRF, as outlined in the SoA for Respiratory AEs Collection. Any 
other AEs/SAEs will continue to be reviewed and recorded as outlined in the SoA for 
AE/SAE Review. If a participant is unable to attend a study visit due to respiratory-
associated hospitalization, study participant’s legally acceptable representative should obtain 
hospitalization medical summary and schedule a visit with the study site as soon as possible 
after hospital discharge. If respiratory symptoms are suggestive of RSV infection, a nasal 
swab should be collected for RT-PCR testing if within 4 weeks of infection symptoms.
Nasal Swab for Respiratory Virus Infection Determination
If the investigator confirms that 2 or more of the symptoms listed in Section 8.8.2 have 
occurred for 2 days or more, or if any of the ARI symptoms are of concern, a nasopharyngeal 
swab should be obtained for respiratory virus detection by RT-PCR. Nasal swab will be 
performed at the unscheduled visit for RSV assessment and analyzed regardless of the
physical exam findings and regardless of the participant’s intervention assignment (MK-1654 
or placebo) or panel (A, B, C, D, or E). The purpose is to estimate the incidence of ARI, 
including RSV, influenza, and hMPV infection, and help to determine the infectious cause of 
the ARI and the relative proportion of RSV A and B infections in the target infant 
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population. Sample collection, storage and shipment instructions for nasal mucosal samples 
will be provided in the operations/laboratory manual.
Future Biomedical Research Sample Collection
If the participant’s legally acceptable representative signs the future biomedical research 
consent, the following specimens will be obtained as part of future biomedical research:
•
Leftover serum from the MK-1654 PK assay
•
Leftover serum from the ADA and SNA assays
Planned Genetic Analysis Sample Collection
Planned genetic analysis samples will not be evaluated in this study.
Biomarkers
Biomarkers will be evaluated as part of the Future Biomedical Research.
Medical Resource Utilization and Health Economics
Medical Resource Utilization and Health Economics are not evaluated in this study.
Visit Requirements
Visit requirements are outlined in Section 1.3. Specific procedure-related details are provided 
in Section 8.
Screening
Within 14 days prior to randomization, potential participants will be evaluated to determine 
that they fulfill the entry requirements as set forth in Section 5. Potential participants will be 
screened at the study site.
Screening procedures may be repeated after consultation with the Sponsor. Rescreening 
should include all screening procedures listed in the SoA, including consent review.
Intervention Period
On Day 1, participants will be randomized and dosed at the study site, as set forth in the SoA 
and Section 6.
After completing all pre-dose procedures, each participant will be assigned a unique 
treatment/randomization number associated with a specific intervention as defined by IRT.
On the scheduled day of dosing (Day 1) at the time specified by the investigator, participants 
will have the IM injection(s) administered as described in Section 6. Participants will be 
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observed at the study site for at least 2 hours post-dose for safety monitoring, including 
assessment for injection-reaction AEs/SAEs, followed by a safety follow-up telephone call 
(or onsite follow-up for inpatients) on the evening of Day 1 and Day 2.
Participants who on Day 1 have an acute illness or fever (see Section 5.2 Exclusion #16) 
prior to the administration of study drug may be rescheduled.
Discontinued Participants Continuing to be Monitored in the Study and Post-
study Visit
The investigator or study coordinator must notify the Sponsor when a participant has been 
discontinued/withdrawn from the study. If a participant discontinues for any reason at any 
time during the course of the study, the participant’s legally acceptable representative may be 
asked to bring the participant back to the study site (or be contacted) for a post-study visit 
(approximately 365 days post-dose for Panels A through C, D1, and E1, and 545 days post-
dose for Panels D2 and E2) to have the applicable procedures conducted. However, the 
investigator may decide to perform the post-study procedures at the time of discontinuation 
or as soon as possible after discontinuation. If the post-study visit occurs prior to Day 365
(Panels A through C, D1, and E1/ Day 545 (Panels D2 and E2), the investigator should 
perform a follow-up telephone call on Day 365/545 to determine if any AEs have occurred 
since the post-study visit.
9. STATISTICAL ANALYSIS PLAN
This section outlines the statistical analysis strategy and procedures for the study. If, after the 
study has begun, but prior to the final database lock, changes are made to the primary or key 
secondary analyses, then the protocol will be amended (consistent with ICH Guideline E9). 
Changes to exploratory or other non-confirmatory analyses made after the protocol has been 
finalized, but prior to final database lock, will be documented in a supplemental Statistical 
Analysis Plan and referenced in the Clinical Study Report (CSR) for the study. Post hoc 
exploratory analyses will be clearly identified in the CSR.
Statistical Analysis Plan Summary
This section contains a brief summary of the statistical analyses for this study; full details are 
provided in the following sections.
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Study Design 
Overview
A Double-Blind, Placebo-controlled, Single Ascending Dose 
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics 
of MK-1654 in Pre-Term and Full-Term Infants
Intervention
Assignment
Pre-term infant participants will be assigned randomly in a 4:1 
ratio to receive one of the following active doses or placebo: 
•
Panel A: 20 mg MK-1654
•
Panel B: 50 mg MK-1654
•
Panel C: 75 mg MK-1654
•
Panel D: 100 mg MK-1654
In Panels B, C and D, the randomization will be stratified by 
weight. At least 12.5% of participants enrolled in Panels B and 
D, and at least 10% of participants enrolled in Panel C will be 
small pre-term infants (weigh 2 to 5 kg [inclusive] at 
randomization) while the remainder of the participants enrolled 
in these panels will be large pre-term infants (weigh more than 
5 kg at randomization). 
Full-term infant participants will be assigned randomly in a 4:1 
ratio to receive the following active dose or placebo:
•
Panel E: 100 mg MK-1654
All participants will receive study intervention administered via
IM injection(s) on Day 1.
Analysis Populations
Safety: All Participants as Treated (APaT)
Pharmacokinetics: Per-Protocol (PP)
Primary Endpoint
Safety:
•
Solicited injection site AEs Day 1 through Day 5 post-dose
•
Solicited systemic AEs Day 1 through Day 5 post-dose
•
SAEs from Day 1 through Day 365 post-dose for Panels A
through C, D1, and E1, and from Day 1 through Day 545 
post-dose for Panels D2 and E2.
