Clinical trial NCT03379675
Conditions: Respiratory Syncytial Virus Infections
Sponsor: Janssen Research & Development, LLC
Start date: 2018-02-06; Completion date: 2019-12-26
Enrollment: 72 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to explore the antiviral effect of JNJ-53718678 at 2 dose levels (80 milligrams \[mg\] and 500 mg) once daily for 7 days in adults with Respiratory Syncytial Virus (RSV) infection, as measured by RSV viral load in nasal secretions by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay.

Detailed description:
This study will be performed to explore the antiviral activity, clinical outcomes, safety, tolerability, and pharmacokinetics of JNJ-53718678 in adult participants infected with RSV. The study will include both participants who are otherwise healthy (ie, without underlying condition) or who have comorbid conditions (eg, asthma, chronic obstructive pulmonary disease (COPD), cardiovascular disease, other chronic diseases), with the exception of immunocompromised participants, presenting for medical care but not requiring hospitalization. The study will include a screening period (Day -1 to Day 1), a treatment Period (Day 1 to Day 8), and a follow-up period (Day 9 to Day 28). Safety evaluations will include adverse events, laboratory tests, electrocardiogram, vital signs, physical examination, and specific toxicities.

Arms: arm 1: Participants will receive 500 mg dose of JNJ-53718678 once daily for 7 days. arm 2: Participants will receive 80 mg dose of JNJ-53718678 along with the matching placebo to the same total volume as for the 500 mg dose once daily for 7 days. arm 3: Participants will receive matching placebo to the same total volume as for the 500 mg dose once daily for 7 days.
Interventions: intervention 1: JNJ-53718678 500 mg intervention 2: JNJ-53718678 80 mg intervention 3: Placebo
Intervention descriptions: intervention 1: Participants will receive 500 mg dose of JNJ-53718678 oral solution once daily for 7 days. intervention 2: Participants will receive 80 mg dose of JNJ-53718678 oral solution along with the matching placebo to the same total volume as for the 500 mg dose once daily for 7 days. intervention 3: In treatment B, participants will receive matching placebo along with JNJ-53718678 to maintain the same total volume as for the 500 mg dose once daily for 7 days. In treatment C, participants will receive matching placebo to the same total volume as for the 500 mg dose once daily for 7 days.

Protocol documents:
Prot_002.pdf: 
1
Status: Approved, Date: 24 April 2019
Janssen Research & Development *
Clinical Protocol
A Pilot Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Explore the 
Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of 
JNJ-53718678 at Two Dose Levels in Non-Hospitalized Adult Subjects Infected With 
Respiratory Syncytial Virus
Protocol 53718678RSV2004; Phase 2a
AMENDMENT 1
JNJ-53718678
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen
Biologics, BV; Janssen-Cilag International NV; Janssen Pharmaceutica NV; Janssen, Inc; Janssen
Sciences Ireland Unlimited Company; or Janssen Research & Development, LLC. The term “sponsor” is
used throughout the protocol to represent these various legal entities; the sponsor is identified on the
Contact Information page that accompanies the protocol.
This study will be conducted under US Food & Drug Administration IND regulations (21 CFR 
Part 312).
EudraCT NUMBER: 2017-003252-24
Status:
Approved
Date:
24 April 2019
Prepared by:
Janssen Research & Development, a division of Janssen Pharmaceutica NV
EDMS number:
EDMS-ERI-145368236, 6.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT03379675


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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 4
PROTOCOL AMENDMENTS....................................................................................................................... 5
SYNOPSIS.................................................................................................................................................... 8
TIME AND EVENTS SCHEDULE .............................................................................................................. 18
ABBREVIATIONS ...................................................................................................................................... 23
DEFINITIONS OF TERMS.......................................................................................................................... 24
1.
INTRODUCTION................................................................................................................................ 25
1.1.
Background .................................................................................................................................... 26
1.2.
Benefit-risk Evaluations.................................................................................................................. 38
1.2.1.
Known Benefits........................................................................................................................... 38
1.2.2.
Potential Benefits........................................................................................................................ 38
1.2.3.
Known Risks............................................................................................................................... 38
1.2.4.
Potential Risks............................................................................................................................ 38
1.2.5.
Overall Benefits/Risks................................................................................................................. 39
1.3.
Overall Rationale for the Study...................................................................................................... 40
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS........................................................................... 40
2.1.
Objectives and Endpoints .............................................................................................................. 40
2.1.1.
Objectives ................................................................................................................................... 40
2.1.2.
Endpoints.................................................................................................................................... 41
2.2.
Hypothesis ..................................................................................................................................... 42
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 43
3.1.
Overview of Study Design.............................................................................................................. 43
3.2.
Study Design Rationale.................................................................................................................. 47
4.
SUBJECT POPULATION.................................................................................................................. 50
4.1.
Inclusion Criteria ............................................................................................................................ 50
4.2.
Exclusion Criteria ........................................................................................................................... 52
4.3.
Prohibitions and Restrictions ......................................................................................................... 54
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 54
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 55
7.
TREATMENT COMPLIANCE............................................................................................................ 56
8.
CONCOMITANT THERAPY.............................................................................................................. 56
9.
STUDY EVALUATIONS .................................................................................................................... 57
9.1.
Study Procedures........................................................................................................................... 57
9.1.1.
Overview..................................................................................................................................... 57
9.1.2.
Screening Phase ........................................................................................................................ 58
9.1.3.
Double-Blind Treatment Phase .................................................................................................. 58
9.1.4.
Posttreatment Phase (Follow-Up) .............................................................................................. 59
9.2.
Efficacy Evaluations....................................................................................................................... 60
9.2.1.
Antiviral Activity........................................................................................................................... 60


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9.2.2.
Clinical Severity and Clinical Course of RSV Infection............................................................... 61
9.2.3.
Viral Sequencing......................................................................................................................... 61
9.3.
Pharmacokinetics........................................................................................................................... 61
9.4.
Pharmacokinetic/Pharmacodynamic Evaluations.......................................................................... 62
9.5.
Biomarkers ..................................................................................................................................... 62
9.6.
Medical Resource Utilization.......................................................................................................... 62
9.7.
Safety Evaluations ......................................................................................................................... 62
9.8.
Other Evaluations........................................................................................................................... 67
9.9.
Sample Collection and Handling.................................................................................................... 67
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL 
FROM THE STUDY ........................................................................................................................... 67
10.1.
Completion ..................................................................................................................................... 67
10.2.
Discontinuation of Study Treatment/Withdrawal from the Study ................................................... 67
10.3.
Withdrawal From the Use of Research Samples........................................................................... 69
11.
STATISTICAL METHODS................................................................................................................. 69
11.1.
Interim Analysis.............................................................................................................................. 69
11.2.
Subject Information ........................................................................................................................ 70
11.3.
Sample Size Determination ........................................................................................................... 70
11.4.
Efficacy Analyses ........................................................................................................................... 71
11.4.1.
Antiviral Effect............................................................................................................................. 71
11.4.2.
Clinical Severity and Clinical Course of RSV Infection............................................................... 72
11.4.3.
Viral Sequencing......................................................................................................................... 72
11.5.
Pharmacokinetic Analyses............................................................................................................. 72
11.6.
Other Analyses............................................................................................................................... 73
11.7.
Medical Resource Utilization Analyses.......................................................................................... 73
11.8.
Safety Analyses ............................................................................................................................. 73
11.9.
Data Review Committee ................................................................................................................ 75
12.
ADVERSE EVENT REPORTING ...................................................................................................... 75
12.1.
Definitions ...................................................................................................................................... 75
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 75
12.1.2.
Attribution Definitions.................................................................................................................. 77
12.1.3.
Severity Criteria .......................................................................................................................... 77
12.2.
Special Reporting Situations.......................................................................................................... 78
12.3.
Procedures..................................................................................................................................... 78
12.3.1.
All Adverse Events...................................................................................................................... 78
12.3.2.
Serious Adverse Events ............................................................................................................. 79
12.3.3.
Pregnancy................................................................................................................................... 80
12.4.
Contacting Sponsor Regarding Safety........................................................................................... 80
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 80
13.1.
Procedures..................................................................................................................................... 81
13.2.
Contacting Sponsor Regarding Product Quality ............................................................................ 81
14.
STUDY DRUG INFORMATION......................................................................................................... 81
14.1.
Physical Description of Study Drug(s) ........................................................................................... 81
14.2.
Packaging ...................................................................................................................................... 81
14.3.
Labeling.......................................................................................................................................... 81
14.4.
Handling and Storage .................................................................................................................... 81
14.5.
Drug Accountability ........................................................................................................................ 82
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 82
16.
ETHICAL ASPECTS ......................................................................................................................... 83
16.1.
Study-Specific Design Considerations........................................................................................... 83
16.2.
Regulatory Ethics Compliance....................................................................................................... 83
16.2.1.
Investigator Responsibilities ....................................................................................................... 83


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16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................... 83
16.2.3.
Informed Consent ....................................................................................................................... 85
16.2.4.
Privacy of Personal Data ............................................................................................................ 86
16.2.5.
Long-Term Retention of Samples for Additional Future Research ............................................ 86
16.2.6.
Country Selection ....................................................................................................................... 87
17.
ADMINISTRATIVE REQUIREMENTS .............................................................................................. 87
17.1.
Protocol Amendments.................................................................................................................... 87
17.2.
Regulatory Documentation ............................................................................................................ 88
17.2.1.
Regulatory Approval/Notification ................................................................................................ 88
17.2.2.
Required Prestudy Documentation............................................................................................. 88
17.3.
Subject Identification, Enrollment, and Screening Logs ................................................................ 89
17.4.
Source Documentation................................................................................................................... 89
17.5.
Case Report Form Completion ...................................................................................................... 90
17.6.
Patient-Reported Assessments ..................................................................................................... 91
17.7.
Data Quality Assurance/Quality Control ........................................................................................ 91
17.8.
Record Retention ........................................................................................................................... 91
17.9.
Monitoring ...................................................................................................................................... 92
17.10.
Study Completion/Termination....................................................................................................... 93
17.10.1.
Study Completion/End of Study.................................................................................................. 93
17.10.2.
Study Termination....................................................................................................................... 93
17.11.
On-Site Audits ................................................................................................................................ 93
17.12.
Use of Information and Publication................................................................................................ 94
REFERENCES............................................................................................................................................ 96
ATTACHMENTS......................................................................................................................................... 98
INVESTIGATOR AGREEMENT ............................................................................................................... 120
LIST OF ATTACHMENTS
Attachment 1:
Toxicity Tables........................................................................................................... 98
Attachment 2:
Respiratory Infection-Patient Reported Outcomes (RI-PRO ©) Symptom 
Questionnaire .......................................................................................................... 107
Attachment 3:
Additional Questions About Health and Functioning ............................................... 109
Attachment 4:
Cardiovascular Safety - Abnormalities .................................................................... 111
Attachment 5:
Visit Schedule for Rash Management for Adult Subjects........................................ 112
Attachment 6:
5-level EuroQol 5-Dimension Questionnaire (EQ-5D-5L) ....................................... 114
Attachment 7:
Respiratory Infection Intensity and Impact Questionnaire (RiiQ) ............................ 117
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Pharmacokinetic Results of JNJ-53718678 After Administration of 75 mg (Cohort 2), 
200 mg and 500 mg JNJ-53718678 Once Daily (Cohort 1+2) in Study 
53718678RSV2001 ................................................................................................... 49
Table 2:
Treatment Overview .................................................................................................. 55
FIGURES
Figure 1:
Schematic Overview of the Study.............................................................................. 46


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PROTOCOL AMENDMENTS
Protocol Version
Date
Original Protocol
26 Sep 2017
Amendment 1
24 April 2019
Amendments below are listed beginning with the most recent amendment.
Amendment 1 (24 April 2019)
The overall reason for the amendment: The overall reason for the amendment is to replace for all newly enrolled 
subjects after approval of this amendment the Respiratory Infection-Patient Reported Outcomes (RI-PRO) 
questionnaire by the Respiratory Infection Intensity and Impact Questionnaire (RiiQ) for the assessment of the 
duration and severity of signs and symptoms of respiratory syncytial virus (RSV) infection as reported by the 
subject.
Applicable Section(s)
Description of Change(s)
Rationale: The RI-PRO questionnaire was replaced by the RiiQ (which consists of the RiiQ Symptom Scale and 
the RiiQ Impact Scale), as RiiQ provides the patient’s evaluation of both the severity of key symptoms of RSV 
disease (through the RiiQ Symptom Scale) and their impact on the patient’s daily life (through the RiiQ Impact 
Scale), thereby providing a brief but more comprehensive assessment of the RSV disease and treatment experience 
than does a symptom severity rating scale (eg, RI-PRO). The RiiQ Symptom Scale measures the severity of 13 key 
symptoms of RSV disease so is suitable for twice daily patient diary by an acutely ill patient without overburdening 
the patient. The RI-PRO measures severity of 34 symptoms that may be associated with an influenza-like 
illness. However, many of the symptoms in the RI-PRO are not commonly experienced by adults with RSV 
disease, which makes RI-PRO unnecessarily long and potentially burdensome for RSV treatment studies. The less 
common symptoms of influenza-like illnesses in the RI-PRO can make scores difficult to interpret because they are 
often confounded with common comorbidities. It poses an unnecessary burden on acutely ill patients to report rare 
and less important symptoms in twice daily diaries. The short RiiQ Symptom Scale may avoid these limitations of 
the RI-PRO and provide insight into impact of RSV disease on the subject's health-related quality of life. As the 
RiiQ Symptom and Impact Scales can be assessed independently, it is possible to assess symptoms in the morning, 
and impact in the evening when the majority of impact issues are most relevant.
All newly enrolled subjects after approval of this amendment will need to complete the RI-PRO questionnaire, in 
addition to the RiiQ Symptom Scale, at Screening/Baseline and at Day 8 to allow for bridging between the RI-PRO 
data and the RiiQ Symptom Scale data to enable conclusions on the totality of the collected PRO data.
SYNOPSIS
ABBREVIATIONS
TIME AND EVENTS SCHEDULE
2.1.2 Endpoints
9.1.2 Screening Phase
9.2.2 Clinical Severity and Clinical Course of RSV Infection
11.4.2 Clinical Severity and Clinical Course of RSV Infection
Attachment 7
Rationale: Inclusion criterion #2 was updated to clarify that the legal age of consent in the jurisdiction in which the 
study is taking place is binding for eligibility, if this is >18 years
SYNOPSIS
4.1 Inclusion Criteria
Rationale: The Time and Events Schedule was updated to include the Medical Resource Utilization assessment to 
align with Section 9.6 (Medical Resource Utilization).
TIME AND EVENTS SCHEDULE


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Applicable Section(s)
Description of Change(s)
Rationale: The protocol was updated to indicate that laboratory abnormalities will be determined according to the 
criteria specified in the DMID adult toxicity tables (instead of the WHO Toxicity Grading Scale) to align with the 
toxicity tables included in Attachment 1.
9.7 Safety Evaluations
11.8 Safety Analyses
Rationale: The precision for the sample size calculation was updated without affecting the sample size itself. While 
correct information was considered for the sample size calculation, a precision estimate for the difference was 
considered to be more relevant. Precision (90% confidence interval [CI] half width) corresponding to the estimates 
for 1 group were included instead of the precision for the difference for 2 equally sized groups (active versus 
placebo).
SYNOPSIS
11.3 Sample Size Determination
Rationale: The protocol was updated to indicate that for some items data may be recorded directly into the eCRF 
and will be considered source data, instead of mandating such recording, to allow more flexibility as the source data 
may differ for each site.
17.4 Source Documentation
Rationale: The protocol was updated to remove inconsistencies between exclusion criterion #16 and Section 8
(CONCOMITANT THERAPY) regarding the administration of investigational vaccines and investigational drugs
prior to the study.
4.2 Exclusion Criteria
Rationale: The TIME AND EVENTS SCHEDULE was updated to extend the time window of the first postdose 
ePRO assessment of the twice-daily schedule from 4 hours to 6 hours to help improve subject compliance with 
completion of the questionnaire.
TIME AND EVENTS SCHEDULE
Rationale: The protocol was updated to include Day 5 as additional timepoint for the assessment of the area under 
the RSV viral load-time curve (AUC), as AUC from immediately prior to first dose of study drug through Day 5 
was also considered relevant to evaluate the antiviral effect.
SYNOPSIS
2.1.2 Endpoints
11.4.1 Antiviral Effect
Rationale: The TIME AND EVENTS SCHEDULE was updated to have the recording of the body temperature as a 
separate assessment to better reflect the actual timing of this assessment.
TIME AND EVENTS SCHEDULE
Rationale: The protocol was updated to provide additional clarification on the concomitant use of herbal 
supplements to align with the wording included in the Clinical Protocols of other clinical studies with 
JNJ-53718678.
8 CONCOMITANT THERAPY
Rationale: The protocol was updated to indicate that concomitant medication is not collected through the electronic 
device; these are captured in the eCRF only.
17.6 Patient-Reported Assessments


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Applicable Section(s)
Description of Change(s)
Rationale: The protocol was updated to remove potential for drug-drug-interaction (DDI) as safety topic of special 
interest based on the evaluation of newly available nonclinical and clinical data. These data mainly indicate an 
increase in JNJ-53718678 exposure when coadministered with strong CYP3A4 inhibitors Given safety measures in 
place to ensure the subject’s safety in this clinical study and because strong CYP3A4 inhibitors are not allowed as 
per Section 8 (CONCOMITANT THERAPY), the sponsor does not consider any longer potential for DDI a safety 
topic of special interest.
1.2.4 Potential Risks
Rationale: The protocol was updated to remove effects on blood coagulation as safety topic of special interest 
based on the evaluation of all available data, including most recent nonclinical and clinical data. Based on this 
evaluation, no signal with respect to blood coagulation is currently seen, and hence the sponsor does not consider 
any longer effects on blood coagulation a safety topic of special interest. However, samples for coagulation testing 
will continue to be collected as planned per TIME AND EVENTS SCHEDULE as a part of the standard safety 
monitoring in the study.
1.2.4 Potential Risks
Rationale: Minor errors were noted and corrected.
Throughout the protocol.


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SYNOPSIS
A Pilot Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Explore the Antiviral Activity, 
Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of JNJ-53718678 at Two Dose Levels in 
Non-Hospitalized Adult Subjects Infected With Respiratory Syncytial Virus.
JNJ-53718678 is an investigational respiratory syncytial virus (RSV) specific fusion inhibitor belonging 
to the indole chemical class and under development for the treatment of RSV infection.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
Objectives
Primary Objective
The primary objective of the study is to explore the antiviral effect of JNJ-53718678 at 2 dose levels 
(80 mg and 500 mg) once daily for 7 days in adults with RSV infection, as measured by RSV viral load in 
nasal secretions by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay.
Secondary Objectives
The secondary objectives are to explore in adults with RSV infection, after repeated oral dosing with 
JNJ-53718678:

The safety and tolerability of JNJ-53718678;

The impact of JNJ-53718678 on the clinical course of RSV infection;

The pharmacokinetics of JNJ-53718678.
Exploratory Objectives
The exploratory objectives are to explore in adults with RSV infection after repeated oral dosing with 
JNJ-53718678:

The relationship between antiviral activity and clinical course;

The relationship between pharmacokinetics and pharmacodynamics (selected antiviral activity
parameters, clinical outcomes, and safety parameters);

Potential differences in antiviral activity and clinical course between:

otherwise healthy and comorbid subjects;

subjects with symptom onset ≤3 days before randomization and subjects with symptom onset 
>3 days before randomization.

The occurrence of complications associated with RSV per investigator assessment after initiation of 
treatment;

Medical resource utilization, including hospitalization, for clinical management of subjects during 
treatment and posttreatment follow-up;

The impact of the baseline RSV viral subtype and genotype on the antiviral activity and clinical 
course;

The emergence of mutations in the viral genome potentially associated with resistance to 
JNJ-53718678;

The RSV infectious virus titers as assessed by quantitative culture of RSV (plaque assay) on selected
nasal swab samples (optional objective, pending feasibility of performing such an assay);


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
Impact of RSV and its treatment on health-related quality of life (HRQOL).
Endpoints
Primary Endpoint
To explore the antiviral effect of JNJ-53718678 on RSV, as measured by qRT-PCR assay in 
mid-turbinate nasal swabs, the following virologic parameters will be assessed:

Area under the RSV viral load-time curve (AUC) from immediately prior to first dose of study drug 
(baseline) through Day 3, Day 5, Day 8, and Day 14;

RSV viral load and change from baseline over time;

Time to undetectable RSV viral load;

Proportion of subjects with undetectable RSV viral load at each time point throughout the study.
Secondary Endpoints
The secondary endpoints are:

Safety and tolerability, as assessed by adverse events (AEs), clinical laboratory testing, 
electrocardiograms (ECGs), vital signs, physical examination, throughout the study;

Clinical course-related endpoints:

Duration and severity of signs and symptoms of RSV infection assessed through an instrument
for patient-reported symptoms (either the Respiratory Infection-Patient Reported Outcomes
[RI-PRO] questionnaire or the Respiratory Infection Intensity and Impact Questionnaire [RiiQ] 
questionnaire) and additional questions about health and functioning;

Time to resolution of selected RSV symptoms as reported by the subject (through either the RI-
PRO or RiiQ);

Respiratory rate, heart rate, body temperature, and peripheral capillary oxygen saturation (SpO2) 
as measured by the investigator;

Pharmacokinetic parameters of JNJ-53718678, as determined by population pharmacokinetics 
(popPK) modelling.
Exploratory Endpoints
Exploratory endpoints include, but are not limited to:

Antiviral activity and clinical course by stratification factor (time of symptom onset [≤3 days vs 
>3 days before randomization], severity of key RSV symptoms at screening), presence of 
comorbidities, baseline RSV viral subtype and genotype;

The occurrence of complications with onset after treatment initiation that are associated with RSV 
per investigator assessment:

Bacterial superinfections (eg, pneumonia, sinusitis, bronchitis, bacteremia of presumed 
respiratory origin per investigator assessment);

Exacerbations of underlying pulmonary disease (eg, asthma, chronic obstructive pulmonary 
disease [COPD]);

Exacerbations of underlying cardiovascular conditions. 

The need for antibiotics related to complications associated with RSV per investigator assessment;


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
Sequence changes (post baseline) in the RSV F-gene, and other regions of the RSV genome (at the 
request of the protocol virologist), as compared to baseline;

Medical resource utilization;

Association between clinical course of RSV and self-rated HRQOL.
Hypothesis
As this is an exploratory, hypothesis-generating study, no formal statistical hypothesis testing will be 
performed.
OVERVIEW OF STUDY DESIGN
This is a Phase 2a, randomized, double-blind, placebo-controlled study to explore the antiviral activity, 
clinical outcomes, safety, tolerability, and pharmacokinetics of JNJ-53718678 at 2 dose levels (80 mg and 
500 mg) once daily for 7 days in adult subjects with respiratory illness due to RSV infection. Subjects 
may be otherwise healthy or comorbid and should not be in need of hospitalization.
A population of 75 subjects is targeted. However, given the recruitment challenges associated with the 
seasonality of RSV, a minimum of 63 subjects may be considered sufficient to complete the study.
The study will include a Screening Period (Day -1 to Day 1), a Treatment Period (Day 1 to Day 8), and a 
Follow-up Period (Day 9 to Day 28[±3]). The total study duration for each subject will be 29 days
(screening included).
Study participants will be identified when they present for medical care with symptoms supporting a 
diagnosis of RSV infection (eg, fever, cough, nasal congestion, runny nose, sore throat, myalgia, lethargy, 
shortness of breath, or wheezing). Screening should be completed as soon as possible; treatment initiation 
should start as soon as possible, but no later than 4 hours after randomization, which should occur within 
a maximum of 5 days after RSV symptom onset. During screening, mid-turbinate nasal swabs will be 
collected for local diagnosis of RSV infection (using a rapid polymerase chain reaction (PCR)-based or 
rapid-antigen-detection test), and for additional post-hoc analysis at a central laboratory to confirm RSV 
infection (and subtype), to determine RSV viral load and the presence of other viral or bacterial 
pathogens.
After screening, eligible subjects will be randomized on Day 1 (1:1:1) to receive 1 of 3 treatments:

Treatment A: 500 mg JNJ-53718678 once daily for 7 days (n = 25 [target]);

Treatment B: 80 mg JNJ-53718678 once daily for 7 days (n = 25 [target]);

Treatment C: placebo once daily for 7 days (n = 25 [target]).
In order to maintain study blind, all subjects will receive once daily the same total volume of study drug
solution divided over 2 separate but sequential intakes at the same time of day.
Randomization will be stratified by time of symptom onset (≤3 days vs >3 days before randomization).
Subjects with symptom onset >3 days before randomization may account for maximum of 50% of all 
enrolled subjects.
Subjects will be required to have a study visit at the study site or, if feasible, at home, on Day 3, Day 8, 
Day 14 (±1), and Day 21 (±3). On Day 28 (±3), subjects will be contacted by site staff for a telephone 
follow-up visit. In case subjects are experiencing ongoing AEs or have clinically significant laboratory 
abnormalities at time of the Day 21 follow-up visit, subjects might be requested, at the discretion of the 
investigator, to have a safety follow-up visit at the site or, if feasible, at home on Day 28 (±3).


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Study drugs will be administered orally. Study drug administration should start as soon as possible, but no 
later than 4 hours after randomization, which should occur within a maximum of 5 days after RSV 
symptom onset. The first dose of study drug will be administered before the subject leaves the site. 
On Day 1, study-site personnel can dispense to the subject all the required study drug for dosing at home, 
but partial dispensing at other visits is also allowed. Study-site personnel will instruct subjects on how to 
use and store study drug for at home dosing. Dosing should occur preferably at approximately the same 
time each day. Study drug can be administered without regard to meals and is preferably followed by 
drinking a glass of water.
As an evaluation of antiviral activity, the RSV viral load in nasal secretions will be measured at the 
central lab using a qRT-PCR assay on mid-turbinate nasal swab specimens, which will be collected at 
several time points during the study. If feasible, the RSV infectious virus titers as measured by 
quantitative culture of RSV (plaque assay) on selected nasal swab samples, may also be assessed.
Viral resistance will be monitored by sequencing of the viral F-gene on all baseline samples and on post 
baseline samples upon request of the sponsor’s protocol virologist. Other regions of the RSV genome 
may also be sequenced at the request of the protocol virologist. Sequencing data will not be reported to 
the investigators.
Clinical course and severity of RSV infection will be assessed through different measures.
Pharmacokinetic assessments during the study will be based on sparse sampling and will be performed 
using a popPK model.
Safety and tolerability, including AEs, laboratory assessments, ECGs, physical examination, and vital 
signs will be assessed throughout the study from signing of the Informed Consent Form (ICF) (including 
diagnostic ICF, if applicable) until the subject’s last study-related activity.
Medical resource utilization will be assessed.
Blood samples for host mRNA assessment may be used for exploratory biomarker analyses to determine 
the effects of JNJ-53718678 on markers of RSV disease at the sponsor’s discretion. Leftover 
mid-turbinate nasal swabs and blood samples collected for other testing may be used as well for the same 
purpose.
An interim analysis is planned after at least 36 subjects have been dosed and have completed the 
assessments of Day 8.
A Data Review Committee (DRC) will be in place for this study. The DRC will monitor safety data 
during study conduct on a regular basis and/or ad hoc in case of emergent safety signals identified 
through medical monitoring. The central sponsor team members will review the unblinded interim 
efficacy, safety, and pharmacokinetic analyses and will make recommendations to the DRC regarding 
possible changes to the design of the study: dropping the lower dose, changing the stratification factor 
(and/or the requirement of maximum 50% of all enrolled subjects with symptom onset >3 days before 
randomization), changing the maximum number of days between RSV symptom onset and randomization 
and/or the number of time points/visits for collecting a nasal swab by HCP. The DRC will decide on the 
implementation of the recommendations based on the review of the interim results and other ongoing 
studies of JNJ-53718678. These changes will be communicated in writing to investigators, health 
authorities, and Independent Ethics Committees (IECs)/Institutional Review Boards (IRBs) and will be 
implemented without amendment to this protocol.
Subjects who prematurely discontinue study drug treatment for any reason (except withdrawal of consent) 
will be asked to continue with their remaining study visits and assessment schedule, or, at a minimum, to 
return to the site for a Withdrawal and a Safety Follow-up Visit. Subjects who withdraw consent during 


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the treatment or follow-up phase will be offered and be encouraged to attend an optional Safety 
Follow-up Visit.
SUBJECT POPULATION
Screening for eligible subjects will be performed as soon as possible after presentation to the healthcare 
facility, such that subjects are randomized (within a maximum of 5 days after RSV symptom onset) and 
treatment is initiated as soon as possible (but no later than 4 hours after randomization).
Key Inclusion Criteria

Male or female, ≥18 years of age. If the legal age of consent in the jurisdiction in which the study is 
taking place is >18 years, this respective legal age is binding for eligibility.

With an acute respiratory illness with signs and symptoms consistent with a viral infection (eg, fever, 
cough, nasal congestion, runny nose, sore throat, myalgia, lethargy, shortness of breath, or wheezing) 
with onset ≤5 days from the anticipated time of randomization. Onset of symptoms is defined as the 
time the subject becomes aware of the first sign and/or symptom consistent with a viral infection. 
Efforts should be made to determine the time of onset of symptoms as accurately as possible (in 
relation to routine daily activities). The viral infection may present in any way as long as the 
underlying precipitant of the illness is considered by the investigator to be due to RSV infection 
(examples: an upper or lower viral respiratory tract infection, pneumonia, respiratory distress, asthma 
exacerbation, COPD exacerbation).

Diagnosed with RSV infection using a rapid PCR-based (preferably locally available) or rapid-
antigen-detection test. (If a patient has a positive similar diagnostic test from another study and 
meets all eligibility criteria for inclusion in this study, this diagnostic test result can be used for 
confirmation of eligibility.)

Medically stable (with the exception of the RSV-related illness) on the basis of physical 
examination, medical history, vital signs, and ECG performed at screening. If there are 
abnormalities, they must be consistent with the underlying condition (RSV disease and/or comorbid 
condition) in the study population as evaluated by the investigator (with exception of QTcF interval
>500 ms, see exclusion criteria).

A woman must be not of childbearing potential defined as premenarchal, postmenopausal, or 
permanently sterile.
Key Exclusion Criteria

Hospitalized or expected to be hospitalized within 24 hours of screening. Any stay in the emergency 
room or in the observational unit of at least 24 hours will be considered hospitalization for the 
purposes of the study.

Immunocompromised, in the opinion of the investigator, within the past 12 months, whether due to 
underlying medical condition (eg, malignancy or genetic disorder other than immunoglobulin A 
deficiency, or human immunodeficiency virus [HIV] infection) or medical therapy (eg, medications 
other than corticosteroids for the treatment of COPD or asthma exacerbations, chemotherapy, 
radiation, stem cell or solid organ transplant).

Known or suspected chronic or acute hepatitis B or C infection.

Unwilling to undergo mid-turbinate nasal swab procedures or any physical abnormality which limits 
the ability to collect regular nasal specimens.

Confirmed QTcF interval >500 ms per the machine read parameter result at screening. Confirmation 
needs to be obtained by repeat triplicate ECG recording prior to dosing.


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DOSAGE AND ADMINISTRATION
The subjects will receive the treatments as described in the table below. Study drugs will be administered 
orally.
Treatment
Dosing Regimen
Volume and Formulation
A
500 mg JNJ-53718678 once daily for 7 days
8 mL + 42 mL oral solution of JNJ-53718678a
B
80 mg JNJ-53718678 + matching placebo once 
daily for 7 days
8 mL oral solution of JNJ-53718678a + 42 mL of 
matching placebo solution
C
placebo once daily for 7 days
8 mL + 42 mL matching placebo solution
a
JNJ-53718678 is formulated as an oral solution containing 10 mg/mL of active drug substance (G024). The matching placebo 
consists of the oral vehicle solution without active drug substance (G026).
Study drug administration should start as soon as possible, but no later than 4 hours after randomization, 
which should occur within a maximum of 5 days after RSV symptom onset. Study drug administration 
should occur once daily at approximately the same time each day. JNJ-53718678/placebo can be 
administered without regard to meals and is preferably followed by drinking a glass of water. Each dosing 
day, the same total volume of study drug solution should be administered, ie, 50 mL, divided over
2 separate but sequential intakes (1 container with 8 mL and 1 container with 42 mL).
EFFICACY EVALUATIONS
Antiviral Activity
As an evaluation of antiviral activity, the RSV viral load in nasal secretions, obtained via mid-turbinate 
nasal swab, will be measured at the central lab using a qRT-PCR assay. Mid-turbinate swab specimens for 
the determination of the RSV viral load will be collected at several time points during the study.
Additional information about the collection, handling, and shipment of biologic samples can be found in 
the laboratory manual.
If feasible, the RSV infectious virus titers as measured by quantitative culture of RSV (plaque assay) on 
selected nasal swab samples, may also be assessed.
Clinical Severity and Clinical Course of RSV Infection
The following evaluations of the clinical course of RSV infection will be performed throughout the study:

Clinical parameters: respiratory rate, heart rate, SpO2, and body temperature as measured during site 
visits. Subjects will be provided a thermometer and asked to record body temperature in the 
electronic device at home.

Evolution and severity of signs and symptoms of RSV disease as assessed by the subject on a 
hand-held electronic device using the RI-PRO, the RiiQ Symptom Scale (if the subject was enrolled 
after approval of this amendment), and additional questions about health and functioning. Symptoms 
reported in the RiiQ Symptom Scale or RI-PRO will not be reported as AEs but constitute a part of 
the efficacy evaluations. Subjects will also complete the 5-level EuroQol 5-Dimension (EQ-5D-5L)
and the RiiQ Impact Scale (for subjects who were enrolled after approval of this amendment) on the 
electronic device to rate their HRQOL.

Need for hospitalization or medically attended visits (other than the study mandated visits) during 
treatment and follow-up.
Viral Sequencing
Viral resistance will be monitored by sequencing of the F-gene of the viral genome on all baseline 
samples and on post baseline samples upon request of the sponsor’s protocol virologist. Other regions of 


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the RSV genome may also be sequenced at the request of the protocol virologist. Sequencing data will not 
be reported to the investigators.
PHARMACOKINETIC EVALUATIONS
Pharmacokinetic assessment during the study will be based on sparse sampling and will be performed 
using a popPK approach by means of nonlinear mixed-effects modeling. Venous blood samples for 
determination of JNJ-53718678 plasma concentrations will be collected. Samples can also be used for the 
analysis of metabolites of JNJ-53718678, excipients (eg, hydroxypropyl-β-cyclodextrin), protein binding,
or endogenous markers for enzymes or transporters involved in the metabolism or distribution of 
JNJ-53718678, at the discretion of the sponsor.
PHARMACOKINETIC/PHARMACODYNAMIC EVALUATIONS
The relationship between the pharmacokinetics and pharmacodynamics (selected antiviral activity
parameters, clinical outcomes, and safety parameters) will be evaluated. 
BIOMARKER EVALUATIONS
Blood samples for host mRNA assessment may be used for exploratory biomarker analyses (eg, proteins 
including cytokines), on the premise that these markers may play a role in the treatment response, safety 
or pharmacokinetics of JNJ-53718678, or RSV-related disease. Leftover mid-turbinate nasal swabs and 
blood samples collected for other testing may be used as well for the same purpose. Analyses of 
biomarkers will be conducted at the sponsor’s discretion and may be reported separately from this study.
MEDICAL RESOURCE UTILIZATION
Medical resource utilization data will be collected in the electronic case report form (eCRF) for all 
subjects throughout the study. Protocol-mandated procedures, tests, and encounters are excluded. The 
data collected will include:

Number and duration of medical care encounters: hospitalizations, physician or emergency room 
visits, test, and procedures, including surgeries, and other procedures (inpatient and outpatient) for 
RSV infection or complications associated with RSV per investigator assessment.
SAFETY EVALUATIONS
Safety and tolerability will be evaluated throughout the study from signing of the ICF (including 
diagnostic ICF, if applicable) onwards until the last study-related activity (end of study/early withdrawal).
Any clinically relevant changes occurring during the study must be recorded on the AE section of the 
eCRF. Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be 
followed by the investigator until resolution or until a clinically stable endpoint is reached.
The study will include the following evaluations of safety and tolerability:

AEs, serious AEs (SAEs), and deaths;

Clinical laboratory tests (blood and urine);

ECG (12-lead);

Vital signs (systolic and diastolic blood pressure):

Physical examination (including height [only at screening] and body weight measurements) and skin 
examination.


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OTHER EVALUATIONS
Mid-turbinate nasal swabs collected at screening will be used to determine the presence of viral (other 
than RSV) or bacterial pathogens (both by multiplex PCR) at the central laboratory.
STATISTICAL METHODS
The primary (final) analysis will be performed after the last subject has completed his/her last visit of the 
study.
An interim analysis, encompassing efficacy, safety, and pharmacokinetics is planned after at least 
36 subjects have been dosed and have completed the assessments of Day 8 as planned. Enrollment will
not be paused during the interim analysis.
Investigators, subject(s) and local sponsor representatives will remain blinded. The central sponsor team 
members will be unblinded at the time of the interim analysis.
Additional interim analyses may be performed at the sponsor’s discretion to support decision making for 
further development of JNJ-53718678 and to support interactions with health authorities.
Sample Size
The interim results (estimates of mean AUC and change from baseline of the RSV viral load ±standard 
deviation [SD]) of study 53718678RSV1005 were the basis of the sample size calculation. In this study, 
median (range) time to onset of symptoms was 5 (2-12) days and baseline viral load was 5.3 (2.1-8.3) 
log10 copies/mL.
For the AUC viral load from Day 1 to Day 7, a (placebo) point estimate of 490 and an SD of 135 log10
copies x hr/mL was observed for the AUC viral load from Day 1 to Day 7. The sample size was 
determined in order to obtain estimates of the mean AUC viral load with a precision of approximately 
50 log10 copies x hr/mL of the true value with 90% confidence; with 20 subjects per treatment group the 
half-width of the 90% confidence would be approximately 52 and with 24 subjects per treatment group 
the precision would be approximately 47 log10 copies x hr/mL.
For the change from baseline (on Day 2 or Day 3), (placebo) point estimates of -0.11 and -0.33 and SDs 
of 1.85 and 1.56 log10 copies/mL, respectively, were observed. The observed difference (active versus 
placebo) was -1 to -2 log10 copies/mL. With an assumed SD of 1.85 log10 copies/mL, 20 subjects per 
treatment group will lead to a precision (90% confidence interval [CI] half width) of 0.986 and 
24 subjects per treatment group to a precision of 0.896 log10 copies/mL for the estimate of the difference 
in mean change from baseline of one dose group versus placebo.
As further guidance for the design, the power to detect a dose-response was calculated. To evaluate a 
potential dose-response, 3 contrasts will be tested: a contrast with no difference between the 2 active 
doses tested against placebo; a contrast with no difference between low dose and placebo tested against 
high dose; and a contrast with a linear dose-response relationship with respect to the active doses. No 
correction for multiplicity is considered in view of the exploratory nature of the study. Based on 
10,000 simulations, and assuming a reduction in AUC viral load of 20% of high dose versus placebo, the 
power to detect a positive dose-response relationship will be between 79% and 86% (depending on the 
effect of the low dose) with a total sample size of 60, and between 83% and 89% with a total sample size 
of 72.
To account for potential false-positive RSV screening testing (ie, diagnosed with RSV infection using a 
rapid PCR-based or rapid antigen-detection test, but negative at the central lab using a qRT-PCR assay, 
and therefore not included in the primary analysis population of ITT-i) and withdrawals from treatment 
for abnormal screening laboratory results, an overage of approximately 5% will be enrolled, 
ie, 75 subjects will be targeted.


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In view of the seasonality of the disease, recruitment will be halted if at the end of an hemispheric RSV 
season 63 or more subjects have been enrolled and dosed. If at the end of an hemispheric RSV season the 
minimum of 63 dosed subjects is not reached, recruitment will continue in a next RSV season until this 
minimum has been reached, up to a maximum of 75 subjects to be enrolled overall.
Efficacy Analyses
The primary population for the efficacy/antiviral activity analysis will be the intent-to-treat infected
population consisting of all randomized subjects who received at least one dose of study treatment and 
who have a central lab-confirmed RSV infection.
To explore the antiviral effect on RSV, as measured by qRT-PCR assay in mid-turbinate nasal swabs, the 
following virologic parameters will be assessed:

AUC from immediately prior to first dose of study drug (baseline) through Day 3, Day 5, Day 8, and 
Day 14

RSV viral load and change from baseline over time

Time to undetectable RSV viral load

Proportion of subjects with undetectable RSV viral load at each time point throughout the study
If feasible, the RSV infectious virus titers as measured by quantitative culture of RSV (plaque assay) on 
selected nasal swab samples, may also be assessed.
Endpoints will be analyzed graphically and descriptively as described in the Statistical Analysis Plan 
(SAP). For continuous variables descriptive statistics (n, mean, SD, median, minimum, and maximum) 
will be calculated. For viral efficacy parameters also 90% CIs will be computed comparing active dose 
groups versus placebo. For categorical variables, frequency tables will be presented. Kaplan-Meier 
Curves will be produced to graphically describe the time to event data.
To explore the antiviral effect, log10 viral load values over time will be analyzed using a restricted 
maximum likelihood-based repeated measures approach. Analyses will include the fixed, categorical 
effects of treatment, strata, visit, and treatment-by-visit interaction, as well as the continuous, fixed 
covariates of baseline log10 viral load and baseline log10 viral load by-visit interaction. An unstructured 
(co)variance structure will be used to model the within-subject errors over time. The differences in the 
AUCs for active versus placebo will be derived using appropriate contrasts deriving least squares mean 
differences, including the 90% 2-sided CIs. Details will be provided in the SAP.
Subject’s severity of their RSV symptoms, functioning, and HRQOL as reported through the PRO 
questionnaires will be summarized descriptively.
The sequencing results of the F-gene (and other regions of the RSV genome at the request of the protocol
virologist) and changes from baseline will be summarized. Sequencing results may be presented in a 
separate report.
Additional analyses will be performed to investigate other endpoints, including exploratory endpoints. 
Details on these analyses will be provided in the SAP.
Pharmacokinetic Analyses
Population pharmacokinetic analysis of concentration-time data of JNJ-53718678 will be performed using 
nonlinear mixed-effects modelling. An updated popPK model will be developed with the current adult 
data combined with those of selected Phase 1 studies to support a relevant structural model. Available 
subject characteristics (demographics, laboratory variables, etc.) will be tested as potential covariates 
affecting pharmacokinetic parameters. This updated model will be used for the final pharmacokinetic 
parameters estimation for each subject with available data. For each dose, descriptive statistics including 


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arithmetic mean, SD, coefficient of variation, geometric mean, median, minimum, and maximum of the 
final pharmacokinetic parameters (AUC, predose plasma concentration, and possibly the maximum 
observed concentration) will be provided. The pharmacokinetic analyses will be detailed in an analysis 
plan. Analyses of other analytes (eg, excipients, metabolites) may be performed at the discretion of the 
sponsor.
A snapshot date for pharmacokinetic samples to be analyzed for the planned interim analysis will be 
defined. Samples collected before this snapshot date will be analyzed for JNJ-53718678 and included in 
the popPK analysis. Samples collected after the snapshot date will be analyzed at a later date, and may be 
included in a popPK re-analysis when they become available after interim analysis database lock.
Pharmacokinetic/pharmacodynamic Analyses
Relationships of JNJ-53718678 population-derived exposure parameters with selected antiviral activity
parameters, clinical outcomes, and safety endpoints will be explored.
Biomarker Analyses
Statistical approaches to explore correlations between clinical outcome, viral load, and biomarkers in 
blood and mid-turbinate nasal swabs vary and depend on the different data types of the applied 
technology platforms, as well as on the extent of observed differences among study subjects. Analyses 
may be conducted at the sponsor’s discretion and reported separately from this study.
Medical Resource Utilization Analyses
Medical resource utilization will be descriptively summarized by treatment group.
Safety Analyses
Safety data will be presented descriptively. No statistical testing of safety data is planned.
Data Review Committee
A DRC, comprised of senior sponsor personnel outside of the central sponsor team and not involved in
study conduct, will be established. The DRC will monitor safety data during study conduct on a regular 
basis and/or ad hoc in case of emergent safety signals identified through medical monitoring. 
The central sponsor team members will review the unblinded interim efficacy, safety, and 
pharmacokinetic analyses and will make recommendations to the DRC regarding possible changes to the 
design of the study: dropping the lower dose, changing the stratification factor (and/or the requirement of 
maximum 50% of all enrolled subjects with symptom onset >3 days before randomization), changing the 
maximum number of days between RSV symptom onset and randomization and/or the number of time 
points/visits for collecting a nasal swab by HCP. The DRC will decide on the implementation of the 
recommendations based on the review of the interim results and other ongoing studies of JNJ-53718678. 
These changes will be communicated in writing to investigators, health authorities, and IECs/IRBs and 
will be implemented without amendment to this protocol.