Key Secondary 
Endpoints
Pharmacokinetics:
•
The MK-1654 PK variable(s) AUC0-inf, Cmax, Tmax, t1/2, 
C7days, C14days, C90days, C150days and C365days
(Panels A through C, D1, and E1)
•
The MK-1654 PK variable(s) AUC0-inf, Cmax, Tmax, t1/2, 
C7days, C150days, and C365days (Panels D2 and E2)
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Statistical Methods 
for Key 
Pharmacokinetic 
Analyses
Separately for each PK parameter of interest (AUC0-inf, Cmax, 
C7days, C14days, C90days, C150days, and C365days), 
individual values at each dose level will be natural log-
transformed and evaluated with a linear effects model containing 
a fixed effect for dose. Ninety-five percent confidence intervals 
(CI) for the least squares means for each dose will be constructed 
on the natural log scale and will reference a t-distribution. 
Exponentiating the least-squares means and lower and upper 
limits of these CIs will yield estimates for the population 
geometric means (GM) and CIs about the GMs on the original 
scale.
The posterior distribution of the natural log mean C150days will 
be calculated for each dose using the estimated mean and 
standard deviation from the above model and using a non-
informative prior. The PostPr (true GM C150days ≥7.5 µg/mL| 
data) will be computed for each dose.
Statistical Methods 
for Key Safety 
Analyses
Safety parameters will be summarized via descriptive statistics.
Interim Analyses
Interim analyses of safety and available PK data will be 
performed for making dose escalation decisions between Panels 
A and B and Panels B and C. 
The decision to dose escalate between Panels C and D in pre-
term infants and between Panel C in pre-term infants and Panel E 
in full-term infants, and on the dose level(s) in Panels D and E
(up to100 mg), will be made in an siDMC meeting based on 
review of safety and PK data.
An interim analysis of safety and PK data will be performed 
when all evaluable pre-term infant participants in Panels A and B 
and at least 10 pre-term infant participants in Panel C have 
completed their Day 150 visit. Available safety and PK data from 
Panel D and Panel E will be included in this analysis. The 
purpose of this interim analysis is to make scientific decisions for 
future studies.
Multiplicity
Since there are no formal hypothesis tests in this study, no 
adjustment will be made for multiplicity.
Sample Size and 
Power
Section 9.9 provides information about the ability of this study to 
estimate the incidence of AEs in recipients of a dose of 
MK-1654.
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Responsibility for Analyses/In-house Blinding
The statistical analysis of the data obtained from this study will be the responsibility of the 
Clinical Biostatistics department of the Sponsor. 
This study will be conducted as a double-blind study, ie, the investigators and participants 
will be blinded to the intervention assignments of the participants. The official, final database 
will not be unblinded until medical/scientific review has been performed, protocol deviations 
have been identified, and data have been declared final and complete.
The Clinical Biostatistics department will generate the randomized allocation schedules for 
study intervention assignment. Randomization will be implemented using IRT.
The planned interim analyses are described in Section 9.7. The results of the interim analyses 
will not be shared with the investigators prior to the completion of the study, with the 
exception of the dose escalation decisions. 
Hypotheses/Estimation
The objectives of the study are stated in Section 3.
Analysis Endpoints
Safety Endpoints
Refer to Section 4.2.1.1 for the description of the safety measures in this study. Safety and 
tolerability will be assessed by clinical review of all relevant parameters including AEs, 
systemic and local injection reaction assessments, physical examinations, and VS. AEs will 
be documented on a validated diary card which will be administered electronically via 
handheld device. All AEs will be assessed for intensity. 
Primary Safety Endpoints
Solicited systemic AEs (irritability, drowsiness, fever, and appetite lost) from Day 1 
through Day 5 post-dose;
Solicited local injection reaction AEs (redness/erythema, swelling, and 
pain/tenderness) from Day 1 through Day 5 post-dose; 
SAEs throughout the study duration (from the time the consent form is signed 
through Day 365 post-dose (Panels A through C, D1, and E1) and Day 545 post-dose 
(Panels D2 and E2) and/or completion of the participant’s participation in the study).
Additional Safety Endpoints
Elevated temperature (≥102.2°F [39.0°C] rectal or ≥101.7°F [38.7°C] axillary 
equivalent) from Day 1 through Day 5 post-dose; 
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Solicited AEs of allergic reactions (hives or welts, lip swelling, wheezing, and 
difficulty breathing) from Day 1 through Day 30 post-dose;
Respiratory AEs from Day 1 through Day 365 post-dose
Any other unsolicited non-serious AEs occurring from Day 1 through Day 14 post-
dose.
Pharmacokinetic Endpoints
Secondary Endpoint
For Panels A through C, D1, and E1, the MK-1654 PK variables: AUC0-inf, Cmax, 
Tmax, t1/2, and concentration (C7days, C14days, C90days, C150days and C365days).
For Panels D2 and E2, the MK-1654 PK variables: AUC0-inf, Cmax, Tmax, t1/2, and 
concentration (C7days, C150days, and C365days).
Other Endpoints
Secondary Endpoint
MK-1654 ADA titer for Panels A through C, D1, and E1 on Days 14, 90, 150, and 
365.
MK-1654 ADA titer for Panels D2 and E2 on Days 150, 365, and 545.
Exploratory Endpoints
Associations between ADA titer, PK parameters, safety endpoints, and RSV serum 
neutralizing antibody titer.
RSV serum neutralizing antibody titers (on Days 150 and 365 for Panels A through 
C, D1, and E1, and Days 150, 365, and 545 for Panels D2 and E2).
MK-1654 PK profile in blood microsamples.
Associations between PK parameters of MK-1654 and body weight.
Incidence of RSV, influenza, and hMPV in nasal swab in infants with symptoms 
consistent with respiratory infection.
Number and proportion of infants with RSV-associated ARI.
Number and proportion of infants with RSV-associated LRI.
Number and proportion of infants with RSV-associated hospitalization.
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Number and proportion of infants with medically attended (including office or clinic 
visit, emergency department, urgent care, or hospitalizations) LRI.
Analysis Populations
PK Analysis Populations
The Per-Protocol (PP) population will be used for the analysis of PK data in this study. The 
PP population consists of all randomized participants with exclusions for important
deviations from the protocol that may substantially affect the results of the PK endpoints. 
Deviations that may result in the exclusion of a participant from the PP population for all PK 
analyses include:
•
Failure to receive study intervention at Day 1,
•
Receipt of prohibited medication or prohibited vaccine prior to study intervention, and
•
Missing PK results.
The final determination on important protocol deviations, and thereby the composition of the 
PP population, will be made prior to the final unblinding of the database and will be 
documented in a separate memo. Participants will be included in the intervention group for 
the treatment actually received for the analysis of PK data using the PP population.
Safety Analysis Populations
The All Participants as Treated (APaT) population will be used for the analysis of safety data 
in this study. The APaT population consists of all randomized participants who received 
study intervention. Participants will be included in the group corresponding to the clinical 
material they actually received for the analysis of safety data using the APaT population. For 
most participants this will be the group to which they are randomized. Participants who 
receive incorrect clinical material will be included in the group corresponding to the clinical 
material actually received.
Statistical Methods
For all analyses, data will be examined for departures from the assumptions of the statistical 
model(s) as appropriate; eg, heteroscedasticity, non-normality of the error terms. 
Distribution-free methods may be used if a serious departure from the assumptions of the 
models(s) is observed, or suitable data transformations may be applied.
Statistical Methods for Pharmacokinetic Analyses
Due to the sparse PK sampling in this study, population PK modeling will be used to 
estimate the PK parameters AUC0-inf, Cmax, Tmax, and t1/2. Population PK modeling may also 
be used to estimate the concentrations at the time points where all participants are not being 
sampled. For the summaries of the PK data, PK data from the pre-term infant panels and full-
term infant panel will be combined for the analysis if the full-term infant panel receives the 
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same dose as one of the pre-term infant panels. PK sample analysis will not be conducted in 
participants who receive placebo.
Model-Based PK Summary
Separately for each PK parameter of interest (AUC0-inf, Cmax, C7days, C14days, C90days, 
C150days, and C365days), individual values at each dose level will be natural log-
transformed and evaluated with a linear effects model containing a fixed effect for dose. 
Ninety-five percent CIs for the least squares means for each dose will be constructed on the 
natural log scale and will reference a t-distribution. Exponentiating the least-squares means 
and lower and upper limits of these CIs will yield estimates for the population GMs and CIs 
about the GMs on the original scale.
The posterior distribution of the natural log mean C150days will be calculated for each dose 
using the estimated mean and standard deviation from the above model and using a non-
informative prior. The PostPr (true GM C150days ≥7.5 µg/mL | data) will be computed for 
each dose.
Additionally, the proportion of participants with C150days >7.5 µg/mL will be summarized 
for each dose. All PK parameters and the number of participants with C150days >7.5 µg/mL
will be summarized by dose and body weight group at time of administration of MK-1654 
(ie, 2 to 5 kg and >5 kg). In addition, the relationship between PK parameters and body 
weight will be assessed graphically.
Dose Proportionality for PK
An exploratory analysis will be conducted to preliminarily assess dose proportionality of 
MK-1654 for each PK parameter of interest separately (AUC0-inf, Cmax, C150days, and 
C365days). Separately for each naturally log-transformed PK parameter, a linear model with 
ln (dose) as a covariate will be used to estimate the overall slope. A plot of the observed PK 
data versus dose will be provided along with an overall estimated regression line on the raw 
scale and a 95% Schéffe confidence band. Dose proportionality of the PK parameters may 
also be assessed using dose on the linear and ordinal scales as a covariate.
Descriptive Statistics for PK
Individual values will be listed for each PK parameter (AUC0-inf, Cmax, C7days, C14days, 
C90days, C150days, C365days, Tmax and t1/2) by dose and panel, and the following (non-
model-based) descriptive statistics will be provided: N (number of participants with non-
missing data), arithmetic mean, standard deviation, arithmetic percent CV (calculated as 
100 x standard deviation/arithmetic mean), median, minimum, maximum, GM, and 
geometric percent CV (calculated as 100 x sqrt(exp(s2) - 1), where s2 is the observed 
variance on the natural log-scale).
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Anti-drug Antibodies (ADAs
The proportion of patients who develop ADAs and/or the ADA titers will be summarized at 
each dose level and time point. The distribution of positive titers will be examined 
graphically for each dose level and time point. The association between ADA positivity 
and/or titers and PK parameters will be evaluated for each dose at the time points where both 
results are available.
Statistical Methods for Safety Analyses
Safety data from participants who receive placebo will be pooled across the panels for the 
safety summaries. If the same dose of MK-1654 is administered in more than one panel, 
those panels will be pooled for the safety summaries. Summary statistics and plots will be 
generated for VS as well as for change from baseline, as deemed clinically appropriate. 
Depending on the safety parameter, the difference from baseline will either be computed on 
the original scale (raw change from baseline) or on the log scale and back-transformed for 
reporting (percent change from baseline).
Safety and tolerability will be assessed by clinical review of all relevant parameters including 
adverse events. Patient-reported outcomes will include temperature and AEs reported in the 
electronic diary card.
Descriptive summaries (point estimates) by MK-1654 dose group and placebo will be 
provided for all safety parameters. In addition, within-group 95% CIs (based on the exact 
binomial method proposed by Clopper and Pearson [Clopper, C. J. and Pearson, E. S. 1934]) 
will be provided for the following safety endpoints for each MK-1654 dose group and 
placebo: 
•
The proportion of participants with elevated temperature (≥102.2°F [39.0°C] rectal or 
≥101.7 °F [38.7°C] axillary equivalent) from Day 1 through Day 5 post-dose; 
•
The proportion of participants with solicited systemic AEs (irritability, drowsiness, fever, 
and appetite lost) Day 1 to Day 5 post-dose;
•
The proportion of participants with solicited injection reaction AEs (redness/erythema, 
swelling, and pain/tenderness) Day 1 to Day 5 post-dose;
•
The proportion of participants with solicited AEs of allergic reactions (hives or welts, lip 
swelling, wheezing, and difficulty breathing) Day 1 to Day 30 post-dose;
•
The proportion of participants with respiratory AEs Day 1 through Day 365 post-dose
•
The proportion of participants with any other unsolicited non-serious AEs Day 1 through 
Day 14 post-dose;
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•
The proportion of participants with any AE, a drug-related AE, a SAE, a death, an AE 
which is both drug-related and serious, and an AE which leads to discontinuation.