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o.
Assessment only to be performed if subject needs to have a follow-up visit on Day 28, per the investigator’s judgement, for the follow-up of AEs or laboratory 
abnormalities on Day 21 (see also footnote e).
p.
Subjects are to measure their body temperature at home on non-visit days using only a digital oral thermometer that will be provided on Day 1. This thermometer 
will also be used at baseline and during site visits. Subjects will be instructed how to use the thermometer, and to wait for the audible beep before recording their 
body temperature in the electronic device at home. Subjects will be instructed to bring the thermometer for use by the site staff during scheduled on-site visits. To 
be recorded in the temperature log on the electronic device when measured at home and in the eCRF during on-site visits.
q.
Mid-turbinate nasal swabs will be taken to assess RSV viral load and emergence of mutations in the viral genome potentially associated with resistance to 
JNJ-53718678. The RSV infectious virus titers as measured by quantitative culture of RSV (plaque assay) may be assessed on selected nasal swab samples
(pending feasibility of performing such an assay). Mid-turbinate swabs should be collected from the same nostril throughout the study (unless precluded due to
bleeding). The first mid-turbinate nasal swab should be collected as close as possible and prior to the first administration of study drug (on Day 1). The next swabs
(from Day 2 to Day 8) should be collected preferably at approximately the same time as on Day 1 each day. On Day 8, the investigator will check whether the 
subject is still symptomatic. For asymptomatic subjects swabbing will be stopped. For subjects still symptomatic, swabbing will be continued daily until the 
subject becomes asymptomatic or until Day 13 at the latest. Whether a subject is still symptomatic will be checked with daily telephone calls between the subject 
and site staff (and/or by review of the transmitted electronic patient-reported outcome [ePRO] data) in case swabbing is performed by the subject (or his/her 
spouse, partner, relative, or other caregiver) or by an HCP other than investigational site staff. On Day 14 and Day 21, a swab will be collected during the 
scheduled visit. During scheduled visits on Day 1, Day 3, Day 8, Day 14, and Day 21, swabs must be collected by a healthcare professional (HCP)
(investigator/study-site personnel). On the other days, mid-turbinate swabs are collected at home preferably by an HCP and, only if not possible by an HCP, by the 
subject (or his/her spouse, partner, relative, or other caregiver) after being properly trained by the investigator/study-site personnel. In case preferred by the subject, 
all mid-turbinate swabbing may also be performed at the site. Date and time of swabs collected at home need to be recorded on the electronic device in a swabbing 
log. All subjects will be given appropriate mid-turbinate nasal swabs and Universal Transport Medium (same supplies as those used to collect nasal samples at the 
sites) to collect mid-turbinate nasal swabs. All swabs collected at home should be stored immediately between 2°C and 8°C (in the refrigerator) and brought to the 
site at the latest at the Day 3, Day 8, and Day 14 visit.
r.
Leftover nasal samples may be used for exploratory biomarker research at the discretion of the sponsor.
s.
. An electronic device will be provided to the subjects during screening and the investigator/study-site personnel will provide sufficient information to enable the 
subjects to complete these assessments.
t.
The assessment of the RiiQ Symptom Scale and the additional questions about healthy and functioning should be completed once at screening, then twice daily 
(bid; in the morning and in the evening) from Day 1 to Day 14 and then once daily in the evening until the Day 21 visit. The first assessment of the twice-daily 
schedule on Day 1 needs to be completed as close as feasible and prior to the first administration of study drug. If screening and dosing are on the same day and the 
subject completed the screening assessment fewer than 3 hours prior to dosing, the predose assessment on Day 1 does not need to be performed. The first postdose 
assessment of the twice-daily schedule must be performed 12 hours ±6 hours after dosing (whether on Day 1 or on Day 2). The next assessment is performed at the 
subsequent time point (morning or evening) of the bid schedule, which will be followed through Day 14. Investigational staff will review regularly (preferably 
daily) the completion of the assessments of patient-reported symptoms and functioning and the logs once data is transmitted from the electronic device and contact 
the subject in case there are issues identified with completion of the assessments.
u.
The assessment of the RI-PRO, the RiiQ Impact Scale, and the EQ-5D-5L on Day 1 needs to be completed as close as feasible and prior to the first administration 
of study drug. If screening and dosing are on the same day and the subject completed the screening assessment fewer than 3 hours prior to dosing, the predose PRO 
assessment on Day 1 does not need to be performed.
v.
Vital signs include systolic and diastolic blood pressure (sitting or supine [same position at each measurement] after at least 5 minutes rest).
w.
Physical examination includes height (only at screening), body weight measurements and skin examination.
x.
Triplicate 12-lead ECGs will be obtained. ECGs may be repeated at the discretion of the investigator to rule out erroneous readings. ECGs will be obtained in a 
supine position after 5 minutes rest. If an ECG is scheduled at the same time point as other assessments, the ECG should be performed first.


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y.
ECG is to be performed post-dose (if feasible, 4 hours after dosing; otherwise as late as possible prior to leaving the site).
z.
Biochemistry blood samples at Day 8 and Day 21 will be taken preferably under fasted conditions (fasted for at least 10 hours). 
aa.
Safety and coagulation laboratory tests will be done for each subject. Samples for clinical laboratory assessments will be collected and analyzed at a central 
laboratory. Any values that indicate a potential safety concern will be assessed by the investigator and appropriate follow-up actions, including potential 
discontinuation from treatment, will be carried out. Leftover blood samples may be used for exploratory biomarker analyses.
bb.
Urinalysis will be performed by the central laboratory and includes dipstick analysis, and if needed microscopic examination.
cc.
Includes determination of serum creatinine and estimation of the Glomerular Filtration Rate (GFR) based on creatinine by the Cockcroft-Gault formula25; 
determination of serum cystatine C and estimation of the GFR based on cystatine C25; determination of urinary creatinine, albumin, N-acetyl-β-glucosaminidase,
β2-microglobulin, urinary phosphorus, sodium, potassium, and calcium.
dd.
Blood samples for determination of plasma concentrations of JNJ-53718678 will be collected on Days 3 and 8 at a random time point during the visit. The 
following information need to be recorded on the requisition form and/or the study medication log: date and time of study drug intake, date and time of 
pharmacokinetic blood sampling, time of meal if any in the time window of 2 hours before and 2 hours after study drug intake on the day of pharmacokinetic 
sampling. Samples can be used for the determination of plasma concentrations of metabolites of JNJ-53718678, excipients (eg, hydroxypropyl-β-cyclodextrin),
protein binding, or endogenous markers for enzymes or transporters involved in the metabolism and distribution of JNJ-53718678, at the discretion of the sponsor.
ee.
All AEs and SAEs will be collected continuously from signing of the ICF (including diagnostic ICF, if applicable) onwards until the last follow-up visit (end of 
study visit). Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be followed by the investigator until resolution or until 
a clinically stable endpoint is reached.
ff.
Concomitant medication will be recorded by the site staff in the eCRF based on the electronic medication log records completed by the subject.


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ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
AUC
area under the RSV viral load-time curve
AUCxh
area under the RSV viral load-time curve from 0 to x hours
AUC∞
area under the RSV viral load-time curve from time 0 to infinity
bid
twice daily
Cavg
average plasma concentration at steady-state over the dosing interval
CI
confidence interval
Cmax
maximum observed concentration
Cmin
minimum observed concentration
COPD
chronic obstructive pulmonary disease
Ctrough
predose plasma concentration
CYP
cytochrome P450
DMID
Division of Microbiology and Infectious Diseases
DNA
deoxyribonucleic acid
DRC
Data Review Committee 
EC50
50% effective concentration
ECG
electrocardiogram
eCRF
electronic case report form
eDC
electronic data capture
(e)GFR
(estimated) Glomerular Filtration Rate
(e)PRO
(electronic) patient-reported outcome(s)
EQ-5D-5L
5-level EuroQol 5-Dimension
GCP
Good Clinical Practice
GGT
gamma-glutamyltransferase
GLP
Good Laboratory Practice
HCP
healthcare professional
HIV
human immunodeficiency virus
HP-β-CD
hydroxypropyl-β-cyclodextrin
HRQOL
health-related quality of life
IB
Investigator’s Brochure
IC50
50% inhibition concentration
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IKr
cardiac inward potassium membrane current
IRB
Institutional Review Board
IWRS
interactive web response system
LRTI
lower respiratory tract infection
MATE
multidrug and toxin extrusion protein
MCH
mean corpuscular hemoglobin
MDE
multiple-dose escalation
MRU
medical resource utilization
NAP
not applicable
NO(A)EL
No Observed (Adverse) Effect Level
OAT
organic anion transporter
OATP
organic anion-transporting polypeptide
OCT
organic cation transporter
PCR
polymerase chain reaction
P-gp
P-glycoprotein
PND
post-natal day
popPK
population pharmacokinetics
PQC
Product Quality Complaint
(e)PRO
(electronic) patient-reported outcome(s)


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PT
prothrombin time
q24h
every 24 hours
qd
once daily
qRT-PCR
quantitative reverse transcription polymerase chain reaction
QTcF
QT-interval corrected for heart rate according to Fridericia
RBC
red blood cell
RI-PRO
Respiratory Infection-Patient Reported Outcomes
RiiQ™
Respiratory Infection Intensity and Impact Questionnaire™ 
RNA
ribonucleic acid
RSV
respiratory syncytial virus
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SpO2
peripheral capillary oxygen saturation
SUSAR
suspected unexpected serious adverse reaction
tmax
time to reach Cmax
TEAE
treatment-related adverse event
UGT
uridine diphosphate glucuronyl transferase
ULN
upper limit of normal
WBC
white blood cell
WHO
World Health Organization
DEFINITIONS OF TERMS
Comorbid subjects
Subjects who have comorbid condition(s) for severe RSV disease
Comorbid conditions for 
severe RSV disease
Eg, asthma, chronic obstructive pulmonary disease, cardiovascular disease, other 
chronic diseases
Electronic device
A device for patient-reported outcomes and functioning assessments
Otherwise healthy subjects
Subjects who do not have comorbid condition(s) for severe RSV disease
RSV viral load
The number of RSV RNA copies, determined in nasal secretions (nasal swab 
samples). The unit is RSV RNA copies/mL.


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1.
INTRODUCTION
Respiratory syncytial virus (RSV) is considered the most important virus causing acute lower 
respiratory tract infection (LRTI) and is a major cause of hospital admissions and death in young 
children worldwide.18,22 In addition, LRTI results in substantial illness and morbidity in the 
elderly and adults with underlying chronic illnesses, underlying disorders of cellular immunity, 
or suppressed immune systems in hospitalized and community-based patients.4,10,11,12,18,19,27
Prospective surveillance from 1975-1995 in 2,960 subjects 18-60 years of age identified 
211 RSV infections (7%) by culture. The infections were symptomatic in 84% of subjects, 
involved only the upper respiratory tract in 74%, and included lower respiratory tract symptoms 
in 26%. Thirty-eight percent of the patients missed work and they were ill for mean of 9.5 days.13
Despite the large medical and economic burden, treatment options for RSV-associated 
bronchiolitis and pneumonia are limited: prophylactic treatment with passive immunization with 
the humanized monoclonal antibody palivizumab in pediatric patients, treatment with ribavirin, 
and supportive treatment such as oxygenation and mechanical ventilation are available in 
hospitalized patients.9,26 In an outpatient setting, standard of care is limited to symptomatic 
treatment of the flu-like manifestations of the disease. There is an unmet medical need for 
prophylactic (pre- and post-exposure) as well as therapeutic treatment in both children and 
adults.
Recent studies in pediatric and adult populations have demonstrated that RSV viral load and
severity of disease symptoms are closely correlated, and that the window between the onset of 
clinical symptoms (day 1 and day 3 for influenza and RSV, respectively) and peak viral load 
(day 2 and day 6 for influenza and RSV, respectively) is considerably longer for RSV than for 
influenza.1,4,7,8 This increases the likelihood that direct antivirals (small-molecules or biologicals) 
can be viable RSV treatments and achieve high and sustained antiviral responses and improve 
disease outcome. Aspired treatment effects include reduction of viral shedding, the prevention of 
acute LRTIs, reduced need for hospitalization, and in case of hospitalization, shortening of stay 
in the hospital or intensive care unit by decreasing the need for mechanical ventilation, and 
reduced incidence of mortality.
Enveloped viruses like RSV have a complex membrane fusion machinery that includes a fusion 
protein that enables the deposition of the viral nucleic acid genome into the host cells and 
initiates their replication.3,16 JNJ-53718678 is an investigational RSV specific fusion inhibitor 
belonging to the indole chemical class and is under development for the treatment of RSV 
infection. The study drug shows in vitro activity against a panel of viruses belonging to both the 
RSV subfamilies A or B. In addition, antiviral activity of JNJ-53718678 was demonstrated 
during clinical studies in healthy adults inoculated with RSV (study 53718678RSV2001) and in 
pediatric subjects hospitalized due to RSV-infection (study 53718678RSV1005). 
For the most comprehensive nonclinical and clinical information regarding JNJ-53718678, refer 
to the latest version of the Investigator's Brochure (IB) for JNJ-53718678.15
The term "sponsor" used throughout this document refers to the entities listed in the Contact 
Information page(s), which will be provided as a separate document.


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1.1.
Background
Nonclinical Studies
Nonclinical Profile
The in vitro effective concentration for 50% inhibition (EC50) of RSV was found to be 
0.23 ng/mL (460 pM) as measured in a cellular infectious assay. The in vivo EC50 was 75 ng/mL 
(150 nM) or 81 ng/mL (160 nM) when the reduction of RSV titer was analyzed in 
bronchoalveolar fluid or lavaged-lung tissue, respectively, from cotton rats that received a single 
dose of different concentrations of JNJ-53718678, 1 hour before infection. Further efficacy and 
mechanism-of-action studies demonstrated that JNJ-53718678 is a selective and extremely 
potent small-molecule RSV fusion inhibitor, capable of significantly reducing the viral titer. 
Concurrently, a decrease of the virus-induced pro-inflammatory response was observed in 
RSV-infected and JNJ-53718678 treated Balb/C mice.
Once daily oral treatment of RSV-infected neonatal lambs with 1, 5, and 25 mg/kg doses of 
JNJ-53718678 resulted in significant concentration-dependent reductions of the viral titer in both 
bronchoalveolar lavage fluid as well as lavaged-lung tissue as compared to animals that received 
vehicle only. Estimated EC50 for the average plasma concentration at steady-state was 
753 ng/mL and 296 ng/mL for bronchoalveolar lavage fluid and lung, respectively, again 
indicating a potent antiviral activity. In addition, a dose-dependent reduction of the production of 
several 
RSV-induced 
pro-inflammatory 
cytokines 
and 
chemokines 
(ie, 
interferon 
gamma-induced protein 10, monocyte chemotactic protein-1, macrophage inflammatory 
protein-1α, and interferon-1) was observed. Furthermore, RSV-induced gross lung lesion 
formation and concomitantly significant improvement of the general lung condition was 
observed (eg, reduction of bronchiolitis and lung neutrophilia). Together, these results 
demonstrate the efficacy of the study drug to inhibit RSV-induced lung pathology sequelae. No 
adverse signs or reactions in the animals that were dosed up to 25 mg/kg JNJ-53718678 were 
observed.21
In high-throughput screening ion channel voltage clamp assays, JNJ-53718678 did not affect 
cardiac inward sodium membrane current up to 10 μM, but slightly to markedly inhibited cardiac 
inward potassium membrane current (IKr) at concentrations starting at 1 μM. In a Good 
Laboratory Practice (GLP) human-ether-à-go-go-related gene study, the IKr blocking was 
confirmed with a 50% inhibition concentration (IC50) of 1.9 μM. When JNJ-53718678 was given 
intravenously to anesthetized female guinea pigs, no significant cardiovascular effects were 
induced up to the 10-mg/kg dose (cumulative dose: 19.69 mg/kg; median plasma exposure: 
7,580 ng/mL). In a single-dose study in male conscious dogs, no notable effects were found on 
the cardiovascular and respiratory parameters up to an oral JNJ-53718678 dose of 100 mg/kg 
(mean JNJ-53718678 peak plasma exposure: 4,270 ng/mL).
After single JNJ-53718678 doses of 75 and 250 mg/kg and 5-day repeated JNJ-53718678 doses 
of 250 mg/kg once daily in conscious dogs, heart rates were increased at all doses in most dogs 
and blood pressure was decreased at all dose levels in all dogs. Respiratory parameters were not 
affected. Mean peak plasma exposure values of JNJ-53718678 after a single JNJ-53718678 dose 


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of 75 mg/kg were 15,400 ng/mL while they increased to 31,000 ng/mL after 5-day repeated 
dosing of JNJ-53718678 250 mg/kg once daily.
Evaluation of neurofunctional integrity of rats revealed minimally and transiently decreased 
neuromuscular function and minimal effects on gastrointestinal function, at single JNJ-53718678 
doses of 150 and 1,500 mg/kg in rats. There were no effects of the single JNJ-53718678 dose of 
25 mg/kg (maximum observed concentration [Cmax] = 826 ng/mL; area under the RSV viral 
load-time curve from 0 to 7 hours [AUC7h] = 3,380 ng.h/mL).
Pharmacokinetics and Metabolism in Animals
Following single intravenous administration to different preclinical species, JNJ-53718678 was 
cleared with a low to moderate clearance in male mice, dogs, and monkeys (equivalent to 
11%-30% of liver blood flow) and a high clearance in male rats (93% of liver blood flow). The 
volume of distribution at steady-state was moderate in all species (1-3 L/kg), indicative of 
moderate distribution to tissues.
Rapid absorption from the gastrointestinal tract was observed across preclinical species after 
single oral JNJ-53718678 doses formulated in hydroxypropyl-β-cyclodextrin (HP-β-CD). 
Absolute bioavailability of JNJ-53718678 at 10 mg/kg (mice, rats) and 5 mg/kg (dogs, monkeys) 
was around 58% in mice, 42% in rats, 90% in dogs, and 21% in monkeys. JNJ-53718678 plasma 
exposure (Cmax, AUC) increased more than dose-proportionally in male rats and close to 
dose-proportionally in monkeys at low doses below 5-10 mg/kg. Feeding status had minimal to 
no impact on oral bioavailability of solution and suspension formulations at 5 mg/kg in dogs.
JNJ-53718678 was found to be a substrate, but not an inhibitor, for P-glycoprotein (P-gp; efflux 
ratio 9.6) and breast cancer resistance protein in vitro. Based on the observed rapid but passive 
uptake of JNJ-53718678 by suspended human hepatocytes, in vivo clearance of JNJ-53718678 
will not likely be hepatic uptake-limited or sensitive to interactions with hepatic uptake 
inhibitors. In vitro, JNJ-53748678 inhibits organic anion-transporting polypeptide (OATP) 1A2 
(IC50 0.6 µM), OATP1B1 (IC50 3.5 µM), organic anion transporter (OAT) 3 (IC50 4.2 µM), 
organic cation transporter (OCT) 1 (IC50 3.7 µM), OCT2 (IC50 2.1 µM), but not OAT1 up to 
9.6 µM, not OATP1B3 up to 12 µM and not OATP2B1 up to 10 µM. JNJ-53748678 is not a 
substrate for OATP1A2 and OATP2B1 up to 15 µM. For multidrug and toxin extrusion protein 1 
(MATE1) the IC50 was >8.5 µM and for MATE2-K the IC50 was ~8.5 µM.
Plasma protein binding of JNJ-53718678 was high in adult preclinical species (88% to 99%) and 
in adult humans (96%), and in juvenile preclinical species (92-93%). JNJ-53718678 
preferentially binds to alfa-1-acid glycoprotein. Major metabolic pathways for JNJ-53718678 
have been identified in human hepatocytes; these were oxidation, N-dealkylation, cleavage in the 
middle part of the molecule, and glucuronidation of oxidative metabolites. There was also 
evidence of direct N-glucuronidation, which was not observed in hepatocytes of rats and dogs. 
Cytochrome P450 (CYP) A4 is the major CYP enzyme involved in JNJ-53718678 phase 1 
metabolism in human hepatocytes. Uridine diphosphate glucuronyl transferase (UGT) A3 and 
UGT1A4 are involved in direct N-glucuronidation. 


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There was no evidence for the formation of reactive intermediates.
In human hepatocytes, JNJ-53718678 did not show any significant inhibition of CYP1A2-, 
CYP2C8-, CYP2C9-, CYP2C19-, and CYP2D6-mediated metabolism up to the highest 
JNJ-53718678 concentration tested (IC50 values >15 μM), while it was shown to be a moderate 
to strong inhibitor of CYP3A4 (IC50=1-2 μM). It was also shown to be an inducer of CYP3A4 
(≥1.5 μM) and CYP2B6 (≥5 μM), but not of CYP1A2 (up to 10 μM) in human hepatocytes.
After giving repeated JNJ-53718678 doses to rats and dogs, JNJ-53718678 plasma exposure 
decreased dose-dependently in rats, indicating clearance via auto-induction, and increased dose-
dependently in dogs.
Toxicology
Single JNJ-53718678 doses up to 1,500 mg/kg (maximum feasible dose) in rats, up to 150 mg/kg 
in dogs and of 50 mg/kg in minipigs were well tolerated. At the highest dose in rats excessive 
salivation was seen, while in dogs vomiting and excessive salivation were observed at all doses. 
No signs were present in minipigs.
The main findings after giving rats repeated JNJ-53718678 doses for 5 days of 750 mg/kg/day or 
for 1 month of 75 and 500 mg/kg/day were rodent-specific adaptive changes (enzyme induction) 
in liver, thyroid, pituitary gland, and/or adrenal gland sometimes accompanied by changes in 
serum parameters such as cholesterol, gamma-glutamyltransferase (GGT) and protein levels. In 
addition, in the 1-month study, dose-related salivation was noted at all doses 
(25-500 mg/kg/day). Minimal effects considered non-adverse, related to fibrinogen and 
thrombocytes were present from 75 mg/kg/day onwards, and functional coagulation parameters 
(prothrombin time [PT] and activated partial thromboplastin time [aPTT]) were prolonged at 
500 mg/kg/day, without increased propensity for bleeding. All changes except for some 
parameters in females dosed at 500 mg/kg/day reverted to normal. The No Observed Adverse 
Effect Level (NOAEL) was set at 75 mg/kg JNJ-53718678 per day. At this dose, mean Cmax and 
AUC24h values for males were 3,240 ng/mL and 11,600 ng.h/mL and for females were 
9,240 ng/mL and 52,600 ng.h/mL, respectively. Adverse effects at the high dose 
(500 mg/kg/day) were related to coagulation.
JNJ-53718678 doses up to 250 mg/kg/day during 2 weeks given to dogs resulted in dose-related 
vomiting, decreased food intake, and salivation at all doses leading to body weight loss from the 
mid-dose (75 mg/kg/day) onwards, and ultimately emaciation in some animals. Small stomach 
erosions as a consequence of frequent vomiting were noted at the high dose (250 mg/kg/day). At 
ophthalmic examination, miosis was seen in dogs given 250 mg/kg/day. Several dogs dosed at 
250 mg/kg/day showed minor to overt increases in liver enzymes (alanine aminotransferase 
[ALT] and aspartate aminotransferase [AST]), which were accompanied by hepatocellular single 
cell necrosis in 1 dog. Recovery was evident after 1 month, except for food consumption in 
females. The NOAEL was set at 25 mg/kg/day. At the NOAEL the mean Cmax and AUC values 
of JNJ-53718678 for males were 4,270 ng/mL and 32,300 ng.h/mL and for females were 


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3,920 ng/mL and 29,800 ng.h/mL, respectively. Target systems for toxicity are the liver and the 
gastrointestinal system.
A 2-day repeated dose study was conducted in minipigs at doses of 0, 50, 150, and 
300 mg/kg/day. The highest dose was considered above the maximum tolerated dose as animals 
showed continuous body weight loss as a result of decreased food consumption, which was 
likely related to the ulceration/necrosis of the nonglandular stomach. Other findings at this dose 
level were extensive vomiting, marked changes in bilirubin which correlated histologically with 
icterus and cholestasis in the bile ducts and canaliculi in 1 animal. In addition, the animals 
presented increased bilirubin, AST and decreased albumin. Red blood cell (RBC) parameters and 
platelets were decreased while reticulocytes were increased. Changes in white blood cell (WBC)
subsets and increased globulin were indicative of an acute inflammatory response. Plasma 
exposures were high and did not decline within 72 hours after the second dose was given. Cmax
increased after the second dose, indicating accumulation after repeated dosing. At this dose the 
mean Cmax and AUC24h values after the second dose were 28,100 ng/mL and 622,000 ng.h/mL, 
respectively. The animals were sacrificed 1 week after the start of dosing. At the 150 mg/kg/day 
dose, changes in bilirubin were observed and body weight loss in relation with decreased food 
consumption was noted. At this dose, almost all changes were reversible. The 50 mg/kg/day dose 
was well tolerated with some minor non-adverse changes in clinical pathology. Target organs 
after dosing twice up to 300 mg/kg/day were stomach, the intestinal tract, and the hepatobiliary 
system.
Oral administration of JNJ-53718678 in adult minipigs for 2 weeks was well tolerated and 
without mortality up to the highest dose of 25 mg/kg/day. Higher body weight gain values and 
minor hematology and serum chemistry changes were observed, and no target organs were 
identified after repeated dosing. High, plateau-like exposure and increasing exposure upon 
repeated dosing (versus single dosing) was seen from the mid-dose (ie, 10 mg/kg/day) onwards. 
After 2 weeks of repeated dosing at 25 mg/kg/day, the mean Cmax and AUC24h values were 
4,710 ng/mL and 87,200 ng.h/mL, respectively. In minipigs dosed for 28 days at 25 mg/kg/day 
in a GLP study, findings were minimal or adaptive in nature in some animals (increased 
reticulocyte count and hematopoiesis). Other animals dosed at 25 mg/kg/day showed exposures 
overlapping with those observed in animals of the 35/50 mg/kg/day dose group, leading to 
adverse effects (decreased WBC count and RBC mass). Target organ systems in 25 and 
35/50 mg/kg/day dose groups were primarily circulating white and RBCs, leading to 
hemosiderin deposition in the liver and adaptive changes in hematopoietic organs (bone marrow, 
spleen). The effects on white and RBCs in animals dosed at 35/50 mg/kg/day after a 28-day
dosing-free period showed signs of ongoing recovery, which was not the case for the liver 
pigment deposition in females. The No Observed Effect Level (NOEL) was 10 mg/kg/day with 
mean Cmax and AUC values for male minipigs of 1,510 ng/mL and 2,120 ng.h/mL, and for 
female minipigs of 1,750 ng/mL and 3,150 ng.h/mL, respectively.
In the first pilot juvenile study in rats, in which pups 1 day of age (post-natal day [PND] 1) or 
8 days of age (PND8) were dosed orally with JNJ-53718678 up to 200 mg/kg/day for a 
maximum of 3 weeks, no test article-related mortality or clinical signs were noted. A transient 


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effect on body weight gain was observed after the first dose on PND1 only, without showing a 
dose relationship. In a second pilot juvenile study in rats, in which pups aged PND4 were dosed 
orally with JNJ-53718678 at 300 and 400 mg/kg/day for 7 days, liquid feces, urogenital 
erythema, and decreased mean body weight gains were observed.
In the GLP juvenile study in rats, doses of 50 up to 400 mg/kg/day were given for 4 weeks from 
PND4 onwards. Excessive salivation (all doses) and a soft distended abdomen were seen, as well 
as periodically slightly lower body weight gain associated with lowered food consumption from 
150 mg/kg/day onwards. Some minor changes were observed in serum parameters (triglycerides 
[all doses], cholesterol [400 mg/kg/day], and albumin [400 mg/kg/day]). Test item-related 
histologic findings comprised of centrilobular hepatocellular hypertrophy from 150 mg/kg/day 
onwards with hepatocellular cytoplasmic vacuolation and thyroid follicular hypertrophy at 
400 mg/kg/day. A higher incidence and severity of papillary mineralization was seen in the 
kidneys in all JNJ-53718678 treated groups. None of the findings described above were 
considered adverse and all findings were (almost) fully recovered (except triglyceride levels in 
high dose males) by the end of the recovery period. Therefore the NOAEL was set at 
400 mg/kg/day. Corresponding Cmax and AUC24h values on Day 0 (PND4) were 28,800 ng/mL 
and 259,000 ng.h/mL for males and 23,700 ng/mL and 330,000 ng.h/mL for females, 
respectively.
Corresponding Cmax and AUC24h values on Day 24 (PND28) were 26,800 ng/mL and 
170,000 ng.h/mL for males and 31,300 ng/mL and 171,000 ng.h/mL for females, respectively.
In the pilot juvenile study in dogs, in which puppies aged PND1 were dosed orally with 
JNJ-53718678 at 10 up to 75 mg/kg/day during 4 weeks, JNJ-53718678 was well tolerated 
without adverse effects. No organ weight changes, gross observations or histological changes 
were seen.
In the pilot juvenile study in minipigs, piglets were dosed orally from PND1 onwards with 
JNJ-53718678 at 10 up to 75 mg/kg/day for up to 4 weeks. The 75-mg/kg/day dose was 
administered to 1 animal and considered to be above the maximum tolerated dose, as the animal 
was sacrificed, after showing a poor clinical condition after vomiting. A relationship with the test 
article cannot be entirely excluded. Dosing up to 50 mg/kg/day resulted in slightly to overtly 
lower body weight gains (all doses), and low RBC parameters and increased reticulocyte levels 
with high total bilirubin concentrations (from 25 mg/kg/day onwards) as main findings. In 
addition, at 50 mg/kg/day slightly increased fibrinogen levels were noted. At 75 mg/kg/day, 
higher total (direct and indirect) bilirubin levels and a higher urea concentration were measured. 
An increase in extramedullary hematopoiesis in spleen and liver, as well as starry-sky 
appearance of the splenic red pulp and bone marrow (from 10 mg/kg/day onwards), lower bone 
marrow cellularity (at 50 mg/kg/day) and thymic atrophy (from 25 mg/kg/day onwards) were 
observed at histopathology.
In the GLP juvenile study in minipigs, doses of 5 up to 25 mg/kg/day were administered from 
PND1 onwards for 5 weeks. A dose of 25 mg/kg/day was not well tolerated, and resulted in 
gastric ulceration and inflammation, low RBC parameters with reticulocyte response and 


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increased (extramedullary) hematopoiesis, increased bilirubin levels, decreased fibrinogen levels, 
and body weight loss upon weaning. These findings were (mostly) reversible at the end of the 
4-week recovery period. Minor to slight, non-adverse histopathologic findings were noted at 
10 mg/kg/day. The NOAEL in this study was set at 10 mg/kg/day. Corresponding Cmax and 
AUC24h values (PND35) were 4,870 ng/mL and 77,300 ng.h/mL for males and 4,180 ng/mL and 
73,300 ng.h/mL for females, respectively.
JNJ-53718678 did not show any genotoxic potential in a bacterial reverse mutation test, and in 
in vitro and in vivo micronucleus tests. Furthermore, it is not irritating to the eye, is not skin 
sensitizing and is not phototoxic in vitro. JNJ-53718678 was classified as moderately cytotoxic 
in a high content screen assay.
The use of HP-β-CD as excipient in the formulation of JNJ-53718678 in clinical studies in the 
adult and pediatric populations is supported by a range of (juvenile) toxicity studies. A dedicated 
GLP juvenile toxicity study in the rat revealed no new target organs or toxicities vs known 
toxicities from studies in adult animals. HP-β-CD is known to increase soft feces due to osmotic 
water retention in the large intestine. Other findings (eg, swelling and microvacuolation of renal 
cortical tubular cells, urothelium cells, increases in several urinary parameters) seen in (juvenile) 
animals were related to the renal excretion of HP-β-CD and were regarded as non-adverse, 
transient, adaptive responses.
The results of the safety pharmacology studies, genetic toxicology studies, and general toxicity 
studies in adult and juvenile rats, dogs, and minipigs support the administration of JNJ-53718678 
to adult and pediatric human subjects. In healthy adult volunteers, JNJ-53718678 was well 
tolerated up to the highest dose tested, ie, 500 mg given once daily for 8 days, corresponding to 
mean exposure parameters of 2,660 ng/mL for Cmax and 31,200 ng.h/mL for AUC on Day 8. In 
pediatric patients, exposure is not anticipated to exceed the exposure achieved in healthy 
volunteers at 500 mg once daily. At this dose, animal/human exposure safety ratios based on 
NOAELs in the GLP studies in juvenile rats and minipigs and data in healthy adult volunteers, 
were 5-11 for juvenile rats and 2 for juvenile minipigs.
Clinical Studies
Pharmacokinetics and Product Metabolism
Single Dose
In the single-dose escalation part of study 53718678RSV1001, Cmax of JNJ-53718678 increased 
proportionally with dose after administration of JNJ-53718678 doses between 25 mg and 
1,000 mg under fasted conditions. Mean AUC from time 0 to infinity (AUC∞) of JNJ-53718678 
increased slightly more than dose-proportionally with increasing JNJ-53718678 dose from 25 mg 
to 1,000 mg. Median time to reach Cmax (tmax) was 1.00 h, except for the 1,000-mg dose group, in 
which it was 2.50 hours. Mean terminal elimination half-life ranged from 9.3 to 10.3 hours for 
the 75-mg dose group to the 1,000-mg dose group and was somewhat lower for the 25-mg dose 
group with a value of 6.6 hours.


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Based upon data from study 53718678RSV1004 in healthy Japanese adult men and study 
53718678RSV1001, Cmax and AUC∞for JNJ-53718678 are similar between Caucasian and 
Japanese subjects after single dose administration.
Multiple Dose
In the multiple-dose escalation (MDE) part of study 53718678RSV1001 under fed conditions 
predose plasma concentrations (Ctrough) reached steady-state after 1 day of treatment with 
JNJ-53718678. On Day 8, JNJ-53718678 Cmax and AUC24h increased dose-proportionally with 
increasing JNJ-53718678 dose from 250 mg every 24 hours (q24h) to 500 mg q24h. Fluctuation 
was lower for the 250 mg twice daily (bid) regimen compared with the 500 mg q24h regimen. 
The total amount of JNJ-53718678 excreted in urine over the dosing interval at steady-state was 
low, 3.74%, 1.89% and 1.76% of the administered dose for, respectively, 250 mg q24h, 500 mg 
q24h and 250 mg twice daily. Renal clearance was very low, and similar between dose regimens.
In study 53718678RSV2001, the pharmacokinetic profile of JNJ-53718678 at multiple doses of 
75 mg, 200 mg, and 500 mg once daily for 7 days was evaluated in healthy adult subjects 
inoculated with RSV-A Memphis 37b virus. The pharmacokinetic results from this study were 
consistent with those from corresponding regimens in study 53718678RSV1001, indicating that 
viral infection did not affect the pharmacokinetics of JNJ-53718678.
Food Interaction
Mean Cmax of JNJ-53718678 was approximately 35% lower and median tmax increased from 
1 hour to 3.5 hours when JNJ-53718678 was administered under fed conditions compared with 
fasted conditions. Mean AUC∞of JNJ-53718678 was 7% lower when JNJ-53718678 was 
administered under fed conditions compared with fasted conditions. Therefore, JNJ-53718678 
can be taken with or without food.
Drug-Drug Interaction
In clinical study 53718678RSV1002, coadministration of JNJ-53718678 and a drug cocktail 
consisting of CYP enzyme probe drugs (for CYP3A4, CYP1A2, and CYP2C9) and a 
non-selective P-gp substrate (fexofenadine) suggested that, after single- and multiple-dose 
administration, JNJ-53718678 is a weak inhibitor and a weak inducer of CYP3A4. 
JNJ-53718678 had no clinically significant effect on CYP2C9 and CYP1A2. Single and multiple 
doses of JNJ-53718678 reduced the plasma exposure of fexofenadine. The observed decrease in 
exposure of fexofenadine after coadministration of a single dose of JNJ 53718678 is likely due to 
the inhibition of OATP1A2, an uptake transporter located in the gut; further reduction of the 
fexofenadine exposure after repeated dosing of JNJ-53718678 is likely due to induction of P-gp.
In clinical study 53718678RSV1006, JNJ-53718678 was coadministered with itraconazole 
(a strong CYP3A4 and P-gp inhibitor) and with rifampicin (an inducer of CYP3A4, UGT, and 
P-gp, and an inhibitor of OATP). The results confirmed that CYP3A4 significantly contributes to 
the elimination of JNJ-53718678, as an approximately 3-fold increase in the total exposure of 


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JNJ-53718678 upon coadministration with itraconazole 200 mg once daily was observed. After 
coadministration of JNJ-53718678 with a single dose of rifampicin, no significant change in the 
total exposure of JNJ-53718678 was observed, suggesting the OATP transporter is not involved 
in the disposition of JNJ-53718678. However, repeated administration of rifampicin 600 mg 
once daily decreased the exposure of JNJ-53718678, primarily due to induction of CYP3A4.
JNJ-53718678 Cmax, AUClast, and AUC∞decreased to 19%, 8%, and 8%, respectively, of the 
reference value (administration of JNJ-53718678 alone).
Efficacy
In study 53718678RSV2001 in healthy adult subjects inoculated with RSV-A Memphis 37b 
virus, mean and median RSV viral load AUC from baseline until discharge were lower for all 
JNJ-53718678 dosing groups (75 mg once daily, 200 mg once daily, or 500 mg once daily 
JNJ-53718678 for 7 days) as compared to the placebo group with a large variability observed in 
each of the JNJ-53718678 dosing groups as well as in the placebo group. No clear dose response 
relationship could be observed. This was paralleled with lower clinical symptom scores and 
mucus production for the JNJ-53718678 dosing groups as compared to the placebo group. 
Hence, clinical proof-of-concept for JNJ-53718678 has been established.
In study 53718678RSV1005 in pediatric subjects hospitalized due to RSV infection, a clear trend 
towards an (early) antiviral effect of JNJ-53718678 is observed. An effect on viral load change 
from baseline on Days 2 and 3, 1 to 2 logs difference compared to placebo, was observed as well 
as an effect on viral load AUC on Days 3 and 7 (20 to 25% reduction compared to placebo). The 
observed trends are similar across JNJ-53718678 dose groups (1 mg/kg, 1.5 mg/kg, 2 mg/kg, or 
6 mg/kg once daily).
Safety and Tolerability
Adult Population
During
clinical
studies 
53718678RSV1001, 
53718678RSV1002, 
53718678RSV1004, 
53718678RSV1006, and 53718678RSV2001, a total of 184 adult subjects were enrolled of 
whom 150 received at least 1 dose of JNJ-53718678 as single doses up to 1,000 mg or multiple 
doses up to a total daily dose of 500 mg (as 500 mg once daily or 250 mg twice daily) for up to 
13 days. Of those, 100 were healthy adult subjects and 50 were healthy adult subjects who were 
inoculated with RSV-A Memphis 37b virus.
During these studies, no deaths or other serious adverse events (SAEs) were reported. Four 
subjects discontinued study treatment due to an adverse event (AE):

1 subject from study 53718678RSV1001 discontinued study treatment due to an AE of 
grade 2 gastroenteritis, which started 52 days after having received a single dose of 75 mg 
JNJ-53718678 and was considered by the investigator to be doubtfully related to study 
treatment;


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
1 subject from study 53718678RSV2001 who received placebo discontinued study treatment 
due to an AE grade 2 urticaria, which was considered by the investigator to be possibly 
related to RSV-infection or study treatment;

1 subject from study 53718678RSV2001 from the 75 mg JNJ-53718678 group was reported 
with a grade 1 AE of electrocardiogram (ECG) QRS complex prolonged (verbatim: 
Prolonged QRS) on the first day of dosing. The ECG findings included a QRS complex 
width at baseline of 117 ms and prolongation to 120 ms at time of the start of the AE (QRS 
width normal range as per protocol: >50 ms to <120 ms). This AE was considered by the 
investigator to be possibly related to RSV infection or study treatment. Duration of the AE 
of ECG QRS complex prolonged was reported as 3 days, after which a grade 2 AE of ECG 
change (verbatim: change in morphology [from incomplete right bundle branch block]) was 
reported. This grade 2 AE led to withdrawal of the study medication and was considered by 
the investigator to be doubtfully related to RSV infection and possibly related to study 
treatment. At the last follow-up visit, 21 days after the onset of the grade 2 AE, this AE was 
considered resolved. The ECG reported an abnormally high QRS width with values 
fluctuating between 120 ms at start of the first AE and 138 ms at the end of the second AE;

1 subject from study 53718678RSV2001 from the 200-mg JNJ-53718678 group was 
reported with a grade 1 AE of ECG change (verbatim: nonspecific ECG change) on the third 
day of dosing, for which the study medication was withdrawn. The ECG was considered 
clinically significantly abnormal. This AE was considered by the investigator to be possibly 
related to RSV infection or study treatment. The AE was considered resolved 23 days after 
its onset.
For the purpose of reviewing the available clinical safety data, tables were created combining the
results on AEs, laboratory abnormalities, abnormalities in vital sign parameters, and ECG
abnormalities from studies 53718678RSV1001, 53718678RSV1002, 53718678RSV1004, and 
53718678RSV2001. It should be noted that in study 53718678RSV2001 the Division of 
Microbiology and Infectious Diseases (DMID) toxicity grading scale was used while the World 
Health Organization (WHO) toxicity grade scale was applied in the other studies. However, as 
the differences between these 2 grading scales are minimal, this did not affect the conclusions 
from this safety data review.
Furthermore, given that there was an unequal allocation of subjects to JNJ-53718678 and 
placebo in most studies and that in study 53718678RSV1002 no placebo group was included, the 
overall number of placebo subjects is low. Hence, this limits the ability to draw firm conclusions 
on the comparisons made in this section. In addition, most individual AEs and abnormalities 
were observed at low frequency, which further limits the comparison between JNJ-53718678 and 
placebo.
During clinical studies 53718678RSV1001, 53718678RSV1002, 53718678RSV1004, and 
53718678RSV2001, among subjects who received at least 1 dose of JNJ-53718678, 70% 
experienced an AE as compared to 46.7% of all subjects who received placebo. All but 1 of the 
treatment-emergent AEs (TEAEs) reported during these studies were either grade 1 or grade 2 in 
severity; 1 subject who received placebo was reported with a grade 3 headache in study 
53718678RSV1001. Adverse events observed more frequently (difference in incidence of ≥5%) 
in subjects who had received at least 1 dose of JNJ-53718678 compared to subjects who received 


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placebo included diarrhea (20.8% vs 11.1%), dysgeusia (10.8% vs 0.0%), epistaxis (7.5% vs 
0.0%), fatigue (6.7% vs 0.0%), abdominal discomfort (5.0% vs 0.0%), and hot flush (5.0% vs 
0.0%). 
In study 53718678RSV1006, 35.7% and 31.3% of the subjects from Panel 1 and Panel 2, 
respectively, experienced at least one AE. In this study, all reported AEs were grade 1, and 
except for abdominal discomfort (reported in 2 subjects [14.3%] in Panel 1), all AEs were 
reported in at most 1 subject.
In study 53718678RSV1001, dysgeusia was frequently reported in subjects receiving 
JNJ-53718678 and in none of the subjects of the placebo group. Dysgeusia was a frequently 
reported AE in subjects receiving JNJ-53718678 due to the bitter taste of the oral JNJ-53718678 
formulation. This observation led to the initiation of study 53718678RSV1003 to select an 
optimized taste of the formulation for future studies. 
In study 53718678RSV1002, diarrhea was reported by the vast majority of subjects. In addition, 
for 2 subjects the AE of “frequent bowel movements” was reported. Of note, no 
HP-β-CD-containing placebo solution was administered in this study. The incidence of the AE of 
diarrhea was similar in subjects receiving JNJ-53718678 and those receiving placebo in study 
53718678RSV2001. The observed AEs of diarrhea in both these studies may be explained by the 
presence of HP-β-CD as an excipient in the JNJ-53718678 and placebo oral formulation, which 
has been correlated with increased incidences of diarrhea as the main AE. Furthermore, the AE 
of diarrhea was not reported in subjects receiving JNJ-53718678 in studies 53718678RSV1004 
and 53718678RSV1001, where HP-β-CD was used as an excipient in the JNJ-53718678 and 
placebo oral formulations, while there was 1 subject reported with the AE of “frequent bowel 
movements”
in study 53718678RSV1001. In study 53718678RSV1006 (no placebo 
administered), no cases of diarrhea or “frequent bowel movements” were reported. Hence, the 
observed imbalance in overall incidence of the AE of diarrhea is most likely the result of bias 
due to the absence of a placebo group in study 53718678RSV1002. Other gastrointestinal tract-
related AEs were rare and generally more frequently reported in subjects receiving 
JNJ-53718678. However, due to their low incidence, no valid comparison could be made with 
subjects receiving placebo. 
Epistaxis as a TEAE was only reported in study 53718678RSV2001, all events were grade 1 in 
severity, all were considered by the investigator to be not related to the study drug but at least 
possibly related to RSV, and were reported as recovered prior to the end of the study. The related 
verbatims included blood stained tissue from nasal mucosa, blood stained nasal wash, blood 
stained tissue from nasal bleeding, nasal bleeding right/left nostril, and blood spotting nasal 
wash. Of the 9 subjects who were reported with treatment-emergent epistaxis, 4 were also 
reported with this AE during the post-challenge phase, 2 during both the pre- and the 
post-challenge phase, 2 during the treatment phase only, and 1 during both the treatment and the 
follow-up phase. No association was observed between any of the events and changes in 
coagulation parameters. While epistaxis as TEAE was not reported in the subjects who received 
placebo, the observed incidence is consistent with the incidences observed in other RSV 
challenge studies.5,6


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The AE of hot flush was only reported in the MDE part of study 53718678RSV1001 and no 
dose-related incidence was observed.
In general, none of the reported AEs occurred consistently across different studies and most 
occurred at a low incidence and low severity. Observed differences in incidence between 
subjects receiving JNJ-53718678 and those from the placebo group were small for most AEs, 
considering the limitations of the comparison in view of the difference in sample size of the 
JNJ-53718678 group and the placebo group. Based upon these AE data, no safety signal was 
identified for JNJ-53718678.
During clinical studies 53718678RSV1001, 53718678RSV1002, 53718678RSV1004, and 
53718678RSV2001, the incidences of graded and non-graded laboratory abnormalities were 
generally low in these studies. All graded laboratory abnormalities were either grade 1 or 
grade 2. Graded and non-graded laboratory abnormalities observed more frequently in subjects 
who had received at least 1 dose of JNJ-53718678 compared to subjects who received only 
placebo (difference in incidence of ≥5%) included prothrombin activity above normal (non-
graded; 72.2% vs 39.1%), triacylglycerol lipase above normal (non-graded; 19.4% vs 13.0%), 
increased cholesterol (graded: 15.0% vs 8.9%), and eosinophil/leukocyte ratio below normal 
(non-graded; 7.5% vs 2.2%). Of note, the incidences of the graded laboratory abnormality of 
increased PT and aPTT were similar between subjects receiving JNJ-53718678 and those 
receiving placebo (15.8% vs 17.8% and 8.3% vs 11.1%, respectively). Changes in liver enzymes 
were observed in few subjects receiving JNJ-53718678 and in subjects receiving placebo, with 
similar incidences. Most of the observed laboratory abnormalities did not demonstrate a distinct 
difference in incidence between subjects receiving JNJ-53718678 and those receiving placebo. 
In study 53718678RSV1006, results regarding graded and non-graded laboratory abnormalities 
were generally consistent with those of other studies.
None of the observed (non-)graded laboratory abnormalities was indicative of a safety signal for 
JNJ-53718678.
Changes in heart rate, blood pressure, or respiratory rate were observed in some subjects and 
were considered generally clinically insignificant during clinical studies 53718678RSV1001, 
53718678RSV1002, 53718678RSV1004, and 53718678RSV2001. These were either grade 1 or 
grade 2 in severity, except for 1 subject from study 53718678RSV1001 who received 1,000 mg 
JNJ-53718678 and in whom a grade 3 increase in respiratory rate was reported. Considering all 
of the safety data from clinical studies, a consistently greater incidence of any of the observed 
abnormalities in vital signs parameters was not apparent in subjects receiving JNJ-53718678 
compared to subjects receiving placebo. 
In study 53718678RSV1006, results on vital signs abnormalities were generally consistent with 
those of other studies.
During clinical studies 53718678RSV1001, 53718678RSV1002, 53718678RSV1004, and 
53718678RSV2001, no prolongations of the QT-interval corrected for heart rate according to 


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Fridericia (QTcF) were reported. Changes in ECG parameters were rare and considered
clinically insignificant. Four ECG abnormalities were reported as AE in 3 subjects (2 subjects 
receiving JNJ-53718678, 1 subject receiving placebo), all during study 53718678RSV2001. 
In study 53718678RSV1006, ECG abnormalities were scarce and results were generally 
consistent with those from other studies.
None of the observed abnormalities in vital signs parameters or ECG abnormalities suggested a 
safety signal for JNJ-53718678.
No clinically relevant physical examination findings were observed during these clinical studies.
In general, no relation was noted between the incidence of AEs, laboratory abnormalities, 
abnormalities in vital signs parameters, ECG abnormalities, or physical examination findings and 
the dose level and/or the dose regimen of JNJ-53718678.
In conclusion, during these clinical studies in healthy adults or adult subjects inoculated with 
RSV, JNJ-53718678 at single doses up to 1,000 mg and at multiple doses up to 500 mg once 
daily and 250 mg twice daily, were generally safe and well tolerated. These studies did not 
identify any safety signal for JNJ-53718678.
Pediatric Population
During the ongoing study 53718678RSV1005, 44 pediatric subjects hospitalized due to RSV 
infection were enrolled up to the cut-off date of 6 June 2017, of whom 37 subjects received 
JNJ-53718678 and 7 received placebo.
Interim results from study 53718678RSV1005 show that treatment with JNJ-53718678 is 
generally safe and well tolerated and no safety signals arose in pediatric subjects compared to the 
previously established safety profile in adults.
No grade 4 AEs or AEs leading to discontinuation were reported. Two grade 3 (severe) AEs of 
bronchiolitis (1 each in the JNJ-53718678 and placebo group, both serious) were reported. Four 
SAEs were reported, 2 in the JNJ-53718678 treatment group: rhinitis and bronchiolitis and 2 in 
the placebo group: pneumonia and bronchiolitis. These were considered not related to the study 
drug by investigator. Adverse events ≥ grade 2 and considered at least possibly related by the 
investigator were grade 2 (moderate) anemia (n = 1) and grade 2 leukocytosis (n = 1), both in the 
JNJ-53718678 treatment group.
Treatment-emergent laboratory abnormalities were infrequently reported and of low severity 
(maximal grade 2) but reported at somewhat higher incidences in the JNJ-53718678 treatment 
group. 
No relevant differences were observed for vital signs abnormalities between JNJ-53718678 and 
placebo and no AEs related to vital signs abnormalities were reported.


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No dose relationship was observed for the AEs, laboratory abnormalities or vital signs 
abnormalities.
1.2.
Benefit-risk Evaluations
1.2.1.
Known Benefits
JNJ-53718678 at daily doses of 75, 200, and 500 mg given for 7 days has shown an antiviral 
effect and reduced the signs and symptoms of RSV infection in healthy adults in an RSV human 
challenge model. In addition, JNJ-53718678 established proof of concept (antiviral effect) in the 
pediatric population based on interim data from study 53718678RSV1005 (Section 1.1).
However, the clinical benefit of this compound remains to be established.
1.2.2.
Potential Benefits
Subjects participating in this study might have a benefit regarding the clinical course of their 
RSV infection. Results from the proposed study may be useful in developing a new antiviral 
therapy for RSV infection.
1.2.3.
Known Risks
As a formal adverse drug reaction analysis has not yet been conducted for JNJ-53718678, known 
risks associated with JNJ-53718678 have not been identified.
1.2.4.
Potential Risks
All therapies have the potential to cause adverse experiences.
During 
studies 
53718678RSV1001, 
53718678RSV1002, 
53718678RSV1004, 
53718678RSV1006, and 53718678RSV2001, a total of 184 adult subjects were enrolled of 
whom 150 received at least 1 dose of JNJ-53718678 as single doses up to 1,000 mg or multiple 
doses up to a total daily dose of 500 mg (as 500 mg once daily or 250 mg bid) for up to 13 days. 
Of those, 100 were healthy adult subjects and 50 were healthy adult subjects who were 
inoculated with RSV-A Memphis 37b virus. In study 53718678RSV1003, 12 subjects were 
enrolled but they were only to taste and not to swallow the oral solutions of JNJ-53718678.
During the ongoing study 53718678RSV1005, 44 pediatric subjects hospitalized due to RSV 
infection were enrolled up to the cut-off date of 6 June 2017, of whom 37 subjects received 
JNJ-53718678 and 7 received placebo.
Please refer to Section 1.1 for details on the reported AEs and laboratory/ECG abnormalities in
the studies conducted to date.
Based upon the limited clinical data available and considering the early stage of development of 
JNJ-53718678, no AEs or clinically significant (non-)graded laboratory abnormalities, 
abnormalities in vital signs parameters, ECG abnormalities, or physical examination findings 
indicative of a safety concern have been identified.


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Based upon the limited available clinical data, no risk related to the hepatobiliary system was 
identified. However, given the hepatobiliary-related nonclinical findings and because the amount 
of clinical data is limited, the sponsor considers hepatobiliary effects to be a safety topic of 
special interest and hepatobiliary function will be monitored by routine hepatobiliary function 
tests.
Based upon the available clinical data, no risk related to the gastrointestinal tract was identified. 
However, given the nonclinical findings and because the amount of clinical data is limited, any 
clinical signs and symptoms related to the gastrointestinal tract will be monitored during clinical 
studies and appropriate clinical management will be installed.
In adult clinical studies with JNJ-53718678, renal-related laboratory abnormalities and AEs were 
only sporadically reported without a distinct difference in incidence between subjects receiving 
JNJ-53718678 and those receiving placebo. As the renal excretion of JNJ-53718678 is very 
limited, the potential for renal adverse effects is considered to be minimal. Based upon these 
data, no renal-related risks are anticipated. However, renal function will be monitored by renal 
function tests.
The evaluation of JNJ-53718678 antiviral activity requires nasal swabbing. However, this is a 
minimally invasive assessment that at most results in some short-term discomfort for the subject 
and is usually well tolerated, though occasionally nose bleeding can occur. The risks associated 
with blood sampling for safety or pharmacokinetic purposes are limited and the volume of blood 
needed is well below the acceptable limits for adults. 
Study treatment will be provided in addition to, not in replacement of, standard-of-care 
supportive and symptomatic therapy.
1.2.5.
Overall Benefits/Risks
Currently the only available treatment for RSV is supportive and symptomatic care. Based on the 
available data and proposed safety measures, the overall risk/benefit assessment for this study is 
acceptable for the following reasons:

Proof of concept was established in adult healthy volunteers challenged with a laboratory 
strain of RSV (study 53718678RSV2001) as well as in naturally RSV infected pediatric 
subjects (study 53718678RSV1005 [interim data]) (Section 1.1);

The completed studies to date identified no safety concerns and most observed AEs and 
laboratory abnormalities were mild to moderate in severity and considered not related to 
JNJ-53718678 by the investigator (Section 1.1);

Available interim data from the ongoing 53718678RSV1005 study in naturally 
RSV-infected pediatric subjects >1 month to ≤24 months of age did not indicate safety 
concerns (Section 1.1);

Several safety measures have been proposed to minimize potential risk to subjects, 
including:


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
Only subjects who meet all of the inclusion criteria and none of the exclusion criteria 
(as specified in the protocol) will be allowed to participate in this study. The selection 
criteria include adequate provisions to minimize the risk and protect the well-being of 
subjects in the study;

Safety data on the highest dose selected for the current study did not identify any safety 
concern;

Utilization of discontinuation and stopping criteria (see Section 10.2);

Safety surveillance in this study will monitor standard safety parameters associated with 
investigational drug development and safety topics of special interest of JNJ-53718678;

The establishment of a Data Review Committee (DRC) to monitor data on a regular 
basis to ensure continuing safety of the subjects enrolled in this study.
1.3.
Overall Rationale for the Study
This study will be performed to explore the antiviral activity, clinical outcomes, safety, 
tolerability, and pharmacokinetics of JNJ-53718678 in adult subjects infected with RSV. The 
results of this study will be used for selection of the dose and endpoints in subsequent studies.
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1.
Objectives and Endpoints
2.1.1.
Objectives
Primary Objective
The primary objective of the study is to explore the antiviral effect of JNJ-53718678 at 2 dose 
levels (80 mg and 500 mg) once daily for 7 days in adults with RSV infection, as measured by 
RSV viral load in nasal secretions by quantitative reverse transcription polymerase chain reaction 
(qRT-PCR) assay.
Secondary Objectives
The secondary objectives are to explore in adults with RSV infection, after repeated oral dosing 
with JNJ-53718678:

The safety and tolerability of JNJ-53718678;

The impact of JNJ-53718678 on the clinical course of RSV infection;

The pharmacokinetics of JNJ-53718678.
Exploratory Objectives
The exploratory objectives are to explore in adults with RSV infection after repeated oral dosing 
with JNJ-53718678:

The relationship between antiviral activity and clinical course;


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
The relationship between pharmacokinetics and pharmacodynamics (selected antiviral 
activity parameters, clinical outcomes, and safety parameters);

Potential differences in antiviral activity and clinical course
based on baseline 
characteristics, including but not limited to:

otherwise healthy and comorbid subjects;

subjects with symptom onset ≤3 days before randomization and subjects with symptom 
onset >3 days before randomization.

The occurrence of complications associated with RSV per investigator assessment after 
initiation of treatment;

Medical resource utilization (MRU), including hospitalization, for clinical management of 
subjects during treatment and posttreatment follow-up;

The impact of the baseline RSV viral subtype and genotype on the antiviral activity and 
clinical course;

The emergence of mutations in the viral genome potentially associated with resistance to 
JNJ-53718678;

The RSV infectious virus titers as assessed by quantitative culture of RSV (plaque assay) on 
selected nasal swab samples (optional objective, pending feasibility of performing such an
assay);

Impact of RSV and its treatment on health-related quality of life (HRQOL).
2.1.2.
Endpoints
Primary Endpoint
To explore the antiviral effect of JNJ-53718678 on RSV, as measured by qRT-PCR assay in 
mid-turbinate nasal swabs, the following virologic parameters will be assessed:

AUC from immediately prior to first dose of study drug (baseline) through Day 3, Day 5, 
Day 8, and Day 14;

RSV viral load and change from baseline over time;

Time to undetectable RSV viral load;

Proportion of subjects with undetectable RSV viral load at each time point throughout the 
study.
Secondary Endpoints
The secondary endpoints are:

Safety and tolerability, as assessed by AEs, clinical laboratory testing, ECGs, vital signs, 
physical examination, throughout the study;

Clinical course-related endpoints:


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
Duration and severity of signs and symptoms of RSV infection assessed through an 
instrument for patient-reported symptoms (either the Respiratory Infection-Patient
Reported Outcomes [RI-PRO] questionnaire or the Respiratory Infection Intensity and 
Impact Questionnaire [RiiQ] questionnaire) and additional questions about health and 
functioning;

Time to resolution of selected RSV symptoms as reported by the subject (through either 
the RI-PRO or the RiiQ);

Respiratory rate, heart rate, body temperature, and peripheral capillary oxygen 
saturation (SpO2) as measured by the investigator;

Pharmacokinetic 
parameters 
of 
JNJ-53718678, 
as 
determined 
by 
population 
pharmacokinetics (popPK) modelling.
Exploratory Endpoints
Exploratory endpoints include, but are not limited to:

Antiviral activity and clinical course by stratification factor (time of symptom onset 
[≤3 days vs >3 days before randomization], severity of key RSV symptoms at screening), 
presence of comorbidities, baseline RSV viral subtype and genotype;

The occurrence of complications with onset after treatment initiation that are associated with 
RSV per investigator assessment:

Bacterial superinfections (eg, pneumonia, sinusitis, bronchitis, bacteremia of presumed 
respiratory origin per investigator assessment);

Exacerbations of underlying pulmonary disease (eg, asthma, chronic obstructive 
pulmonary disease [COPD]);

Exacerbations of underlying cardiovascular conditions. 

The need for antibiotics related to complications associated with RSV per investigator 
assessment;

Sequence changes (post baseline) in the RSV F-gene, and other regions of the RSV genome 
(at the request of the protocol virologist), as compared to baseline;

Medical resource utilization;

Association between clinical course of RSV and self-rated HRQOL.
Refer to Section 9 for evaluations related to endpoints.
2.2.
Hypothesis
As this is an exploratory, hypothesis-generating study, no formal statistical hypothesis testing 
will be performed.


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3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a Phase 2a, randomized, double-blind, placebo-controlled study to explore the antiviral 
activity, clinical outcomes, safety, tolerability, and pharmacokinetics of JNJ-53718678 at 2 dose 
levels (80 mg and 500 mg) once daily for 7 days in adult subjects with respiratory illness due to 
RSV infection. Subjects may be otherwise healthy or comorbid and should not be in need of 
hospitalization.
A population of 75 subjects is targeted. However, given the recruitment challenges associated 
with the seasonality of RSV, a minimum of 63 subjects may be considered sufficient to complete 
the study.
The study will include a Screening Period (Day -1 to Day 1), a Treatment Period (Day 1 to 
Day 8), and a Follow-up Period (Day 9 to Day 28[±3]). The total study duration for each subject 
will be 29 days (screening included).
Study participants will be identified when they present for medical care with symptoms 
supporting a diagnosis of RSV infection (eg, fever, cough, nasal congestion, runny nose, sore 
throat, myalgia, lethargy, shortness of breath, or wheezing). Screening should be completed as 
soon as possible; treatment initiation should start as soon as possible, but no later than 4 hours 
after randomization, which should occur within a maximum of 5 days after RSV symptom onset.
During screening, mid-turbinate nasal swabs will be collected for local diagnosis of RSV 
infection (using a rapid polymerase chain reaction (PCR)-based or rapid-antigen-detection test), 
and for additional post-hoc analysis at a central laboratory to confirm RSV infection (and 
subtype), to determine the RSV viral load and the presence of other viral or bacterial pathogens.
After screening, eligible subjects will be randomized on Day 1 (1:1:1) to receive 1 of 
3 treatments:

Treatment A: 500 mg JNJ-53718678 once daily for 7 days (n = 25 [target]);

Treatment B: 80 mg JNJ-53718678 once daily for 7 days (n = 25 [target]);

Treatment C: placebo once daily for 7 days (n = 25 [target]).
In order to maintain study blind, all subjects will receive once daily the same total volume of 
study drug solution divided over 2 separate but sequential intakes at the same time of day (see 
Section 6 for more details).
Randomization will be stratified by time of symptom onset (≤3 days vs >3 days before 
randomization). Subjects with symptom onset >3 days before randomization may account for 
maximum of 50% of all enrolled subjects.
Subjects will be required to have a study visit at the study site or, if feasible, at home, on Day 3, 
Day 8, Day 14 (±1), and Day 21 (±3). On Day 28 (±3), subjects will be contacted by site staff for 
a telephone follow-up visit. In case subjects are experiencing ongoing AEs or have clinically 


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significant laboratory abnormalities at time of the Day 21 follow-up visit, subjects might be 
requested, at the discretion of the investigator, to have a safety follow-up visit at the site or, if 
feasible, at home on Day 28 (±3).
Study drugs will be administered orally. Study drug administration should start as soon as 
possible, but no later than 4 hours after randomization, which should occur within a maximum of 
5 days after RSV symptom onset. The first dose of study drug will be administered before the 
subject leaves the site. On Day 1, study-site personnel can dispense to the subject all the required 
study drug for dosing at home, but partial dispensing at other visits is also allowed. Study-site 
personnel will instruct subjects on how to use and store study drug for at home dosing. Dosing 
should occur once daily preferably at approximately the same time each day. Study drug can be 
administered without regard to meals and is preferably followed by drinking a glass of water.
As an evaluation of antiviral activity, the RSV viral load in nasal secretions will be measured at 
the central lab using a qRT-PCR assay on mid-turbinate nasal swab specimens, which will be 
collected at several time points during the study as indicated in the TIME AND EVENTS 
SCHEDULE (see Section 9.2.1). If feasible, the RSV infectious virus titers as measured by 
quantitative culture of RSV (plaque assay) on selected nasal swab samples, may also be assessed.
Viral resistance will be monitored by sequencing of the viral F-gene on all baseline samples and 
on post baseline samples upon request of the sponsor’s protocol virologist. Other regions of the 
RSV genome may also be sequenced at the request of the protocol virologist. Sequencing data 
will not be reported to the investigators (see Section 11.4.3).
Clinical course and severity of RSV infection will be assessed through different measures (see 
Section 9.2.2).
Pharmacokinetic assessments during the study will be based on sparse sampling and will be 
performed using a popPK model (see Section 9.3).
Safety and tolerability, including AEs, laboratory assessments, ECGs, physical examination, and 
vital signs will be assessed throughout the study from signing of the Informed Consent Form 
(ICF) (including diagnostic ICF, if applicable) until the subject’s last study-related activity (see 
Section 9.7).
Medical resource utilization will be assessed (see Section 11.7).
Blood samples for host mRNA assessment may be used for exploratory biomarker analyses to 
determine the effects of JNJ-53718678 on markers of RSV disease at the sponsor’s discretion. 
Leftover mid-turbinate nasal swabs and blood samples collected for other testing may be used as 
well for the same purpose (see Section 11.6).
An interim analysis is planned after at least 36 subjects have been dosed and have completed the 
assessments of Day 8 (see Section 11.1).
A DRC will be in place (see Section 11.9).


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Subjects who prematurely discontinue study drug treatment for any reason (except withdrawal of 
consent) will be asked to continue with their remaining study visits and assessment schedule, or, 
at a minimum, to return to the site for a Withdrawal and a Safety Follow-up Visit. Subjects who 
withdraw consent during the treatment or follow-up phase will be offered and be encouraged to 
attend an optional Safety Follow-up Visit.
A diagram of the study design is provided in Figure 1.


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Figure 1:
Schematic Overview of the Study
Abbreviation: qd: once daily
a
Subjects with symptom onset >3 days before randomization may account for maximum of 50% of all enrolled subjects.
b
If feasible, home visits are allowed instead of on-site visits.


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3.2.
Study Design Rationale
This is a Phase 2a, randomized, double-blind, placebo-controlled study to explore the antiviral 
activity, clinical outcomes, safety, tolerability, and pharmacokinetics of JNJ-53718678 at 2 dose 
levels (80 mg and 500 mg) once daily for 7 days in adult subjects with respiratory illness due to 
RSV infection. Subjects may be otherwise healthy or comorbid and should not be in need of 
hospitalization.
RSV is considered the most important virus causing acute LRTI. LRTI results in substantial 
illness and morbidity in the elderly and adults with underlying chronic illnesses, underlying 
disorders of cellular immunity, or suppressed immune systems in hospitalized and community 
based patients.4,10,11,12,18,19,27 In the United States alone, among patients >65 years of age, 
177,000 hospitalizations and approximately 14,000 deaths per year are attributable to RSV 
infection.2 In other countries, the 60-day mortality rate for adults hospitalized with RSV 
infection has been observed to be as high as 13.8%.17 Currently the only available treatment for 
RSV is supportive and symptomatic care. As such, there is an unmet medical need for 
prophylactic (pre- and post-exposure) as well as therapeutic treatment in both children and 
adults. Disease interception at time of the initial healthcare professional (HCP) contact may 
shorten disease course and may prevent worsening of RSV disease, and as such also avoid the 
need for or shortening hospitalization.8 Therefore, this study will be conducted in outpatients 
infected with RSV not in need of hospitalization.
In a previous study in healthy adult subjects infected through inoculation with a laboratory strain 
of RSV (study 53718678RSV2001), antiviral activity as well as an improvement in clinical 
symptoms of different doses of JNJ-53718678 was observed. Antiviral activity was also 
observed 
in 
pediatric 
subjects 
who 
were 
hospitalized 
due 
to 
RSV-infection 
(study 53718678RSV1005).
The current study is designed to explore the antiviral activity, clinical outcomes, safety, 
tolerability, and pharmacokinetics of 80 mg and 500 mg JNJ-53718678 once daily for 7 days in 
naturally infected adults. The study will include both subjects who are otherwise healthy 
(ie, without underlying condition) or who have comorbid conditions (eg, asthma, COPD, 
cardiovascular disease, other chronic diseases), with the exception of immunocompromised 
subjects, presenting for medical care but not requiring hospitalization.
Blinding, Control, Study Phase/Periods, Treatment Groups, and Stratification
There is currently no approved treatment routinely used for the treatment of RSV infection. 
A placebo control will be used to establish the frequency and magnitude of changes in virologic 
and clinical endpoints that may occur in the absence of active treatment. The use of a placebo 
control will allow for any AEs or laboratory abnormalities observed during the course of the 
study to be evaluated properly, ie, to differentiate between events potentially related to the use of 
JNJ-53718678 vs those related to the underlying disease. 
Randomization will be used to minimize bias in the assignment of subjects to treatment groups, 
to increase the likelihood that known and unknown subject attributes (eg, demographic and 


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baseline characteristics) are evenly balanced across treatment groups, and to enhance the validity 
of statistical comparisons across treatment groups. Blinded treatment will be used to reduce 
potential bias during data collection and evaluation of clinical endpoints.
Subjects will be randomized 1:1:1 into 3 different treatments (Treatment A [8 mL + 42 mL oral 
solution of JNJ-53718678], B [8 mL oral solution of JNJ-53718678 + 42 mL of matching 
placebo solution], and C [8 mL + 42 mL of matching placebo solution]). Subjects randomized to 
placebo (ie, Treatment C) will receive matching placebo for each of the doses being evaluated in 
the active regimens.
Randomization will be stratified by time of symptom onset (≤3 days vs >3 days before 
randomization). Subjects with symptom onset >3 days before randomization may account for 
maximum of 50% of all enrolled subjects. In another respiratory disease (flu), time since 
symptom onset was an important determinant of efficacy, with early (within 2 days) treatment 
start being more efficacious than a later start.24 Whether the same is true for RSV remains to be 
established.
Population
Adult subjects of ≥18 years of age are targeted. Comorbid subjects are included as certain 
comorbidities are known risk factors for severe RSV disease. Outpatients are targeted as this is 
the population with the highest incidence of RSV infection and given that early intervention 
(ie, upon first HCP contact) might be beneficial in terms of clinical outcomes.
Dose Selection
The active regimens evaluated in this design are selected to provide a range of plasma 
concentrations of JNJ-53718678 aimed at providing information on antiviral activity, clinical 
outcomes, safety, tolerability, and pharmacokinetics in the target population of adult subjects 
infected with RSV.
The doses selected for this study are based on the results of the human challenge study 
53718678RSV2001, in which proof of concept for JNJ-53718678 was demonstrated. In the 
53718678RSV2001 study, exposure to JNJ-53718678 resulted in a reduction of viral load over 
time in all three JNJ-53718678 dose groups (75, 200, and 500 mg once daily) as compared to the 
placebo group. Mean (± standard deviation [SD]) exposures (minimum observed concentration 
[Cmin] and AUC24h) observed in this study ranged between 44.3 ng/mL (±16.2) and 
3,874 ng.h/mL (±831) at 75 mg and 307 ng/mL (±192) and 26,520 ng.h/mL (±7,520) at 500 mg 
at Day 7 (Table 1). In addition to study 53718678RSV2001, results from the interim analysis of 
study 53718678RSV1005 in hospitalized pediatric subjects showed antiviral activity at exposure 
ranges similar to exposures in adult subjects obtained in the human challenge study 
537186478RSV2001. Overall, based on the currently available data, it is anticipated that the 
proposed doses will be in the therapeutic range of JNJ-53718678 for adults. For dosing accuracy 
reasons, 80 mg was selected over 75 mg as this dose results in a rounded number of volume, 
while still falling within the range of exposures with the 75-mg dose.


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Table 1:
Pharmacokinetic Results of JNJ-53718678 After Administration of 75 mg (Cohort 2), 200 mg 
and 500 mg JNJ-53718678 Once Daily (Cohort 1+2) in Study 53718678RSV2001
Pharmacokinetics of JNJ-53718678
75 mg 
JNJ-53718678 qd
(Cohort 2)
200 mg 
JNJ-53718678 qd
(Cohort 1+2)
500 mg 
JNJ-53718678 qd
(Cohort 1+2)
(mean ± SD, tmax: median [range])
N
13a
17b
18c
Day 7
Ctrough, ng/mL
49.7 ± 16.6
84.6
±
44.0
334
±
197
Cmin, ng/mL
44.3 ± 16.2
77.1
±
45.5
307
±
192
Cmax, ng/mL
355 ± 91.1
827
±
203
2,184
±
604
tmax, h
2.00  (0.50 – 4.02)
2.00 (0.98 – 4.00)
3.98 (1.08 – 4.00)
AUC24h, ng.h/mL
3,874 ± 831
8,362
±
1,920
26,520
±
7,520
Cavg, ng/mL
161 ± 34.6
349
±
80.2
1,103
±
314
Fluctuation index, %
194 ± 38.8
218
±
42.0
173
±
26.0
a N = 15 for Cmax, tmax and AUC24h on Day 1, N = 14 for Ctrough on Day 3, Day 5 and Day 6, and for the 
dose-normalized pharmacokinetic parameters on these days.
b N = 15 for Ctrough, and Ctrough,dose normalized on Day 5, N = 16 for all pharmacokinetic parameters of Day 6 and Day 7.
c N = 17 for all pharmacokinetic parameters of Day 7.
qd: once daily; Cavg: average plasma concentration at steady-state over the dosing interval
Study Duration
Dosing will last for 7 days as data have shown that the duration of viral shedding upon RSV 
infection is at least that long. In addition, this was also the duration of dosing in the healthy 
volunteer challenge study in adults (study 53718678RSV2001), which was generally safe and 
well tolerated (see Section 1.1) and the same dosing duration is being investigated in the ongoing 
study 53718678RSV1005 in pediatric subjects.
Biomarker Collection
Blood samples for host mRNA assessment will be collected at time points indicated in the TIME 
AND EVENTS SCHEDULE and may be used for exploratory biomarker analyses (eg, proteins 
including cytokines), on the premise that these markers may play a role in the treatment 
response, safety or pharmacokinetics of JNJ-53718678, or RSV-related disease. Leftover 
mid-turbinate nasal swabs and blood samples collected for other testing may be used as well for 
the same purpose. Analyses of biomarkers will be conducted at the sponsor’s discretion and may 
be reported separately from this study.
Biomarker samples may be used to help address emerging issues and to enable the development 
of safer, more effective, and ultimately individualized therapies.
No human DNA analysis will be performed.


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Medical Resource Utilization Data Collection
Treatment of RSV infection with JNJ-53718678 versus placebo may result in lower utilization of
hospital or outpatient healthcare services; therefore, comparison will be done across treatment 
groups.
Interim Analysis
An interim analysis is planned after at least 36 subjects have been dosed and have completed the 
assessments of Day 8 as planned per the TIME AND EVENTS SCHEDULE. The central 
sponsor team members will review the unblinded interim efficacy, safety, and pharmacokinetic 
analyses and will make recommendations to the DRC regarding possible changes to the design of 
the study: dropping the lower dose, changing the stratification factor (and/or the requirement of 
maximum 50% of all enrolled subjects with symptom onset >3 days before randomization), 
changing the maximum number of days between RSV symptom onset and randomization and/or 
the number of time points/visits for collecting a nasal swab by HCP. The DRC will decide on the 
implementation of the recommendations based on the review of the interim results and other 
ongoing studies of JNJ-53718678.
4.
SUBJECT POPULATION
Screening for eligible subjects will be performed as soon as possible after presentation to the 
healthcare facility, such that subjects are randomized (within a maximum of 5 days after RSV 
symptom onset) and treatment is initiated as soon as possible (but no later than 4 hours after 
randomization).
The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the 
investigator must consult with the appropriate sponsor representative and resolve any issues 
before enrolling a subject in the study.  Waivers are not allowed. 
For a discussion of the statistical considerations of subject selection, refer to Section 11.3, 
Sample Size Determination.
4.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1.
Male or female.
2.
≥18 years of age.
Note: If the legal age of consent in the jurisdiction in which the study is taking place is 
>18 years, this respective legal age is binding for eligibility.
3.
Must sign an ICF indicating they understand the purpose of, and procedures required 
for, the study and is willing to participate in the study.


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Note: Prior to signing the main consent form for the study, subjects may specifically 
allow for the collection and testing of nasal mid-turbinate swabs by signing the 
pre-screening (diagnostic) ICF.
4.
Subjects must have an acute respiratory illness with signs and symptoms consistent with 
a viral infection (eg, fever, cough, nasal congestion, runny nose, sore throat, myalgia, 
lethargy, shortness of breath, or wheezing) with onset ≤5 days from the anticipated time 
of randomization. Onset of symptoms is defined as the time the subject becomes aware 
of the first sign and/or symptom consistent with a viral infection. Efforts should be 
made to determine the time of onset of symptoms as accurately as possible (in relation 
to routine daily activities).
Note: The viral infection may present in any way as long as the underlying precipitant 
of the illness is considered by the investigator to be due to RSV infection. Examples of 
such an illness include:

An upper or lower viral respiratory tract infection (eg, “flu-like illness”);

Pneumonia;

Respiratory distress;

Asthma exacerbation;

COPD exacerbation.
5.
Subject has been diagnosed with RSV infection using a rapid PCR-based (preferably 
locally available) or rapid-antigen-detection test.
Note: If a patient has a positive similar diagnostic test from another study and meets all 
eligibility criteria for inclusion in this study, this diagnostic test result can be used for 
confirmation of eligibility.
6.
Before randomization, a woman must be not of childbearing potential defined as:

Premenarchal
A premenarchal state is one in which menarche has not yet occurred.

Postmenopausal
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. An available high follicle-stimulating hormone level 
(>40 IU/L or mIU/mL) in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy, however in the absence of 12 months of amenorrhea, a 
single follicle-stimulating hormone measurement is insufficient.

Permanently sterile
Permanent 
sterilization 
methods 
include 
hysterectomy,
bilateral 
salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral 
oophorectomy.


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7.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for a period of 30 days after the last dose of study
drug.
8.
All women must have a negative urine β-human chorionic gonadotropin pregnancy test 
at screening.
9.
A male subject must wear a condom when engaging in any activity that allows for 
passage of ejaculate to another person. Male subjects should also be advised of the 
benefit for a female partner to use a highly effective method of contraception as a
condom may break or leak.
Note: Contraceptive (birth control) use by subjects should be consistent with local 
regulations regarding the acceptable methods of contraception for those participating in 
clinical studies.
10.
A male subject must agree not to donate sperm for the purpose of reproduction during 
the study and for a minimum of 90 days after receiving the last dose of study drug.
11.
Willing and able to adhere to the lifestyle restrictions specified in this protocol 
(Section 4.3).
12.
With the exception of the RSV-related illness the subject must be medically stable on 
the basis of physical examination, medical history, vital signs, and ECG performed at 
screening. If there are abnormalities, they must be consistent with the underlying 
condition (RSV disease and/or comorbid condition) in the study population as evaluated 
by the investigator (with exception of QTcF interval >500 ms, see exclusion 
criterion 13). This determination must be recorded in the subject’s source documents 
and initialed by the investigator.
4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study:
1.
Hospitalized subjects or subjects expected to be hospitalized within 24 hours of 
screening.
Note: Any stay in the emergency room or in the observational unit of at least 24 hours 
will be considered hospitalization for the purposes of the study.
2.
History of or concurrent illness (beyond a comorbid condition) that in the opinion of the 
investigator, might confound the results of the study or pose an additional risk in 
administering study drug to the subject or that could prevent, limit, or confound the
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3.
Subjects who had major surgery within the 28 days prior to randomization or have
planned major surgery through the course of the study.
4.
Subjects who are considered by the investigator to be immunocompromised within the 
past 12 months, whether due to underlying medical condition (eg, malignancy or genetic 
disorder other than immunoglobulin A deficiency, or human immunodeficiency virus 
[HIV] infection) or medical therapy (eg, medications other than corticosteroids for the 
treatment of COPD or asthma exacerbations, chemotherapy, radiation, stem cell or solid 
organ transplant).
5.
Subject has known or suspected chronic or acute hepatitis B or C infection.
6.
Subject has known allergies, hypersensitivity, or intolerance to JNJ-53718678 or to any 
of the excipients of the JNJ-53718678 or placebo formulation (refer to the IB15).
7.
Subject with current or planned participation in another clinical study where study 
drug/investigational device is being administered while participating in the current
study.
8.
Subjects unwilling to undergo mid-turbinate nasal swab procedures or with any physical 
abnormality which limits the ability to collect regular nasal specimens.
9.
Subjects unable to take medications orally or with a known gastrointestinal-related
condition that is considered by the sponsor or investigator to be likely to interfere with 
study drug ingestion or absorption.
10.
Women who are pregnant or breastfeeding.
11.
Men who plan to father a child while enrolled in this study or within 90 days after the 
last dose of study drug.
12.
Subject with clinically significant abnormal ECG findings (other than QTcF interval 
>500 ms, see exclusion criterion 13) not consistent with the underlying condition in the 
study population, as judged by the investigator.
13.
Confirmed QTcF interval >500 ms per the machine read parameter result at screening. 
Confirmation needs to be obtained by repeat triplicate ECG recording prior to dosing.
14.
Subjects who are using any disallowed medication as listed in Section 8.
15.
Subjects with history of drug or alcohol abuse according to Diagnostic and Statistical 
Manual of Mental Disorders (5th edition) criteria within 1 year before screening.
16.
Subjects who received an investigational vaccine at any time prior to the study, or an
investigational drug, or used an invasive investigational medical device within 30 days 
or 5 elimination half-lives (whichever is longer) prior to screening or is currently 


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enrolled in an investigational study.
17.
Subject is a family member of the employees of the investigator or study-site with direct 
involvement in the proposed study or other studies under the direction of that 
investigator or study-site or of the investigator.
Note: Investigators should ensure that all study enrollment criteria have been met at screening. If 
a subject's clinical status changes (including any available laboratory results or receipt of
additional medical records) after screening but before the first dose of study drug is given such 
that he or she no longer meets all eligibility criteria, then the subject should be excluded from 
participation in the study.
4.3.
Prohibitions and Restrictions
Potential subjects must be willing and able to adhere to the following prohibitions and 
restrictions during the course of the study to be eligible for participation:
1.
Agree to follow all requirements that must be met during the study as noted in the 
inclusion and exclusion criteria (eg, contraceptive requirements).
2.
Agree to the daily completion of the patient-reported outcomes, additional questions, 
study medication and concomitant medication log, swabbing log, and temperature log.
3.
Concurrent administration of medications/use of licensed devices is allowed as 
supportive therapy per local standard of care, as long as the medication/licensed device
will not affect the subject’s participation in the study and is in accordance with allowed
concomitant therapy.
Refer to Section 8 for details regarding prohibited and restricted therapy during the 
study.
5.
TREATMENT ALLOCATION AND BLINDING
Treatment Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Subjects will be randomly assigned to 
1 of 3 treatments (Treatments A to C; 1:1:1 randomization). Randomization will be based on a 
computer-generated randomization schedule prepared before the study by or under the 
supervision of the sponsor. The randomization will be balanced by using randomly permuted 
blocks and will be stratified by time since symptom onset at randomization (≤3 days and 
>3 days). The interactive web response system (IWRS) will assign a unique treatment code, 
which will dictate the treatment assignment and matching study drug kits for the subject. The 
requestor must use his or her own user identification and personal identification number when 
contacting the IWRS, and will then give the relevant subject details to uniquely identify the 
subject.


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Blinding
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual subject.
In general, randomization codes will be disclosed fully only if the study is completed and the 
clinical database is closed. However, if an interim analysis is specified, the randomization codes 
and, if required, the translation of randomization codes into treatment and control groups will be 
disclosed to those authorized and only for those subjects included in the interim analysis.
Otherwise, the blind should be broken only if specific emergency treatment/course of action 
would be dictated by knowing the treatment status of the subject. In such cases, the investigator 
may in an emergency determine the identity of the treatment by contacting the IWRS. It is 
recommended that the investigator contacts the sponsor or its designee, if possible, to discuss the 
particular situation, before breaking the blind. Telephone contact with the sponsor or its designee 
will be available 24 hours per day, 7 days per week. In the event the blind is broken, the sponsor 
must be informed as soon as possible. The date and reason for the unblinding must be 
documented in the appropriate section of the electronic case report form (eCRF). The 
documentation received from the IWRS indicating the code break is filed in the Trial Master 
File.
6.
DOSAGE AND ADMINISTRATION
The subjects will receive the treatments as described in Table 2. Study drugs will be 
administered orally.
Table 2:
Treatment Overview
Treatment
Dosing Regimen
Volume and Formulation
A
500 mg JNJ-53718678 once daily for 7 days
8 mL + 42 mL oral solution of JNJ-53718678a
B
80 mg JNJ-53718678 + matching placebo
once daily for 7 days
8 mL oral solution of JNJ-53718678a + 42 mL of
matching placebo solution
C
placebo once daily for 7 days
8 mL + 42 mL matching placebo solution
a
JNJ-53718678 is formulated as an oral solution containing 10 mg/mL of active drug substance (G024). The matching 
placebo consists of the oral vehicle solution without active drug substance (G026).
Study drug administration should start as soon as possible, but no later than 4 hours after 
randomization, which should occur within a maximum of 5 days after RSV symptom onset. 
Study drug administration should occur once daily at approximately the same time each day. 
JNJ-53718678/placebo can be administered without regard to meals and is preferably followed 
by drinking a glass of water. Each dosing day, the same total volume of study drug solution 
should be administered, ie, 50 mL, divided over 2 separate but sequential intakes (1 container 
with 8 mL and 1 container with 42 mL).
On Day 1, date and time of dosing will be captured by the site staff in the eCRF. At home, date 
and time of dosing will be captured in the study medication log, to be completed by the subject
in the electronic device. On Day 3 and Day 8 (days with pharmacokinetic sampling), the time of 
the meal, if any within 2 hours before or after dosing, will also be recorded in the study 
medication log.