The proportion of participants with specific AEs or System Organ Classes will be 
summarized using point estimates only. For Panels C, D, and E where MK-1654 will be 
administered as 2 divided-dose IM injections, the injection-site AEs will be summarized 
separately for each injection site and combined across the 2 injection sites.
Interim Analyses
Interim analyses of safety and PK data will be performed for making dose escalation 
decisions between the panels. The decision to escalate the dose between Panels A and B and 
Panels B and C will be made based on review of: 1) available safety data through at least 
Day 14 for at least 50% of participants in the previous panel(s); and 2) available PK data 
from the previous panel(s). Ongoing safety monitoring and PK analyses will continue 
throughout Panels A, B, and C.
The decision to dose escalate between Panels C and D in pre-term infants and between
Panel C in pre-term infants and Panel E in full-term infants, and on the dose level(s) in 
Panels D and E (up to 100 mg), will be made in an siDMC meeting based on review of: 
1) available safety data through at least Day 14 from Panels A, B, and C; 2) PK data through 
Day 90 for evaluable participants in Panel A and PK data through Day 30 for at least 50% of 
evaluable participants in Panel B; and 3) available PK data from Panel C. 
An interim analysis of safety and PK data will be performed when all evaluable pre-term 
infant participants from Panels A and B and at least 10 pre-term infant participants from 
Panel C have completed their Day 150 visit. Available safety and PK data from Panels D and  
E will be included in this analysis. Group-level summaries will be reviewed by the Sponsor 
study team in order to make scientific decisions for future studies. 
Multiplicity
Since there are no formal hypothesis tests in this study, no adjustment will be made for 
multiplicity.
Sample Size and Power Calculations
Sample Size and Power for Safety Analyses
The probability of observing at least one SAE in this study depends on the number of 
participants dosed and the underlying percentage of participants with a SAE in the study 
population. Calculations below assume that 100% of the randomized participants will be 
evaluable for safety analyses. There is an 80% chance of observing at least 1 SAE among 
144 participants in any MK-1654 dose group if the underlying incidence of a SAE is 1.2% 
(1 of every 83 participants receiving MK-1654). There is a 50% chance of observing at least 
one SAE among 144 participants in any MK-1654 dose group if the underlying incidence of 
a SAE is 0.5% (1 of every 200 participants receiving MK-1654). If no SAEs are observed 
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among the 144 participants in any MK-1654 dose group, this study will provide 97.5% 
confidence that the underlying percentage of participants with a SAE is <2.5% (1 in every 
40 participants) in any MK-1654 dose group.
Sample Size and Power for Pharmacokinetic Analyses
An estimate of variability was obtained from the available data from Study P001. The largest 
variability computed for any PK parameter in that study was 0.45 (standard deviation on 
natural log scale). Since the variability in the PK of pre-term and full-term infants is expected 
to be larger than the variability in healthy adults, the log scale standard deviation was 
assumed to be 1 and 1.5 for computing the precision around the estimate of the GM 
C150days.
Assuming that there are 27 out of 32 evaluable participants (85% evaluability rate) on 
MK-1654 in each of Panels B, D, and E, at Day 150, the 95% CIs for various hypothetical 
GM C150days and natural log scale standard deviation estimates are displayed in Table 3.
Table 3
95% CIs for Varying Standard Deviations and GM C150days with 27 Evaluable 
Participants on MK-1654 in Panels B, D, and E
Standard Deviation on Natural Log Scale
MK-1654 GM C150days
5
7
10
15
1.0
(3.37, 7.43)
(4.71, 10.40)
(6.73, 14.85)
(10.10, 22.28)
1.5
(2.76, 9.05)
(3.87, 12.67)
(5.52, 18.10)
(8.29, 27.15)
C150days=concentration in blood at 150 days; CI=Confidence Interval; GM=Geometric Mean.
Subgroup Analyses
Not applicable for this study.
Compliance (Medication Adherence)
Not applicable for this study.
Extent of Exposure
The number of participants receiving MK-1654 and placebo will be summarized by dose 
group.
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
Code of Conduct for Clinical Trials
Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc. (MSD)
Code of Conduct for Interventional Clinical Trials
I. Introduction
A. Purpose
MSD, through its subsidiaries, conducts clinical trials worldwide to evaluate the safety and effectiveness of our 
products. As such, we are committed to designing, implementing, conducting, analyzing, and reporting these trials 
in compliance with the highest ethical and scientific standards. Protection of participants in clinical trials is the 
overriding concern in the design and conduct of clinical trials. In all cases, MSD clinical trials will be conducted 
in compliance with local and/or national 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. Participants must meet protocol entry criteria to be enrolled in the trial. 
2. Site Selection
MSD selects investigative sites based on medical expertise, access to appropriate participants, adequacy of 
facilities and staff, previous performance in clinical trials, as well as budgetary considerations. Prior to trial 
initiation, sites are evaluated by MSD personnel (or individuals acting on behalf of MSD) to assess the ability 
to successfully conduct the trial.
3. Site Monitoring/Scientific Integrity
Investigative trial sites are monitored to assess compliance with the trial protocol and Good Clinical Practice
(GCP). MSD reviews clinical data for accuracy, completeness, and consistency. Data are verified versus 
source documentation according to standard operating procedures. Per MSD policies and procedures, if fraud, 
scientific/research misconduct or serious GCP-non-compliance is suspected, the issues are investigated. 
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When necessary, the clinical site will be closed, the responsible regulatory authorities and ethics review 
committees notified.
B. Publication and Authorship
Regardless of trial outcome, MSD commits to publish 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. Unless required by 
law, only the investigator, Sponsor (or individuals acting on behalf of MSD), ethics committee, and/or regulatory 
authorities will have access to confidential medical records that might identify the participant by name.
D. Genomic Research
Genomic research will only be conducted in accordance with a protocol and informed consent authorized by an 
ethics committee.
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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.
Financial Disclosure
Financial Disclosure requirements are outlined in the US Food and Drug Administration 
Regulations, Financial Disclosure by Clinical Investigators (21 CFR Part 54). It is the 
Sponsor's responsibility to determine, based on these regulations, whether a request for 
Financial Disclosure information is required. It is the investigator's/subinvestigator's 
responsibility to comply with any such request.
The investigator/subinvestigator(s) agree, if requested by the Sponsor in accordance with 21 
CFR Part 54, to provide his/her financial interests in and/or arrangements with the Sponsor to 
allow for the submission of complete and accurate certification and disclosure statements. 
The investigator/subinvestigator(s) further agree to provide this information on a 
Certification/Disclosure Form, commonly known as a financial disclosure form, provided by 
the Sponsor. The investigator/subinvestigator(s) also consent to the transmission of this 
information to the Sponsor in the United States for these purposes. This may involve the 
transmission of information to countries that do not have laws protecting personal data.
Data Protection
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names 
or any information that would make the participant identifiable will not be transferred.
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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.
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.
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 report form data. By signing the consent form, the participant agrees 
to this process. If study documents will be photocopied during the process of verifying 
worksheet/CRF information, the participant will be identified by unique code only; full 
names/initials will be masked prior to transmission to the Sponsor.
By signing this protocol, the investigator agrees to treat all participant data used and 
disclosed in connection with this study in accordance with all applicable privacy laws, rules 
and regulations.
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.
Committees Structure
Internal Data Monitoring Committee
To supplement the routine monitoring outlined in this protocol, a separate Standing Internal 
Data Monitoring Committee (siDMC) will monitor the interim data from this study. The 
siDMC is comprised of members of Sponsor Senior Management, none of whom are directly 
associated with the conduct of this study. The siDMC will monitor the study at an 
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appropriate frequency (Section 9.7 Interim Analyses) for evidence of adverse effects of study 
intervention and for dose selection (escalation) per Section 6.6 and the Dose Escalation 
Diagram in Section 1.2, as described in the detailed monitoring guidelines. The siDMC will 
determine whether the study should continue (or other modifications, prespecified or 
otherwise, should be made) according to the protocol, considering the overall risk and benefit 
to study participants. The siDMC will also make recommendations to the Sponsor protocol 
team regarding steps to ensure both participant safety and the continued ethical integrity of 
the study.
Specific details regarding responsibilities of the siDMC will be described in a separate 
charter that is reviewed and approved by the siDMC.
Publication Policy
The results of this study may be published or presented at scientific meetings. The Sponsor 
will comply with the requirements for publication of study results. In accordance with 
standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement.
If publication activity is not directed by the Sponsor, the investigator agrees to submit all 
manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect 
proprietary information and to provide comments.  
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements.
Compliance with Study Registration and Results Posting Requirements
Under the terms of the Food and Drug Administration Amendments Act (FDAAA) of 2007 
and the European Medicines Agency (EMA) clinical trial Directive 2001/20/EC, the Sponsor 
of the study is solely responsible for determining whether the study and its results are subject
to the requirements for submission to http://www.clinicaltrials.gov, 
www.clinicaltrialsregister.eu or other local registries. MSD, as Sponsor of this study, will 
review this protocol and submit the information necessary to fulfill these requirements. MSD 
entries are not limited to FDAAA or the EMA clinical trial directive mandated trials. 
Information posted will allow participants to identify potentially appropriate studies for their 
disease conditions and pursue participation by calling a central contact number for further 
information on appropriate study locations and study site contact information.
By signing this protocol, the investigator acknowledges that the statutory obligations under 
FDAAA, the EMA clinical trials directive or other locally mandated registries are that of the 
Sponsor and agrees not to submit any information about this study or its results to those 
registries. 
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Compliance with Law, Audit, and Debarment
By signing this protocol, the investigator agrees to conduct the study in an efficient and 
diligent manner and in conformance with this protocol; generally accepted standards of GCP
(eg, International Conference on Harmonization of Technical Requirements for Registration 
of Pharmaceuticals for Human Use GCP: Consolidated Guideline and other generally 
accepted standards of good clinical practice); and all applicable federal, state and local laws, 
rules and regulations relating to the conduct of the clinical study. The Code of Conduct, a 
collection of goals and considerations that govern the ethical and scientific conduct of 
clinical investigations sponsored by MSD, is provided in this appendix under the Code of 
Conduct for Clinical Studies.
The investigator agrees not to seek reimbursement from participants, their insurance 
providers, or from government programs for procedures included as part of the study 
reimbursed to the investigator by the Sponsor.
The investigator will promptly inform the Sponsor of any regulatory authority inspection 
conducted for this study.
The investigator agrees to provide the Sponsor with relevant information from inspection 
observations/findings to allow the Sponsor to assist in responding to any citations resulting 
from regulatory authority inspection and will provide the Sponsor with a copy of the 
proposed response for consultation before submission to the regulatory authority. 
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.
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.
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Study documentation will be promptly and fully disclosed to the Sponsor by the investigator 
upon request and also shall be made available at the study site upon request for inspection, 
copying, review, and audit at reasonable times by representatives of the Sponsor or any 
regulatory authorities. The investigator agrees to promptly take any reasonable steps that are 
requested by the Sponsor or any regulatory authorities as a result of an audit or inspection to 
cure deficiencies in the study documentation and worksheets/CRFs.
The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data.
Study monitors will perform ongoing source data review and verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that the 
study is being conducted in accordance with the currently approved protocol and any other 
study agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICF, 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.
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. 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 may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
Study and Site Closure
The Sponsor or its designee may stop the study or study site participation in the study for 
medical, safety, regulatory, administrative, or other reasons consistent with applicable laws, 
regulations, and GCP.