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Study-site personnel will instruct subjects on how to store study drug for at home use as 
indicated for this protocol.
7.
TREATMENT COMPLIANCE
On Day 1, study drug will be administered orally at the study site.
In case of vomiting, the subject should not be redosed.
In case a dose was missed, the dose should be given as soon as possible but within 12 hours after 
the scheduled time. If more than 12 hours have elapsed, the dose should be skipped and the next 
dose should be given at the next scheduled time point per the initial dosing schedule.
8.
CONCOMITANT THERAPY
Concomitant medications, except those listed below, are allowed during this study. All 
concomitant medications and supportive therapy are to be recorded in the eCRF, as well as in the
source documents, from the date the ICF is signed through to the end of study visit. The dosage, 
route of administration, frequency, start and stop dates, and the indication should be noted in the 
source documentation and the eCRF.
Subjects will be required to document use of concomitant medication in the electronic
medication log from signing of the ICF until the last study visit, which will serve as source 
document for the site staff to complete the eCRF.
Subjects can receive medications such as acetaminophen/paracetamol, non-steroidal 
anti-inflammatory drugs, or antihistamines, taking into account their respective package insert, at 
the investigator’s discretion.
Prescription medications intended to treat the symptoms/sequelae of the RSV infection are 
permitted, including:

Inhaled β-agonists or anticholinergics (also permitted as maintenance therapy for the 
underlying asthma or COPD);

Inhaled corticosteroids and, to a certain extent, systemic corticosteroids (see below);

Oral/intravenous/intramuscular antibiotics such as β-lactams and azithromycin.
Note: The temporary use of over-the-counter medications in the 14 days prior to randomization 
is permitted. The use of vitamins and mineral supplements is also permitted.
The following therapies are not permitted during the study and for the time period prior to 
screening as noted:

Herbal supplements with active metabolic enzyme inducing components (eg, St-John’s 
Wort) within 21 days prior to randomization and during the study with the exception of 
topically administered products;

The following prescription medications:


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
Macrolide antibiotics (with the exception of azithromycin).

Systemic corticosteroids if used for >7 consecutive days immediately prior to 
randomization at doses higher than 20 mg/day of prednisone or equivalent. Subjects 
meeting the eligibility criteria at screening but requiring increased doses of systemic 
corticosteroids (>20 mg/day of prednisone or equivalent) for a prolonged period 
(>7 consecutive days) during the study are allowed to continue participating in the 
study.

Prescription medications used within 14 days prior to randomization and during the 
study with an antiviral effect on RSV to treat the RSV infection itself (eg, inhaled/oral 
ribavirin, intravenous RSV immunoglobulin). Prescription medications intended to treat 
the symptoms/sequelae of the RSV infection are permitted.

Prescription medications which are known to be a strong inducer or a strong inhibitor of 
CYP3A4 enzymes, such as, but not limited to, erythromycin, clarithromycin, ritonavir, 
and rifampin, within 14 days prior to screening and during the study or CYP3A 
substrates with narrow therapeutic index such as, but not limited to, anti-arrhythmics 
(amiodarone, disopyramide, flecainide, mexiletine, systemic lidocaine, propafenone, 
quinidine), 
antihistamines 
(astemizole, 
terfenadine), 
or 
gastrointestinal/
gastroesophageal reflux disease drugs (cisapride).

Any other investigational drug within 30 days or 5 elimination half-lives of that drug 
(whichever is longer) prior to screening and during the study;

Any investigational vaccine, including investigational RSV vaccines, at any time prior to 
and during the study;

JNJ-53718678 prior to screening.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The TIME AND EVENTS SCHEDULE summarizes the frequency and timing of antiviral effect,
clinical course, safety, pharmacokinetic, biomarker, and MRU assessments applicable to this 
study.
If multiple assessments are scheduled for the same time point, it is recommended that procedures 
be performed in the following sequence: ECG, vital signs, clinical parameters, blood sampling, 
and physical examination. Actual dates and times of assessments will be recorded in the source 
documentation and CRF.
Medical resource utilization data will be collected. Refer to Section 9.6, for details.
The maximum amount of blood drawn from each subject for study-specific purposes will not 
exceed 450 mL over the duration of the study.


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Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
Assessments which should be performed around the dosing time point as per the TIME AND 
EVENTS SCHEDULE should be done prior to actual dosing on Day 1 and preferably prior to 
dosing on the other days.
9.1.2.
Screening Phase
The procedures specified in the TIME AND EVENTS SCHEDULE will only be performed after 
written informed consent has been obtained.
Screening will be completed and randomization will be performed within a maximum of 5 days 
after the onset of RSV symptoms to ensure the eligibility of the subject. Procedures that are 
standard of care and performed within approximately 48 hours prior to randomization may be 
used in determining study eligibility. 
Blood samples for serum chemistry and hematology and a urine sample for urinalysis will be 
collected at screening and analyzed at the central laboratory. Subjects can start treatment before 
the laboratory results are available. In case abnormalities as described in Section 10.2 are 
observed in the blood samples collected at screening after the subject has started treatment, 
treatment may need to be discontinued.
During screening, one mid-turbinate nasal swab will be collected for:

RSV diagnosis using a rapid PCR-based (preferably locally available) or rapid-antigen-
detection test. In case the test detects more than one virus, the subject is eligible as long as 
RSV is one of the viruses detected.

RSV diagnosis confirmation using a PCR-based assay post-hoc (at the central laboratory).

Examination for the presence of other viruses or bacteria using multiplex PCR post-hoc (at 
the central laboratory).
Note: Leftover samples will be stored for biomarker research if warranted.
A clinical evaluation will be performed. This includes but is not limited to respiratory rate, heart 
rate, SpO2, and body temperature (measured by the same method and preferably by the same 
person throughout the study). In addition, to evaluate RSV symptoms’ presence and severity,
subjects will have to complete the RI-PRO, answer the additional questions about health and 
functioning, and subjects enrolled after approval of this amendment will also have to complete
the RiiQ Symptom Scale. Subjects will have to rate their HRQOL by completing the 5-level 
EuroQol 5-Dimension (EQ-5D-5L), and subjects enrolled after approval of this amendment will 
also have to complete the RiiQ Impact Scale.
9.1.3.
Double-Blind Treatment Phase
Assessments to be performed during the treatment phase are specified in the TIME AND 
EVENTS SCHEDULE.


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Day 1/Day of Randomization
Eligible subjects will be randomized on Day 1. Study drug administration should start as soon as 
possible, but no later than 4 hours after randomization, which should occur within a maximum of 
5 days after RSV symptom onset. Subjects will receive the first dose of study drug on Day 1 at 
the healthcare facility. Date and time of dosing will be captured by the site staff in the eCRF. 
Assessments to be performed on Day 1 are specified in the TIME AND EVENTS SCHEDULE.
Day 2 to Day 8 (End of Treatment)
Study drug administration continues until 7 doses have been taken. Subjects will receive 7 doses 
in total without regard to meals, administered once daily preferably at approximately the same 
time as on Day 1 each day. Study drug administration is preferably followed by drinking a glass 
of water. On Day 1, study-site personnel can dispense to the subject all the required study drug 
for dosing at home, but partial dispensing at other visits is also allowed. Study-site personnel will 
instruct subjects on how to use and store study drug for at home dosing. Date and time of dosing 
will be captured in the study medication log, to be completed by the subject in the electronic 
device.
Assessments will be performed as detailed in the TIME AND EVENTS SCHEDULE.
Telephone calls to the subjects to facilitate compliance with study procedures between outpatient 
study visits are permitted.
9.1.4.
Posttreatment Phase (Follow-Up)
Day 9 to Day 28(±3)
Subjects will be evaluated for a total of 28 days post randomization. Subjects will be required to 
return to the healthcare facility as an outpatient or, if feasible, have a home visit scheduled, for 
follow-up assessments on Day 14 and Day 21 as indicated in the TIME AND EVENTS 
SCHEDULE. On Day 28, subjects will be contacted by site staff for a telephone follow-up visit.
In case subjects are experiencing ongoing AEs or have clinically significant laboratory 
abnormalities at time of the Day 21 follow-up visit, subjects might be requested, at the discretion 
of the investigator, to have a safety follow-up visit at the site or, if feasible, at home on Day 28.
On Day 28 all subjects will complete the study. Assessments will be performed as indicated in 
the TIME AND EVENTS SCHEDULE.
Subjects who prematurely discontinue study drug treatment for any reason (except withdrawal of 
consent) will be asked to continue with their remaining study visits and assessment schedule, or, 
at a minimum, to return to the site for a Withdrawal and a Safety Follow-up Visit. Subjects who 
withdraw consent during the treatment or follow-up phase will be offered and be encouraged to 
attend an optional Safety Follow-up Visit. At the Withdrawal and Safety Follow-up Visits, the 
same assessments as on the Day 8 and Day 21 visits, respectively, will be performed. 
Assessments will be performed as indicated in the TIME AND EVENTS SCHEDULE.


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9.2.
Efficacy Evaluations
9.2.1.
Antiviral Activity
As an evaluation of antiviral activity, the RSV viral load in nasal secretions, obtained via 
mid-turbinate nasal swab, will be measured at the central lab using a qRT-PCR assay. 
Mid-turbinate swab specimens for the determination of RSV viral load will be collected at 
several time points during the study as indicated in the TIME AND EVENTS SCHEDULE. 
Mid-turbinate swabs should be collected from the same nostril throughout the study (unless 
precluded due to bleeding). It will be collected in the eCRF or the electronic device (for home
swabs) which nostril was sampled.
The first mid-turbinate nasal swab should be collected as close as possible and prior to the first 
administration of study drug (on Day 1). The next swabs (from Day 2 to Day 8) should be 
collected preferably at approximately the same time as on Day 1 each day. On Day 8, the 
investigator will check whether the subject is still symptomatic. For asymptomatic subjects 
swabbing will be stopped. For subjects still symptomatic, swabbing will be continued daily until 
the subject becomes asymptomatic or until Day 13 at the latest. Whether a subject is still 
symptomatic will be checked with daily telephone calls between the subject and site staff (and/or 
by review of the transmitted ePRO data) in case swabbing is performed by the subject (or his/her 
spouse, partner, relative, or other caregiver) or by an HCP other than investigational site staff. 
On Day 14 and Day 21, a swab will be collected during the scheduled visit. During scheduled 
visits on Day 1, Day 3, Day 8, Day 14, and Day 21, swabs must be collected by an HCP
(investigator/study-site personnel). On the other days, mid-turbinate swabs are collected at home 
preferably by an HCP and, only if not possible by an HCP, by the subject (or his/her spouse, 
partner, relative, or other caregiver) after being properly trained by the investigator/study-site 
personnel. In case preferred by the subject, all mid-turbinate swabbing may also be performed at 
the site.
The sampling should be documented in the electronic device or the eCRF (for the sampling at the 
scheduled visits).
Additional information about the collection, handling, and shipment of biologic samples can be 
found in the laboratory manual.
Changes in viral load will be evaluated but will not be reported as AEs.
If feasible, the RSV infectious virus titers as measured by quantitative culture of RSV (plaque 
assay) on selected nasal swab samples, may also be assessed.


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9.2.2.
Clinical Severity and Clinical Course of RSV Infection
The following evaluations of the clinical course of RSV infection will be performed throughout 
the study as indicated in the TIME AND EVENTS SCHEDULE:

Clinical parameters: respiratory rate, heart rate, SpO2, and body temperature as measured 
during site visits. Subjects will be provided a thermometer and asked to record body 
temperature in the electronic device as indicated in the TIME AND EVENTS SCHEDULE.

Evolution and severity of signs and symptoms of RSV disease as assessed by the subject on 
a hand-held electronic device using the RI-PRO, the RiiQ Symptom Scale (if the subject was 
enrolled after approval of this amendment) and additional questions about health and 
functioning. Symptoms reported in the RI-PRO or RiiQ Symptom Scale will not be reported 
as AEs but constitute a part of the efficacy evaluations. Subjects will also complete the EQ-
5D-5L and the RiiQ Impact Scale (for subjects who were enrolled after approval of this 
amendment) on the electronic device to rate their HRQOL.

Need for hospitalization or medically attended visits (other than the study mandated visits) 
during treatment and follow-up.
9.2.3.
Viral Sequencing
Viral resistance will be monitored by sequencing of the F-gene of the viral genome on all 
baseline samples and on post baseline samples upon request of the sponsor’s protocol virologist. 
Other regions of the RSV genome may also be sequenced at the request of the protocol
virologist. Sequencing data will not be reported to the investigators.
Changes in viral sequence will be evaluated but will not be reported as AEs.
9.3.
Pharmacokinetics
Pharmacokinetic assessment during the study will be based on sparse sampling and will be 
performed using a popPK approach by means of nonlinear mixed-effects modeling.
Venous blood samples for determination of JNJ-53718678 plasma concentrations will be 
collected at the time points indicated in the TIME AND EVENTS SCHEDULE. Samples can
also be used for the analysis of metabolites of JNJ-53718678, excipients (eg, hydroxypropyl-β-
cyclodextrin), protein binding, or endogenous markers for enzymes or transporters involved in 
the metabolism and distribution of JNJ-53718678, at the discretion of the sponsor. Blood 
samples collected for pharmacokinetics may additionally be used to evaluate safety or efficacy 
aspects that address concerns arising during or after the study period. Genetic analyses will not 
be performed on these samples. Subject confidentiality will be maintained.
Samples will be analyzed (applicable treatment groups only [not the placebo group]) to 
determine concentrations of JNJ-53718678 using a validated, specific and sensitive method 
under the supervision of the sponsor.
Based on the individual concentration-time data, using the actual dose taken and the actual 
sampling times, pharmacokinetic parameters and exposure information of JNJ-53718678 will be 


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derived using popPK modelling, including, but not limited to: AUC, Ctrough, and possibly Cmax. 
Baseline covariates (eg, body weight, age, sex, creatinine clearance, race) may be included in the 
model, if relevant. Other pharmacokinetic parameters may be determined at the discretion of the 
sponsor if deemed useful to evaluate the pharmacokinetics of the analytes in scope. If deemed 
useful to evaluate the safety or efficacy of JNJ-53718678, popPK modeling of other analytes 
(eg, excipients) may be performed at the discretion of the sponsor.
The following times need to be recorded on the requisition form and/or the study medication log: 
date and time of study drug intake, date and time of pharmacokinetic blood sampling, and time 
of meal if any in the time window of 2 hours before and 2 hours after study drug intake on the 
day of pharmacokinetic sampling.
9.4.
Pharmacokinetic/Pharmacodynamic Evaluations 
Obtained pharmacokinetic and pharmacodynamic data (selected antiviral activity parameters, 
clinical outcomes, and safety parameters) will be used to explore the relationship between the 
pharmacokinetics and pharmacodynamics.
9.5.
Biomarkers
Blood samples for host mRNA assessment will be collected at time points indicated in the TIME 
AND EVENTS SCHEDULE and may be used for exploratory biomarker analyses (eg, proteins 
including cytokines), on the premise that these markers may play a role in the treatment 
response, safety or pharmacokinetics of JNJ-53718678, or RSV-related disease. Leftover 
mid-turbinate nasal swabs and blood samples collected for other testing may be used as well for 
the same purpose. Analyses of biomarkers will be conducted at the sponsor’s discretion and may 
be reported separately from this study.
9.6.
Medical Resource Utilization
Medical resource utilization data will be collected in the eCRF for all subjects throughout the 
study at time points indicated in the TIME AND EVENTS SCHEDULE. Protocol-mandated 
procedures, tests, and encounters are excluded. The data collected will include:

Number and duration of medical care encounters: hospitalizations, physician or emergency 
room visits, test, and procedures, including surgeries, and other procedures (inpatient and 
outpatient) for RSV infection or complications associated with RSV per investigator 
assessment.
9.7.
Safety Evaluations
Safety and tolerability will be evaluated throughout the study from signing of the ICF (including 
diagnostic ICF, if applicable) onwards until the last study-related activity (end of study/early 
withdrawal).
Details regarding the DRC are provided in Section 11.9.
Any clinically relevant changes occurring during the study must be recorded on the AE section 
of the eCRF.


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Any clinically significant abnormalities persisting at the end of the study/early withdrawal will 
be followed by the investigator until resolution or until a clinically stable endpoint is reached. 
The study will include the following evaluations of safety and tolerability according to the time 
points provided in the TIME AND EVENTS SCHEDULE:
Adverse Events
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, surrogate, 
or the subject's legally acceptable representative) for the duration of the study. Adverse events 
will be followed by the investigator as specified in Section 12. Grading will be determined 
according to the criteria specified in the DMID adult toxicity tables (see Attachment 1).
Special attention will be paid to those subjects who discontinue the study for an AE, or who 
experience an AE of at least grade 3, or an SAE.
Exacerbations of underlying pulmonary disease (eg, asthma, COPD) occurring after treatment 
start, bacterial superinfections of presumed respiratory origin per investigator assessment, and 
exacerbations of underlying cardiovascular conditions should be reported as AE and are 
considered events of interest (complications associated with RSV per investigator assessment).
Further details on these events of interest will be captured separately in the eCRF.
Evaluations of signs and symptoms of RSV disease that are part of the efficacy evaluations (with 
exception of the complications mentioned above) will not be reported as AEs.
Clinical Laboratory Tests
Blood samples for serum chemistry and hematology and a urine sample for urinalysis will be 
collected at time points indicated in the TIME AND EVENTS SCHEDULE and analyzed at the 
central laboratory. The investigator must review the laboratory results, document this review, 
and record any clinically relevant changes occurring during the study in the AE section of the 
eCRF. Laboratory reports must be filed with the source documents.
In case a grade 3 or grade 4 laboratory abnormality occurs, a confirmatory test must be 
performed preferably within 48 hours but no later than 72 hours after the results have become 
available.
Any values that indicate a potential safety concern will be assessed by the investigator and 
appropriate follow-up actions, including potential discontinuation from treatment, will be carried
out.
The following tests will be performed by the central laboratory:

Hematology Panel
-hemoglobin
-WBC differential:
-hematocrit
* neutrophils
-RBC count
* lymphocytes


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-reticulocyte count
* monocytes
-RBC parameters:
* eosinophils
* mean corpuscular hemoglobin (MCH)
* basophils
* MCH concentration
-platelet count
* mean corpuscular volume
-WBC count
Note: A WBC evaluation may include any abnormal cells, which will then be reported by 
the laboratory. An RBC evaluation may include abnormalities in the RBC count, RBC 
parameters, or RBC morphology, which will then be reported by the laboratory.
In addition, any other abnormal cells in a blood smear will also be reported.

Coagulation parameters: PT, aPTT and international normalized ratio

Serum Chemistry Panel
-alkaline phosphatase
-glucose
-ALT
-potassium
-AST
-sodium
-bicarbonate
-total bilirubin (direct and indirect)
-uric acid
-urea
-chloride
-phosphorus
-magnesium
-calcium

Urinalysis
Dipstick
Sediment (if dipstick result is
-specific gravity
abnormal)
-pH
-RBC
-glucose
-WBC
-protein
-epithelial cells
-blood
-crystals
-ketones
-casts
-bilirubin
-bacteria
-urobilinogen
-nitrite
-leukocyte esterase
Dipstick will be performed per the TIME AND EVENTS SCHEDULE. If dipstick result is 
abnormal, flow cytometry or microscopy will be used to measure sediment. In case of 
discordance between the dipstick results and the flow cytometric results, the sediment will 
be examined microscopically.
In the microscopic examination, observations other than the presence of WBC, RBC and 
casts may also be reported by the laboratory.

Renal function testing: 

Serum creatinine and estimated Glomerular Filtration Rate (eGFR) based on creatinine 
by Cockcroft-Gault formula25

Serum cystatine C and eGFR based on cystatine C25


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
Urinary creatinine, albumin, N-acetyl--glucosaminidase, β2-microglobulin, urinary 
phosphorus, sodium, potassium, and calcium (spot urine sample)

Urine pregnancy testing for all women
Electrocardiogram
Twelve-lead triplicate ECGs will be collected at the time points specified in the TIME AND 
EVENTS SCHEDULE and when clinically indicated.
Central ECG readings will be performed by a central ECG lab. Instructions for ECG acquisition 
and ECG transmission will be described in the manual provided by the ECG lab. There will be 
2 ECG reports: a preliminary report and a final report. Both ECG reports generated by the central 
ECG lab will need to be interpreted for clinical significance, signed and dated by the 
investigator, and filed in the subject’s medical record. Clinically relevant abnormalities occurring 
during the study should be recorded by the investigator in the AE section of the eCRF.
During the collection of ECGs, subjects should be in a quiet setting without distractions 
(eg, television, cell phones). Subjects should rest in a supine position for at least 5 minutes 
before ECG collection and should refrain from talking or moving arms or legs.
In the event that an invasive procedure such as a blood draw or nasal aspirate and an ECG are 
required at the same time, ECGs should be collected first. Electrocardiograms may be repeated at 
the investigator’s discretion to account for erroneous readings.
At each time point at which triplicate ECGs are required, 3 individual ECG tracings should be 
obtained as closely as possible in succession, but no more than 2 minutes apart. The full set of 
triplicates should be completed in less than 4 minutes.
Vital Signs
Systolic and diastolic blood pressure are to be collected at the time points specified in the TIME 
AND EVENTS SCHEDULE.
Blood pressure measurements will be assessed in a sitting or supine position (same position at 
each measurement) with a completely automated device. Manual techniques will be used only if 
an automated device is not available.
Blood pressure measurements should be preceded by at least 5 minutes of rest in a quiet setting 
without distractions (eg, television, cell phones).
Clinically relevant abnormalities occurring during the study should be recorded by the 
investigator in the AE section of the eCRF.


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Physical Examination
A physical examination (including height [only at screening] and body weight measurements) 
and skin examination will be performed at the visits indicated in the TIME AND EVENTS 
SCHEDULE.
A skin examination includes an examination of the mucous membranes, but does not include a 
vaginal or rectal examination. However, if the subject develops a cutaneous reaction/rash, 
vaginal and rectal examinations may be done if clinically relevant.
Any clinically relevant changes occurring during the study must be recorded in the AE Section 
of the eCRF.
Specific Toxicities
Rash
In case there are skin changes, a correct diagnosis has to be made by the investigator or a 
dermatologist, preferably within 24 hours of detection. If a diagnosis of rash is made, the 
investigator will discuss this with the sponsor, preferably within 24 hours of the investigator’s 
awareness of the rash. An assessment of severity grade should be made using the criteria 
specified in the DMID adult toxicity tables (see Attachment 1).
If the rash is considered to be most likely due to RSV, concomitant illness or non-study 
medication, standard management, including discontinuation of the likely causative agent, 
should be undertaken.
If a causal relationship between the rash and the study drug is reasonably suspected, then the 
visits and assessments will be performed as indicated in Attachment 5. Unscheduled follow-up 
visits for close follow-up of rash will be performed based on the grade (severity) of the rash. At 
the investigator’s discretion, additional visits and assessments can be performed.
AST and ALT Evaluation
Management will be at the discretion of the investigator and should follow generally accepted 
medical standards.
For grade 3 or 4 laboratory abnormalities, subjects should have a confirmatory measurement, 
preferably within 48 hours after the laboratory results become available to the site. This 
management scheme is for confirmed laboratory abnormalities and not for isolated events.
Grade 1 (1.1 to <2.0 x upper limit of normal [ULN]), or Grade 2 (>2.0 to ≤3.0 x ULN)
Subjects may continue the intake of study drug.
Subjects should be followed until resolution (return to baseline) or stabilization of AST/ALT 
elevation (to be agreed upon with the sponsor).


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Grade 3 (>3.0 to 8.0 x ULN), or Grade 4 (>8.0 x ULN)
Subjects will permanently discontinue the intake of study drug.
It is recommended that the investigator contacts the sponsor to discuss the case. Subjects should 
be followed until resolution (return to baseline) or stabilization of AST/ALT elevation.
9.8.
Other Evaluations
Mid-turbinate nasal swabs collected at screening will be used to determine the presence of viral 
(other than RSV) or bacterial pathogens (both by multiplex PCR) at the central laboratory.
9.9.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory 
requisition form.
Refer to the TIME AND EVENTS SCHEDULE for the timing and frequency of all sample 
collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the 
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples 
must be under the specified, and where applicable, controlled temperature conditions as indicated 
in the laboratory manual.
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ 
WITHDRAWAL FROM THE STUDY
10.1.
Completion
A subject will be considered to have completed the treatment period of the study if he or she has 
completed dosing on the 7 days of the dosing period and the Day 8 visit. A subject is considered 
to have completed the study if he or she has also completed assessments of the last follow-up 
visit.
10.2.
Discontinuation of Study Treatment/Withdrawal from the Study
Discontinuation of Study Treatment
A subject will not be automatically withdrawn from the study if he or she has to discontinue 
treatment before the end of the treatment regimen.
A subject's study treatment must be discontinued if:

The subject withdraws consent.

The investigator believes that for safety reasons or tolerability reasons (eg, AE) it is in the 
best interest of the subject to discontinue study treatment.

The subject becomes pregnant.


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
The subject has a confirmed QTcF interval >500 ms at the Day 3 visit, per the machine read 
parameter result. Confirmation needs to be obtained during the visit by repeat triplicate ECG 
recording.

The subject is reported with the following laboratory abnormalities: AST or ALT increases 
≥3 x ULN at screening, confirmed in a repeat test, to be performed within 48 hours of the 
result being available at the site.

The subject is reported with any other laboratory abnormality of grade 3 or 4, except for 
grade 3 or 4 elevations of triglycerides, low density lipoprotein cholesterol, and/or 
cholesterol at screening, confirmed in a repeat test, to be performed within 48 hours of the 
result being available at the site.
Subjects who prematurely discontinue study drug treatment for any reason (except withdrawal of 
consent) will be asked to continue with their remaining study visits and assessment schedule, or, 
at a minimum, to return to the site for a Withdrawal and a Safety Follow-up Visit. Subjects who 
withdraw consent during the treatment or follow-up phase will be offered and be encouraged to 
attend an optional Safety Follow-up Visit. At the Withdrawal and Safety Follow-up Visits, the 
same assessments as on the Day 8 and Day 21 visits, respectively, will be performed.
Withdrawal From the Study
A subject will be withdrawn from the study for any of the following reasons:

Lost to follow-up.

Withdrawal of consent.

Death.

The subject is poorly compliant with study procedures, study drug administration, visits, and 
assessments, after evaluation and discussion between the investigator and sponsor.

Decision by the sponsor to stop or cancel the study.

Decision by the investigator to withdraw subjects.

Decision by local regulatory authorities and Independent Ethics Committee (IEC)/
Institutional Review Board (IRB) to stop or cancel the study.
Subjects who withdraw consent during the follow-up phase will be offered an optional Safety 
Follow-up Visit. At the Safety Follow-up Visits, the same assessments as on the Day 21 visits 
will be performed.
If a subject is lost to follow-up, every reasonable effort must be made by the study-site personnel 
to contact the subject and determine the reason for discontinuation/withdrawal. The measures 
taken to follow up must be documented.
When a subject withdraws before completing the study, the reason for withdrawal is to be 
documented in the eCRF and in the source document. Study drug assigned to the withdrawn 
subject may not be assigned to another subject.


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10.3.
Withdrawal From the Use of Research Samples
A subject who withdraws from the study will have the following options regarding the optional
research samples:

The collected samples will be retained and used in accordance with the subject's original 
separate informed consent for optional research samples.

The subject may withdraw consent for exploratory biomarker research, in which case the 
samples will be destroyed and no further testing will take place. To initiate the sample 
destruction process, the investigator must notify the sponsor study site contact of withdrawal 
of consent for the optional research samples and to request sample destruction. The sponsor 
study site contact will, in turn, contact the biomarker representative to execute sample 
destruction. If requested, the investigator will receive written confirmation from the sponsor 
that the samples have been destroyed.
Withdrawal From the Use of Samples in Future Research
The subject may withdraw consent for use of samples for research (refer to Section 16.2.5). In 
such a case, samples will be destroyed after they are no longer needed for the clinical study. 
Details of the sample retention for research are presented in the main ICF.
11.
STATISTICAL METHODS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below. Specific details will be provided in the Statistical Analysis Plan (SAP).
11.1.
Interim Analysis
An interim analysis, encompassing efficacy, safety, and pharmacokinetics is planned after at 
least 36 subjects have been dosed and have completed the assessments of Day 8 as planned in the 
TIME AND EVENTS SCHEDULE. Enrollment will not be paused during the interim analysis.
Investigators, subject(s) and local sponsor representatives will remain blinded. The central 
sponsor team members will be unblinded at time of the interim analysis.
Further details regarding the interim analysis will be specified in an interim SAP.
The central sponsor team members will review the unblinded interim efficacy, safety, and 
pharmacokinetic analyses and will make recommendations to the DRC regarding possible 
changes to the design of the study: dropping the lower dose, changing the stratification factor 
(and/or the requirement of maximum 50% of all enrolled subjects with symptom onset >3 days 
before randomization), changing the maximum number of days between RSV symptom onset 
and randomization and/or the number of time points/visits for collecting a nasal swab by HCP. 
The DRC will decide on the implementation of the recommendations based on the review of the 
results and other ongoing studies of JNJ-53718678 (see Section 11.9). The DRC will consist of 
senior sponsor personnel outside of the central sponsor team and not involved in study conduct.


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Additional interim analyses may be performed at the sponsor’s discretion to support decision 
making for further development of JNJ-53718678 and to support interactions with health 
authorities.
The primary (final) analysis will be performed after the last subject has completed his/her last 
visit of the study.
11.2.
Subject Information
For all subjects who receive at least 1 dose of study drug descriptive statistics will be provided.
All demographic (eg, age, length, weight, race, gender) and other initial subject characteristics
(physical examination, medical and surgical history, family history, concomitant diseases) will 
be tabulated and analyzed descriptively by treatment group.
11.3.
Sample Size Determination
The interim results (estimates of mean AUC and change from baseline of RSV viral load ±SD) 
of study 53718678RSV1005 were the basis of the sample size calculation. In that study, median 
(range) time to onset of symptoms was 5 (2-12) days and baseline viral load was 5.3 (2.1-8.3) 
log10 copies/mL.
For the AUC viral load from Day 1 to Day 7, a (placebo) point estimate of 490 and an SD of 
135 log10 copies x hr/mL was observed for the AUC viral load from Day 1 to Day 7. The sample 
size was determined in order to obtain estimates of the mean AUC viral load with a precision of 
approximately 50 log10 copies x hr/mL of the true value with 90% confidence; with 20 subjects 
per treatment group the half-width of the 90% confidence would be approximately 52 and with
24 subjects per treatment group the precision would be approximately 47 log10 copies x hr/mL.
For the change from baseline (on Day 2 or Day 3), (placebo) point estimates of -0.11 and -0.33 
and SDs of 1.85 and 1.56 log10 copies/mL, respectively, were observed. The observed difference 
(active versus placebo) was -1 to -2 log10 copies/mL. With an assumed SD of 1.85 log10
copies/mL, 20 subjects per treatment group will lead to a precision (90% confidence interval [CI]
half width) of 0.986 and 24 subjects per treatment group to a precision of 0.896 log10 copies/mL
for the estimate of the difference between active dose and placebo .
As further guidance for the design, the power to detect a dose-response was calculated. To 
evaluate a potential dose-response, 3 contrasts will be tested: a contrast with no difference 
between the 2 active doses tested against placebo; a contrast with no difference between low 
dose and placebo tested against high dose; and a contrast with a linear dose-response relationship 
with respect to the active doses. No correction for multiplicity is considered in view of the 
exploratory nature of the study. Based on 10,000 simulations, and assuming a reduction in AUC 
viral load of 20% of high dose versus placebo, the power to detect a positive dose-response 
relationship will be between 79% and 86% (depending on the effect of the low dose) with a total 
sample size of 60, and between 83% and 89% with a total sample size of 72.


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To account for potential false-positive RSV screening testing (ie, diagnosed with RSV infection 
using a rapid PCR-based or rapid antigen-detection test, but negative at the central lab using a 
qRT-PCR assay, and therefore not included in the primary analysis population of ITT-i) and 
withdrawals from treatment for abnormal screening laboratory results, an overage of 
approximately 5% will be enrolled, ie, 75 subjects will be targeted.
In view of the seasonality of the disease, recruitment will be halted if at the end of an 
hemispheric RSV season 63 or more subjects have been enrolled and dosed. If at the end of an 
hemispheric RSV season the minimum of 63 dosed subjects is not reached, recruitment will 
continue in a next RSV season until this minimum has been reached, up to a maximum of 
75 subjects to be enrolled overall.
11.4.
Efficacy Analyses
The primary population for the efficacy/antiviral activity analysis will be the intent-to-treat 
infected population consisting of all randomized subjects who received at least one dose of study 
treatment and who have a central lab-confirmed RSV infection.
11.4.1.
Antiviral Effect
To explore the antiviral effect on RSV, as measured by qRT-PCR assay in mid-turbinate nasal 
swabs, the following virologic parameters will be assessed:

AUC from immediately prior to first dose of study drug (baseline) through Day 3, Day 5, 
Day 8, and Day 14

RSV viral load and change from baseline over time

Time to undetectable RSV viral load

Proportion of subjects with undetectable RSV viral load at each time point throughout the 
study
If feasible, the RSV infectious virus titers as measured by quantitative culture of RSV (plaque 
assay) on selected nasal swab samples, may also be assessed.
Endpoints will be analyzed graphically and descriptively as described in the SAP. For continuous 
variables descriptive statistics (n, mean, SD, median, minimum, and maximum) will be 
calculated. For viral efficacy parameters also 90% CIs will be computed comparing active dose 
groups versus placebo. For categorical variables, frequency tables will be presented. 
Kaplan-Meier Curves will be produced to graphically describe the time to event data.
To explore the antiviral effect, log10 viral load values over time will be analyzed using a 
restricted maximum likelihood-based repeated measures approach. Analyses will include the 
fixed, categorical effects of treatment, strata, visit, and treatment-by-visit interaction, as well as 
the continuous, fixed covariates of baseline log10 viral load and baseline log10 viral load by-visit 
interaction. An unstructured (co)variance structure will be used to model the within-subject 
errors over time. The differences in the AUCs for active versus placebo will be derived using 


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appropriate contrasts deriving least squares mean differences, including the 90% 2-sided CIs.
Details will be provided in the SAP.
Additional analyses will be performed to investigate other endpoints, including exploratory 
endpoints. Details on these analyses will be provided in the SAP.
11.4.2.
Clinical Severity and Clinical Course of RSV Infection
All data from PRO questionnaires for the assessment of the subject’s severity of RSV symptoms, 
health and functioning, and HRQOL (see Section 9.2.2) will be summarized descriptively by 
treatment group.
More details regarding the analysis of these data will be described in the SAP.
11.4.3.
Viral Sequencing
The sequencing results of the F-gene (and other regions of the RSV genome at the request of the 
protocol virologist) and changes from baseline will be summarized. Sequencing results may be 
presented in a separate report.
11.5.
Pharmacokinetic Analyses
Population pharmacokinetic analysis of concentration-time data of JNJ-53718678 will be 
performed using nonlinear mixed-effects modelling. An updated popPK model will be developed 
with the current adult data combined with those of selected Phase 1 studies to support a relevant 
structural model. Available subject characteristics (demographics, laboratory variables, etc.) will 
be tested as potential covariates affecting pharmacokinetic parameters. This updated model will 
be used for the final pharmacokinetic parameters estimation for each subject with available data. 
For each dose, descriptive statistics including arithmetic mean, SD, coefficient of variation, 
geometric mean, median, minimum, and maximum of the final pharmacokinetic parameters 
(AUC, Ctrough, and possibly Cmax) will be provided. The pharmacokinetic analyses will be 
detailed in an analysis plan. Analyses of other analytes (eg, excipients, metabolites) may be 
performed at the discretion of the sponsor.
A snapshot date for pharmacokinetic samples to be analyzed for the planned interim analysis will 
be defined. Samples collected before this snapshot date will be analyzed for JNJ-53718678 and 
included in the popPK analysis. Samples collected after the snapshot date will be analyzed at a 
later date, and may be included in a popPK re-analysis when they become available after interim 
analysis database lock.
Subjects will be excluded from the pharmacokinetic analysis if their data do not allow for 
accurate assessment of the pharmacokinetics (eg, incomplete administration of the study drug; 
missing information of dosing and sampling times; concentration data not sufficient for 
pharmacokinetic parameter calculation).
All concentrations below the lowest quantifiable concentration or missing data will be labeled as 
such in the concentration database. All subjects and samples excluded from the analysis will be 
clearly documented in the study report.


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For each treatment group, descriptive statistics, including arithmetic mean, SD, coefficient of 
variation, median, minimum, and maximum will be calculated for all individual derived 
pharmacokinetic parameters including exposure information of JNJ-53718678.
11.6.
Other Analyses
Biomarker Analyses
Statistical approaches to explore correlations between clinical outcome, viral load, and 
biomarkers in blood and mid-turbinate nasal swabs vary and depend on the different data types 
of the applied technology platforms, as well as on the extent of observed differences among 
study subjects. Analyses may be conducted at the sponsor’s discretion and reported separately 
from this study.
Pharmacokinetic/Pharmacodynamic Analyses
Relationships of JNJ-53718678 population-derived exposure parameters with selected antiviral 
activity parameters, clinical outcomes, and safety endpoints will be explored. These relationships 
will be presented in a tabular and/or graphical display.
Results of pharmacokinetic/pharmacodynamic analyses may be presented in a separate report.
11.7.
Medical Resource Utilization Analyses
Medical resource utilization will be descriptively summarized by treatment group.
11.8.
Safety Analyses
Safety data will be presented descriptively. No statistical testing of safety data is planned. For 
safety, baseline is defined as the last assessment prior to the first intake of study drug.
The population for the safety analysis will consist of all randomized subjects who received at 
least one dose of study drug.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the 
Medical Dictionary for Regulatory Activities. Treatment-emergent AEs are AEs with onset 
during the treatment phase or that are a consequence of a pre-existing condition that has
worsened since baseline. All reported AEs will be included in the analysis. For each AE, the 
percentage of subjects who experience at least 1 occurrence of the given event will be 
summarized by treatment group.
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those 
subjects who die, who discontinue treatment due to an AE, or who experience an AE of at least 
grade 3, or an SAE.


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Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test and by treatment. Descriptive 
statistics of absolute values and changes from baseline will be calculated for each laboratory 
analyte at baseline and at each scheduled time point.
The laboratory abnormalities will be determined according to the criteria specified in the DMID 
adult toxicity tables (see Attachment 1)and in accordance with the normal ranges of the clinical 
laboratory if no gradings are available.
Changes from baseline results will be presented in pre- versus posttreatment cross-tabulations
(with classes for below, within, and above normal ranges).
Urinary renal function parameters will be analyzed for the analyte as well as for the analyte ratio 
over urinary creatinine.
Laboratory abnormalities will be tabulated by scheduled time point.
Electrocardiogram
The effects on cardiovascular variables will be evaluated by means of descriptive statistics and 
frequency tabulations.
The ECG variables that will be analyzed are heart rate, PR interval, QRS interval, QT interval, 
and corrected QT (QTc) interval using the following correction methods: QT corrected according 
to Bazett's formula, and QTcF.1,12,14,23
Descriptive statistics of QTc intervals and changes from baseline will be summarized at each 
scheduled time point. The percentage of subjects with QTc interval >450 ms, >480 ms, or 
>500 ms will be summarized, as will the percentage of subjects with QTc interval increases from 
baseline >30 ms or >60 ms.
All clinically relevant abnormalities in ECG waveform that are changes from the baseline 
readings will be reported (eg, changes in T-wave morphology or the occurrence of U-waves).
The percentage of subjects with abnormalities (as defined in Attachment 4) will be tabulated by 
treatment.
Vital Signs
Descriptive statistics of blood pressure (systolic and diastolic) will be summarized at each 
scheduled time point. The percentage of subjects with values beyond clinically important limits 
(as defined in Attachment 4) will be summarized by treatment.
Physical Examination
Physical examination findings and changes from baseline will be listed at each scheduled time 
point.


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11.9.
Data Review Committee
A DRC, comprised of senior sponsor personnel outside of the central sponsor team and not 
involved in study conduct, will be established. The DRC will monitor safety data during study 
conduct on a regular basis and/or ad hoc in case of emergent safety signals identified through 
medical monitoring.
After the review of the accumulating safety data from this study, the DRC will make 
recommendations regarding the continuation of the study.
The central sponsor team members will review the unblinded interim efficacy, safety, and 
pharmacokinetic analyses and will make recommendations to the DRC regarding possible 
changes to the design of the study: dropping the lower dose, changing the stratification factor 
(and/or the requirement of maximum 50% of all enrolled subjects with symptom onset >3 days 
before randomization), changing the maximum number of days between RSV symptom onset 
and randomization and/or the number of time points/visits for collecting a nasal swab by HCP. 
The DRC will decide on the implementation of the recommendations based on the review of the 
interim results and other ongoing studies of JNJ-53718678. Given the challenges of ensuring 
study site preparation in time to recruit for an acute seasonal infection like RSV and the delays 
caused by implementing an amendment during an RSV season, the changes recommended by the 
study team and endorsed by the DRC will be communicated in writing to investigators, health 
authorities, and IECs/IRBs and will be implemented without amendment to this protocol.
Further details of the DRC, eg, composition and activities, will be described in the DRC charter.
12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of subjects, investigators, and the sponsor, and are mandated by 
regulatory agencies worldwide. The sponsor has established Standard Operating Procedures in 
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety 
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in 
accordance with those procedures.
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and 
nonleading verbal questioning of the subject is the preferred method to inquire about 
AE occurrence.
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study subject administered a medicinal 
(investigational or non-investigational) product. An AE does not necessarily have a causal 


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relationship with the treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational or non-investigational) product, whether or not related to that 
medicinal (investigational or non-investigational) product. (Definition per International Council 
for Harmonisation [ICH])
This includes any occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note: The sponsor collects AEs starting with the signing of the (diagnostic, if applicable) ICF
(refer to Section 12.3.1 for time of last AE recording).
Serious Adverse Event
An SAE based on ICH and European Union Guidelines on Pharmacovigilance for Medicinal 
Products for Human Use is any untoward medical occurrence that at any dose:

Results in death.

Is life-threatening.
(The subject was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.)

Requires inpatient hospitalization or prolongation of existing hospitalization.

Results in persistent or significant disability/incapacity.

Is a congenital anomaly/birth defect.

Is a suspected transmission of any infectious agent via a medicinal product.

Is medically important*.
*Medical and scientific judgment should be exercised in deciding whether expedited 
reporting is also 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 subject or may require intervention to prevent one of the other outcomes listed in the 
definition above. These should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal 
relationship between the study drug and the event (eg, death from anaphylaxis), the event must 
be reported as a serious and unexpected suspected adverse reaction even if it is a component of 
the study endpoint (eg, all-cause mortality).
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For JNJ-53718678, the expectedness of an AE will be 
determined by whether or not it is listed in the IB.


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Adverse Event Associated With the Use of the Drug
An AE is considered associated with the use of the drug if the attribution is possible, probable, or 
very likely by the definitions listed in Section 12.1.2.
12.1.2.
Attribution Definitions
Not Related
An AE that is not related to the use of the drug.
Doubtful
An AE for which an alternative explanation is more likely, eg, concomitant drug(s), concomitant 
disease(s), or the relationship in time suggests that a causal relationship is unlikely.
Possible
An AE that might be due to the use of the drug. An alternative explanation, eg, concomitant 
drug(s), concomitant disease(s), is inconclusive. The relationship in time is reasonable; therefore, 
the causal relationship cannot be excluded.
Probable
An AE that might be due to the use of the drug. The relationship in time is suggestive 
(eg, confirmed by dechallenge). An alternative explanation is less likely, eg, concomitant 
drug(s), concomitant disease(s).
Very Likely
An AE that is listed as a possible adverse reaction and cannot be reasonably explained by an 
alternative explanation, eg, concomitant drug(s), concomitant disease(s). The relationship in time 
is very suggestive (eg, it is confirmed by dechallenge and rechallenge).
12.1.3.
Severity Criteria
An assessment of severity grade will be made using the following general categorical 
descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
Severe: Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the subject (eg, laboratory abnormalities).


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12.2.
Special Reporting Situations
Safety events of interest on a sponsor study drug that may require expedited reporting or safety 
evaluation include, but are not limited to:

Overdose of a sponsor study drug.

Suspected abuse/misuse of a sponsor study drug.

Accidental or occupational exposure to a sponsor study drug.

Medication error involving a sponsor product (with or without subject exposure to the 
sponsor study drug, eg, name confusion).