In the event the Sponsor prematurely terminates a particular study site, the Sponsor will 
promptly notify that study site’s IRB/IEC.
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Appendix 2: Clinical Laboratory Tests
•
The tests detailed in Table 4 will be performed by your local laboratory.
•
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol.
•
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations.
Table 4
Protocol-required Screening Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count 
RBC Indices:
MCV
MCH
%Reticulocytes
WBC count with 
Differential:2
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
RBC Count
Hemoglobin
Hematocrit
Chemistry
Blood Urea 
Nitrogen 
(BUN)1
Potassium
Aspartate 
Aminotransferase (AST)/ 
Serum Glutamic-
Oxaloacetic Transaminase 
(SGOT)
Total bilirubin (and direct 
bilirubin, if total bilirubin is 
elevated above the upper 
limit of normal)
Albumin
Bicarbonate
Chloride
Phosphorous
Creatinine3
Sodium
Alanine Aminotransferase 
(ALT)/ Serum Glutamic-
Pyruvic Transaminase 
(SGPT)
Total Protein
Glucose 
(nonfasting)
Calcium
Alkaline phosphatase
MCH=mean corpuscular hemoglobin; MCV=mean corpuscular volume; RBC=red blood cell. 
NOTES:
1
Urea is acceptable if BUN is not available as per institutional standard.
2
Absolute or % acceptable per institutional standard.
3
Glomerular Filtration Rate (measured or calculated) or creatinine clearance can be used in place of 
creatinine.
Investigators must document their review of each laboratory safety report. Only the 
laboratory assessments outlined in the inclusion/exclusion criteria are considered for study 
eligibility.
Laboratory/analyte results that could unblind the study will not be reported to investigative 
sites or other blinded personnel until the study has been unblinded.
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Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
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, device, 
diagnostic agent, or protocol specified procedure whether investigational (including 
placebo or active comparator product) or marketed, manufactured by, licensed by, 
provided by, or distributed by the Sponsor for human use in this study.
Events meeting the AE definition
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the investigator.
•
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.
•
For all reports of overdose (whether accidental or intentional) with an associated AE, the 
AE term should reflect the clinical symptoms or abnormal test result. An overdose 
without any associated clinical symptoms or abnormal laboratory results is reported using 
the terminology “accidental or intentional overdose without adverse effect.”
     
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Events NOT meeting the AE definition
•
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.
•
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
•
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
•
Surgery planned prior to informed consent to treat a pre-existing condition that has not 
worsened.
•
Refer to Section 8.4.6 for protocol-specific exceptions.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met.
An SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b. Is life-threatening
•
The term “life-threatening” in the definition of “serious” refers to an event in which 
the participant was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
•
Hospitalization is defined as an inpatient admission, regardless of length of stay, even 
if the hospitalization is a precautionary measure for continued observation. (Note: 
Hospitalization for an elective procedure to treat a pre-existing condition that has not 
worsened is not an SAE. A pre-existing condition is a clinical condition that is 
diagnosed prior to the use of an MSD product and is documented in the participant’s 
medical history.
d. Results in persistent or significant disability/incapacity
•
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.
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•
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.
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
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.
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•
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to the Sponsor in lieu of completion of the AE CRF page.
•
There may be instances when copies of medical records for certain cases are requested by 
the Sponsor. In this case, all participant identifiers, with the exception of the participant 
number, will be blinded on the copies of the medical records before submission to the 
Sponsor.
•
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of intensity
•
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, not when it is rated as severe.
•
The investigator will make an assessment of intensity for each AE and SAE (and other 
reportable safety event) according to the NCI Common Terminology Criteria for Adverse 
Events (CTCAE), version 4.0.3. 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 activities of daily living (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
•
The investigator will also make an assessment of intensity for each AE and SAE (and 
other reportable safety event) reported during the study and assign it to 1 of the following 
categories: 
-
Mild: An event that is easily tolerated by the participant, causing awareness of 
symptoms, but easily tolerated.
-
Moderate: An event that causes sufficient discomfort, definitely acting like something 
is wrong.
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-
Severe: An event that causes the participant to be extremely distressed or unable to do 
usual activities. An AE that is assessed as severe should not be confused with an 
SAE. Severe is a category utilized for rating the intensity of an event; and both AE 
and SAE can be assessed as severe.
•
Injection site redness or swelling from the day of injection through Day 5 post-dose will 
be evaluated by maximum size.
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 initialled 
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 (diary, 
etc.), seroconversion or identification of vaccine virus 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 vaccine-induced effect?
-
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?
-
Rechallenge: Was the participant re-exposed to the Sponsor’s product in the study?
-
If yes, did the AE recur or worsen?
-
If yes, this is a positive rechallenge.
-
If no, this is a negative rechallenge.
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(Note: This criterion is not applicable if: (1) the initial AE resulted in death or permanent 
disability, or (2) the study is a single-dose vaccine 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 his/her best clinical judgment, 
including consideration of the above elements.
-
Use the following scale of criteria as guidance (not all criteria must be present to be 
indicative of a Sponsor’s product relationship).
-
Yes, there is a reasonable possibility of Sponsor’s product relationship:
-
There is evidence of exposure to the Sponsor’s product. The temporal sequence of the 
AE onset relative to the administration of the Sponsor’s product is reasonable. The 
AE is more likely explained by the Sponsor’s product than by another cause.
-
No, there is not a reasonable possibility of Sponsor’s product relationship:
-
Participant did not receive the Sponsor’s product OR temporal sequence of the AE 
onset relative to administration of the Sponsor’s product is not reasonable OR the AE 
is more likely explained by another cause than the Sponsor’s product. (Also entered 
for a participant with overdose without an associated AE.)
•
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.
•
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important 
that the investigator always make an assessment of causality for every event before the 
initial transmission of the SAE data to the Sponsor.
•
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment.
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The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements.
Follow-up of AE and SAE
•
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Sponsor to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals.
•
New or updated information will be recorded in the CRF.
•
The investigator will submit any updated SAE data to the Sponsor within 24 hours of 
receipt of the information.