Exposure to a sponsor study drug from breastfeeding.
Special reporting situations should be recorded in the eCRF. Any special reporting situation that 
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.
12.3.
Procedures
12.3.1.
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from 
the time a signed and dated ICF is obtained until completion of the subject's last study-related 
procedure, which may include contact for follow-up of safety. Serious AEs, including those 
spontaneously reported to the investigator within 30 days after the last dose of study drug, must 
be reported using the SAE Form. The sponsor will evaluate any safety information that is 
spontaneously reported by an investigator beyond the time frame specified in the protocol.
All events that meet the definition of an SAE will be reported as SAEs, regardless of whether 
they are protocol-specific assessments.
Signs and symptoms of RSV disease, such as rhinitis, rhinorrhea, nasal congestion, sneezing, 
nasopharyngitis, earache, malaise (tiredness), cough, shortness of breath and/or wheezing, 
muscle and/or joint pain, headache, fever, nasal blood spotting, and decreased oxygen saturation 
are part of the efficacy-related assessments and hence should not be reported as AEs.
All AEs, regardless of seriousness, severity, or presumed relationship to study drug, must be 
recorded using medical terminology in the source document and the eCRF. Whenever possible, 
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough, 
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory 
infection"). Investigators must record in the eCRF their opinion concerning the relationship of 
the AE to study therapy. All measures required for AE management must be recorded in the 
source document and reported according to sponsor instructions.
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities. 
The sponsor will also report to the investigator (and the head of the investigational institute 
where required) all suspected unexpected serious adverse reactions (SUSARs). The investigator 
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unless otherwise required and documented by the IEC/IRB. A SUSAR will be reported to 
regulatory authorities unblinded. Participating investigators and IEC/IRB will receive a blinded 
SUSAR summary, unless otherwise specified.
For all studies with an outpatient phase, including open-label studies, the subjects must be
provided with a "wallet (study) card" and instructed to carry this card with them for the duration 
of the study indicating the following:

Study number.

Statement, in the local language(s), that the subject is participating in a clinical study.

Investigator's name and 24-hour contact telephone number.

Local sponsor's name and 24-hour contact telephone number (for medical staff only).

Site number.

Subject number.

Any other information that is required to do an emergency breaking of the blind.
12.3.2.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor contact person 
by study-site personnel within 24 hours of their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor using the SAE Form, which must 
be completed and signed by a physician from the study site, and transmitted to the sponsor 
within 24 hours. The initial and follow-up reports of an SAE should be made by facsimile (fax).
All SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the subject's participation in the study, must be followed until any of the 
following occurs:

The event resolves.

The event stabilizes.

The event returns to baseline, if a baseline value/status is available.

The event can be attributed to agents other than the study drug or to factors unrelated to 
study conduct.

It becomes unlikely that any additional information can be obtained (subject or HCP refusal 
to provide additional information, lost to follow-up after demonstration of due diligence 
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Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE. 
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the 
course of a subject's participation in a study must be reported as an SAE, except hospitalizations 
for the following:

Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as 
pending placement in long-term care facility).

Surgery or procedure planned before entry into the study (must be documented in the 
eCRF). 
Note: Hospitalizations that were planned before the signing of the ICF, and where the 
underlying condition for which the hospitalization was planned has not worsened, will not 
be considered SAEs. Any AE that results in a prolongation of the originally planned 
hospitalization is to be reported as a new SAE.
The cause of death of a subject in a study within 30 days of the last dose of study drug, whether 
or not the event is expected or associated with the study drug, is considered an SAE.
12.3.3.
Pregnancy
All initial reports of pregnancy in female subjects or partners of male subjects must be reported 
to the sponsor by the study-site personnel within 24 hours of their knowledge of the event using 
the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous 
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs
and must be reported using the SAE Form. Any subject who becomes pregnant during the study 
must be promptly withdrawn from the study and discontinue further study treatment.
Because the study drug may have an effect on sperm, pregnancies in partners of male subjects 
included in the study will be reported as noted above.
Follow-up information regarding the outcome of the pregnancy and any post-natal sequelae in 
the infant will be required.
12.4.
Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.
13.
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, 
durability, or reliability of a product, including its labeling or package integrity. A PQC may have 
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and 
analysis of PQC information from studies are crucial for the protection of subjects, investigators, 
and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor has 
established procedures in conformity with regulatory requirements worldwide to ensure 


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appropriate reporting of PQC information; all studies conducted by the sponsor or its affiliates 
will be conducted in accordance with those procedures.
13.1.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after 
being made aware of the event.
If the defect is combined with an SAE, the study-site personnel must report the PQC to the 
sponsor according to the SAE reporting timelines (refer to Section 12.3.2). A sample of the 
suspected product should be maintained for further investigation if requested by the sponsor.
13.2.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact Information page(s), which will be 
provided as a separate document.
14.
STUDY DRUG INFORMATION
14.1.
Physical Description of Study Drug(s)
JNJ-53718678 supplied for this study is formulated as an oral solution containing 10 mg/mL 
JNJ-53718678-AAA drug substance, HP-β-CD, acetic acid, sodium hydroxide, concentrated 
hydrochloride acid, sucralose, strawberry flavor, and purified water. It will be manufactured and 
provided under the responsibility of the sponsor.
The matching placebo consists of the oral vehicle solution without active drug substance. The 
placebo solution will be manufactured and provided under the responsibility of the sponsor.
14.2.
Packaging
JNJ-53718678 and placebo will be packed in appropriate containers under responsibility of the 
sponsor. Multiple containers will be required to cover the entire dose schedule.
Secondary packaging will be child-resistant to accommodate outpatient use.
Packaging and labeling of JNJ-53718678 and placebo will be done in a double-blind way.
No study drugs can be repacked without prior approval from the sponsor.
14.3.
Labeling
Study drug labels will contain information to meet the applicable regulatory requirements.
14.4.
Handling and Storage
All study drug should be stored on site in the original package at controlled temperatures ranging 
from 2°C to 8°C. It will be advised to also store the study drugs at temperatures between 2°C to 
8°C at the subjects’ homes.


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Refer to the pharmacy manual/study site investigational product and procedures manual for 
additional guidance on study drug handling and storage.
14.5.
Drug Accountability
The investigator is responsible for ensuring that all study drug received at the site is inventoried 
and accounted for throughout the study. The dispensing of study drug to the subject, and the 
return of study drug from the subject (if applicable), must be documented on the drug 
accountability form. Subjects, or their legally acceptable representatives where applicable, must 
be instructed to return all original containers, whether empty or containing study drug. The study 
drug administered to the subject must be documented on the drug accountability form. All study 
drug will be stored and disposed of according to the sponsor's instructions. Study-site personnel
must not combine contents of the study drug containers.
Study drug must be handled in strict accordance with the protocol and the container label, and 
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused study drug, and study drug returned by the subject, must be 
available for verification by the sponsor's study site monitor during on-site monitoring visits. The 
return to the sponsor of unused study drug, or used returned study drug for destruction, will be 
documented on the drug return form. When the study site is an authorized destruction unit and 
study drug supplies are destroyed on-site, this must also be documented on the drug return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for drug accountability purposes.
Study drug should be dispensed under the supervision of the investigator or a qualified member 
of the study-site personnel, or by a hospital/clinic pharmacist. Study drug will be supplied only 
to subjects participating in the study. Returned study drug must not be dispensed again, even to 
the same subject. Study drug may not be relabeled or reassigned for use by other subjects. The 
investigator agrees neither to dispense the study drug from, nor store it at, any site other than the 
study sites agreed upon with the sponsor.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

JNJ-53718678 IB and any addenda.

Pharmacy manual/study site investigational product and procedures manual.

Laboratory manual.

Electronic device for assessments of patient-reported symptoms and functioning, EQ-5D-5L, 
and for recording of study and concomitant medication, temperature, and swabbing in the 
respective logs and completion guidelines.

Thermometers for subjects to measure body temperature at home during treatment and 
follow-up.


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
Specimen collection kits for pharmacokinetic, safety blood, and urine samples and 
mid-turbinate nasal swabs.

Contact information page(s).

Dose dispensing instructions.

IWRS manual.

eCRF and ePRO/logs completion guidelines.
16.
ETHICAL ASPECTS
16.1.
Study-Specific Design Considerations
Potential subjects will be fully informed of the risks and requirements of the study and, during the 
study, subjects will be given any new information that may affect their decision to continue 
participation. They will be told that their consent to participate in the study is voluntary and may be 
withdrawn at any time with no reason given and without penalty or loss of benefits to which they 
would otherwise be entitled. Only subjects who are fully able to understand the risks, benefits, and 
potential AEs of the study, and provide their consent voluntarily will be enrolled.
The total blood volume to be collected is considered to be acceptable.
16.2.
Regulatory Ethics Compliance
16.2.1.
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and 
country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human subjects. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
16.2.2.
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the 
IEC/IRB with current and complete copies of the following documents (as required by local 
regulations):

Final protocol and, if applicable, amendments.

Sponsor-approved ICF (and any other written materials to be provided to the subjects).

Investigator’s Brochure (or equivalent information) and amendments/addenda.

Sponsor-approved subject recruiting materials.


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
Information on compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable.

Investigator’s curriculum vitae or equivalent information (unless not required, as 
documented by the IEC/IRB).

Information regarding funding, name of the sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for subjects.

Any other documents that the IEC/IRB requests to fulfill its obligation.
This study will be undertaken only after the IEC/IRB has given full approval of the final 
protocol, amendments (if any, excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct, unless required locally), the ICF, applicable 
recruiting materials, and subject compensation programs, and the sponsor has received a copy of 
this approval. This approval letter must be dated and must clearly identify the IEC/IRB and the 
documents being approved.
During the study the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct).

Revision(s) to ICF and any other written materials to be provided to subjects.

If applicable, new or revised subject recruiting materials approved by the sponsor.

Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable.

New edition(s) of the IB and amendments/addenda.

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually).

Reports of AEs that are serious, unlisted/unexpected, and associated with the study drug.

New information that may adversely affect the safety of the subjects or the conduct of the 
study.

Deviations from or changes to the protocol to eliminate immediate hazards to the subjects.

Report of deaths of subjects under the investigator's care.

Notification if a new investigator is responsible for the study at the site.

Development Safety Update Report and Line Listings, where applicable.

Any other requirements of the IEC/IRB.
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of 
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At least once a year, the IEC/IRB will be asked to review and reapprove this study, where 
required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB 
about the study completion (if applicable, the notification will be submitted through the head of 
investigational institution).
16.2.3.
Informed Consent
Each subject (or a legally acceptable representative) must give written consent according to local 
requirements after the nature of the study has been fully explained. The ICF(s) must be signed 
before performance of any study-related activity. The ICF that is used must be approved by both 
the sponsor and by the reviewing IEC/IRB and be in a language that the subject can read and 
understand. The informed consent should be in accordance with principles that originated in the 
Declaration of Helsinki, current ICH and GCP guidelines, applicable regulatory requirements, 
and sponsor policy.
Prior to signing the main consent form for the study, patients may specifically allow for the 
collection and testing of nasal mid-turbinate swabs by signing the pre-screening (diagnostic) ICF
if such testing is not standard of care at the investigational site.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects or their legally acceptable representatives the aims, 
methods, reasonably anticipated benefits, and potential hazards of the study, and any discomfort 
participation in the study may entail. Subjects will be informed that their participation is 
voluntary and that they may withdraw consent to participate at any time. They will be informed 
that choosing not to participate will not affect the care the subject will receive for the treatment 
of his or her disease. Subjects will be told that alternative treatments are available if they refuse 
to take part and that such refusal will not prejudice future treatment. Finally, they will be told 
that the investigator will maintain a subject identification register for the purposes of long-term 
follow up if needed and that their records may be accessed by health authorities and authorized 
sponsor personnel without violating the confidentiality of the subject, to the extent permitted by 
the applicable law(s) or regulations. By signing the ICF the subject or legally acceptable 
representative is authorizing such access, which includes permission to obtain information about 
his or her survival status. It also denotes that the subject agrees to allow his or her study 
physician to recontact the subject for the purpose of obtaining consent for additional safety 
evaluations, and subsequent disease-related treatments, if needed.
The subject or legally acceptable representative will be given sufficient time to read the ICF and 
the opportunity to ask questions. After this explanation and before entry into the study, consent 
should be appropriately recorded by means of either the subject's or his or her legally acceptable 
representative's personally dated signature. After having obtained the consent, a copy of the ICF
must be given to the subject.
If the subject or legally acceptable representative is unable to read or write, an impartial witness 
should be present for the entire informed consent process (which includes reading and explaining 


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all written information) and should personally date and sign the ICF after the oral consent of the 
subject or legally acceptable representative is obtained.
When prior consent of the subject is not possible and the subject's legally acceptable 
representative is not available, enrollment procedures should be described in the protocol with 
documented approval/favorable opinion by the IEC/IRB to protect the rights, safety, and well-
being of the subject and to ensure compliance with applicable regulatory requirements. The 
subject or legally acceptable representative must be informed about the study as soon as possible 
and give consent to continue.
16.2.4.
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must be 
put in place. Sponsor personnel whose responsibilities require access to personal data agree to 
keep the identity of subjects confidential.
The informed consent obtained from the subject (or his or her legally acceptable representative)
includes explicit consent for the processing of personal data and for the investigator/institution to 
allow direct access to his or her original medical records (source data/documents) for 
study-related monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also 
addresses the transfer of the data to other entities and to other countries.
The subject has the right to request through the investigator access to his or her personal data and 
the right to request rectification of any data that are not correct or complete. Reasonable steps 
will be taken to respond to such a request, taking into consideration the nature of the request, the 
conditions of the study, and the applicable laws and regulations.
Exploratory biomarker and pharmacokinetic research is not conducted under standards 
appropriate for the return of data to subjects. In addition, the sponsor cannot make decisions as to 
the significance of any findings resulting from exploratory research. Therefore, exploratory 
research data will not be returned to subjects or investigators, unless required by law or local 
regulations. Privacy and confidentiality of data generated in the future on stored samples will be 
protected by the same standards applicable to all other clinical data.
16.2.5.
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local 
regulations) for additional research. Samples will only be used to understand JNJ-53718678, to 
understand RSV infection, to understand differential drug responders, and to develop tests/assays 
related to JNJ-53718678 and RSV infection.  The research may begin at any time during the 


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study or the post-study storage period. No human genetic testing will be performed on these 
samples.
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Subjects may withdraw their consent for their samples to be 
stored for research (refer to Section 10.3).
16.2.6.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise 
help ensure access to the developed product if the need for the product persists, unless explicitly 
addressed as a specific ethical consideration in Section 16.1.
17.
ADMINISTRATIVE REQUIREMENTS
17.1.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment 
by the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by 
the investigator. Protocol amendments must not be implemented without prior IEC/IRB 
approval, or when the relevant competent authority has raised any grounds for non-acceptance, 
except when necessary to eliminate immediate hazards to the subjects, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
sponsor. When the change(s) involves only logistic or administrative aspects of the study, the 
IEC/IRB (where required) only needs to be notified.
The central sponsor team members will review the unblinded interim efficacy, safety, and 
pharmacokinetic analyses and will make recommendations to the DRC regarding possible 
changes to the design of the study: dropping the lower dose, changing the stratification factor 
(and/or the requirement of maximum 50% of all enrolled subjects with symptom onset >3 days 
before randomization), changing the maximum number of days between RSV symptom onset 
and randomization and/or the number of time points/visits for collecting a nasal swab by HCP. 
The DRC will decide on the implementation of the recommendations based on the review of the 
interim results and other ongoing studies of JNJ-53718678. Given the challenges of ensuring 
study site preparation in time to recruit for an acute seasonal infection like RSV and the delays 
caused by implementing an amendment during an RSV season, the changes recommended by the 
study team and endorsed by the DRC will be communicated in writing to investigators, health 
authorities, and IECs/IRBs and will be implemented without amendment to this protocol.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor 
representative listed in the Contact Information page(s), which will be provided as a separate
document. Except in emergency situations, this contact should be made before implementing any 
departure from the protocol. In all cases, contact with the sponsor must be made as soon as 
possible to discuss the situation and agree on an appropriate course of action. The data recorded 


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in the eCRF and source documents will reflect any departure from the protocol, and the source 
documents will describe this departure and the circumstances requiring it.
17.2.
Regulatory Documentation
17.2.1.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
17.2.2.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study drug to the 
study site:

Protocol and amendment(s), if any, signed and dated by the principal investigator

A copy of the dated and signed (or sealed, where appropriate per local regulations), written 
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if 
applicable, subject compensation programs. This approval must clearly identify the specific 
protocol by title and number and must be signed (or sealed, where appropriate per local 
regulations) by the chairman or authorized designee.

Name and address of the IEC/IRB, including a current list of the IEC/IRB members and 
their function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, 
from the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 
member of the study-site personnel is a member of the IEC/IRB, documentation must be 
obtained to state that this person did not participate in the deliberations or in the 
vote/opinion of the study.

Regulatory authority approval or notification, if applicable.

Signed and dated statement of investigator (eg, Form FDA 1572), if applicable.

Documentation of investigator qualifications (eg, curriculum vitae).

Completed investigator financial disclosure form from the principal investigator, where 
required.

Signed and dated Clinical Trial Agreement, which includes the financial agreement.

Any other documentation required by local regulations.
The following documents must be provided to the sponsor before enrollment of the first subject:

Completed investigator financial disclosure forms from all subinvestigators.

Documentation of subinvestigator qualifications (eg, curriculum vitae).

Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable.


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
Local 
laboratory 
documentation 
demonstrating 
competence 
and 
test 
reliability 
(eg, accreditation/license), if applicable.
17.3.
Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy 
identification of each subject during and after the study. This document will be reviewed by the 
sponsor study-site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by 
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All 
reports and communications relating to the study will identify subjects by subject identification
and date of birth (as allowed by local regulations). In cases where the subject is not randomized 
into the study, the date seen and date of birth (as allowed by local regulations) will be used.
The investigator must also complete a subject screening log, which reports on all subjects who 
were seen to determine eligibility for inclusion in the study.
17.4.
Source Documentation
At a minimum, source documents consistent in the type and level of detail with those commonly 
recorded at the study site as a basis for standard medical care must be available for the following: 
subject identification, eligibility, and study identification; study discussion and date of signed 
informed consent; dates of visits; results of safety and efficacy parameters as required by the 
protocol; record of all AEs and follow-up of AEs; concomitant medication; drug 
receipt/dispensing/return records; study drug administration information; and date of study 
completion and reason for early discontinuation of study drug or withdrawal from the study, if 
applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring 
guidelines (or other equivalent document).
The following data may be recorded directly into the eCRF and will be considered source data: 

Race.

History of smoking and all nicotine use, eg, cigarettes (including e-cigarettes or the
equivalent of e-cigarettes), cigars, chewing tobacco, patch, gum.

Blood pressure and heart rate.

Height and weight.

Details of physical examination.


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The minimum source documentation requirements for Section 4.1 and Section 4.2 that specify a 
need for documented medical history are as follows:

Referral letter from treating physician or

Complete history of medical notes at the site

Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by subject interview or other protocol-required assessment (eg, physical examination, 
laboratory assessment) and documented in the source documents.
An electronic source system may be utilized, which contains data traditionally maintained in a 
hospital or clinic record to document medical care (eg, electronic source documents) as well as 
the clinical study-specific data fields as determined by the protocol. This data is electronically 
extracted for use by the sponsor. If the electronic source system is utilized, references made to 
the eCRF in the protocol include the electronic source system but information collected through 
the electronic source system may not be limited to that found in the eCRF. Data in this system 
may be considered source documentation.
17.5.
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each subject in electronic format.
All data relating to the study must be recorded in eCRF. All eCRF entries, corrections, and 
alterations must be made by the investigator or authorized study-site personnel. The investigator 
must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any 
such worksheets will become part of the subject's source documents. Data must be entered into 
eCRF in English. The eCRF must be completed as soon as possible after a subject visit and the 
forms should be available for review at the next scheduled monitoring visit.
All subjective measurements (eg, pain scale information or other questionnaires) will be 
completed by the same individual who made the initial baseline determinations whenever 
possible.
If necessary, queries will be generated in the electronic data capture (eDC) tool. If corrections to 
an eCRF are needed after the initial entry into the eCRF, this can be done in either of the 
following ways:

Investigator and study-site personnel can make corrections in the eDC tool at their own 
initiative or as a response to an auto query (generated by the eDC tool).

Sponsor or sponsor delegate can generate a query for resolution by the investigator and 
study-site personnel.


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17.6.
Patient-Reported Assessments
Patient-reported assessments (see Attachment 2, Attachment 3, Attachment 6, and Attachment 7) 
will be completed on an electronic device provided to the subject at the study-site. Responses 
provided will be recorded directly in the electronic database.
The subject will provide information about his/her health status, symptoms, and functional 
status, as well as on his/her HRQOL, on an electronic device at time points noted in the TIME 
AND EVENTS SCHEDULE. In addition, the subject will record study drug intake on the 
electronic device in medication logs. The date and time of nasal swabs collected at home during 
the study will also be recorded on the electronic device in a swabbing log. The subject will also 
complete temperature logs at home. All subject self-assessments and logs will be provided in the 
native language of the subject. The electronic device will include instructions and training that 
will be completed upon first use by the subject (or by the subject’s spouse, partner, relative, or 
friend) and will be available on demand thereafter if the subject chooses this option. If the 
subject is unable to complete the assessments on the electronic device, the subject’s spouse, 
partner, relative, or friend who has completed the training on use of the electronic device can 
read the questions and response options aloud to the subject and enter the subject’s responses in 
the electronic device on the subject’s behalf. At screening and on Day 1, if the subject is unable 
to complete the assessment on the device and the subject’s spouse, partner, relative, or friend is 
not available to enter the subject’s responses on the device for the subject, trained study-site 
personnel can read the questions and response options to the subject and record the subject’s 
responses on the device on the subject’s behalf. Investigational staff will regularly (preferably 
daily) review the completion of the assessments of patient-reported symptoms and functioning
and the logs once data is transmitted from the electronic device and contact the subject in case 
there are issues identified with completion of the assessments.
17.7.
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study sites, review of protocol procedures with the investigator and 
study-site personnel before the study, and periodic monitoring visits by the sponsor, and direct 
transmission of clinical laboratory data from a central laboratory into the sponsor's database.
Written instructions will be provided for collection, handling, storage, and shipment of samples. 
Guidelines for eCRF completion will be provided and reviewed with study-site personnel before 
the start of the study. The sponsor will review eCRF for accuracy and completeness during 
on-site monitoring visits and after transmission to the sponsor; any discrepancies will be resolved 
with the investigator or designee, as appropriate. After upload of the data into the study database 
they will be verified for accuracy and consistency with the data sources.
17.8.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF 
and all source documents that support the data collected from each subject, as well as all study 
documents as specified in ICH/GCP Section 8, and all study documents as specified by the 


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applicable regulatory requirement(s). The investigator/institution will take measures to prevent 
accidental or premature destruction of these documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents will be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the sponsor. It is the responsibility of the sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The sponsor must be notified in writing of the name and address of the 
new custodian. Under no circumstance shall the investigator relocate or dispose of any study 
documents before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such 
reports.
17.9.
Monitoring
The sponsor will use a combination of monitoring techniques as specified in the monitoring 
guidelines to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study site visit log that will be kept at the study site. The first 
post-initiation visit will be made as soon as possible after enrollment has begun. At these visits, 
the monitor will compare the data entered into the eCRF with the source documents
(eg, hospital/clinic/physician’s office medical records); a sample may be reviewed. The nature 
and location of all source documents will be identified to ensure that all sources of original data 
required to complete the eCRF are known to the sponsor and study-site personnel and are 
accessible for verification by the sponsor study-site contact. If electronic records are maintained 
at the study site, the method of verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of 
verifying that the recorded data are consistent with the original source data. Findings from this 
review will be discussed with the study-site personnel. The sponsor expects that, during 
monitoring visits, the relevant study-site personnel will be available, the source documents will 
be accessible, and a suitable environment will be provided for review of study-related 
documents. The monitor will meet with the investigator on a regular basis during the study to 
provide feedback on the study conduct.


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In addition to on-site monitoring visits, remote contacts can occur. It is expected that during 
these remote contacts, study-site personnel will be available to provide an update on the progress 
of the study at the site.
17.10. Study Completion/Termination
17.10.1.
Study Completion/End of Study
The study is considered completed with the last visit for the last subject participating in the 
study. The final data from the study site will be sent to the sponsor (or designee) after completion 
of the final subject visit at that study site, in the time frame specified in the Clinical Trial 
Agreement.
17.10.2.
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. 
A study site is considered closed when all required documents and study supplies have been 
collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, the sponsor's procedures, or GCP guidelines.

Inadequate recruitment of subjects by the investigator.

Discontinuation of further study drug development.
17.11. On-Site Audits
Representatives of the sponsor's clinical quality assurance department may visit the study site at 
any time during or after completion of the study to conduct an audit of the study in compliance 
with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection. Subject privacy must, however, be 
respected. The investigator and study-site personnel are responsible for being present and 
available for consultation during routinely scheduled study-site audit visits conducted by the 
sponsor or its designees. 
Similar auditing procedures may also be conducted by agents of any regulatory body, either as 
part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.


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17.12. Use of Information and Publication
All information, including but not limited to information regarding JNJ-53718678 or the 
sponsor's operations (eg, patent application, formulas, manufacturing processes, basic scientific 
data, prior clinical data, formulation information) supplied by the sponsor to the investigator and 
not previously published, and any data, including exploratory biomarker research data, generated 
as a result of this study, are considered confidential and remain the sole property of the sponsor. 
The investigator agrees to maintain this information in confidence and use this information only 
to accomplish this study, and will not use it for other purposes without the sponsor's prior written 
consent.
The investigator understands that the information developed in the study will be used by the 
sponsor in connection with the continued development of JNJ-53718678, and thus may be 
disclosed as required to other clinical investigators or regulatory agencies. To permit the 
information derived from the clinical studies to be used, the investigator is obligated to provide 
the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and 
will contain data from all study sites that participated in the study as per protocol. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 
study will be used to determine a coordinating investigator. Results of exploratory biomarker
analyses performed after the Clinical Study Report has been issued will be reported in a separate 
report and will not require a revision of the Clinical Study Report. Results of the viral 
sequencing analysis may be reported in a separate report and will not require a revision of the 
Clinical Study Report. Study subject identifiers will not be used in publication of results. Any 
work created in connection with performance of the study and contained in the data that can 
benefit from copyright protection (except any publication by the investigator as provided for 
below) shall be the property of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines, the sponsor shall have the right to publish such primary (multicenter) data 
and information without approval from the investigator. The investigator has the right to publish 
study site-specific data after the primary data are published. If an investigator wishes to publish 
information from the study, a copy of the manuscript must be provided to the sponsor for review 
at least 60 days before submission for publication or presentation. Expedited reviews will be 
arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in 
writing, the investigator will withhold such publication for up to an additional 60 days to allow 
for filing of a patent application. In the event that issues arise regarding scientific integrity or 
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor 
will not mandate modifications to scientific content and does not have the right to suppress 
information. For multicenter study designs and substudy approaches, secondary results generally
should not be published before the primary endpoints of a study have been published. Similarly, 
investigators will recognize the integrity of a multicenter study by not submitting for publication 
data derived from the individual study site until the combined results from the completed study
have been submitted for publication, within 12 months of the availability of the final data (tables, 


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listings, graphs), or the sponsor confirms there will be no multicenter study publication. 
Authorship of publications resulting from this study will be based on the guidelines on 
authorship, such as those described in the Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals, which state that the named authors must have made a significant 
contribution to the design of the study or analysis and interpretation of the data, provided critical 
review of the paper, and given final approval of the final version.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as 
required by law.


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Open Forum Infectious Diseases. 2016:3; Issue suppl_1.
5.
DeVincenzo JP, McClure MW, Symons JA, et al. Activity of Oral ALS-008176 in a respiratory syncytial virus 
challenge study. N Engl J Med. 2015;373:2048-2058.
6.
DeVincenzo JP, Whitley RJ, Mackman RL, et al. GS-5806 activity in a respiratory syncytial virus challenge 
study. N Engl J Med. 2014;371:711-722.
7.
DeVincenzo JP, Wilkinson T, Vaishnaw A, et al. Viral load drives disease in humans experimentally infected 
with respiratory syncytial virus. Am. J. Respir. Crit. Care Med. 2010;182(10):1305-1314.
8.
El Saleeby CM, Bush AJ, Harrison LM, et al. Respiratory syncytial virus load, viral dynamics, and disease 
severity in previously healthy naturally infected children. J. Infect. Dis. 2011;204(7):996-1002.
9.
Empey KM, Peebles Jr RS, Kolls JK. Pharmacologic Advances in the Treatment and Prevention of Respiratory 
Syncytial Virus. Clin Infect Dis. 2010;50(9):1258–1267.
10.
Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in the elderly 
and high-risk adults, N Engl J Med. 2005;352(17):1749-1759.
11.
Falsey AR, Walsh EE. Respiratory syncytial virus infection in elderly adults. Drugs Aging. 2005;22:577-587.
12.
Fleming DM, Taylor RJ, Lustig RL, et al. Modelling estimates of the burden of respiratory syncytial virus
infection in adults and the elderly in the United Kingdom. BMC Infect Dis. 2015;15:443.
13.
Hall CB, Long CE, Schnabel KC. Respiratory syncytial virus infections in previously healthy working adults. 
Clin Infect Dis. 2001;33:792-796.
14.
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for 
Human Use. ICH Harmonized Tripartite Guideline E14: Clinical evaluation of QT/QTc interval prolongation 
and proarrhythmic potential for non-antiarrhythmic drugs. ICH 12 May 2005.
15.
Investigator's Brochure for JNJ-53718678, Edition 04. Janssen Research & Development (September 2017).
16.
Kielian M, Rey FA. Virus membrane-fusion proteins: More than one way to make a hairpin. Nat. Rev. 
Microbiol. 2006;4(1):67-76.
17.
Lee N, Chan M, Lui G, et al. High viral load and respiratory failure in adults hospitalized for respiratory 
syncytial virus infections. J Infect Dis. 2015;212(8):1237-1240.
18.
Louie JK, Hacker JK, Gonzales R, et al. Characterization of viral agents causing acute respiratory infection in a 
San Francisco University Medical Center Clinic during the influenza season. Clin Infect Dis. 2005;41:822-828.
19.
McClure DL, Kieke BA, Sundaram ME, et al. Seasonal incidence of medically attended respiratory syncytial 
virus infection in a community cohort of adults ≥50 years old. PLoS One. 2014;9:e102586.
20.
National Institute of Allergy and Infectious Diseases. Division of Microbiology and Infectious Diseases 
(DMID) Adult toxicity tables. November 2007 (draft). Available on: 
https://www.niaid.nih.gov/sites/default/files/dmidadulttox.pdf. Accessed on 7 September 2017.
21.
Roymans D, Efficacy of JNJ-53718678 in a neonatal lamb model of RSV bronchiolitis, DR15003, 16/06/2015.


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Rudan I, Boschi-Pinto C, Biloglav Z, et al. Epidemiology and etiology of childhood pneumonia. Bull. World 
Health Organ. 2008;86(5):408-416.
23.
Sagie A, Larson MG, Goldberg RJ, et al. An improved method for adjusting the QT interval for heart rate (the 
Framingham Heart Study). Am J Cardiol. 1992;70:797-801.
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Tamiflu® (oseltamivir phosphate), Prescribing Information. Available on 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021087s057lbl.pdf.
Accessed on 7 September 2017.
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Thomas L, Huber AR. Renal function–estimation of glomerular filtration rate. Clin Chem Lab Med. 
2006;44(11):1295–302.
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Wainwright C. Acute viral bronchiolitis in children – a very common condition with few therapeutic options. 
Paediatr Respir Rev. 2010;11(1):39-45.
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Widmer K, Griffin MR, Zhu Y, et al. Respiratory syncytial virus- and human metapneumovirus-associated 
emergency department and hospital burden in adults. Influenza Other Respir Viruses. 2014;8:347-352.


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ATTACHMENTS
Attachment 1:
Toxicity Tables
DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASES (DMID) ADULT 
TOXICITY TABLE20 – NOVEMBER 2007
ABBREVIATIONS: Abbreviations utilized in the Table:
ULN = Upper Limit of Normal
LLN = Lower Limit of Normal 
Rx = Therapy
Req = Required
Mod = Moderate
IV = Intravenous
ADL = Activities of Daily Living
Dec = Decreased
ESTIMATING SEVERITY GRADE
For abnormalities NOT found elsewhere in the Toxicity Tables use the scale below to estimate 
grade of severity:
GRADE 1
Mild Transient or mild discomfort (< 48 hours); no medical 
intervention/therapy required
GRADE 2
Moderate Mild to moderate limitation in activity - some assistance may be 
needed; no or minimal medical intervention/therapy required
GRADE 3
Severe Marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalizations possible
GRADE 4
Life-threatening Extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or 
hospice care probable
SERIOUS OR LIFE-THREATENING AEs
ANY clinical event deemed by the clinician to be serious or life-threatening should be 
considered a grade 4 event. Clinical events considered to be serious or life-threatening include, 
but are not limited to: seizures, coma, tetany, diabetic ketoacidosis, disseminated intravascular 
coagulation, diffuse petechiae, paralysis, acute psychosis, severe depression.
COMMENTS REGARDING THE USE OF THESE TABLES

Standardized and commonly used toxicity tables (Division of AIDS, NCI’s Common 
Toxicity Criteria (CTC), and World Health Organization [WHO]) have been adapted for 
use by the Division of Microbiology and Infectious Diseases (DMID) and modified to 
better meet the needs of participants in DMID trials.

For parameters not included in the following Toxicity Tables, sites should refer to the 
“Guide For Estimating Severity Grade” located above.

Criteria are generally grouped by body system.

Some protocols may have additional protocol-specific grading criteria, which will 
supersede the use of these tables for specified criteria.


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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
9.5 - 10.5 gm/dL
8.0 - 9.4gm/dL
6.5 - 7.9 gm/dL
< 6.5 gm/dL
Absolute Neutrophil Count
1,000-1,500/ mm3
750-999/ mm3
500-749/ mm3
<500/ mm3
Platelets
75,000-
99,999/ mm3
50,000-
74,999/ mm3
20,000-49,999/ mm3
<20,000/ mm3
WBCs
11,000-13,000/
mm3
13,000-
15,000 / mm3
15,000-
30,000/ mm3
>30,000 or
<1,000 / mm3
% Polymorphonuclear
Leucocytes + Band Cells
> 80%
90 – 95%
>95%
----------
Abnormal Fibrinogen
Low:
100-200 mg/dL
High:
400-600 mg/dL
Low:
<100 mg/dL
High:
>600 mg/dL
Low:
< 50 mg/dL
----------
Fibrinogen
associated with gross 
bleeding or with 
disseminated 
coagulation
Fibrin Split Product
20-40 mcg/ mL
41-50 mcg/ mL
51-60 mcg/ mL
> 60 mcg/ mL
Prothrombin Time (PT)
1.01 - 1.25 x ULN
1.26-1.5 x ULN
1.51 -3.0 x ULN
>3 x ULN
Activated Partial 
Thromboplastin (APPT)
1.01 -1.66 x ULN
1.67 - 2.33 x ULN
2.34 - 3 x ULN
> 3 x ULN
Methemoglobin
5.0 - 9.9 %
10.0 - 14.9 %
15.0 - 19.9%
> 20.0 %


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CHEMISTRIES
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia
130-135 mEq/ L
123-129 mEq/ L
116-122 mEq/ L
< 116 mEq/ L or abnormal sodium 
with mental
status changes or seizures
Hypernatremia
146-150 mEq/ L
151-157 mEq/ L
158-165 mEq/ L
> 165 mEq/ L or abnormal sodium 
with mental
status changes or seizures
Hypokalemia
3.0 - 3.4 mEq/ L
2.5 - 2.9 mEq/ L
2.0 - 2.4 mEq/ L or 
intensive replacement 
therapy or 
hospitalization 
required
< 2.0 mEq/ L or abnormal 
potassium with
paresis, ileus or life-threatening 
arrhythmia
Hyperkalemia
5.6 - 6.0 mEq/ L
6.1 - 6.5 mEq/ L
6.6 - 7.0 mEq/l
> 7.0 mEq/ L or abnormal
potassium with life-threatening 
arrhythmia
Hypoglycemia
55-64 mg/dL
40-54 mg/dL
30-39 mg/dL
<30 mg/dL or abnormal glucose 
with mental
status changes or coma
Hyperglycemia
(nonfasting and no 
prior diabetes)
116 - 160 mg/dL 161- 250 mg/d L
251 - 500 mg/dL
> 500 mg/dL or abnormal glucose 
with ketoacidosis or seizures
Hypocalcemia
(corrected for 
albumin)
8.4 - 7.8 mg/dL
7.7 - 7.0 mg/dL
6.9 - 6.1 mg/dL
< 6.1 mg/dL or abnormal
calcium with life-threatening 
arrhythmia or tetany


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CHEMISTRIES (continued)
Grade 1
Grade 2
Grade 3
Grade 4
Hypercalcemia (correct for 
albumin)
10.6 - 11.5 mg/dL
11.6 - 12.5
mg/d L
12.6 - 13.5 mg/dL
> 13.5 mg/dL or abnormal 
calcium with life-
threatening arrhythmia
Hypomagnesemia
1.4 - 1.2 mEq/ L
1.1 - 0.9 mEq/ L
0.8 - 0.6 mEq/ L
< 0.6 mEq/ L or abnormal 
magnesium with life-
threatening arrhythmia
Hypophosphatemia
2.0 - 2.4 mg/dL
1.5 -1.9 mg/dL or
replacement Rx 
required
1.0 -1.4 mg/dL 
intensive therapy or 
hospitalization 
required
< 1.0 mg/dL or abnormal
phosphate with life-
threatening arrhythmia
Hyperbilirubinemia (when 
accompanied by any 
increase in other liver 
function test)
1.1 - <1.25 x ULN
1.25 - <1.5 x 
ULN
1.5 – 1.75 x ULN
> 1.75 x ULN
Hyperbilirubinemia (when 
other liver function are in 
the normal range)
1.1 - <1.5 x ULN
1.5 - <2.0 x ULN
2.0 – 3.0 x ULN
> 3.0 x ULN
BUN
1.25 - 2.5 x ULN
2.6 - 5 x ULN
5.1 - 10 x ULN
> 10 x ULN
Hyperuricemia (uric acid)
7.5 – 10.0 mg/dL
10.1 – 12.0 
mg/dL
12.1 – 15.0 mg/d L
>15.0 mg/d L
Creatinine
1.1 - 1.5 x ULN
1.6 - 3.0 x ULN
3.1 - 6 x ULN
>6 x ULN or dialysis 
required
ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT)
1.1 - <2.0 x ULN
2.0 – <3.0 x ULN
3.0 – 8.0 x ULN
> 8 x ULN
ALT (SGPT)
1.1 - <2.0 x ULN
2.0 – <3.0 x ULN
3.0 – 8.0 x ULN
> 8 x ULN
GGT
1.1 - <2.0 x ULN
2.0 – <3.0 x ULN
3.0 – 8.0 x ULN
> 8 x ULN
Alkaline Phosphatase
1.1 - <2.0 x ULN
2.0 – <3.0 x ULN
3.0 – 8.0 x ULN
> 8 x ULN
Amylase
1.1 - 1.5 x ULN
1.6 - 2.0 x ULN
2.1 - 5.0 x ULN
> 5.1 x ULN
Lipase
1.1 - 1.5 x ULN
1.6 - 2.0 x ULN
2.1 - 5.0 x ULN
> 5.1 x ULN


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URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Proteinuria
1+
or
200 mg - 1 gm 
loss/day
2-3+
or
1- 2 gm loss/day
4+
or
2-3.5 gm loss/day
nephrotic syndrome
or
>3.5 gm loss/day
Hematuria
microscopic only
<10 rbc/hpf
gross, no clots
>10 rbc/hpf
gross, with or without 
clots, OR RBC casts
obstructive or 
required
transfusion
CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Cardiac Rhythm
asymptomatic, 
transient signs, no
Rx required
recurrent/persistent; 
symptomatic Rx 
required
unstable dysrythmia;
hospitalization
and treatment 
required
Hypertension
transient increase
>20 mm/ Hg; no 
treatment
recurrent, chronic 
increase
> 20mm/ Hg
/treatment required
acute treatment 
required; outpatient 
treatment or 
hospitalization
possible
end organ damage or 
hospitalization 
required
Hypotension
transient orthostatic
hypotension with 
heart rate increased 
by <20 beat/min or 
decreased by <10 mm 
Hg systolic BP, No 
treatment required
symptoms due to 
orthostatic 
hypotension or BP 
decreased by <20 mm 
Hg systolic; 
correctable with oral 
flu id treatment
requires IV fluids; no 
hospitalization 
required
mean arterial pressure
<60mm/ Hg or end 
organ damage or 
shock; requires 
hospitalization and 
vasopressor treatment
Pericarditis
minimal effusion
mild/ moderate 
asymptomatic 
effusion, no treatment
symptomatic 
effusion; pain; EKG 
changes
tamponade; 
pericardiocentesis or 
surgery required
Hemorrhage, Blood Loss
microscopic/occult
mild, no transfusion
gross blood loss;
1-2 units transfused
massive blood loss; 
>3 units transfused


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RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Cough
transient- no 
treatment
persistent cough; 
treatment responsive
Paroxysmal cough; 
uncontrolled with 
treatment
--------------------
Bronchospasm, Acute
transient; no 
treatment;
70% - 80% FEV1
of peak flow
requires
treatment; normalizes 
with bronchodilator; 
FEV1 50% -
70%
(of peak flow)
no normalization 
with bronchodilator; 
FEV1 25% - 50%
of peak flow; or
retractions present
cyanosis: FEV1
<25%
of peak flow or 
intubation necessary
Dyspnea
dyspnea on exertion dyspnea with normal 
activity
dyspnea at rest
dyspnea requiring 
oxygen therapy
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Nausea
mild or transient; 
maintains
reasonable intake
moderate discomfort; 
intake decreased
significantly; some 
activity limited
no significant intake; 
requires IV flu ids
hospitalization 
required;
Vomiting
1 episode in 24 hours
2-5 episodes in
24 hours
>6 episodes in 
24 hours or needing 
IV fluids
physiologic 
consequences 
requiring
hospitalization or 
requiring parenteral 
nutrition
Constipation
requiring stool
softener or dietary 
modification
requiring
laxatives
obstipation
requiring manual 
evacuation or enema
obstruction or
toxic megacolon
Diarrhea
mild or transient; 3-4 
loose
stools/day or mild
diarrhea last <1 week
moderate or 
persistent; 5-7 loose 
stools/day or diarrhea
lasting >1 week
>7 loose stools/day
or bloody diarrhea; or 
orthostatic 
hypotension or 
electrolyte imbalance 
or >2L IV fluids 
required
hypotensive shock or 
physiologic 
consequences 
requiring
hospitalization
Oral Discomfort/Dysphagia mild discomfort; no 
difficulty
swallowing
some limits on 
eating/drinking
eating/talking very 
limited; unable to 
swallow solid foods
unable to drink flu 
ids; requires IV fluids


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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Neuro-Cerebellar
slight incoordination 
dysdiadochokinesis
intention tremor, 
dysmetria,
slurred speech; 
nystagmus
locomotor ataxia
incapacitated
Psychiatric
mild anxiety or 
depression
moderate anxiety or 
depression; therapy 
required; change in 
normal routine
severe mood changes 
requiring therapy; or 
suicidal ideation; or 
aggressive ideation
acute psychosis 
requiring 
hospitalization; or 
suicidal 
gesture/attempt or 
hallucinations
Muscle Strength
subjective weakness 
no objective
symptoms/ signs
mild objective
signs/symptoms no 
decrease in function
objective weakness 
function limited
paralysis
Paresthesia (burning, 
tingling, etc.)
mild discomfort; no 
treatment required
moderate discomfort;
non-narcotic 
analgesia required
severe discomfort; or 
narcotic analgesia 
required with 
symptomatic 
improvement
incapacitating; or not 
responsive to narcotic 
analgesia
Neuro-sensory
mild impairment in 
sensation
(decreased
sensation, eg, 
vibratory, pinprick, 
hot/cold in great toes) 
in focal area or 
symmetrical
distribution; or 
change in taste, 
smell, vision and/or 
hearing
moderate
impairment (mod 
decreased sensation, 
eg, vibratory, 
pinprick, hot/cold to 
ankles) and/or joint 
position or mild
impairment that is not
symmetrical
severe impairment 
(decreased or loss of 
sensation to knees or 
wrists) or loss of 
sensation of at least 
mod degree in 
multiple
different body areas 
(ie, upper and lower
extremities)
sensory loss involves 
limbs and trunk; 
paralysis; or seizures


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MUSCULOSKELATEL
Grade 1
Grade 2
Grade 3
Grade 4
Arthralgia (joint pain)
mild pain not 
interfering with 
function
moderate pain, 
analgesics and/or pain 
interfering with 
function but not with 
activities of daily 
living
severe pain; pain 
and/or analgesics 
interfering with 
activities of daily 
living
disabling pain
Arthritis
mild pain with
inflammation,
erythema or joint
swelling – but not
interfering with
function
moderate pain with
inflammation,
erythema or joint 
swelling – interfering 
with function, but not 
with activities of
daily living
severe pain with
inflammation,
erythema or joint
swelling –and
interfering with
activities of daily
living
permanent and/or 
disabling joint
destruction
Myalgia
Myalgia with no 
limitation of activity
muscle
tenderness (at other 
than injection site) or 
with moderate
impairment of activity
severe muscle
tenderness with
marked impairment of 
activity
frank
myonecrosis
SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Mucocutaneous
erythema; pruritus
diffuse, 
maculopapular rash, 
dry desquamation
vesiculation or
moist desquamation 
or ulceration
exfoliative
dermatitis, mucous 
membrane
involvement or 
erythema,
multiforme or 
suspected
Stevens-Johnson
or necrosis requiring 
surgery
Induration
<15mm
15-30 mm
>30mm
Erythema
<15mm
15-30 mm
>30mm
Edema
<15mm
15-30 mm
>30mm
Rash at Injection Site
<15mm
15-30 mm
>30mm
Pruritus
slight itching at 
injection site
moderate itching at 
injection extremity
itching over entire 
body


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SYSTEMIC
Grade 1
Grade 2
Grade 3
Grade 4
Allergic Reaction
pruritus without rash
localized urticaria
generalized urticaria; 
angioedema
anaphylaxis
Headache
mild, no treatment 
required
transient, moderate; 
treatment required
severe; responds to 
initial narcotic 
therapy
intractable; requires 
repeated narcotic 
therapy
Fever: oral
37.7 - 38.5 C or 
100.0 - 101.5 F
38.6 - 39.5 C or 
101.6 - 102.9 F
39.6 - 40.5 C or 103 -
105 F
>40 C or
>105 F
Fatigue
normal activity 
reduced < 48 hours
normal activity 
decreased 25-
50% > 48 hours
normal activity
decreased > 50%
can’t work
unable to care for self






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Attachment 3:
Additional Questions About Health and Functioning
Adult RSV Additional Questionsa
For each of the following questions please select one response only
1. Did you take any medicine for your respiratory infection symptoms today?
Yes
No
2. Did you use any rescue medicine today for asthma or COPD?
I do not take medicine for asthma or COPD
Yes
No
3. Since this time yesterday, how much of the time did you breathe oxygen from an oxygen 
tank?
None of the time
Less than an hour
1 to 4 hours
More than 4 hours
4. Overall, how severe were your respiratory infection symptoms today?
No respiratory infection symptoms today
Mild
Moderate
Severe
Very Severe
5. Overall, how were your respiratory infection symptoms today compared to yesterday?
Much better
Somewhat better
A little better
About the same
A little worse
Somewhat worse
Much worse


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6. How much did your respiratory infection symptoms interfere with your usual activities 
today?
Not at all
A little bit
Somewhat
Quite a bit
Very much
7. Have you returned to your usual activities today?
Yes
No
8. In general, how would you rate your physical health today?
Excellent
Very good
Good
Fair
Poor
9. Have you returned to your usual health today?
Yes
No
a Questions 1, 2,-4-9 adapted for RSV from the FLU-PRO User Manual; question 3 adapted from Janssen 
Observational Protocol NOPRODRSV0004.