Reporting of AEs, SAEs, and Other Reportable Safety Events to the Sponsor
AE, SAE, and other reportable safety event reporting to Sponsor via electronic data 
collection tool
•
The primary mechanism for reporting to the Sponsor will be the electronic data collection 
(EDC) tool.
•
Electronic reporting procedures can be found in the EDC data entry guidelines (or 
equivalent).
•
If the electronic system is unavailable for more than 24 hours, then the site will use 
the paper AE Reporting form.
•
Reference Section 8.4.1 for reporting time requirements.
•
The site will enter the SAE data into the electronic system as soon as it becomes 
available.
•
After the study is completed at a given site, the EDC tool will be taken off-line to prevent
the entry of new data or changes to existing data.
•
If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the EDC tool has been taken off-line, then the site can 
report this information on a paper SAE form or by telephone (see next section).
•
Contacts for SAE reporting can be found in the Investigator Study File Binder (or 
equivalent).
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SAE reporting to the Sponsor via paper CRF
•
If the EDC tool is not operational, facsimile transmission or secure e-mail of the SAE 
paper CRF is the preferred method to transmit this information to the Sponsor.
•
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service.
•
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames.
•
Contacts and instructions for SAE reporting and paper reporting procedures can be found 
in the Investigator Study File Binder (or equivalent).
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Appendix 4: Medical Device Incidents: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Not applicable.
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Appendix 5: Contraceptive Guidance and Pregnancy Testing
Not applicable for this study in infants.
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Appendix 6: Collection and Management of Specimens for Future Biomedical 
Research
1. Definitions
a.
Biomarker: A biological molecule found in blood, other body fluids, or tissues that is
a sign of a normal or abnormal process or of a condition or disease. A biomarker may
be used to see how well the body responds to a treatment for a disease or condition.1
b. Pharmacogenomics: The investigation of variations of DNA and RNA characteristics 
as related to drug/vaccine response.2
c.
Pharmacogenetics: A subset of pharmacogenomics, pharmacogenetics is the influence 
of variations in DNA sequence on drug/vaccine response.2
d. DNA: Deoxyribonucleic acid.
e.
RNA: Ribonucleic acid.
2. Scope of Future Biomedical Research
The specimens consented and/or collected in this study as outlined in Section 8.9 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 drugs/vaccines may interact with
•
The biology of disease
The specimen(s) may be used for future assay development and/or drug/vaccine 
development.
It is now well recognized that information obtained from studying and testing clinical 
specimens offers unique opportunities to enhance our understanding of how individuals 
respond to drugs/vaccines, enhance our understanding of human disease and ultimately 
improve public health through development of novel treatments targeted to populations with
the greatest need. All specimens will be used by the Sponsor or those working for or with the 
Sponsor.
3. Summary of Procedures for Future Biomedical Research
a.
Participants for Enrollment
All participants enrolled in the clinical study will be considered for enrollment in future 
biomedical research.
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b. Informed Consent
Informed consent for specimens (ie, DNA, RNA, protein, etc.) will be obtained during 
screening for protocol enrollment from the participant’s legally acceptable representative, at 
a study visit by the investigator or his or her designate. Informed consent for future 
biomedical research should be presented to the participant’s legally acceptable representative
on the visit designated in the SoA. If delayed, present consent at next possible Participant 
Visit. Consent forms signed by the participant’s legally acceptable representative will be kept 
at the clinical study site under secure storage for regulatory reasons.
A template of each study site’s approved informed consent will be stored in the Sponsor’s 
clinical document repository.
c.
eCRF Documentation for Future Biomedical Research Specimens
Documentation of participant consent for future biomedical research will be captured in the 
eCRFs. Any specimens for which such an informed consent cannot be verified will be 
destroyed.
d. Future Biomedical Research Specimen(s)
Collection of specimens for future biomedical research will be performed as outlined in the 
SoA. In general, if additional blood specimens are being collected for future biomedical 
research, these will usually be obtained at a time when the participant is having blood drawn 
for other study purposes.
4. Confidential Participant Information for Future Biomedical Research
In order to optimize the research that can be conducted with future biomedical research 
specimens, it is critical to link the participant’s clinical information with future test results. In 
fact, little or no research can be conducted without connecting the clinical study data to the 
specimen. The clinical data allow specific analyses to be conducted. Knowing participant 
characteristics like gender, age, medical history and treatment outcomes are critical to 
understanding clinical context of analytical results.
To maintain privacy of information collected from specimens obtained for future biomedical 
research, the Sponsor has developed secure policies and procedures. All specimens will be 
single-coded per ICH E15 guidelines as described below.
At the clinical study site, unique codes will be placed on the future biomedical research 
specimens. This code is a random number which does not contain any personally identifying 
information embedded within it. The link (or key) between participant identifiers and this 
unique code will be held at the study site. No personal identifiers will appear on the specimen 
tube.
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5. Biorepository Specimen Usage
Specimens obtained for the Sponsor will be used for analyses using good scientific practices. 
Analyses utilizing the future biomedical research specimens may be performed by the 
Sponsor, or an additional third party (eg, a university investigator) designated by the 
Sponsor. The investigator conducting the analysis will follow the Sponsor’s privacy and 
confidentiality requirements. Any contracted third-party analyses will conform to the specific 
scope of analysis. Future biomedical research specimens remaining with the third party after 
specific analysis is performed will be reported to the Sponsor.
6. Withdrawal From Future Biomedical Research
Participants and/or a legally acceptable representative may withdraw consent for future 
biomedical research and ask that the participant’s biospecimens not be used for future 
biomedical research. Participants and/or a legally acceptable representative may withdraw 
consent at any time by contacting the principal investigator for the main study. If medical 
records for the main study are still available, the investigator will contact the Sponsor using 
the designated mailbox (clinical.specimen.management@merck.com). Subsequently, the 
participant's specimens will be flagged in the biorepository and restricted to main study use 
only. If specimens were collected from study participants specifically for future biomedical 
research, these specimens will be removed from the biorepository and destroyed. 