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Attachment 4:
Cardiovascular Safety - Abnormalities
ECG
All important abnormalities from the ECG readings will be listed.
Abnormality Code
ECG parameter
HR
PR
QRS
QTcorrected
Abnormalities on actual values
Abnormally low
< 45 bpm
NAP
-
-
Abnormally high
≥120 bpm
≥210 ms
≥120 ms
-
Borderline prolonged QT
-
-
-
450 ms < QTc < 480 ms
Prolonged QT
-
-
-
480 ms < QTc < 500 ms
Pathologically prolonged QT
-
-
-
QTc > 500 ms
Abnormalities on changes from baseline (∆QTc)
Normal QTc change
-
-
-
∆QTc < 30 ms
Borderline QTc change
-
-
-
30 ms < ∆QTc < 60 ms
Abnormally high QTc change
-
-
-
∆QTc > 60 ms
NAP = not applicable
For absolute QTc parameters the categories are defined based on the ICH E14 Guidance13F13F13F13F13Fa
Vital Signsb
The following abnormalities will be defined for vital signs:
Abnormality Code
Vital Signs parameter
Pulse
Diastolic blood pressure
Systolic blood pressure
Abnormalities on actual values
Abnormally low
45 bpm
50 mmHg
90 mmHg
Grade 1 or mild
-
> 90 mmHg - < 100 mmHg
> 140 mmHg - < 160 mmHg
Grade 2 or moderate
-
100 mmHg - < 110 mmHg
160 mmHg - < 180 mmHg
Grade 3 or severe
-
110 mmHg
180 mmHg
Abnormally high
120 bpm
-
-
                                                
a The clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs 
CHMP/ICH/2/04, May 2005.
b The classification of AEs related to hypotension and hypertension will be done according to the DMID grading
scale.






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Attachment 6:
5-level EuroQol 5-Dimension Questionnaire (EQ-5D-5L)
Health Questionnaire
English version for the USA
USA (English) © 2009 EuroQol Group. EQ-5D™ is a trade mark of the EuroQol Group


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Under each heading, please check the ONE box that best describes your health TODAY
MOBILITY
I have no problems walking

I have slight problems walking 

I have moderate problems walking

I have severe problems walking

I am unable to walk

SELF-CARE
I have no problems washing or dressing myself 

I have slight problems washing or dressing myself 

I have moderate problems washing or dressing myself 

I have severe problems washing or dressing myself 

I am unable to wash or dress myself 

USUAL ACTIVITIES (e.g. work, study, housework,
family or leisure activities)
I have no problems doing my usual activities 

I have slight problems doing my usual activities 

I have moderate problems doing my usual activities 

I have severe problems doing my usual activities 

I am unable to do my usual activities 

PAIN / DISCOMFORT
I have no pain or discomfort 

I have slight pain or discomfort 

I have moderate pain or discomfort 

I have severe pain or discomfort 

I have extreme pain or discomfort 

ANXIETY / DEPRESSION
I am not anxious or depressed 

I am slightly anxious or depressed 

I am moderately anxious or depressed 

I am severely anxious or depressed 

I am extremely anxious or depressed 

USA (English) © 2009 EuroQol Group. EQ-5D™ is a trade mark of the EuroQol Group


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
We would like to know how good or bad your health is 
TODAY.

This scale is numbered from 0 to 100.

100 means the best health you can imagine.
0 means the worst health you can imagine.

Mark an X on the scale to indicate how your health is TODAY.

Now, please write the number you marked on the scale in the box 
below.
YOUR HEALTH TODAY =
USA (English) © 2009 EuroQol Group. EQ-5D™ is a trade mark of the EuroQol Group
10
0
20
30
40
50
60
80
70
90
100
5
15
25
35
45
55
75
65
85
95
The best health       
you can imagine
The worst health
you can imagine




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CCI


JNJ-53718678
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Approved, Date: 24 April 2019
CCI


JNJ-53718678
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INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will 
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who 
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully 
informed regarding the study drug, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature:
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature:
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed):
Institution:
Janssen Research & Development
Signature:
electronic signature appended at the end of the protocol
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the course of the study, written 
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD


 
 
SIGNATURES 
 
 
 
 
Signed by  
Date  
 
Justification  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
24Apr2019, 16:09:42 PM, UTC
Document Approval by Delegation
PPD

SAP_003.pdf: 
1
Approved, Date: 27 September 2019
Janssen Research & Development
Statistical Analysis Plan
A Pilot Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Explore the 
Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics ofJNJ-
53718678 at Two Dose Levels in Non-Hospitalized Adult Subjects Infected With 
Respiratory Syncytial Virus
Protocol 53718678RSV2004; Phase 2a
AMENDMENT 1
JNJ-53718678
Status:
Approved
Date:
27 September 2019
Prepared by:
Janssen Research & Development, LLC; Janssen Research & Development, a 
division of Janssen Pharmaceutica NV
Document No.: EDMS-ERI-171344037; 2.0
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT03379675


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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 4
AMENDMENT HISTORY.............................................................................................................................. 5
ABBREVIATIONS ...................................................................................................................................... 13
1.
INTRODUCTION................................................................................................................................ 14
1.1.
Trial Objectives .............................................................................................................................. 14
1.2.
Trial Design .................................................................................................................................... 15
1.3.
Statistical Hypotheses for Trial Objectives..................................................................................... 16
1.4.
Sample Size Justification ............................................................................................................... 16
1.5.
Randomization and Blinding .......................................................................................................... 17
2.
GENERAL ANALYSIS DEFINITIONS .............................................................................................. 17
2.1.
Phase Definitions, Visit Windows and Baseline............................................................................. 17
2.1.1.
Phase Definitions........................................................................................................................ 18
2.1.2.
Analysis Windows for Analysis Visits and Timepoints................................................................ 19
2.1.3.
Study Day and Relative Day....................................................................................................... 22
2.1.4.
Baseline ...................................................................................................................................... 23
2.2.
Pooling Algorithm for Analysis Centers.......................................................................................... 23
2.3.
Analysis Sets.................................................................................................................................. 24
2.3.1.
All Randomized Analysis Sets.................................................................................................... 24
2.3.1.1.
All Randomized Analysis (RAND) Set..................................................................................... 24
2.3.2.
Efficacy Analysis Set(s) .............................................................................................................. 24
2.3.2.1.
Intent-To-Treat infected (ITT-i) Set.......................................................................................... 24
2.3.2.2.
Modified Intent-To-Treat infected (mITT-i) Set........................................................................ 24
2.3.2.3.
Per Protocol Analysis (PP) Set................................................................................................ 24
2.3.3.
Safety Analysis Set..................................................................................................................... 25
2.3.3.1.
Safety Analysis Set (SAF) ....................................................................................................... 25
2.4.
Definition of Subgroups.................................................................................................................. 25
2.5.
Imputation Rules for Missing AE Date/Time of Onset/Resolution ................................................. 26
3.
INTERIM ANALYSIS AND DATA REVIEW COMMITTEE ............................................................... 27
3.1.
Interim Analysis.............................................................................................................................. 27
3.2.
Data Review Committee ................................................................................................................ 27
4.
SUBJECT INFORMATION................................................................................................................ 28
4.1.
Demographics and Baseline Characteristics ................................................................................. 28
4.2.
Disposition Information................................................................................................................... 30
4.3.
Treatment Compliance................................................................................................................... 30
4.4.
Extent of Exposure......................................................................................................................... 30
4.5.
Protocol Deviations ........................................................................................................................ 30
4.6.
Medical History............................................................................................................................... 30
4.7.
Prior and Concomitant Medications ............................................................................................... 31
4.8.
Co-Infections .................................................................................................................................. 31
5.
EFFICACY ......................................................................................................................................... 31
5.1.
Analysis Specifications................................................................................................................... 33
5.1.1.
Level of Significance................................................................................................................... 33
5.1.2.
Data Handling Rules................................................................................................................... 33
5.2.
Primary Efficacy Endpoints – Viral Load........................................................................................ 34
5.2.1.
Definition..................................................................................................................................... 34
5.2.2.
Analysis Methods........................................................................................................................ 37
5.3.
Secondary Endpoints - Clinical Course ......................................................................................... 39


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5.3.1.
Definition..................................................................................................................................... 40
5.3.1.1.
ePROs ..................................................................................................................................... 40
5.3.1.2.
Clinical Course Endpoints related to Respiratory, Heart Rate and Body Temperature .......... 49
5.3.1.2.1.
Respiratory Rate, Heart Rate, Oxygen Saturation and Body Temperature......................... 49
5.3.1.2.2.
Other Clinical Course Parameters ....................................................................................... 51
5.3.2.
Analysis Methods........................................................................................................................ 52
5.3.2.1.
Endpoint-specific analysis methods ........................................................................................ 52
5.4.
Sensitivity Analyses ....................................................................................................................... 54
5.5.
Other Efficacy Variable(s) .............................................................................................................. 54
5.5.1.
Definition..................................................................................................................................... 54
5.5.2.
Analysis Methods........................................................................................................................ 55
5.6.
Exploratory Analyses ..................................................................................................................... 55
6.
SAFETY............................................................................................................................................. 56
6.1.
Adverse Events .............................................................................................................................. 56
6.1.1.
Definitions ................................................................................................................................... 56
6.1.2.
Analysis Methods........................................................................................................................ 56
6.2.
Clinical Laboratory Tests................................................................................................................ 57
6.2.1.
Definitions ................................................................................................................................... 57
6.2.2.
Analysis Methods........................................................................................................................ 58
6.3.
Vital Signs and Physical Examination Findings ............................................................................. 59
6.3.1.
Definitions ................................................................................................................................... 59
6.3.2.
Analysis Methods........................................................................................................................ 60
6.4.
Electrocardiogram.......................................................................................................................... 61
6.4.1.
Definitions ................................................................................................................................... 61
6.4.2.
Analysis Methods........................................................................................................................ 62
7.
HEALTH ECONOMICS ..................................................................................................................... 62
7.1.
Definitions ...................................................................................................................................... 62
7.2.
Analysis Methods ........................................................................................................................... 62
8.
VIROLOGY ........................................................................................................................................ 63
8.1.
Definitions ...................................................................................................................................... 63
8.2.
Analysis Methods ........................................................................................................................... 64
8.2.1.
Viral Strain Typing ...................................................................................................................... 64
8.2.2.
Viral Sequencing......................................................................................................................... 64
REFERENCES............................................................................................................................................ 66
ATTACHMENTS......................................................................................................................................... 67
Attachment [1]:
Division of Microbiology and Infectious Diseases  (DMID) Adult Toxicity Table 
– November 2007 ....................................................................................................... 67
Attachment [2]:
Inclusion/exclusion criteria.......................................................................................... 75
Attachment [3]:
79
Respiratory infection-patient reported outcomes (ri-pro © ) symptom questionnaire ................................. 79
Adult RSV additional questions................................................................................................................... 80
Respiratory Infection Intensity and Impact Questionnaire (RiiQ™) ............................................................ 81
Attachment [4]:
EQ-5D-5L.................................................................................................................... 84
EQ-5D-5L Dimensions ................................................................................................................................ 84
EQ-5D-5L VAS
85
Valuation Index
86


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LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Definition of Analysis Phases ................................................................................................... 18
Table 2:
Visit Windows............................................................................................................................ 20
Table 3:
Visit Windows for ePRO............................................................................................................ 21
Table 4:
Worst per Day........................................................................................................................... 22
Table 5:
ePRO Time Slot in a Day.......................................................................................................... 22
Table 6:
Subgroups................................................................................................................................. 25
Table 7:
Demographic Variables............................................................................................................. 28
Table 8:
Time Slot in a Day..................................................................................................................... 29
Table 9:
Correction Factor for Time Slot in a Day .................................................................................. 29
Table 10:
Baseline Characteristics ........................................................................................................... 29
Table 11:
AUC viral load........................................................................................................................... 34
Table 12:
Clinically Important Abnormalities in Vital Signs....................................................................... 60
Table 13:
ECG Abnormalities ................................................................................................................... 61
FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................. 18


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AMENDMENT HISTORY
Version
Effective Date
Description of Changes
1.0
18DEC2018
This is the original SAP.
2.0
27AUG2019
All changes and clarifications of planned analyses in the SAP 
Version 2.0 compared with the SAP Version 1.0 are listed below.
Topic or Section
Description of Changes and Clarifications of Planned 
Analyses 
1. Introduction
The following text was added:
This SAP (Version 2.0) is based on the Clinical Protocol 
finalized on 26 September 2018 and the Clinical Protocol 
Amendment INT-1 finalized on 12 April 2019. Any changes of
the text in the original SAP (Version 1.0) are explicitly stated in 
this updated SAP.
1.4 Sample Size 
Justification
The statement on the RSV viral load mean change from baseline
to Day 8 associated with the sample size calculation was updated 
without affecting the sample size itself. Using the same 
assumptions on the mean change and its SD, the measure of 
precision was updated to be the half width of the 90% 
confidence interval for the between-group difference in RSV 
viral load change from baseline, instead of the single treatment 
arm 90% CI. 
The following text:
With an assumed SD of 1.85 log10 copies/mL, 20 subjects per 
treatment group will lead to a precision (90% confidence interval 
[CI] half width) of 0.715 and 24 subjects per treatment group to 
a precision of 0.647 log10 copies/mL for the estimate of the mean 
change from baseline per treatment group.
was replaced by:
With an assumed SD of 1.85 log10 copies/mL, 20 subjects per 
treatment group will lead to a precision (90% confidence interval 
[CI] half width) of 0.986 and 24 subjects per treatment group to 
a precision of 0.896 log10 copies/mL for the estimate of the 
difference between treatment groups in the mean change from 
baseline to Day 8.


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2.1.2 Analysis Windows 
for Analysis Visits and 
Timepoints
1. In Table 3, the following typos were corrected for Days 10.5 
and 11:
Day 10.5: 231h 59 min was replaced by 233h 59 min
Day 11: 232h was replaced by 234h
2. The following text was added to clarify Table 4:
The secondary selection approach will only be considered in the 
analysis if no record is assigned to Day 3, Day 5, Day 8 and Day 
14 according to the rules in the primary selection column. If
‘worst per day’ as per primary selection is available, same value 
will be assigned for the secondary selection of ‘worst per day’. 
Otherwise, ‘worst per day’ as per secondary selection will be 
derived considering all possible values within the relative day 
window. The worst possible results will be selected regardless of 
being the closest one to target day.
2.3.2 Efficacy Analysis 
Set(s)
1. The following text was moved to section 5. Efficacy and 
further clarified:
Efficacy will be analyzed on the ITT infected (ITT-i) set. The 
primary endpoint will also be analyzed on the Per Protocol (PP) 
set.
2. The following sub-section was added to ensure a minimal 
level of viral load at the start of treatment, allowing the antiviral 
effect of JNJ8678 to be evaluated:
2.3.2.2 Modified Intent-To-Treat infected (mITT-i) Set
All subjects in the ITT-i analysis set with RSV viral load >= 1 
log10 copies/mL above the Lower Limit of Quantification 
(LLOQ) at baseline.
3.1 Interim Analysis
As a clarification for completeness, the following text 
An interim analysis, encompassing efficacy, safety, and 
pharmacokinetics is planned after at least 36 subjects have been 
dosed and have completed the assessments of Day 8.
was replaced by:
An interim analysis, encompassing efficacy, safety, and 
pharmacokinetics is planned after at least 36 subjects have been 
dosed and have completed the assessments of Day 8, or 


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discontinued earlier.
4.1 Demographics and 
Baseline Characteristics
The following baseline characteristics were added to Table 10:

Baseline RSV Viral Load (log10 copies/ml) by RSV Subtype

Baseline RSV Viral Load (log10 copies/ml) by symptom 
onset day
5. Efficacy
The following text was added:
The primary endpoint will also be analyzed on mITT-i set and 
PP set.
5.1 Analysis Specifications
1. The following text was added:
In addition, descriptive summaries will be presented by the 
randomization stratification factor, time of symptom onset (≤3 
days vs >3 days before randomization).
2. The following clarification was added:
For all the stratified statistical analyses, the derived 
randomization stratification factor will be used instead of the 
randomization stratification factor as collected in the IWRS.
5.2.1 Definitions
1. As the protocol was updated (Protocol-Amendment 1 dated on 
12 April 2019) to include Day 5 as an additional timepoint for 
the assessment of the area under the RSV viral load-time curve 
(AUC), the following text was removed:
Change from planned analyses; For viral load the AUC for Day 
5 has been included.
2. The following text was added as a clarification on the 
calculation of the viral load of AUC with missing data:
Carrying forward should only be performed if the time between 
the available observation and the value at xxh is at most 24 
hours. 
In case the last observation is before xxh, and the value at xxh 
cannot be determined, the AUCs through xxh and through any 
later timepoint will not be derived.
5.2.2 Analysis Methods
1. A clarification about the subgroup analyses for AUC viral 
load was added:
The homogeneity of treatment effect on the occurrence of AUC 
viral load from baseline to Days 3, 5, and 8 across subgroups 


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will be examined using the same MMRM model approach for 
the primary analysis, but also includes the subgroup-by-
treatment and subgroup-by-visit interaction terms in the model. 
A forest plot will present the Least Square means and 95% CI 
for all subgroups of interest.
2.A clarification about the stratified Cox proportional hazard 
model as well as the calculation of the 90% confidence intervals 
based on the Kaplan-Meier method was added:
Time-to event variable will be analyzed and plotted using 
Kaplan-Meier estimates analysis. The estimate of the hazard 
ratio (HR) and the 90% confidence intervals for the treatment 
effect will be provided based on a stratified Cox proportional 
hazard model (derived randomization stratification factor: ≤3 
days, >3 days) and including treatment group as a covariate.
A summary table including number of subjects included in the 
analysis, number of subjects censored, 25th and 75th percentiles 
and median time-to event, with 90% confidence intervals based 
on the Kaplan-Meier method, will be presented by treatment 
group.
3.A clarification about the subgroup analyses for the time to 
virus undetectable was added:
The potential impact of selected variables that identify the 
subgroups of interest on the time to virus undetectable will be 
assessed by the stratified Cox proportional hazard model. The 
model will be stratified by the randomization stratification 
factors and include treatment group and subgroup variable as 
covariates, and the subgroup-by-treatment interaction term. A 
forest plot will present the HRs and 90% CI for all subgroups of 
interest. 
4. A clarification about the calculation of the difference in 
proportion of subjects with undetectable RSV viral load was 
added. The subjects with detectable or quantifiable RSV viral 
load are grouped into one category, so the subjects can be 
classified as either with RSV viral load ‘undetectable’ or 
‘detectable or quantifiable’:
The difference in 
proportions 
for undetectable versus 
detectable/quantifiable between each active group and placebo, 
will be tabulated descriptively (n and % per treatment group), for 


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each post baseline timepoint.
5.3. Secondary Endpoints -
Clinical Course
According to Protocol-Amendment 1, the RI-PRO (for newly 
recruited subjects) was replaced by RiiQ (RI-PRO still being 
collected at certain timepoints). Therefore, endpoints derived 
from RiiQ were added:

Duration and severity of signs and symptoms of RSV 
infection assessed through either the Respiratory Infection 
Patient Reported Outcome (RI-PRO) or the Respiratory 
Infection Intensity and Impact Questionnaire [RiiQ] 
questionnaire, and Additional Questions about Health and 
Functioning.

Time to resolution of selected RSV symptoms as reported 
by the subject through either the RI-PRO or RiiQ.
5.3.1.1 ePROs
According to Protocol-Amendment 1, the RI-PRO (for newly 
recruited subjects) was replaced by RiiQ (RI-PRO still being 
collected 
at 
certain 
timepoints). 
Therefore, 
information 
regarding the RiiQ, calculation and analyses of the RiiQ 
(symptom or impact) domain scores, RiiQ key symptom score, 
and related time to (complete) resolution were added to this 
section. 
In addition, details about the RI-PRO key RSV symptom score 
and related time to (complete) resolution analyses were added. 
Time to (complete) resolution analyses based on the common 
key symptoms from either RI-PRO or RiiQ were also added to 
this section.
5.3.2.1 Endpoint-specific 
analysis methods
1. According to Protocol-Amendment 1, the RI-PRO (for newly 
recruited subjects) was replaced by RiiQ (RI-PRO still being 
collected at certain timepoints). Therefore, the following text 
was added:
Changes from baseline on each of the RI-PRO and RiiQ 
domains will be analyzed using a restricted maximum likelihood 
based repeated measures approach as per Section 5.2.2. An 
unstructured covariance structure will be selected. 
2. The typo regarding the confidence level for the confidence 
interval based on Wilson score test was corrected: ‘95% 
confidence interval’ was replaced by ‘90% confidence interval’:
The difference in proportions between each active group and 


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placebo will be tabulated, and summaries will include 2-sided 
90% confidence intervals based on the Wilson score test.
3. The following text was added under ‘Time to resolution of 
symptoms, Time to return to usual health and Time to return to 
usual activity’:
The estimate of the hazard ratio (HR) and the 90% confidence 
intervals for the treatment effect will be provided based on a 
stratified Cox proportional hazard model (derived randomization 
stratification factor: ≤3 days, >3 days) and including treatment 
group as a covariate.
4. A clarification about the calculation of the 90% confidence 
intervals was added under ‘Time to resolution of symptoms, 
Time to return to usual health and Time to return to usual 
activity’:
A summary table including number of subjects included in the 
analysis, number of subjects censored, 25th and 75th percentiles 
and median time-to event, with 90% confidence intervals based 
on the Kaplan-Meier method, will be presented by treatment 
group.
5. A clarification on the subgroup analyses for the time to 
resolution of symptoms was added:
The potential impact of selected variables that identify the 
subgroups of interest on the time to resolution of symptoms will 
be assessed by the stratified Cox proportional hazard model. The 
model will be stratified by the randomization stratification 
factors and include treatment group and subgroup variable as 
covariates, and the subgroup by treatment interaction term. A 
forest plot will present the HRs and 90% CI for all subgroups of 
interest.
5.4. Sensitivity Analyses
The following sensitivity analyses were added:
Sensitivity analyses to assess the robustness of the primary 
efficacy analysis of viral load AUC will be performed by 
including the stratification factor, RSV symptom onset (≤3 days 
or > 3 days) as collected in the IWRS, in the mixed-effects 
model. Additionally, the primary efficacy analysis will be 
repeated on the mITT-I set.
For the time to resolution of selected RSV symptoms, sensitivity 


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analyses will be performed considering 4 different imputation 
methods:

Method 1: from first resolution (score 0 or 1) after last 
unresolved value onwards, impute missing data as 
resolution.

Method 2: impute all missing values as unresolved (score 
>1).

Method 3: impute all missing values in-between resolved 
observations (score 0 or 1) as resolved.

Method 4: impute all missing values as unresolved ( 
score >1), except when in-between resolved values 
where resolved is imputed.
5.6 Exploratory Analyses
According to Protocol-Amendment 1, the RI-PRO (for newly 
recruited subjects) was replaced by RiiQ (RI-PRO still being 
collected 
at 
certain 
timepoints). 
Therefore, 
information 
regarding the RiiQ analyses was added under the ‘Clinical 
course endpoints’.
7.2. Analysis Methods
A clarification about the method used in calculating the 90% 
confidence interval for a binomial proportion was added as 
follows:
The proportion of subjects requiring any medical encounter will 
be shown in a frequency tabulation by treatment group with the 
corresponding 90% confidence interval (exact Clopper-Pearson
method). 
8.1 Definitions
1. Position 127 was added to the following text:
Long list of 20 F-gene positions of interest for the class of RSV 
fusion inhibitors, based on in vitro selection experiments, 
clinical observations, and/or in vitro reduced susceptibility to 
RSV fusion inhibitors: positions 127, 138, 140, 141, 143, 144, 
323, 338, 392, 394, 398, 399, 400, 401, 474, 486, 487, 488, 489, 
and 517.
2. The following clarification was added for the ‘Last Evaluable 
On-Treatment Time Point’, under ‘Analysis Time Points’:
In case no On-Treatment assessment is available, the first 
assessment during Follow-Up is selected instead.
3. ‘During the follow-up phase’ was added as a clarification to 
the definition of the ‘Time Point of Sequence during the 
Follow-Up phase’, under ‘Analysis Time Points’.


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ABBREVIATIONS
AE
adverse event
AFT
Accelerated Failure Time
ALT/SGPT
alanine aminotransferase
AST/SGOT
aspartate aminotransferase
ATC
anatomic and therapeutic Class
AUC
area under the curve
BMI
body mass index
CI
confidence interval
COPD
chronic obstructive pulmonary disease
CPAP
Clinical Pharmacology Analysis Plan
CRF
case report form
CSR
Clinical Study Report
CV
coefficient of variation
DMID
Division of Microbiology and Infectious Diseases
DRC
Data Review Committee
DPS
Data Presentation Specifications
ECG
Electrocardiogram
eCRF
electronic case report form
FDA
Food and Drug Administration
HCP
Health Care Provider
HRQOL
Health-Related Quality of Life
IA
Interim Analysis
ICF
Informed Consent Form
ICH
International Conference on Harmonization
IQ
Interquartile
ITT-i
Intent-to-Treat infected
IRBs
Institutional Review Boards 
IWRS
interactive web response system
LLOQ
Lower limit of quantification
LOCF
last observation carried forward
LOD
Limit of detection
LS
Least Squares
MedDRA
Medical Dictionary for Regulatory Activities
mITT-i
Modified Intent-to-Treat infected
PD
Pharmacodynamic
PI
principal investigator
PK
pharmacokinetic(s)
PP
per protocol
PRO
Patient Reported Outcome
qRT-PCR
quantitative reverse transcription polymerase chain reaction
RI-PRO
RiiQ
Respiratory Infection-Patient Reported Outcomes questionnaire
Respiratory Infection Intensity and Impact Questionnaire
SAE
serious adverse event
SAF
Safety Analysis Set
SAP
Statistical Analysis Plan
SD
standard deviation
SDTM
Study Data Tabulation Model
SE
Standard Error
SpO2
peripheral capillary oxygen saturation
TD
Target Detected
TND
Target Not Detected
TEAE
treatment-emergent adverse event


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1.
INTRODUCTION
This Statistical Analysis Plan (SAP) contains definitions of analysis sets, derived variables and 
statistical methods for the efficacy and safety analyses of the study JNJ-57318678RSV2004. The 
SAP is to be interpreted in conjunction with the protocol. 
This SAP (Version 2.0) is based on the Clinical Protocol finalized on 26 September 2018 and the 
Clinical Protocol Amendment INT-1 finalized on 12 April 2019. Any changes from the text in 
the original SAP (Version 1.0) are explicitly stated in this updated SAP.
A detailed analysis plan for the pharmacokinetic and pharmacokinetic/pharmacodynamics data 
will be described in a Clinical Pharmacology Analysis Plan (CPAP).
JNJ-53718678 is an investigational RSV specific fusion inhibitor belonging to the indole 
chemical class and is under development for the treatment of RSV infection. The study drug 
shows in vitro activity against a panel of viruses belonging to both the RSV subfamilies A or B. 
In addition, antiviral activity of JNJ-53718678 was demonstrated during clinical studies in 
healthy adults inoculated with RSV (study 53718678RSV2001) and in pediatric subjects 
hospitalized due to RSV-infection (study 53718678RSV1005).
1.1.
Trial Objectives
Primary Objective
The primary objective of the study is to explore the antiviral effect of JNJ-53718678 at 2 dose 
levels (80 mg and 500 mg) once daily for 7 days in adults with RSV infection, as measured by 
RSV viral load in nasal secretions by quantitative reverse transcription polymerase chain reaction 
(qRT-PCR) assay.
Secondary Objectives
The secondary objectives are to explore in adults with RSV infection, after repeated oral dosing 
with JNJ-53718678:

The safety and tolerability of JNJ-53718678

The impact of JNJ-53718678 on the clinical course of RSV infection

The pharmacokinetics of JNJ-53718678.
Exploratory Objectives
The exploratory objectives are to explore in adults with RSV infection after repeated oral dosing 
with JNJ-53718678:

The relationship between antiviral activity and clinical course

The relationship between pharmacokinetics and pharmacodynamics (selected antiviral 
activity

parameters, clinical outcomes, and safety parameters)


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
Potential differences in antiviral activity and clinical course between:
o
otherwise healthy and comorbid subjects;
o
subjects with symptom onset ≤3 days before randomization and subjects with 
symptom onset >3 days before randomization.

The occurrence of complications associated with RSV per investigator assessment after 
initiation of treatment

Medical resource utilization, including hospitalization, for clinical management of subjects 
during treatment and posttreatment follow-up

The impact of the baseline RSV viral subtype and genotype on the antiviral activity and 
clinical course

The emergence of mutations in the viral genome potentially associated with resistance to
JNJ-53718678

The RSV infectious virus titers as assessed by quantitative culture of RSV (plaque assay) on 
selected nasal swab samples (optional objective, pending feasibility of performing such an 
assay)

Impact of RSV and its treatment on health-related quality of life (HRQOL).
1.2.
Trial Design
This is a Phase 2a, randomized, double-blind, placebo-controlled study to explore the antiviral 
activity, clinical outcomes, safety, tolerability, and pharmacokinetics of JNJ-53718678 at 2 dose 
levels (80 mg and 500 mg) once daily for 7 days in adult subjects with respiratory illness due to 
RSV infection. Subjects may be otherwise healthy or comorbid and should not be in need of 
hospitalization. 
A population of 75 subjects is targeted. However, given the recruitment challenges associated 
with the seasonality of RSV, a minimum of 63 subjects may be considered sufficient to complete 
the study.
The study includes a Screening Period (Day -1 to Day 1), a Treatment Period (Day 1 to Day 8), 
and a Follow-up Period (Day 9 to Day 28[±3]). The total study duration for each subject is 
29 days (screening included).
After screening, eligible subjects are randomized on Day 1 (1:1:1) to receive 1 of 3 treatments:

Treatment A: 500 mg JNJ-53718678 once daily for 7 days (n = 25 [target]);

Treatment B: 80 mg JNJ-53718678 once daily for 7 days (n = 25 [target]);

Treatment C: placebo once daily for 7 days (n = 25 [target]).
Randomization is stratified by time of symptom onset (≤3 days vs >3 days before 
randomization). Subjects with symptom onset >3 days before randomization may account for 
maximum of 50% of all enrolled subjects.


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An interim analysis is planned after at least 36 subjects have been dosed and have completed the
assessments of Day 8.
A Data Review Committee (DRC) is in place for this study. The DRC monitors safety data 
during study conduct on a regular basis and/or ad hoc in case of emergent safety signals 
identified through medical monitoring.
1.3.
Statistical Hypotheses for Trial Objectives
The primary objective of the study is to explore the antiviral effect of JNJ-53718678 at 2 dose 
levels (80 mg and 500 mg) once daily for 7 days in adults with RSV infection, as measured by 
RSV viral load in nasal secretions by quantitative reverse transcription polymerase chain reaction 
(qRT-PCR) assay. 
No statistical hypotheses are to be tested.
1.4.
Sample Size Justification
The interim results (estimates of mean AUC and change from baseline of RSV viral load ±SD)
of study 53718678RSV1005 were the basis of the sample size calculation. In that study, median
(range) time to onset of symptoms was 5 (2-12) days and baseline viral load was 5.3 (2.1-8.3)
log10 copies/mL.
For the AUC viral load from Day 1 to Day 7, a (placebo) point estimate of 490 and an SD of
135 log10 copies x hr/mL was observed for the AUC viral load from Day 1 to Day 7. The sample
size was determined in order to obtain estimates of the mean AUC viral load with a precision of
approximately 50 log10 copies x hr/mL of the true value with 90% confidence; with 20 subjects
per treatment group the half-width of the 90% confidence would be approximately 52 and with
24 subjects per treatment group the precision would be approximately 47 log10 copies x hr/mL.
For the change from baseline (on Day 2 or Day 3), (placebo) point estimates 
of -0.11 and -0.33 and SDs of 1.85 and 1.56 log10 copies/mL, respectively, were observed. The 
observed difference (active versus placebo) was -1 to -2 log10 copies/mL. With an assumed SD 
of 1.85 log10 copies/mL, 20 subjects per treatment group will lead to a precision (90% 
confidence interval [CI] half width) of 0.986 and 24 subjects per treatment group to a precision 
of 0.896 log10 copies/mL for the estimate of the difference between treatment groups in the 
mean change from baseline.
As further guidance for the design, the power to detect a dose-response was calculated. To
evaluate a potential dose-response, 3 contrasts will be tested: a contrast with no difference
between the 2 active doses tested against placebo; a contrast with no difference between low
dose and placebo tested against high dose; and a contrast with a linear dose-response relationship
with respect to the active doses. No correction for multiplicity is considered in view of the
exploratory nature of the study. Based on 10,000 simulations, and assuming a reduction in AUC
viral load of 20% of high dose versus placebo, the power to detect a positive dose-response
relationship will be between 79% and 86% (depending on the effect of the low dose) with a total
sample size of 60, and between 83% and 89% with a total sample size of 72.


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To account for potential false-positive RSV screening testing (ie, diagnosed with RSV infection
using a rapid PCR-based or rapid antigen-detection test, but negative at the central lab using a
qRT-PCR assay, and therefore not included in the primary analysis population of ITT-i) and
withdrawals from treatment for abnormal screening laboratory results, an overage of
approximately 5% will be enrolled, ie, 75 subjects are targeted.
In view of the seasonality of the disease, recruitment will be halted if at the end of a hemispheric 
RSV season 63 or more subjects have been enrolled and dosed. If at the end of a hemispheric 
RSV season the minimum of 63 dosed subjects is not reached, recruitment will continue in a next 
RSV season until this minimum has been reached, up to a maximum of 75 subjects to be enrolled 
overall.
1.5.
Randomization and Blinding
Central randomization is implemented in this study. The codes will be maintained within the 
IWRS, which has the functionality to allow the investigator to break the blind for an individual 
subject. Subjects are randomly assigned to 1 of the 3 treatments to receive either a high 
(500 mg/day) or a low (80mg/day) dose of JNJ53718678 or placebo in 1:1:1 ratio. The 
randomization is balanced by using randomly permuted blocks and stratified by time since 
symptom onsent at randomization (≤3 days vs >3 days). Subjects with symptom onset >3 days 
before randomization may account for maximum of 50% of all enrolled subjects.
In order to maintain study blind, all subjects receive once daily the same total volume of study 
drug solution divided over 2 separate but sequential intakes at the same time of day.
2.
GENERAL ANALYSIS DEFINITIONS
All analysis dataset preparations and statistical analyses will be performed using SAS® version 
9.2 (or higher).
2.1.
Phase Definitions, Visit Windows and Baseline
A diagram of the study design is provided in Figure 1.




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2.1.2.
Analysis Windows for Analysis Visits and Timepoints
As subjects do not always adhere to the protocol visit schedule, the following rules are applied to 
assign actual visits to analysis visits. All assignments will be made in chronological order. Once 
a visit date is assigned to a visit window, it will no longer be used for a later time point except 
for the endpoint. Listed below (please see Table 2, Table 3 and Table 4) are the visit windows 
and the target days for each visit defined in the protocol.
For the analyses of measurements scheduled once daily the following rules will be applied to 
have only one evaluation per subject per analysis visit: 

If two assessments fall within the same visit window, the measurement closest to the target 
day will be used.

If the assessments are equidistant, the last measurement within the interval will be used. 

If there are two measurements on the same date and time, then the measurement with the 
highest sequence number will be used. 
Once baseline is assigned, any assessment performed prior to the defined baseline, will be 
assigned to Screening. Screening visits will not be used in summary tables but only in listings.
Any assessment performed within Day 1 but after first drug intake, will be assigned to Day 1 
post-dose.
Exceptions to the general rule:

Viral Load
For the analyses of viral load (scheduled once daily), if multiple nasal swabs were taken on a 
single day, the above rules will only be applied after having determined per day the 
maximum viral load. The maximum viral load on a day will be used for windowing. Please 
notice that baseline viral load follows the rules described in Section 2.1.4.

Electrocardiogram
In case there is more than one assessment per analysis visit window, the following rule will 
be used to have only one evaluation per analysis timepoint:

The average of the last available complete ECG triplicate should be considered in first
instance.

In absence of complete triplicate ECGs, the average of the last available ECG duplicate 
should be considered.

In absence of complete or partial triplicates, the last available single ECG can be used. 
If an assessment is performed but not planned per protocol, it may be assigned to a visit window 
for consistency, based on the relative day. However, it will not be shown in the summary tables 
and figures as only scheduled visits per protocol are used. 
Screening visits will not be used in summary tables but only in listings. All information will be 
listed.








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and for visits before the reference day (Day 1)
reldy = visit day – reference day
There is no ‘Day 0’.
2.1.4.
Baseline
In general, the baseline record is defined as the last record before the first intake of the study 
drug except for the following assessments where additional rules will be applied:

RSV RNA viral load:  

Last available assessment within the 24h prior to or at the same time of first drug intake 
will be considered as baseline.

If no assessment within the 24h prior to or at the same time of first drug intake, but 
there is a result available no later than 1h post first study drug intake, the baseline 
assessment will be the first assessment completed within 1h post first drug intake. 

If none of the above assessments are available, but there is an assessment available 
before the 24h prior to first drug intake, it will be considered as baseline.

ePRO: 

Last available assessment within the 8h prior to first drug intake.

if no assessment is available within 8 hours prior to first drug intake, but there is an 
assessment completed within 1-hour post first intake, then baseline assessment will be 
the assessment completed within 1-hour post first intake.

If none of the above assessments are available, but there is an assessment available 
before the 8h prior to first drug intake, it will be considered as baseline.
If no record available at all before first drug intake, baseline will be considered as missing.
2.2.
Pooling Algorithm for Analysis Centers
Since it is expected that for this trial subjects will be recruited over a large number of centers 
with a small number of subjects per study center, there is no need to check for treatment by 
center interactions. In addition, the primary endpoint is an objective endpoint, which is evaluated 
by a central assay, no heterogeneity across centers is anticipated. Therefore, there is no need for 
a pooling algorithm for analysis centers.


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2.3.
Analysis Sets
2.3.1.
All Randomized Analysis Sets
2.3.1.1.
All Randomized Analysis (RAND) Set
All randomized subjects with a randomization date regardless of being treated or not.
2.3.2.
Efficacy Analysis Set(s)
2.3.2.1.
Intent-To-Treat infected (ITT-i) Set
All randomly assigned subjects who received at least 1 dose of study drug and who have an RSV 
infection confirmed by a PCR-based assay at the central laboratory at baseline (records up to 1 
hour after first medication intake can be used in case no pre-treatment observation is available).
Subjects in the ITT-i set will be analyzed according to the treatment they were randomly 
assigned to.
The ITT-i set definition applies also to the interim analysis. However, if a subject has no central 
lab confirming the RSV infection at baseline, that subject will not be included in the ITT-i set for 
the interim analysis purpose.
2.3.2.2.
Modified Intent-To-Treat infected (mITT-i) Set
All subjects in the ITT-i analysis set with RSV viral load ≥1 log10 copies/mL above the Lower 
Limit of Quantification (LLOQ) at baseline.
2.3.2.3.
Per Protocol Analysis (PP) Set
All subjects in the ITT-i analysis set with the exclusion of any subjects deemed to have a major 
protocol deviation that may affect the assessment of efficacy. Such major protocol deviations 
will be identified, revised and documented prior to database lock based on the following criteria:

Entered but did not satisfy criteria, violation of: 

inclusion criteria 4 or 5, 
AND/OR

exclusion criteria 1, 4, 7, 8, 9,14 or 16
Please see Section 4.1 and 4.2 of the protocol for full description of the criteria.

Received wrong treatment or incorrect dose 

The actual treatment not the same as the planned treatment

Subjects missed more than 1 dose.

Other:

Unplanned unblinding has taken place during the study.


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
Insufficient post-baseline viral load samples collected (should have at least baseline and 
2 post-dose samples between Day 2 and Day 5).

Received concomitant treatment that may affect the efficacy of the trial medication. 
Complete list of concomitant medications to be considered for major protocol violation will be 
finalized before the database lock.
Note that in the PP set, subjects will be treated as randomized (by definition). Analyses on the PP 
set will only be performed if >10% subjects in the ITT-i set are excluded from the PP set.
2.3.3.
Safety Analysis Set
2.3.3.1.
Safety Analysis Set (SAF)
The safety analysis set includes all subjects who received at least 1 dose of study agent, analyzed 
as treated.
The actual treatment is determined as the treatment for which the majority of drug dose is taken.
The Safety set will be used to perform the evaluation of all safety variables and will be used for 
listings.
2.4.
Definition of Subgroups
The following subgroups will be investigated for efficacy, including the primary endpoint (viral 
load) and key clinical course endpoints (duration and severity of sign and symptoms, time to 
resolution of RSV symptoms and respiratory rate, heart rate, body temperature and peripheral 
capillary oxygen saturation (SpO2).  For safety, subgroup analyses will be limited to age group 
and presence of any comorbid disease associated with risk factors for severe RSV disease.
Table 6:
Subgroups
Subgroup
Definition
Symptom Onset

Subjects with symptom onset ≤3 days before 
randomization 

Subjects with symptom onset >3 days before 
randomization
Baseline RSV Viral Subtype

RSV A

RSV B

RSV A+B
Age

<65 years and >=65
Baseline Viral Load
Central Viral Load (VL)

VL≥1 log10 copies/mL above the LLOQ at baseline

otherwise
Presence of any Comorbidities

No

Yes
Presence of any comorbid disease 
associated with risk for severe RSV 
disease

No 

Yes


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Table 6:
Subgroups
Subgroup
Definition
Comorbid diseases associated with 
risk for severe RSV disease

Asthma [Yes/No]

COPD [Yes/No]

CHF [Yes/No]

CAD (coronary artery disease) [Yes/No]
Other conditions/therapy of 
potential interest due to risk of 
infections in general

Diabetes mellitus [Yes/No]

CRF (Chronic Renal Failure) [Yes/No]

Use of systemic corticosteroids prior to or during the 
treatment phase [Yes/No], 
Prior use of systemic corticosteroids
Note: use in the 7 days
prior to randomization
and not continued after
first dose

No

Yes
Co-infection
Note: based on respiratory 
pathogens panel assay performed at 
baseline

No

Yes
Subgroup analyses will be performed for efficacy primary endpoint and key clinical course 
endpoints in case at least 15 subjects are enrolled in any of the subgroup categories.
Medical review will be done immediately before database lock on a list with unique coded 
medical history terms (MedDRA Preferred Terms) to indicate which subjects had comorbidities.
2.5.
Imputation Rules for Missing AE Date/Time of Onset/Resolution
Partial AE onset dates will be imputed as follows in derivations, but original information should 
remain in the database:

If the onset date of an adverse event is missing day only, it will be set to:

First day of the month that the AE occurred, if month/year of the onset of AE is 
different than the month/year of first dosing of the study medication.

The day of first dosing of the study medication, if the month/year of the onset of AE is 
the same as month/year of the first dosing of the study medication and month/year of 
the AE resolution date is different.

The day of first dosing of the study medication or day of AE resolution date, whichever 
is earliest, if month/year of the onset of AE and month/year of the first dosing of the 
study medication and month/year of the AE resolution date are same.

If the onset date of an adverse event is missing both day and month, it will be set to the 
earliest of:

January 1 of the year of onset, as long as this date is on or after the first dosing of the 
study medication.


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
Month and day of the first dosing of the study medication, if this date is the same year 
that the AE occurred.

Last day of the year if the year of the AE onset is prior to the year of the first dosing of 
the study medication.

The AE resolution date.
Completely missing onset dates will not be imputed.
Partial AE resolution dates not marked as ongoing will be imputed as follows:

If the resolution date of an adverse event is missing day only, it will be set to the earliest of 
the last day of the month of occurrence of resolution or the day of the date of death, if the 
death occurred in that month.

If the resolution date of an adverse event is missing both day and month, it will be set to the 
earliest of December 31 of the year or the day and month of the date of death, if the death 
occurred in that year.
Completely missing resolution dates will not be imputed.
3.
INTERIM ANALYSIS AND DATA REVIEW COMMITTEE 
3.1.
Interim Analysis
An interim analysis, encompassing efficacy, safety, and pharmacokinetics is planned after at 
least 36 subjects have been dosed and have completed the assessments of Day 8, or discontinued 
earlier. Enrollment will not be paused during the interim analysis.
From the subgroup analyses planned for the final analysis, the following will be included for the 
interim analysis irrespective of the number of subjects within the subgroup:

Efficacy analysis: Symptoms onset day

Safety analysis: age group and presence of any comorbid disease associated with risk factors 
for severe RSV disease.
Exploratory endpoints will not be included in the interim analysis except for an evaluation of the 
possible effect of the time since onset of symptoms on antiviral activity and clinical course.
Additional interim analyses may be performed at the sponsor’s discretion to support decision 
making for further development of JNJ-53718678 and to support interactions with health 
authorities. The primary (final) analysis will be performed after the last subject has completed 
his/her last visit of the study. Since this is an exploratory, hypothesis-generating study, no 
adjustments for multiplicity will be performed.
3.2.
Data Review Committee
A Data Review Committee (DRC), comprised of senior sponsor personnel outside of the central 
sponsor team and not involved in study conduct, will be established. The DRC will monitor 


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safety data during study conduct on a regular basis and/or ad hoc in case of emergent safety 
signals identified through medical monitoring.
The central sponsor team, composed by clinical leader, statistician(s), virologist, PK leader,
pharmacometrician and statistical programmers will review the unblinded interim efficacy, 
safety, and pharmacokinetic analyses and will make recommendations to the DRC regarding 
possible changes to the design of the study. The DRC will decide on the implementation of the 
recommendations based on the review of the interim results of the study.
Further details of the DRC, eg, composition and activities, are described in the DRC charter.
4.
SUBJECT INFORMATION
All subject information analyses will be done on the ITT-i Set and the Safety Set, unless 
specified otherwise for a specific display (in the DPS).
4.1.
Demographics and Baseline Characteristics
Table 7 presents a list of the demographic variables that will be summarized by treatment group
and overall.
Table 7:
Demographic Variables
Summary Type
Continuous Variables:
Age (years)
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum]).
Weight at baseline (kg)
Height at baseline (cm)
Body Mass Indexb at baseline (BMI) (kg/m2) = weight (kg)/(height (m))²
Categorical Variables
Age (<65 years and >=65)
Frequency distribution with the 
number and percentage of subjects 
in each category.
Sex (male, female)
Racea (American Indian or Alaska Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, Other, 
Multiple)
Ethnicity (Hispanic or Latino, not Hispanic or Latino)
Country
a:
If multiple race categories are indicated, the Race is recorded as 'Multiple'. The specifications of the categories 
‘Other’ and ‘Multiple’ will only be listed.
b:
Rounded to 1 decimal. Even if available in the raw data, BMI will be calculated from baseline weight and height.
Symptom Onset at Randomization will be calculated by considering:

Symptom onset start date and time slot of the day 

Randomization date and time slot of the day
as indicated in Table 8.


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Table 8:
Time Slot in a Day
Slot of the Day
Time
Night
00:00 midnight – 05:59 am
Morning
06:00 am – 11:59 noon
Afternoon
12:00 noon – 17:59 (or 5:59 pm)
Evening
18:00 – 23:59
symptom onset days = randomization date – reported symptom onset date + correction factor for 
time of the day
The correction factor is:

0: in case time slot on day of randomization ≤ time slot on day of symptoms

1: in case time slot on day of randomization > time slot on day of symptoms
Table 9:
Correction Factor for Time Slot in a Day
Randomization Day
Symptom Onset Day 
Night
Morning
Afternoon
Evening
Night
0
1
1
1
Morning
0
0
1
1
Afternoon
0
0
0
1
Evening
0
0
0
0
In case the time slot of the day of symptom onset is missing, no correction factor will be applied.
Similar definition will be used to calculate time for symptom onset at first treatment.
Table 10 presents a list of the baseline characteristics that will be summarized by treatment 
group and overall.  Baseline characteristics will also be summarized by presence of 
comorbidities (yes, no) and by symptom onset (≤3 days, >3 days). 
Table 10:
Baseline Characteristics
Summary Type
Continuous Variables:
Duration of RSV symptoms prior to randomization (days)
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum]).
Duration of RSV symptoms prior to first treatment (days)
Baseline RSV Viral Load (log10 copies/ml)
Baseline RSV Viral Load (log10 copies/ml) by RSV Subtype
Baseline RSV Viral Load (log10 copies/ml) by symptom onset day
Respiratory Rate (breaths/min)
Heart Rate (beats/min)
Oxygen Saturation (%)
Categorical Variables
Baseline RSV Subtype (RSV A, RSV B, RSV A+B)
Frequency distribution with the 
Symptom Onset (≤3 days, >3 days)
Co-infection (no, yes)
Presence of ANY Comorbidities (no, yes)
Comorbid disease associated with risk for severe RSV disease (no, yes)
Each of the following diseases (subcategories of the above):
- Asthma
- COPD


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Table 10:
Baseline Characteristics
Summary Type
- CHF
- CAD
number and percentage of subjects 
in each category.
Other conditions/therapy of potential interest due to risk of infections in 
general (yes, no)
Each of the following conditions/therapies (subcategories of the above):
- diabetes mellitus
- CRF
- use of systemic corticosteroids prior to or during the treatment
History of wheezing associated with acute respiratory infection? (no, yes)
Contact with HCP before presenting (no, yes)
        If Yes, specify the type of HCP (General Practitioner, Other)
History of Tobacco use (current, former, never)
4.2.
Disposition Information
Summaries will be provided for the following disposition information:

Number of screen failures, randomized (RAND), randomized and not treated, not 
randomized and treated, safety set (SAF), ITT-i set and PP set (PPS).

Number of subjects who completed or discontinued treatment and the study, with a 
breakdown of the reason of discontinuation.

Number of subjects per phase and per visit in the trial.
4.3.
Treatment Compliance
Study treatment compliance will be listed as well as the reasons for non-dispensing assigned 
drug, or for adjusting the dose.
4.4.
Extent of Exposure
Extent of exposure (days) is defined as (date of the last dose of study treatment – date of the first 
dose of study treatment) +1.
Note: treatment interruptions will not be taken into account.
Extent of exposure will be summarized descriptively by treatment group. 
4.5.
Protocol Deviations
Only major protocol deviations will be defined in this trial. All major protocol deviations (please 
see Section 2.3.2.3 for details) will be tabulated and listed. Those that may affect the assessment 
of efficacy will be documented prior to database lock.
4.6.
Medical History
The medical history records will be listed; separate listings will be provided for comorbid 
diseases associated with RSV.


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4.7.
Prior and Concomitant Medications
Medications taken from the date the ICF is signed through to the end of study will be 
summarized by preferred term using the World Health Organization-Drug Dictionary as 
frequency tables in 2 parts: 
1.
Prior medication: medication that started before the first dose of study drug, regardless of 
when dosing of the medication ended 
2.
Concomitant medication: medication received at or after the first dose of study drug, 
medication that was received before initial dosing and continued after initial dosing of study 
drug, or medication with missing stop date. 
(Medication that started before the first dose of study drug and continued after the first dose of 
study drug will be summarized as prior medication and separately as concomitant medication.) 
The part on concomitant medication will be shown by ATC class level up to level 3. 
If a prior/concomitant therapy record missed components of its start and/or stop dates (time 
and/or day and/or month and/or year), the following actions will be taken: 
1.
In case of partial start or stop datetimes, the concomitant therapy records will be allocated to 
prior/concomitant using the available partial information, without imputations. 
2.
In case of a completely missing start date, the prior/concomitant therapy will be considered 
as having started before the trial. 
3.
In case of a completely missing end date, the prior/concomitant therapy will be considered 
as ongoing at the end of the trial. 
4.8.
Co-Infections
Data on viral (other than RSV) or bacterial pathogens determined in mid-turbinate nasal swabs 
collected at screening (both by multiplex PCR) will be listed. 
Proportions of positive and negative results will be tabulated by treatment group.
5.
EFFICACY
All efficacy will be analyzed on the ITT-i set. The primary endpoint will also be analyzed on 
mITT-i set and PP set.
The efficacy analyses include the following primary, secondary and exploratory endpoints. 
Primary Endpoints
To explore the antiviral effect of JNJ-53718678 on RSV, as measured by qRT-PCR assay in 
mid-turbinate nasal swabs, the following virologic parameters will be assessed:

AUC from immediately prior to first dose of study drug (baseline) through Day 3, Day 5, 
Day 8, and Day 14

RSV viral load and change from baseline over time


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
Time to undetectable RSV viral load

Proportion of subjects with undetectable RSV viral load at each time point throughout the
study.
Secondary Endpoints

Clinical endpoints:

Duration and severity of signs and symptoms of RSV infection assessed through an 
instrument for patient-reported symptoms (either the Respiratory Infection-Patient 
Reported Outcomes [RI-PRO] questionnaire or the Respiratory Infection Intensity and 
Impact Questionnaire [RiiQ] questionnaire) and additional questions about health and 
functioning

Time to resolution of selected RSV symptoms as reported by the subject (through either 
the RI-PRO or RiiQ)

Respiratory rate, heart rate, body temperature, and SpO2 as measured by the 
investigator.
Exploratory Endpoints 
Exploratory endpoints include:

Antiviral activity and clinical course by 
-
time of symptom onset [≤3 days vs >3 days before randomization] 
-
presence of comorbidities
-
baseline RSV viral subtype
-
severity of key RSV symptoms at screening, and 
-
baseline RSV genotype

The occurrence of complications associated with onset after treatment initiation that are 
associated with RSV per the investigator assessment:

Bacterial superinfections (eg, pneumonia, sinusitis, bronchitis, bacteremia of presumed 
respiratory origin per investigator assessment)

Exacerbations of underlying pulmonary disease (eg, asthma, chronic obstructive 
pulmonary disease [COPD])

Exacerbations of underlying cardiovascular conditions

The need for antibiotics related to complications associated with RSV per investigator 
assessment

Sequence changes (post baseline) in the RSV F-gene, and other regions of the RSV genome 
(if applicable), as compared to baseline

Medical resource utilization collected as medical encounters

Association between clinical course of RSV and self-rated HRQOL (ie EQ-5D-5L).


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5.1.
Analysis Specifications
All efficacy summaries will be presented with descriptive statistics by treatment group and 
scheduled visit unless specified otherwise. In addition, descriptive summaries will be presented 
by the randomization stratification factor, time of symptom onset (≤3 days vs >3 days before 
randomization). If the endpoint is continuous, the descriptive statistics will include the number of 
subjects, mean standard deviation, standard error, median, range and interquartile range. If the 
endpoint is binary or categorical, the frequency distribution with the number and percentage of 
subjects in each category will be calculated.
For time to event variables, a summary table including number of subjects included in the 
analysis, number of subjects censored, 25th and 75th percentiles and median time-to event will be 
shown by treatment group.
For all the stratified statistical analyses, the derived randomization stratification factor will be 
used instead of the randomization stratification factor as collected in the IWRS.
5.1.1.
Level of Significance
Since this is an exploratory, hypothesis-generating study, no hypothesis testing will be 
performed. However, two-sided 90% confidence intervals may be calculated without adjustments 
for multiplicity for comparing active dose groups versus placebo.
5.1.2.
Data Handling Rules
Viral Load
Rule of maximum: Before any imputation is applied, the value for each Day is defined as the
maximum value of all RSV assessments performed on that day. Please notice that this rule
doesn’t apply for baseline. For baseline details please see Section 2.1.2. 
For analysis purposes, the log10 qRT-PCR viral load will be imputed with the midpoint on the 
log scale between the limit of detection and lower limit of quantification (LLOQ) when the result 
is ‘target detected’ (TD) but non-quantifiable.

For the RSV-A qRT-PCR assay, the LOD is 620 copies/mL and the LLOQ is 
1000 copies/mL, a result that is TD will be imputed with 2.90 log10 copies/mL.

For the RSV-B qRT-PCR assay, the LOD is 80 copies/mL and the LLOQ is 
250 copies/mL, a result that is TD will be imputed with 2.15 log10 copies/mL.
When the result is ‘target not detected’ (TND) (i.e., below the LOD), for both RSV A and RSV 
B the value of TND will be imputed with 0 log10 copies/mL.
For the overall analysis of viral load, all the viral load results of the RSV type with which the 
subject has been infected will be used.


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In case of co-infection with both subtypes RSV A and B, the rules below will be applied for the 
overall analyses of viral load from the time the co-infection is detected (i.e. result of TD or 
>LLOQ):

In case of two quantifiable results: the log10 of the sum of the RSV A and RSV B results in 
copies/mL will be used.

In case of a quantifiable result and a TD/TND result: use the imputed TD/TND on the 
original scale and then use the log10 of the sum of the quantifiable result and the imputed 
value. copies/mL scale value and then use the log10 of the sum of the imputed value and 
quantifiable result.

In case of two TD results, or one TD and one TND result: use the imputed TD/TND on the 
copies/mL scale values and then use the log10 of the sum of the imputed values.

In case of two TND results: impute the TND as 0 log10.
5.2.
Primary Efficacy Endpoints – Viral Load
5.2.1.
Definition
To explore the antiviral effect of JNJ-53718678 on RSV, as measured by qRT-PCR assay in 
mid-turbinate nasal swabs, the following virologic parameters will be assessed:

AUC from immediately prior to first dose of study drug (baseline) through Day 3 (48h), 
Day 5 (96h), Day 8 (168h), and Day 14 (312h);

RSV viral load and change from baseline over time;

Time to undetectable RSV viral load;

Proportion of subjects with undetectable RSV viral load at each time point throughout the 
study.
The AUC viral load will be analyzed by two different methods:

using a restricted maximum likelihood based repeated measures approach (mixed model)  

by trapezoidal method
Terminology is clarified in Table 11.
Table 11:
AUC viral load
Method
Mixed model
Trapezoidal 
AUC Day 3
AUC0-48h
AUC Day 5
AUC0-96h
AUC Day 8
AUC0-168h
AUC0-312h
Formulae to be used for derived variables, including data conversions, are provided in the table 
below. Note that for time-to-event variables the actual dates will be used.


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Measurement
Formula
Log10 viral load actual 
values
Log10 of the actual values as measured with qRT-PCR, including 
both swabs collected at the clinic visits and at home.
Log10 viral load change 
from baseline
Change = Log10 viral load actual value – log10 baseline value
RSV viral load AUC0-48h
[trapezoidal method]
RSV viral load AUC0-48h from 0 hours until 48 hours (Day 3) using 
the trapezoidal method (see below).
RSV viral load AUC0-96h
[trapezoidal method]
RSV viral load AUC0-96h from 0 hours until 96 hours (Day 5) using 
the trapezoidal method (see below).
RSV viral load 
AUC0-168h
[trapezoidal method]
RSV viral load AUC0-168h from 0 hours until 168h (Day 8) hours 
using the trapezoidal method (see below).
RSV viral load 
AUC0-312h
[trapezoidal method]
RSV viral load AUC0-312h from 0 hours until 312h (Day 14) hours 
using the trapezoidal method (see below).


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Measurement
Formula
Time to virus 
undetectable (hours) 
[Time-to event]
Time to virus undetectable will be evaluated using two approaches:
1) The time in hours from initiation of study treatment until the 
first post-baseline time point at which the virus is 
undetectable and after which time, no more detectable virus 
assessment (= event). 
Situation
Censoring
Last recording baseline 
assessment
time 0h
Last available assessment is 
detectable 
(right-censored) at last 
available assessment
2) The time in hours from initiation of study treatment until the 
first post-baseline time point at which the virus is confirmed 
undetectable (=event). 
A confirmed undetectable sample is defined as the first of at 
least, two consecutive undetectable virus assessments. 
Last obtained sample is always considered confirmed.
Situation
Censoring
Last record is baseline 
assessment
time 0h
Last available assessment is 
detectable 
(right-censored) at last 
available assessment
(Date and time of event or censoring - date and time of first dose of 
study drug)/3600, rounded to one decimal.
Viral load status at each 
time point (categorical)
Each RSV viral load measurement will be assigned to one of the 
3 categories below:
Undetectable (TND)
Detectable (TD)
Quantifiable 
Viral load status at each 
time point (binary)
Each RSV viral load measurement will be assigned to one of the 
2 categories to identify if it is detectable.

Detectable or quantifiable = Yes (1)

Undetectable = No (0)
The trapezoidal method will be used to calculate viral load AUC between 0 and xx hours, based 
on date times of sampling, including the timepoints with (imputed) values available:  


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		 
 = 1
2 ( + ) × ( −)


where i=1,2,3,… are the time points when post baseline samples are collected, yi is the log10
viral load at the time ti and ti is the time in hours post baseline. yo is the (imputed) log10 viral 
load at baseline, t0 is time 0 hours, tn is time xx. 
The following rules will be applied to deal with missing values before calculating the viral 
load AUC:
1.
The value at time point 0h, if not exactly at 0h, will be calculated based on linear 
interpolation between the last observed pre-dose value and the first observed post-dose 
value.
2.
In case the first available observation is after 0 hours, the value at 0h will be imputed by 
carrying backward the first available observation.
3.
The value at xx hours, if not exactly at xxh, will be calculated based on interpolation 
between the last observed value before xxh and the first observed value after xxh. 
4.
In case the last available observation is before xxh, the value at xxh will be imputed by 
carrying forward the last available observation. Carrying forward should only be 
performed if the time between the available observation and the value at xxh is at most 
24 hours. 
5.
Missing values between 0h and xxh will be imputed by interpolation (automatically by 
trapezoidal rule).
6.
In case the last observation is before xxh, and the value at xxh cannot be determined, the 
AUCs through xxh and through any later timepoint will not be derived.
Note that additionally the AUC will be derived using a mixed model approach.
5.2.2.
Analysis Methods
Mean log10 viral load values over time will be analyzed using a restricted maximum likelihood 
based repeated measures approach. Analysis will include fixed categorical effects of treatment, 
strata (symptoms onset [≤3 days vs >3 days before randomization), visit, treatment-by-visit 
interaction, and the continuous covariates of baseline log10 viral load and baseline log10 viral 
load-by-visit interaction as well as a random effect to model the within-subject error covariance. 
An unstructured covariance structure will be selected. In case this model will not converge, the 
Toeplitz covariance structure will be applied. The Kenward-Roger approximation will be used to 
estimate denominator degrees of freedom.
No imputations of missing data from nasal swabs post-baseline will be done in this model, as this 
mixed model would allow to make inferences under the missing at random assumption. Note that 
for this analysis only values as provided by the central lab will be used.
To evaluate the difference in the AUC between active and placebo, 3 contrasts will be explored: 
a contrast with no difference between the 2 active doses tested against placebo; a contrast with 
no difference between low dose and placebo tested against high dose; and a contrast with a linear 


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dose-response relationship with respect to the active doses. These contrasts will be used to derive 
the least square mean differences in the AUCs for active versus placebo, and their 90%CIs, with 
no multiplicity correction.
RSV RNA Viral Load 
Descriptive statistics, mean (SE) graphs and median (IQR) graphs will be shown for the log10
viral load actual values and changes from baseline by visit and by treatment group. 
Differences on RSV RNA log10 viral load by qRT PCR between treatment groups and by 
analysis visit will be determined by using appropriate contrasts in a similar repeated measure 
mixed effects model, including 90% 2-sided confidence intervals.
The potential associations with RSV RNA log10 viral load and the following covariates and/or 
baseline indicators will be explored graphically:
- baseline log10 viral load
- smoking history (never/current/former)
- history of wheezing (yes/no)
- presence/absence of comorbid diseases associated with risk for severe RSV disease
- presence/absence of other conditions/therapy of potential interest
- days since symptom initiation (0,1,2,3,4,5)
- RSV subtype
- use of corticosteroids
- supplemental oxygen at baseline 
- age as continuous variable. 
- severity of key RSV symptoms at screening
- baseline RSV genotype;
The homogeneity of treatment effect on the occurrence of AUC viral load from baseline to Days 
3, 5, and 8 across subgroups will be examined using the same MMRM model approach for the 
primary analysis, but also includes the subgroup-by-treatment and subgroup-by-visit interaction 
terms in the model. A forest plot will present the Least Square means and 90% CI for all 
subgroups of interest.
RSV Viral Load AUC
The individual AUC as calculated using the trapezoidal rule will be considered as a supportive 
analysis and will be analyzed using a linear model with AUC as a dependent variable and 
treatment group and stratum as fixed factor and baseline log10 viral load as covariate. The 
differences versus placebo will be estimated using appropriate contrasts with 90% 2-sided 
confidence intervals.


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Time to virus undetectable [time-to event]
Time-to event variable will be analyzed and plotted using Kaplan-Meier estimates analysis. The 
estimate of the hazard ratio (HR) and the 90% confidence intervals for the treatment effect will 
be provided based on a stratified Cox proportional hazard model (derived randomization 
stratification factor: ≤3 days, >3 days) and including treatment group as a covariate.
A summary table including number of subjects included in the analysis, number of subjects 
censored, 25th and 75th percentiles and median time-to event, with 90% confidence intervals 
based on the Kaplan-Meier method, will be presented by treatment group.
First approach to evaluate virus undetectable, as described in Section 5.2.1 will considered for 
this analysis.
The potential impact of selected variables that identify the subgroups of interest on the time to 
virus undetectable will be assessed by the stratified Cox proportional hazard model. The model 
will be stratified by the randomization stratification factors and include treatment group and 
subgroup variable as covariates, and the subgroup by treatment interaction term. A forest plot 
will present the HRs and 90% CI for all subgroups of interest. 
Proportion of subjects with undetectable RSV viral load
The proportion of subjects within the RSV RNA viral load categories (undetectable, detectable 
and quantifiable) will be shown in a frequency tabulation, by treatment group and visit. Subjects 
with missing data on that analysis visit will not be counted in the denominator for the proportion.
The difference in proportions for undetectable versus detectable/quantifiable between each active 
group and placebo, will be tabulated descriptively (n and % per treatment group), for each post 
baseline timepoint. Summaries of the difference between groups will include 2-sided 90% 
confidence intervals based on the Wilson score test. 
In case of co-infection with both RSV A and B, the worst category will be used for the analysis.
As higher viral loads so denote worse degree of infection, the ordering will be from worst to 
better namely quantifiable – detectable – undetectable.
Information will also be presented graphically.
5.3.
Secondary Endpoints - Clinical Course
Clinical course related endpoints are as follows:

Duration and severity of signs and symptoms of RSV infection assessed through either the 
Respiratory Infection Patient Reported Outcome (RI-PRO) or the Respiratory Infection 
Intensity and Impact Questionnaire [RiiQ] questionnaire, and Additional Questions about 
Health and Functioning.

Time to resolution of selected RSV symptoms as reported by the subject through either the 
RI-PRO or RiiQ.

Respiratory rate, heart rate, body temperature, peripheral capillary oxygen saturation (SpO2) 
as measured by the investigator.






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Measurement
Formula
missing.
Body/Systemic
Arithmetic mean of the available items.
Score will be calculated if at least 8 out of 
11 items are available, otherwise it will be 
set to missing.
Each RI-PRO domain score ranges from 0 (symptom free) to 4
(very severe symptoms)
Please see Attachment [3].
RI-PRO key symptom 
score + change from 
baseline
Arithmetic mean of the following 7 key items (congested or stuffy 
nose, sore or painful throat, trouble breathing, chest tightness, 
coughing, coughed up mucus or phlegm, weak or tired) will be 
calculated if at least 5 out of 7 items are available, otherwise it will 
be set to missing.
Daily average RI-PRO 
domain scores + change 
from baseline
The worst result observed for each of the items within a domain, 
will be used to calculate the average of the RI-PRO domain scores 
per day (in case of BID) 
Time to resolution of 
selected RSV symptoms 
from RI-PRO (hours) 
[Time-to event]
Time (in hours) from first dose of study drug until the first time of 
resolution of RSV symptoms.
Resolution of RSV symptoms occurs when items within a selected 
domain in the RI-PRO are scored as ‘Not at all’ (score = 0) or ‘A 
little bit’ (score =1) (ie alleviated) for at least 24 hours.
Selected domains to consider are nose, throat, chest/respiratory and 
body/systemic symptoms.

Three consecutive recordings
indicating resolution are 
required, if the first (of these 3 consecutive) recording is 
before the second analysis timepoint of the BID schedule at 
Day 13. These 3 consecutive recordings should have been done 
over 4 scheduled consecutive analysis timepoints, 1 missing 
timepoint is allowed. 

Two consecutive recordings
indicating resolution are 
required, if the first (of these 2 consecutive) recording is at or 
after the second analysis timepoint of the BID schedule at Day 
13. These 2 consecutive recordings should have been done over 
3 scheduled consecutive analysis timepoints, 1 missing 
timepoint is allowed
In case RSV symptoms are not resolved, data will be censored.
Censoring will be done as follows:
Situation
Censoring
Last record(s) indicate 
first record of resolution from 


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Measurement
Formula
resolution of RSV symptoms
but insufficient recordings to 
meet the time to resolution
the last series of recordings of 
resolution of RSV symptoms
Last record does not indicate 
resolution of RSV symptoms
after the last observation, at 
20:00 on the same day if the 
last observation was a 
morning diary entry (from 
02:00 until 13:59)
at 8:00 the next day if the last 
entry was an evening diary 
(from 14:00 until 01:59)
Death (without previous 
resolution)
date of death. 
If time is not available, it will 
be imputed as per 00:01 of the 
date of death
missing information to 
determine resolution or 
resolution of symptoms 
because of hospitalization
date of hospitalization
If time is not available, it will 
be imputed as per 00:01 of the 
date of hospitalization
(Date and time of event or censoring - date and time of first dose of 
study drug)/3600, rounded to one decimal
Time to complete 
resolution of selected RSV 
symptoms from RI-PRO
(hours) [Time-to event]
Time (in hours) from first dose of study drug until first complete 
resolution of RSV symptoms.
Complete resolution of RSV symptoms occurs when items within a 
selected domain in the RI-PRO are scored as ‘Not at all’ (score = 
0) for at least 24 hours.
Censoring will be applied as defined above.
Time to resolution of all 
RSV symptoms from RI-
PRO
(hours) 
[Time-to 
event]
Time (in hours) from first dose of study drug until the first time of 
resolution of RSV symptoms.
Resolution of RSV symptoms occurs when all items within a 
domain in the RI-PRO are scored as ‘Not at all’ (score=0) or ‘A 
little bit’ (score =1) (ie alleviated) for at least 24 hours.
Censoring will be applied as defined above.
Time to complete 
resolution of all RSV 
symptoms from RI-PRO 
(hours) [Time-to event]
Time (in hours) from first dose of study drug until first complete 
resolution of all RSV symptoms.
Complete resolution of RSV symptoms occurs when all items 
within a domain in the RI-PRO are scored as ‘Not at all’ (score = 
0) for at least 24 hours.


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Measurement
Formula
Censoring will be applied as defined above.
Time to resolution of key
RSV symptoms from RI-
PRO (hours) [Time-to 
event]
Time (in hours) from first dose of study drug until the first time of 
resolution of key RSV symptoms.
Resolution of key RSV symptoms occurs when all 7 key items are 
scored as ‘Not at all’ (score = 0) or ‘A little bit’ (score =1) (ie 
alleviated) for at least 24 hours.
Censoring will be applied as defined above.
Time to complete 
resolution of key RSV 
symptoms from RI-PRO 
(hours) [Time-to event]
Time (in hours) from first dose of study drug until complete 
resolution of all 7 key RSV symptoms.
Complete resolution of key RSV symptoms occurs when all items 
within a domain in the RI-PRO are scored as ‘Not at all’ (score = 
0) for at least 24 hours.
Censoring will be applied as defined above.
RiiQ
RiiQ symptom score + 
change from baseline
RiiQ symptom domain is a 13 items questionnaire which ranges 
from 0 (symptom free) to 3 (severe symptoms). Arithmetic mean
will be calculated if at least 9 out of 13 items are available, 
otherwise it will be set to missing.
Please see Attachment [3].
RiiQ key symptom score + 
change from baseline
Arithmetic mean of the following 7 key items (nasal congestion, 
sore throat, short of breath, wheezing, cough, coughing up phlegm 
[sputum], fatigue [tiredness]) will be calculated if at least 5 out of 7 
items are available, otherwise it will be set to missing.
Daily average RiiQ 
symptom score + RiiQ key 
symptom score + change 
from baseline
The worst result observed for each of the items will be used to 
calculate the average of the RiiQ symptom score per day (in case 
of BID).
RiiQ 
impact 
scores 
+ 
change from baseline
There are 3 RiiQ impact domains: Daily activity (7 items), 
Emotions (4 items), and Relationship (5 items). Each item ranges 
from 0 (no impact) to 3 (severe impact).
Domain
Score calculation
Daily activity
Arithmetic mean will be calculated if at 
least 5 out of 7 items are available, 
otherwise it will be set to missing.
Emotions
Arithmetic mean will be calculated if at 
least 3 out of 4 items are available, 
otherwise it will be set to missing.
Relationship
Arithmetic mean will be calculated if at 


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Measurement
Formula
least 3 out of 5 items are available, 
otherwise it will be set to missing.
Time to resolution of all 
RSV symptoms from RiiQ 
(hours) [Time-to event]
Time (in hours) from first dose of study drug until the first time of 
resolution of all RSV symptoms.
Resolution of RSV symptoms occurs when all items within the 
symptom domain of RiiQ are scored as ‘None’ (score = 0) or 
‘Mild’ (score =1) for at least 24 hours.
Censoring will be applied as defined above.
Time to complete 
resolution of all RSV 
symptoms from RiiQ 
(hours) [Time-to event]
Time (in hours) from first dose of study drug until first complete 
resolution of all RSV symptoms.
Complete resolution of RSV symptoms occurs when all items 
within the symptom domain of the RiiQ are scored as ‘None’ 
(score = 0) for at least 24 hours.
Censoring will be applied as defined above.
Time to resolution of key 
RSV symptoms from RiiQ 
(hours) [Time-to event]
Time (in hours) from first dose of study drug until the first time of 
resolution of all 7 key RSV symptoms.
Resolution of key RSV symptoms occurs when all 7 key items 
within the symptom domain of the RiiQ are scored as ‘None’ 
(score = 0) or ‘Mild’ (score =1) for at least 24 hours.
Censoring will be applied as defined above.
Time to complete 
resolution of key RSV 
symptoms from RiiQ
(hours) [Time-to event]
Time (in hours) from first dose of study drug until first complete 
resolution of all 7 key RSV symptoms.
Complete resolution of RSV symptoms occurs when all 7 key
items within the symptom domain in the RiiQ are scored as ‘None’ 
(score = 0) for at least 24 hours.
Censoring will be applied as defined above.
Common endpoints for RI-PRO and RiiQ
Key RSV symptom score 
from either RI-PRO or 
RiiQ + daily average + 
change from baseline
Arithmetic mean of the key items from either RI-PRO or RiiQ will 
be calculated if at least 10 out of 14 items are available, otherwise 
it will be set to missing. When a key item is available in both RI-
PRO and RiiQ, only the key item from RiiQ will be considered.
The worst result observed for each of the items will be used to 
calculate the average of the RI-PRO or RiiQ symptom score per 
day (in case of BID).
Time to resolution of key 
RSV 
symptoms 
(hours) 
from either RI-PRO or 
Time (in hours) from first dose of study drug until the first time of 
resolution of all 7 key RSV symptoms from either RI-PRO or 




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Measurement
Formula
the time to return to usual 
activity
Last record does not indicate 
return to usual activity
after the last observation, at 
20:00 on the same day if the 
last observation was a 
morning diary entry (from 
02:00 until 13:59)
at 8:00 the next day if the last 
entry was an evening diary 
(from 14:00 until 01:59)
Death (without previous return 
to usual activity)
date of death. 
If time is not available, it will 
be imputed as per 00:01 of the 
date of death
missing information to 
determine return to usual 
activity because of 
hospitalization
date of hospitalization
If time is not available, it will 
be imputed as per 00:01 of the 
date of hospitalization
(Date and time of event or censoring - date and time of first dose of 
study drug)/3600, rounded to one decimal
Time to return to usual 
health (hours) [Time-to-
event]
Time (in hours) from the first dose of study drug until the time of 
return to usual health.
Return to usual health occurs when the response is ‘Yes’ on RI-
PRO additional question 9 (“Have you returned to your usual 
health today?”) for at least 24 hours. 

Three consecutive recordings are required, if the first (of 
these 3 consecutive) recording is before the second analysis 
timepoint of the BID schedule at Day 13. These 3 consecutive 
recordings 
should 
have 
been 
done 
over 
4 scheduled 
consecutive analysis timepoints, 1 missing timepoint is 
allowed. 

Two consecutive recordings are required, if the first (of these 
2 consecutive) recording is at or after the second analysis 
timepoint of the BID schedule at Day 13. These 2 consecutive 
recordings 
should 
have 
been 
done 
over 
3 scheduled 
consecutive analysis timepoints, 1 missing timepoint is allowed
In case return to usual health is not reached, data will be censored.
Censoring will be done as follows:






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Measurement
Formula

No Abnormal (1)
Heart Rate actual values + 
changes from baseline
Heart Rate measured at baseline, Day 3, Day 8, Day 14 and Day 
21.
Heart Rate status at each 
visit (binary)
Each measurement will be assigned to one of the 2 categories to 
identify if the heart rate is normalized to the pre-RSV disease 
status, rated by the investigator at baseline, Day 3, Day 8, Day 14 
and Day 21.
Normalization of heart rate (HR) will be derived from the answer 
to the corresponding question in the eCRF “Is this value similar to 
the pre-RSV infection value for this patient?”

Yes  Normalized (0)

No Abnormal (1)
Oxygen Saturation actual 
values + changes from 
baseline
Oxygen Saturation measured at baseline, Day 3, Day 8, Day 14 and 
Day 21.
Oxygen Saturation status at 
each visit (binary)
Each measurement will be assigned to one of the 2 categories to 
identify if the oxygen saturation is normalized to the pre-RSV 
disease status, rated by the investigator at baseline/Day 1, Day 3, 
Day 8, Day 14 and Day 21.
Normalization of oxygen saturation (SpO2) will be derived from 
the answer to the corresponding question in the eCRF “Is this value 
similar to the pre-RSV infection value for this patient?”

Yes  Normalized (0)

No Abnormal (1)
Body Temperature actual 
values + changes from 
baseline
Body Temperature measured at on-site clinic visits (baseline, Day 
3, Day 8, Day 14 and Day 21), as well as measured at home.




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Measurement
Formula
“On auscultation are the following present”

Rales (crackles) Yes/No

Ronchi Yes/No
5.3.2.
Analysis Methods
5.3.2.1.
Endpoint-specific analysis methods
RI-PRO and RiiQ domain scores and daily average domain scores 
Descriptive statistics, mean (SE) graphs and median (IQR) graphs will be shown for the actual 
values and changes from baseline for both Ri-PRO and RiiQ scores. 
Changes from baseline on each of the RI-PRO and RiiQ domain scores will be analyzed using a 
restricted maximum likelihood based repeated measures approach as per Section 5.2.2. An 
unstructured covariance structure will be selected. 
Additional Questions about Health and Functioning
Frequency tabulations for the 9 additional questions about health and functioning will provided.
EQ-5D-5L VAS
Frequency tabulations of the EQ-5D-5 L dimensions will be provided. 
EQ-5D VAS descriptive statistics for the actual values and changes from baseline will be 
summarized.
Changes from baseline at each day of assessment will be analyzed using a restricted maximum 
likelihood based repeated measures approach as per Section 5.2.2. An unstructured covariance 
structure will be selected. 
Respiration Rate, Heart Rate, Oxygen Saturation and Body Temperature 
Descriptive statistics, mean (SE) graphs and median (IQR) graphs will be shown for the actual 
values and changes from baseline by visit and by treatment group. 
Respiration Rate Status, Heart Rate Status and Oxygen Saturation Status
The proportion of subjects within the two categories (abnormal, normalized) for each status 
(respiration rate, heart rate, and oxygen saturation) will be shown in a frequency tabulation by 
treatment group and analysis time point. The difference in proportions for abnormal status 
between each active group and placebo will be tabulated, and summaries will include 2-sided 
90% confidence intervals based on the Wilson score test.


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Subjects with missing data on that analysis visit will not be counted in the denominator for the 
proportion.
Need of Oxygen supplementation
The requirement for oxygen supplementation will only be calculated for those subjects that don’t
require oxygen supplementation before first dose of study drug.
The proportion of subjects with oxygen supplementation (yes and no) will be shown in a 
frequency tabulation by treatment group. The difference in proportions between each active 
group and placebo will be tabulated, summaries will include 2-sided 90% confidence intervals 
based on the Wilson score test.
Note that these incidences are only analyzed if any subjects require oxygen supplementation.
Respiratory infection complication
The proportion of subjects with presence/absence of complications (overall category and 
subcategories) will be shown in a frequency tabulation by treatment group including a column 
for the total JNJ-8678 irrespective of the doses.
Note that these incidences are only analyzed if any subjects have complications occur.
Time to resolution of symptoms, Time to return to usual health and Time to return to usual 
activity 
Time-to event variable will be analyzed and plotted using Kaplan-Meier estimates analysis. The 
estimate of the hazard ratio (HR) and the 90% confidence intervals for the treatment effect will 
be provided based on a stratified Cox proportional hazard model (derived randomization 
stratification factor: ≤3 days, >3 days) and including treatment group as a covariate. Due to 
limited available RiiQ data, these analyses will not be applied to the RiiQ time to event variables.
A summary table including number of subjects included in the analysis, number of subjects 
censored, 25th and 75th percentiles and median time-to event, with 90% confidence intervals 
based on the Kaplan-Meier method, will be presented by treatment group. 
The potential impact of selected variables that identify the subgroups of interest on the time to 
resolution of symptoms will be assessed by the stratified Cox proportional hazard model. The 
model will be stratified by the randomization stratification factors and include treatment group 
and subgroup variable as covariates, and the subgroup by treatment interaction term. A forest 
plot will present the HRs and 90% CI for all subgroups of interest.
Breathing Sounds 
Frequency tabulations of each wheezing status will be provided by treatment group and visit.
The proportion of subjects with Rales and Ronchi (yes and no) will be shown in a frequency 
tabulation by treatment group. The difference in proportions between each active group and 


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placebo will be tabulated, summaries will include 2-sided 90% confidence intervals based on the 
Wilson score test.
5.4.
Sensitivity Analyses
As a sensitivity analysis, the analysis on change from baseline on Day 3 and Day 8 will be 
repeated but excluding viral load data not collected by a Health Care Professional (HCP). If 
different results will be observed from this sensitivity and the primary analysis, then additional 
analyses may be performed to investigate further.
Time to virus undetectable will be also repeated but considering the second approach (please see 
Section 5.2.1) to evaluate virus undetectable.
Sensitivity analyses to assess the robustness of the primary efficacy analysis of viral load AUC 
will be performed by including the stratification factor, RSV symptom onset (≤3 days or > 3 
days), as collected by the IWRS in the mixed-effects model. Additionally, the primary efficacy 
analysis will be repeated on the mITT-I set.
For the time to resolution of selected RSV symptoms of RI-PRO, sensitivity analyses will be 
performed considering 4 different imputation methods:

Method 1: from first resolution (score 0 or 1) after last unresolved value onwards, impute 
missing data as resolution.

Method 2: impute all missing values as unresolved (score >1).

Method 3: impute all missing values in-between resolved observations (score 0 or 1) as 
resolved.

Method 4: impute all missing values as unresolved (score >1), except when in-between 
resolved values where resolved is imputed.
5.5.
Other Efficacy Variable(s)
5.5.1.
Definition
Measurement
Formula
Need for antibiotics related 
to complications associated 
with RSV
Need for antibiotics is defined as ‘Yes’ if the answers to the 
following 4 questions on the AE page in the eCRF are answered 
with ‘Yes’ to all of them.