Documentation will be sent to the investigator confirming withdrawal and/or destruction, if 
applicable. It is the responsibility of the investigator to inform the participant of completion 
of the withdrawal and/or destruction, if applicable. Any analyses in progress at the time of 
request for withdrawal/destruction or already performed prior to the request being received 
by the Sponsor will continue to be used as part of the overall research study data and results. 
No new analyses would be generated after the request is received.
In the event that the medical records for the main study are no longer available (eg, if the 
investigator is no longer required by regulatory authorities to retain the main study records) 
or the specimens have been completely anonymized, there will no longer be a link between 
the participant’s personal information and their specimens. In this situation, the request for 
withdrawal of consent and/or destruction cannot be processed.
7. Retention of Specimens
Future biomedical research specimens will be stored in the biorepository for potential 
analysis for up to 20 years from the end of the main study. Specimens may be stored for 
longer if a regulatory or governmental authority has active questions that are being answered. 
In this special circumstance, specimens will be stored until these questions have been 
adequately addressed.
Specimens from the study site will be shipped to a central laboratory and then shipped to the 
Sponsor-designated biorepository. If a central laboratory is not utilized in a particular study, 
the study site will ship directly to the Sponsor-designated biorepository. The specimens will 
be stored under strict supervision in a limited access facility which operates to assure the 
integrity of the specimens. Specimens will be destroyed according to Sponsor policies and 
procedures and this destruction will be documented in the biorepository database.
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8. Data Security
Databases containing specimen information and test results are accessible only to the 
authorized Sponsor representatives and the designated study administrator research personnel 
and/or collaborators. Database user authentication is highly secure and is accomplished using 
network security policies and practices based on international standards to protect against 
unauthorized access.
9. Reporting of Future Biomedical Research Data to Participants
No information obtained from exploratory laboratory studies will be reported to the 
participant, family, or physicians. Principle reasons not to inform or return results to the 
participant include: Lack of relevance to participant health, limitations of predictive 
capability, and concerns regarding misinterpretation.
If important research findings are discovered, the Sponsor may publish results, present results 
in national meetings, and make results accessible on a public website in order to rapidly 
report this information to doctors and participants. Participants will not be identified by name 
in any published reports about this study or in any other scientific publication or presentation.
10. Future Biomedical Research Study Population
Every effort will be made to recruit all participants diagnosed and treated on Sponsor clinical 
studies for future biomedical research.
11. Risks Versus Benefits of Future Biomedical Research
For future biomedical research, risks to the participant have been minimized and are 
described in the Future Biomedical Research informed consent.
The Sponsor has developed strict security, policies, and procedures to address participant 
data privacy concerns. Data privacy risks are largely limited to rare situations involving 
possible breach of confidentiality. In this highly unlikely situation, there is risk that the 
information, like all medical information, may be misused.
12. Questions
Any questions related to the future biomedical research should be emailed directly to 
clinical.specimen.management@merck.com.
13. References
1.
National Cancer Institute [Internet]: Available from 
https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45618
2.
International Conference on Harmonization [Internet]: E15: Definitions for Genomic 
Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding 
Categories. Available from http://www.ich.org/products/guidelines/efficacy/efficacy-
single/article/definitions-for-genomic-biomarkers-pharmacogenomics-
pharmacogenetics-genomic-data-and-sample-cod.html 
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3.
Industry Pharmacogenomics Working Group [Internet]: Understanding the Intent, Scope 
and Public Health Benefits of Exploratory Biomarker Research: A Guide for IRBs/IECs 
and Investigational Site Staff. Available at http://i-pwg.org/ 
4.
Industry Pharmacogenomics Working Group [Internet]: Pharmacogenomics 
Informational Brochure for IRBs/IECs and Investigational Site Staff. Available at 
http://i-pwg.org/
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Appendix 7: Country-specific Requirements
Not applicable.
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Appendix 8: Abbreviations
Abbreviation
Expanded Term
ADA
Anti-drug antibody
ADL
Activities of daily living
AE
Adverse event 
ALT
Alanine aminotransferase (serum glutamic-pyruvic transaminase [SGPT])
APaT
All participants as treated
ARI
Acute respiratory infection
AST
Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase [SGOT])
AUC0-inf
Area under the concentration-time curve from time 0 extrapolated to infinity
C#days
Concentration in blood at # days
CDC
Centers for Disease Control
CI
Confidence interval
Cmax
Maximum concentration in blood
CRF
Case Report Form 
CSR
Clinical Study Report
CTCAE
Common Terminology Criteria for Adverse Events 
CV
Coefficient of variation
DILI
Drug-induced liver injury
DNA
Deoxyribonucleic acid 
ECG
Electrocardiogram 
ECI
Event of clinical interest
eCRF
Electronic Case Report Form
EDC
Electronic data collection 
EMA
European Medicines Agency
F protein
Fusion protein
FDAAA
Food and Drug Administration Amendments Act
FIH
First-In-Human
GCP
Good Clinical Practice 
GLP
Good Laboratory Practice
GM
Geometric mean
HBsAg+
Hepatitis B surface antigen
HCV
Hepatitis C
HHS
Health and Human Services
HIV
Human immunodeficiency virus
hMPV
Human metapneumovirus
IB
Investigator’s Brochure 
ICF
Informed Consent Form 
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use
IEC
Independent Ethics Committee
IM
Intramuscular(ly)
IRB
Institutional Review Board 
IRT
Interactive Response Technology
IV
Intravenous(ly)
LRI
Lower respiratory tract infection
mAb
Monoclonal antibody
NCI
National Cancer Institute
NREVSS
National Respiratory and Enteric Virus Surveillance System
PK
Pharmacokinetic(s)
PK/PD
Pharmacokinetic(s)/pharmacodynamic(s)
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Abbreviation
Expanded Term
PP
Per protocol
RNA
Ribonucleic acid
RSV
Respiratory syncytial virus
RT-PCR
Reverse transcription polymerase chain reaction
SAE
Serious adverse event 
siDMC
Standing internal Data Monitoring Committee
SNA
Serum neutralizing antibodies against RSV
SoA
Schedule of Activities
t1/2
Half-life
Tmax
Time to maximum concentration in blood
USP
United States Pharmacopeia
VS
Vital signs
WBC
White blood cell
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