Is this AE a complication related to the current respiratory 
infection?

Is this an infection?

If yes, was infection treated with oral or parenteral 
antibiotics?
If 
yes, 
specify 
the 
type 
of 
complication 
“Respiratory 
Complications”


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5.5.2.
Analysis Methods
Summary tables will be presented by treatment group, stratification factor and visits.
Need for antibiotics related to complications associated with RSV
The proportion of subjects with a need for antibiotics (yes and no) will be shown in a frequency 
tabulation. The difference in proportions between each active group and placebo will be 
tabulated, summaries will include 2-sided 90% confidence intervals based on the Wilson score 
test
5.6.
Exploratory Analyses
Relationships between primary antiviral effect endpoints and clinical course endpoints will be 
investigated as follows
Antiviral activity endpoints:

RSV RNA log10 viral load AUCs.

Time to virus undetectable.

Time to virus confirmed undetectable
Clinical course endpoints:

RI-PRO score per domain

Key RSV symptom score from RI-PRO

Key RSV symptom score from either RI-PRO or RiiQ (if available RiiQ data)

Time to resolution of selected RSV symptoms from RI-PRO

Time to resolution of key RSV symptoms from RI-PRO

Time to resolution of key RSV symptoms from either RI-PRO or RiiQ (if available RiiQ 
data)

Time to resolution of all RSV symptoms from RI-PRO

EQ-5D-5L each dimension and Visual Analog Scale
The relationships for each pair of variables described above will be explored using the 
Spearman’s rank correlation coefficients. Scatterplots with smoother curve per treatment group 
will be used for continuous and time-to-event variables (ignoring censoring). Boxplots will be 
created to graphically present the association between continuous and binary variables. For 
association between time-to-event clinical course parameters and continuous or binary variables, 
Kaplan-Meier plots will be generated by quartiles of the continuous variable, or by yes/no status 
of the binary variable, respectively.
The association between each EQ-5D-5L dimension and time to alleviation will also be explore 
using the spearman’s rank correlation coefficient and graphically.


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6.
SAFETY
All safety analyses will be done on the Safety Set.
6.1.
Adverse Events
All safety analyses will be done on the Safety Set.
6.1.1.
Definitions
Coding of AE
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the 
Medical Dictionary for Regulatory Activities. Events are looked at on the level of their preferred 
term.
Emergent Adverse Event
Emergent AEs are AEs with onset after first study medication intake or that are a consequence of 
a pre-existing condition that has worsened since baseline. All reported emergent AEs will be 
included in the analysis. For each AE, the percentage of subjects who experience at least 
1 occurrence of the given event will be summarized by treatment group.
Phase allocation of AE
Adverse events present in the SDTM database are allocated to phases based on their start date. If 
the start date of an event falls between (or on) the start and stop date of a phase, the AE is 
attributed to that phase (emergent principle).
Incomplete dates (i.e. time and/or day and/or month and/or year missing) are imputed according 
to the rules in Section 2.5.
6.1.2.
Analysis Methods
Treatment-emergent adverse events will be summarized by body system, preferred term and 
treatment group (including a column for total JNJ-8678).  
A summary will be provided for the following emergent adverse events by phase (treatment 
phase, follow-up phase) and by treatment: 

any adverse events, 

serious adverse events, 

deaths due to AE, 

adverse events by toxicity grade, 

AEs at least possibly related to study medication, 

AEs for which study medication was permanently stopped, 

AEs for which study was discontinues prematurely.

serious adverse events that were at least possibly related to study medication. 


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There will be no formal statistical testing.
Incidence tabulations will be provided for individual adverse events in the above categories (in 
case there are at least 5 events). Additionally, tabulation of AEs of at least grade 2 and 
considered related to study drug will be provided.
Listings will be provided for at least the following categories: all AEs, serious AEs, AEs leading 
to death, AEs leading to permanent stop, grade 3-4 AEs.
The summary, incidence tabulation for the individual preferred terms and subject listing will be 
provided for the RSV-related complications. 
The following adverse events will be tabulated; or listed (in case there are less than 5 events) by 
subgroups (see Section 2.4): any AE, any RSV-related complications, any grade 3-4 AE, AEs 
that are at least possibly related to study medication, AEs leading to death, serious AEs, AEs 
leading to permanent stop of study medication.
6.2.
Clinical Laboratory Tests
6.2.1.
Definitions
Laboratory parameters of hematology, serum chemistry and urinalysis will be investigated: All 
analyses will be done on SI-converted values as available in the database.
Coagulation function will be monitored during this study through evaluation of partial 
thromboplastin time (PTT) activated partial thromboplastin time (aPTT) in seconds and of the 
International normalized ratio.
Renal Function will be monitored during the study through evaluation of the estimated 
Glomerular Filtration (eGFR) based on:

Serum creatinine by Cockcroft-Gault formula
CCr (mL/min) = sex * [(140 - age) * weight(kg) / 72 * SCr(mg/dL)]; if female, correction 
factor is 0.85

Serum cystatin C
GFR (mL/min/1.73m2) = 84.69 * cystatin C (mg/L)-1.680
Toxicity grades and abnormalities for laboratory parameters:
The laboratory abnormalities will be determined according to the DMID adult toxicity grading 
scale (see Attachment [3]), available toxicity grades provided by the central lab (Covance) will 
be used. In case no toxicity grades are defined for a test, the abnormalities (above/below normal 
range) will be used. 
In determining toxicity grades/abnormalities for each subject the following rules are applied:


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
Worst grades/abnormalities are determined over the whole observational period, per phase 
(treatment, follow-up and combination treatment + follow-up), including unscheduled 
measurements. 

The abnormalities “abnormally low” and “abnormally high” are considered equally 
important, i.e. if a subject has as well an abnormally low as an abnormally high value post-
baseline, both abnormalities are shown in the tables. (This means that the sum of the 
percentages can be more than 100%).

If, for a specific test, the grading list provides distinct limits for abnormally low (=hypo) 
values as well as for abnormally high (=hyper) values, this test should be repeated for hyper 
and hypo limits separately in cross-tabulations.
Emergent definition for toxicity grades and abnormalities
An abnormality (toxicity grade or abnormality based on normal ranges) will be considered 
emergent if it is worse than the baseline abnormality. If the baseline abnormality is missing, the 
abnormality is always considered as emergent. A shift from “abnormally low” at baseline to 
“abnormally high” post baseline (or vice versa) is also emergent. The emergent definition is 
applicable in both, the treatment and follow-up phase.
In case of missing date or partial dates
Laboratory records with missing assessment date- or partially missing (any: day, month or year) 
will not be used in descriptive statistics, unless the scheduled target day or time is known, and a 
unique phase allocation is possible taking this additional information into account. These 
assessments will be allocated to the correct phase using the available date information, and the 
information on their assessment schedule. In case it is not possible to assign a unique phase (e.g. 
unscheduled time points), the assessment will be assigned to all possible active phases based on 
the available date and time information. These cases will be flagged in the respective listings.
Imputations of numerical values expressed as characters
In case a laboratory test result is censored (no numeric value is available, but only a verbatim 
term), the following rules are applied:

‘<x’ or ‘>x’: a numeric value will be imputed by a value exceeding the cut-off value with 
one unit

‘≤x’ or ‘≥x’: imputation by x.
This also applies to normal limits expressed as such.
No such imputations will
be done for urinalysis parameters as these are usually 
character/categorical expressions
6.2.2.
Analysis Methods
Laboratory data will be summarized by type of laboratory test. Actual values and changes from 
baseline will be summarized by treatment group at each scheduled time point. 


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A cross-tabulation of the worst toxicity/abnormality versus baseline will be presented per phase 
(treatment phase, follow-up phase) and for the combination of treatment and follow-up phase. 
This table will also show the number and percentage of subjects per worst toxicity/abnormality, 
the number and percentage of subjects per emergent worst toxicity/abnormality and the 
cumulative number of subjects per emergent toxicity/abnormality or worse. 
Mean ± SE graphs over time for the actual values and changes from baseline will be generated 
for all tests performed by treatment group. 
A listing of abnormal individual subject hematology and clinical chemistry values from 
scheduled and unscheduled time points will be provided. This listing will include all other time 
points for the corresponding subject/parameter. Grade 2 or higher toxicity laboratory values will 
be listed separately. Urinalysis results will be listed. 
6.3.
Vital Signs and Physical Examination Findings
Systolic and Diastolic blood pressure, heart rate, respiratory rate, body temperature and oxygen 
saturation (SpO2) will be investigated. 
6.3.1.
Definitions
The vital signs abnormalities will be defined as indicated in Table 12. In determining the 
abnormalities, the following rules are applied:

Worst grades/abnormalities are determined over the whole observational period for each 
trial phase separately, including post-baseline scheduled and unscheduled measurements of 
that phase.

The abnormalities ‘abnormally low’ and ‘abnormally high’/grades are considered equally 
important, i.e. if a subject has as well an abnormally low as an abnormally high or graded 
value post-baseline, both abnormalities are shown in the tables. (This means that the sum of 
the percentages can be more than 100%).


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Table 12:
Clinically Important Abnormalities in Vital Signs
Vital Sign
Abnormality Code
Criteria
Systolic blood 
pressure
Abnormally low
≤ 90 mmHg
Grade 1 or mild
> 140 mmHg - < 160 mmHg
Grade 2 or moderate
≥ 160 mmHg - < 180 mmHg
Grade 3 or severe
≥ 180 mmHg
Diastolic blood 
pressure
Abnormally low
≤ 50 mmHg
Grade 1 or mild
> 90 mmHg - < 100 mmHg
Grade 2 or moderate
≥ 100 mmHg - < 110 mmHg
Grade 3 or severe
≥ 110 mmHg
Respiratory rate
Grade 1 or mild
17-20 breaths per minute
Grade 2 or moderate
21-25 breaths per minute
Grade 3 or severe
> 25 breaths per minute
Grade 4 or potentially 
life threatening
Intubation
Oxygen Saturation
Abnormally low
< 95%
Temperature (oral)
Abnormally high
> 38.0 o C
Pulse/Heart Rate
Abnormally low
≤ 45 bpm
Abnormally high
≥ 120 bpm
Emergent definition for abnormalities
An abnormality will be considered emergent if it is worse than baseline. If baseline is missing, 
the abnormality is always considered emergent. A shift from ‘abnormally low’ at baseline to 
‘abnormally high’ post baseline (or vice versa) is also emergent.
6.3.2.
Analysis Methods
Actual values and changes from baseline will be summarized by treatment group at each 
scheduled time point. 
A cross-tabulation of the worst toxicity/abnormality versus baseline will be presented per phase 
(treatment phase, follow-up phase) and for the combination of treatment and follow-up phase. 
This table will also show the number and percentage of subjects per worst toxicity/abnormality, 
the number and percentage of subjects per emergent worst toxicity/abnormality and the 
cumulative number of subjects per emergent toxicity/abnormality or worse. 
Mean ± SE graphs over time for the actual values and changes from baseline will be generated 
for all tests performed by treatment group. 
A listing of abnormal (or grade 2 or higher) individual subject vital signs values will be 
provided. This listing will include all other time points for the corresponding subject/parameter.


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6.4.
Electrocardiogram
PR, QT, QRS, QTc intervals and heart rate will be investigated. QTcB and QTcF values will be 
used as reported by the central ECG provider, they will not be recalculated.
6.4.1.
Definitions
The ECG abnormalities will be defined as indicated in Table 13. In determining the 
abnormalities, the following rules are applied:

Worst grades/abnormalities are determined over the whole observational period and for each 
trial phase separately, including post-baseline scheduled and unscheduled measurements of 
that phase.

The abnormalities ‘abnormally low’ and ‘abnormally high’/grades are considered equally 
important, i.e. if a subject has as well an abnormally low as an abnormally high or graded 
value post-baseline, both abnormalities are shown in the tables. (This means that the sum of 
the percentages can be more than 100%).
Table 13:
ECG Abnormalities 
ECG parameter
Abnormality Code
Criteria
Abnormalities on actual values
Pulse/Heart Rate
Abnormally low
≤ 45 bpm
Abnormally high
≥ 120 bpm
PR
Abnormally high
≥ 210 ms
QRS
Abnormally high
≥ 120 ms
QTcorrected
Borderline prolonged QT
450 ms < QTc < 480 ms
Prolonged QT
480 ms < QTc < 500 ms
Pathologically prolonged QT
QTc > 500 ms
Abnormalities on changes from baseline (∆QTc)
QTcorrected
Normal QTc change
∆QTc < 30 ms
Borderline QTc change
30 ms < ∆QTc < 60 ms
Abnormally high QTc change
∆QTc > 60 ms
Emergent definition for abnormalities
An abnormality will be considered emergent if it is worse than baseline. If baseline is missing, 
the abnormality is always considered as emergent. A shift from ‘abnormally low’ at baseline to 
‘abnormally high’ or ‘grade …’ post baseline (or vice versa) is also emergent.
Triplicate ECG assessments
For time points on which triplicate ECGs apply (expected for all time points), a mean value per 
triplet cluster, will be calculated per time point before any further handling. This mean value will 
be used through the entire analysis. In the analysis dataset, the time of the first triplet member 
will be retained for this average record.


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Rounding
When ECG parameters need to be derived or any operations should be performed (e.g. averaging 
over many assessments/triplicates), no rounding to the integer/unit will be performed; the 
maximum stored resolution of these vales in the derived dataset(s) will be limited to 8 decimal 
positions. When used in tables, these values will be presented using formats reflecting the 
resolution of the unit applicable to the respective parameter (milliseconds, beats per minute).
6.4.2.
Analysis Methods
Actual values and changes from baseline will be summarized by treatment group at each 
scheduled time point. 
A cross-tabulation of the worst toxicity/abnormality versus baseline will be presented per phase 
(treatment phase, follow-up phase) and for the combination of treatment and follow-up phase. 
This table will also show the number and percentage of subjects per worst toxicity/abnormality, 
the number and percentage of subjects per emergent worst toxicity/abnormality. 
A tabulation of the worst QT/QTc change versus baseline per treatment per phase (treatment 
phase, follow-up phase) and for the combination of treatment and follow-up phase will be 
presented
Mean ± SE graphs over time for the actual values and changes from baseline will be generated 
for all tests performed by treatment group.
A listing of abnormal individual subject ECG values will be provided. This listing will include 
all other time points for the corresponding subject/parameter.
7.
HEALTH ECONOMICS
7.1.
Definitions
Medical Resource Utilization will be assessed by the number and duration of medical care 
encounters for RSV infection or complications associated with RSV per investigator assessment.
Information will be provided as:

Number of medical encounters and rationale (AE, Other)

Type of encounter such as medical practitioner office, emergency room, hospitalization, 
intensive care unit, palliative care unit among others

Specialist involved

Frequency of visits.
7.2.
Analysis Methods
The proportion of subjects requiring any medical encounter will be shown in a frequency 
tabulation by treatment group with the corresponding 90% confidence interval (exact Clopper-
Pearson method). 


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Similar frequency tables will be provided for type of medical encounter. Data will also be 
summarized stratifying by presence of any comorbidity.
Additional information on medical encounters (frequency of visits, type of practitioner) will be 
listed.
8.
VIROLOGY
The sequencing results of the F-gene (and other regions of the RSV genome at the request of the 
protocol virologist) and changes from baseline will be summarized. Sequencing results may be 
presented in a separate report.
8.1.
Definitions
Viral Strain Typing
The RSV subtype is determined at baseline using the RSV-A/B RT-qPCR assay performed in the 
central lab.
Viral Sequencing
Viral resistance will be evaluated by next-generation sequencing (NGS) of the RSV Fusion (F) 
gene using a read frequency cut-off that will be defined in the Data Presentation Sheet. 
Baseline samples from all subjects will be sequenced to identify pre-existing polymorphisms in 
the F gene. Post-baseline sequencing will be performed on the last evaluable on-treatment 
sample and/or during follow-up for all subjects (if viral load is high enough) to identify emerging 
amino acid substitutions in the F gene. Additional post-baseline sequencing can be performed on 
request of the sponsor virologist.
Genetic variations
Genetic variations are defined as changes (on amino acid or nucleotide level) in the subject’s 
virus’s sequence compared to a reference sequence. Genetic variations can include substitutions, 
insertions and deletions. The reference sequences used will be RSV-A Long strain (GenBank 
Accession number AY911262) for RSV-A samples and RSV-B strain 9320 (GenBank Accession 
number AY353550) for RSV-B samples.  Genetic variations will be reported on amino acid 
level.

Baseline polymorphism: amino acid difference from the RSV-A or RSV-B reference strain 
detected at baseline above a certain NGS read frequency cut-off, which is to be defined.

Emerging genetic variation: a genetic variation (amino acid substitution, insertion or 
deletion) that is absent (i.e. below a to be defined NGS read frequency cut-off) at baseline
but present above a certain to be defined NGS read frequency cut-off at a later post-baseline 
time point.

Enriched genetic variation: a genetic variation (amino acid substitution, insertion or 
deletion) that is present at baseline with an NGS read frequency cut-off that will be defined 
and detected post-baseline with an increase in NGS read frequency compared to baseline. 


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The minimum increase in NGS read frequency to meet the definition of enriched genetic 
variation will be defined.

Genetic variation profile: a specific genetic variation or combination of genetic variations 
at one or more time points.

RSV F-gene amino acid positions of interest: 
o
Short list of 8 F-gene positions of interest for JNJ-53718678, based on in vitro 
selection experiments with JNJ-53718678 and/or in vitro reduced susceptibility to 
JNJ-53718678: positions 141, 143, 394, 398, 400, 486, 488, and 489.
o
Long list of 20 F-gene positions of interest for the class of RSV fusion inhibitors, 
based on in vitro selection experiments, clinical observations, and/or in vitro 
reduced susceptibility to RSV fusion inhibitors: positions 127, 138, 140, 141, 143, 
144, 323, 338, 392, 394, 398, 399, 400, 401, 474, 486, 487, 488, 489, and 517.
The read frequency cut-off that will be used for reporting RSV F-gene NGS data, as well as the 
read frequency cut-offs used in the definitions of baseline polymorphisms, emerging and 
enriched genetic variations will be defined in the Data Presentation Specifications.
Analysis Time Points
Virology results will be assigned to the visit windows as described in Sections 2.1.2 Phase 
Definitions and 2.1.4 Visit Windows. In addition to the time points corresponding to the visits at 
which samples for RSV F gene sequencing are collected, the below time points will be 
considered: 

Baseline (BL): Time point with sequencing data available closest prior to the first dose. This 
will be the Day 1 pre-treatment sample; however, if RSV F gene sequencing data cannot be 
obtained from this sample, the screening sample may be used for sequencing.

Last Evaluable On-Treatment Time Point: Last available post-baseline time point during the 
treatment phase with sequencing data available. In case no On-Treatment assessment is 
available, the first assessment during Follow-Up is selected instead.

Time Point of Sequence during the Follow-Up phase: Last available post-baseline time point 
during the follow-up phase with sequencing data available.

Entire post-baseline phase: Aggregate of all available post-baseline time points in the study 
with sequencing data available
8.2.
Analysis Methods
8.2.1.
Viral Strain Typing
The number of subjects by RSV subtype will be tabulated in frequency outputs (n, %).
8.2.2.
Viral Sequencing
Baseline
The prevalence of baseline polymorphisms in the RSV F-gene, ie the number of subjects with 
baseline polymorphisms in the RSV F-gene, will be tabulated in frequency outputs (n, %). 


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Amino acid changes from reference sequence at baseline will be listed for all subjects using a 
defined NGS read frequency cut-off (will be defined in the Data Presentation Specifications).
Post-baseline
Emerging and enriched genetic variations will be tabulated by analysis time point in frequency 
outputs (n, %). Amino acid changes from reference sequence will be listed for all subjects with 
post-baseline sequencing data using a defined NGS read frequency cut-off (will be defined in the 
Data Presentation Specifications).


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REFERENCES

Duncan CB, Walsh EE et al. Risk Factors for Respiratory Failure Associated with 
Respiratory Syncytial Virus Infection in Adults. J Infect Dis. 2009 October 15; 200(8):
1242–1246.

Walsh EE, Peterson DR et al. Risk Factors for Severe Respiratory Syncytial Virus Infection 
in Elderly Persons. J Infect Dis. 2004; 189:233–8

EQ-5D-5L User Guide. Basic information on how to use the EQ-5D-5L instrument, Version 
2.1, April 2015, Mandy van Reenen / Bas Janssen, EuroQol Research Foundation, 
www.euroqol.org

E.D. Bacci, K. Kim, S. Stringer, N. K. Leidy, User Manual for the InFLUenza Patient-
Reported Outcome (FLU-PRO) Diary, Version 1.1

Akaike H., A new look at the statistical model identification, IEEE Transactions on 
Automatic Control, 1974: 19 (6): 716–723.

Kaplan E. L., Meier P. Nonparametric estimation from incomplete observations. Journal of 
the American Statistical Association, 1958; 53 (282): 457–481.

Mehta CR. and Patel NR, Exact Logistic Regression: Theory and Examples, Statistics in 
Medicine, 1995: 14, 2143–2160.


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ATTACHMENTS
Attachment [1]:
Division of Microbiology and Infectious Diseases  (DMID) Adult
Toxicity Table – November 2007
ABBREVIATIONS: Abbreviations utilized in the Table:
ULN = Upper Limit of Normal
LLN = Lower Limit of Normal 
Rx = Therapy
Req = Required
Mod = Moderate
IV = Intravenous
ADL = Activities of Daily Living
Dec = Decreased
ESTIMATING SEVERITY GRADE
For abnormalities NOT found elsewhere in the Toxicity Tables use the scale below to estimate 
grade of severity:
GRADE 1
Mild Transient or mild discomfort (< 48 hours); no medical 
intervention/therapy required
GRADE 2
Moderate Mild to moderate limitation in activity - some assistance may be 
needed; no or minimal medical intervention/therapy required
GRADE 3
Severe Marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalizations possible
GRADE 4
Life-threatening Extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or 
hospice care probable
SERIOUS OR LIFE-THREATENING AEs
ANY clinical event deemed by the clinician to be serious or life-threatening should be 
considered a grade 4 event. Clinical events considered to be serious or life-threatening include, 
but are not limited to: seizures, coma, tetany, diabetic ketoacidosis, disseminated intravascular 
coagulation, diffuse petechiae, paralysis, acute psychosis, severe depression.
COMMENTS REGARDING THE USE OF THESE TABLES

Standardized and commonly used toxicity tables (Division of AIDS, NCI’s Common 
Toxicity Criteria (CTC), and World Health Organization [WHO]) have been adapted for 
use by the Division of Microbiology and Infectious Diseases (DMID) and modified to 
better meet the needs of participants in DMID trials.

For parameters not included in the following Toxicity Tables, sites should refer to the 
“Guide For Estimating Severity Grade” located above.

Criteria are generally grouped by body system.

Some protocols may have additional protocol-specific grading criteria, which will 
supersede the use of these tables for specified criteria.


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HEMATOLOGY
Grade 1
Grade 2
Grade 3
Grade 4
Hemoglobin
9.5 - 10.5 gm/dL
8.0 - 9.4gm/dL
6.5 - 7.9 gm/dL
< 6.5 gm/dL
Absolute Neutrophil Count
1,000-1,500/ mm3
750-999/ mm3
500-749/ mm3
<500/ mm3
Platelets
75,000-
99,999/ mm3
50,000-
74,999/ mm3
20,000-49,999/ mm3
<20,000/ mm3
WBCs
11,000-13,000/
mm3
13,000-
15,000 / mm3
15,000-
30,000/ mm3
>30,000 or
<1,000 / mm3
% Polymorphonuclear
Leucocytes + Band Cells
> 80%
90 – 95%
>95%
----------
Abnormal Fibrinogen
Low:
100-200 mg/dL
High:
400-600 mg/dL
Low:
<100 mg/dL
High:
>600 mg/dL
Low:
< 50 mg/dL
----------
Fibrinogen
associated with gross 
bleeding or with 
disseminated 
coagulation
Fibrin Split Product
20-40 mcg/ mL
41-50 mcg/ mL
51-60 mcg/ mL
> 60 mcg/ mL
Prothrombin Time (PT)
1.01 - 1.25 x ULN
1.26-1.5 x ULN
1.51 -3.0 x ULN
>3 x ULN
Activated Partial 
Thromboplastin (APPT)
1.01 -1.66 x ULN
1.67 - 2.33 x ULN
2.34 - 3 x ULN
> 3 x ULN
Methemoglobin
5.0 - 9.9 %
10.0 - 14.9 %
15.0 - 19.9%
> 20.0 %
CHEMISTRIES
Grade 1
Grade 2
Grade 3
Grade 4
Hyponatremia
130-135 mEq/ L
123-129 mEq/ L
116-122 mEq/ L
< 116 mEq/ L or abnormal sodium 
with mental
status changes or seizures
Hypernatremia
146-150 mEq/ L
151-157 mEq/ L
158-165 mEq/ L
> 165 mEq/ L or abnormal sodium 
with mental
status changes or seizures
Hypokalemia
3.0 - 3.4 mEq/ L
2.5 - 2.9 mEq/ L
2.0 - 2.4 mEq/ L or 
intensive replacement 
therapy or 
hospitalization 
required
< 2.0 mEq/ L or abnormal 
potassium with
paresis, ileus or life-threatening 
arrhythmia
Hyperkalemia
5.6 - 6.0 mEq/ L
6.1 - 6.5 mEq/ L
6.6 - 7.0 mEq/l
> 7.0 mEq/ L or abnormal
potassium with life-threatening 
arrhythmia
Hypoglycemia
55-64 mg/dL
40-54 mg/dL
30-39 mg/dL
<30 mg/dL or abnormal glucose 
with mental
status changes or coma
Hyperglycemia
(nonfasting and no 
prior diabetes)
116 - 160 mg/dL 161- 250 mg/d L
251 - 500 mg/dL
> 500 mg/dL or abnormal glucose 
with ketoacidosis or seizures
Hypocalcemia
(corrected for 
albumin)
8.4 - 7.8 mg/dL
7.7 - 7.0 mg/dL
6.9 - 6.1 mg/dL
< 6.1 mg/dL or abnormal
calcium with life-threatening 
arrhythmia or tetany


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CHEMISTRIES (continued)
Grade 1
Grade 2
Grade 3
Grade 4
Hypercalcemia (correct for 
albumin)
10.6 - 11.5 mg/dL
11.6 - 12.5
mg/d L
12.6 - 13.5 mg/dL
> 13.5 mg/dL or abnormal 
calcium with life-
threatening arrhythmia
Hypomagnesemia
1.4 - 1.2 mEq/ L
1.1 - 0.9 mEq/ L
0.8 - 0.6 mEq/ L
< 0.6 mEq/ L or abnormal 
magnesium with life-
threatening arrhythmia
Hypophosphatemia
2.0 - 2.4 mg/dL
1.5 -1.9 mg/dL or
replacement Rx 
required
1.0 -1.4 mg/dL 
intensive therapy or 
hospitalization 
required
< 1.0 mg/dL or abnormal
phosphate with life-
threatening arrhythmia
Hyperbilirubinemia (when 
accompanied by any 
increase in other liver 
function test)
1.1 - <1.25 x ULN
1.25 - <1.5 x 
ULN
1.5 – 1.75 x ULN
> 1.75 x ULN
Hyperbilirubinemia (when 
other liver function are in 
the normal range)
1.1 - <1.5 x ULN
1.5 - <2.0 x ULN
2.0 – 3.0 x ULN
> 3.0 x ULN
BUN
1.25 - 2.5 x ULN
2.6 - 5 x ULN
5.1 - 10 x ULN
> 10 x ULN
Hyperuricemia (uric acid)
7.5 – 10.0 mg/dL
10.1 – 12.0 
mg/dL
12.1 – 15.0 mg/d L
>15.0 mg/d L
Creatinine
1.1 - 1.5 x ULN
1.6 - 3.0 x ULN
3.1 - 6 x ULN
>6 x ULN or dialysis 
required
ENZYMES
Grade 1
Grade 2
Grade 3
Grade 4
AST (SGOT)
1.1 - <2.0 x ULN
2.0 – <3.0 x ULN
3.0 – 8.0 x ULN
> 8 x ULN
ALT (SGPT)
1.1 - <2.0 x ULN
2.0 – <3.0 x ULN
3.0 – 8.0 x ULN
> 8 x ULN
GGT
1.1 - <2.0 x ULN
2.0 – <3.0 x ULN
3.0 – 8.0 x ULN
> 8 x ULN
Alkaline Phosphatase
1.1 - <2.0 x ULN
2.0 – <3.0 x ULN
3.0 – 8.0 x ULN
> 8 x ULN
Amylase
1.1 - 1.5 x ULN
1.6 - 2.0 x ULN
2.1 - 5.0 x ULN
> 5.1 x ULN
Lipase
1.1 - 1.5 x ULN
1.6 - 2.0 x ULN
2.1 - 5.0 x ULN
> 5.1 x ULN


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URINALYSIS
Grade 1
Grade 2
Grade 3
Grade 4
Proteinuria
1+
or
200 mg - 1 gm 
loss/day
2-3+
or
1- 2 gm loss/day
4+
or
2-3.5 gm loss/day
nephrotic syndrome
or
>3.5 gm loss/day
Hematuria
microscopic only
<10 rbc/hpf
gross, no clots
>10 rbc/hpf
gross, with or without 
clots, OR RBC casts
obstructive or 
required
transfusion
CARDIOVASCULAR
Grade 1
Grade 2
Grade 3
Grade 4
Cardiac Rhythm
asymptomatic, 
transient signs, no
Rx required
recurrent/persistent; 
symptomatic Rx 
required
unstable dysrythmia;
hospitalization
and treatment 
required
Hypertension
transient increase
>20 mm/ Hg; no 
treatment
recurrent, chronic 
increase
> 20mm/ Hg
/treatment required
acute treatment 
required; outpatient 
treatment or 
hospitalization
possible
end organ damage or 
hospitalization 
required
Hypotension
transient orthostatic
hypotension with 
heart rate increased 
by <20 beat/min or 
decreased by <10 mm 
Hg systolic BP, No 
treatment required
symptoms due to 
orthostatic 
hypotension or BP 
decreased by <20 mm 
Hg systolic; 
correctable with oral 
flu id treatment
requires IV fluids; no 
hospitalization 
required
mean arterial pressure
<60mm/ Hg or end 
organ damage or 
shock; requires 
hospitalization and 
vasopressor treatment
Pericarditis
minimal effusion
mild/ moderate 
asymptomatic 
effusion, no treatment
symptomatic 
effusion; pain; EKG 
changes
tamponade; 
pericardiocentesis or 
surgery required
Hemorrhage, Blood Loss
microscopic/occult
mild, no transfusion
gross blood loss;
1-2 units transfused
massive blood loss; 
>3 units transfused


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RESPIRATORY
Grade 1
Grade 2
Grade 3
Grade 4
Cough
transient- no 
treatment
persistent cough; 
treatment responsive
Paroxysmal cough; 
uncontrolled with 
treatment
--------------------
Bronchospasm, Acute
transient; no
treatment;
70% - 80% FEV1
of peak flow
requires
treatment; normalizes 
with bronchodilator; 
FEV1 50% -
70%
(of peak flow)
no normalization 
with bronchodilator; 
FEV1 25% - 50%
of peak flow; or
retractions present
cyanosis: FEV1
<25%
of peak flow or 
intubation necessary
Dyspnea
dyspnea on exertion dyspnea with normal 
activity
dyspnea at rest
dyspnea requiring 
oxygen therapy
GASTROINTESTINAL
Grade 1
Grade 2
Grade 3
Grade 4
Nausea
mild or transient; 
maintains
reasonable intake
moderate discomfort; 
intake decreased
significantly; some 
activity limited
no significant intake; 
requires IV flu ids
hospitalization 
required;
Vomiting
1 episode in 24 hours
2-5 episodes in
24 hours
>6 episodes in 
24 hours or needing 
IV fluids
physiologic 
consequences 
requiring
hospitalization or 
requiring parenteral 
nutrition
Constipation
requiring stool
softener or dietary 
modification
requiring
laxatives
obstipation
requiring manual 
evacuation or enema
obstruction or
toxic megacolon
Diarrhea
mild or transient; 3-4 
loose
stools/day or mild
diarrhea last <1 week
moderate or 
persistent; 5-7 loose 
stools/day or diarrhea
lasting >1 week
>7 loose stools/day
or bloody diarrhea; or 
orthostatic 
hypotension or 
electrolyte imbalance 
or >2L IV fluids 
required
hypotensive shock or 
physiologic 
consequences 
requiring
hospitalization
Oral Discomfort/Dysphagia mild discomfort; no 
difficulty
swallowing
some limits on 
eating/drinking
eating/talking very 
limited; unable to 
swallow solid foods
unable to drink flu 
ids; requires IV fluids


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NEUROLOGICAL
Grade 1
Grade 2
Grade 3
Grade 4
Neuro-Cerebellar
slight incoordination 
dysdiadochokinesis
intention tremor, 
dysmetria,
slurred speech; 
nystagmus
locomotor ataxia
incapacitated
Psychiatric
mild anxiety or 
depression
moderate anxiety or 
depression; therapy 
required; change in 
normal routine
severe mood changes 
requiring therapy; or 
suicidal ideation; or 
aggressive ideation
acute psychosis 
requiring 
hospitalization; or 
suicidal 
gesture/attempt or 
hallucinations
Muscle Strength
subjective weakness 
no objective
symptoms/ signs
mild objective
signs/symptoms no 
decrease in function
objective weakness 
function limited
paralysis
Paresthesia (burning, 
tingling, etc.)
mild discomfort; no 
treatment required
moderate discomfort;
non-narcotic 
analgesia required
severe discomfort; or 
narcotic analgesia 
required with 
symptomatic 
improvement
incapacitating; or not 
responsive to narcotic 
analgesia
Neuro-sensory
mild impairment in 
sensation
(decreased
sensation, eg, 
vibratory, pinprick, 
hot/cold in great toes) 
in focal area or 
symmetrical
distribution; or 
change in taste, 
smell, vision and/or 
hearing
moderate
impairment (mod 
decreased sensation, 
eg, vibratory, 
pinprick, hot/cold to 
ankles) and/or joint 
position or mild
impairment that is not
symmetrical
severe impairment 
(decreased or loss of 
sensation to knees or 
wrists) or loss of 
sensation of at least 
mod degree in 
multiple
different body areas 
(ie, upper and lower
extremities)
sensory loss involves 
limbs and trunk; 
paralysis; or seizures


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MUSCULOSKELATEL
Grade 1
Grade 2
Grade 3
Grade 4
Arthralgia (joint pain)
mild pain not 
interfering with 
function
moderate pain, 
analgesics and/or pain 
interfering with 
function but not with 
activities of daily 
living
severe pain; pain 
and/or analgesics 
interfering with 
activities of daily 
living
disabling pain
Arthritis
mild pain with
inflammation,
erythema or joint
swelling – but not
interfering with
function
moderate pain with
inflammation,
erythema or joint 
swelling – interfering 
with function, but not 
with activities of
daily living
severe pain with
inflammation,
erythema or joint
swelling –and
interfering with
activities of daily
living
permanent and/or 
disabling joint
destruction
Myalgia
Myalgia with no 
limitation of activity
muscle
tenderness (at other 
than injection site) or 
with moderate
impairment of activity
severe muscle
tenderness with
marked impairment of 
activity
frank
myonecrosis
SKIN
Grade 1
Grade 2
Grade 3
Grade 4
Mucocutaneous
erythema; pruritus
diffuse, 
maculopapular rash, 
dry desquamation
vesiculation or
moist desquamation 
or ulceration
exfoliative
dermatitis, mucous 
membrane
involvement or 
erythema,
multiforme or 
suspected
Stevens-Johnson
or necrosis requiring 
surgery
Induration
<15mm
15-30 mm
>30mm
Erythema
<15mm
15-30 mm
>30mm
Edema
<15mm
15-30 mm
>30mm
Rash at Injection Site
<15mm
15-30 mm
>30mm
Pruritus
slight itching at 
injection site
moderate itching at 
injection extremity
itching over entire 
body


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SYSTEMIC
Grade 1
Grade 2
Grade 3
Grade 4
Allergic Reaction
pruritus without rash
localized urticaria
generalized urticaria; 
angioedema
anaphylaxis
Headache
mild, no treatment 
required
transient, moderate; 
treatment required
severe; responds to 
initial narcotic 
therapy
intractable; requires 
repeated narcotic 
therapy
Fever: oral
37.7 - 38.5 C or 
100.0 - 101.5 F
38.6 - 39.5 C or 
101.6 - 102.9 F
39.6 - 40.5 C or 103 -
105 F
>40 C or
>105 F
Fatigue
normal activity 
reduced < 48 hours
normal activity 
decreased 25-
50% > 48 hours
normal activity
decreased > 50%
can’t work
unable to care for self


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Attachment [2]:
Inclusion/exclusion criteria
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1.
Male or female.
2.
≥18 years of age.
3.
Must sign an ICF indicating they understand the purpose of, and procedures required 
for, the study and is willing to participate in the study.
Note: Prior to signing the main consent form for the study, subjects may specifically 
allow for the collection and testing of nasal mid-turbinate swabs by signing the 
pre-screening (diagnostic) ICF.
4.
Subjects must have an acute respiratory illness with signs and symptoms consistent with 
a viral infection (eg, fever, cough, nasal congestion, runny nose, sore throat, myalgia, 
lethargy, shortness of breath, or wheezing) with onset ≤5 days from the anticipated time 
of randomization. Onset of symptoms is defined as the time the subject becomes aware 
of the first sign and/or symptom consistent with a viral infection. Efforts should be 
made to determine the time of onset of symptoms as accurately as possible (in relation 
to routine daily activities).
Note: The viral infection may present in any way as long as the underlying precipitant 
of the illness is considered by the investigator to be due to RSV infection. Examples of 
such an illness include:

An upper or lower viral respiratory tract infection (eg, “flu-like illness”); 

Pneumonia;

Respiratory distress;

Asthma exacerbation;

COPD exacerbation.
5.
Subject has been diagnosed with RSV infection using a rapid PCR-based (preferably 
locally available) or rapid-antigen-detection test.
Note: If a patient has a positive similar diagnostic test from another study and meets all 
eligibility criteria for inclusion in this study, this diagnostic test result can be used for 
confirmation of eligibility.
6.
Before randomization, a woman must be not of childbearing potential defined as:

Premenarchal
A premenarchal state is one in which menarche has not yet occurred.


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
Postmenopausal
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. An available high follicle-stimulating hormone level 
(>40 IU/L or mIU/mL) in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy, however in the absence of 12 months of amenorrhea, a 
single follicle-stimulating hormone measurement is insufficient.

Permanently sterile
Permanent 
sterilization 
methods 
include 
hysterectomy, 
bilateral 
salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral 
oophorectomy.
7.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for a period of 30 days after the last dose of study
drug.
8.
All women must have a negative urine β-human chorionic gonadotropin pregnancy test 
at screening.
9.
A male subject must wear a condom when engaging in any activity that allows for 
passage of ejaculate to another person. Male subjects should also be advised of the 
benefit for a female partner to use a highly effective method of contraception as a 
condom may break or leak.
Note: Contraceptive (birth control) use by subjects should be consistent with local 
regulations regarding the acceptable methods of contraception for those participating in 
clinical studies.
10.
A male subject must agree not to donate sperm for the purpose of reproduction during 
the study and for a minimum of 90 days after receiving the last dose of study drug.
11.
Willing and able to adhere to the lifestyle restrictions specified in this protocol (please 
see protocol Section 4.3).
12.
With the exception of the RSV-related illness the subject must be medically stable on 
the basis of physical examination, medical history, vital signs, and ECG performed at 
screening. If there are abnormalities, they must be consistent with the underlying 
condition (RSV disease and/or comorbid condition) in the study population as evaluated 
by the investigator (with exception of QTcF interval >500 ms, see exclusion 
criterion 13). This determination must be recorded in the subject’s source documents 
and initialed by the investigator.


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Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study:
1.
Hospitalized subjects or subjects expected to be hospitalized within 24 hours of 
screening.
Note: Any stay in the emergency room or in the observational unit of at least 24 hours 
will be considered hospitalization for the purposes of the study.
2.
History of or concurrent illness (beyond a comorbid condition) that in the opinion of the 
investigator, might confound the results of the study or pose an additional risk in 
administering study drug to the subject or that could prevent, limit, or confound the
protocol-specified assessments.
3.
Subjects who had major surgery within the 28 days prior to randomization or have 
planned major surgery through the course of the study.
4.
Subjects who are considered by the investigator to be immunocompromised within the 
past 12 months, whether due to underlying medical condition (eg, malignancy or genetic 
disorder other than immunoglobulin A deficiency, or human immunodeficiency virus 
[HIV] infection) or medical therapy (eg, medications other than corticosteroids for the 
treatment of COPD or asthma exacerbations, chemotherapy, radiation, stem cell or solid 
organ transplant).
5.
Subject has known or suspected chronic or acute hepatitis B or C infection.
6.
Subject has known allergies, hypersensitivity, or intolerance to JNJ-53718678 or to any 
of the excipients of the JNJ-53718678 or placebo formulation (refer to the IB).
7.
Subject with current or planned participation in another clinical study where study 
drug/investigational device is being administered while participating in the current 
study.
8.
Subjects unwilling to undergo mid-turbinate nasal swab procedures or with any physical 
abnormality which limits the ability to collect regular nasal specimens.
9.
Subjects unable to take medications orally or with a known gastrointestinal-related
condition that is considered by the sponsor or investigator to be likely to interfere with 
study drug ingestion or absorption.
10.
Women who are pregnant or breastfeeding.


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11.
Men who plan to father a child while enrolled in this study or within 90 days after the 
last dose of study drug.
12.
Subject with clinically significant abnormal ECG findings (other than QTcF interval 
>500 ms, see exclusion criterion 13) not consistent with the underlying condition in the 
study population, as judged by the investigator.
13.
Confirmed QTcF interval >500 ms per the machine read parameter result at screening. 
Confirmation needs to be obtained by repeat triplicate ECG recording prior to dosing.
14.
Subjects who are using any disallowed medication as listed in Section 8 of the protocol.
15.
Subjects with history of drug or alcohol abuse according to Diagnostic and Statistical 
Manual of Mental Disorders (5th edition) criteria within 1 year before screening.
16.
Subjects who received an investigational drug, an investigational vaccine, or used an 
invasive investigational medical device within 30 days or 5 elimination half-lives 
(whichever is longer) before the planned first dose of study drug or is currently enrolled 
in an investigational study.
17.
Subject is a family member of the employees of the investigator or study-site with direct 
involvement in the proposed study or other studies under the direction of that 
investigator or study-site or of the investigator.


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Attachment [3]:
Respiratory infection-patient reported outcomes (ri-pro © ) symptom 
questionnaire
Domain 
Items 
Scoring and Minimum Data 
Requirement 
Nose 
Runny or dripping nose 
Congested or stuffy nose 
Sneezing 
Sinus pressure 
Arithmetic mean of 4 items 
Daily score for 3 of 4 items 
must be present to calculate 
domain score 
Throat 
Scratchy or itchy throat 
Sore or painful throat 
Difficulty swallowing 
Arithmetic mean of 3 items 
Daily score for 2 of 3 items 
must be present to calculate 
domain score 
Eyes 
Teary or watery eyes 
Sore or painful eyes 
Eyes sensitive to light 
Arithmetic mean of 3 items 
Daily score for 2 of 3 items 
must be present to calculate 
domain score
Chest/Respiratory 
Trouble breathing 
Chest congestion 
Chest tightness 
Dry or hacking cough 
Wet or loose cough 
Coughing 
Coughed up mucus or 
phlegm 
Arithmetic mean of 7 items 
Daily score for 5 of 7 items 
must be present to calculate 
domain score 
Gastrointestinal 
Felt nauseous 
Stomach ache 
Vomit (frequency) 
Diarrhea (frequency) 
Arithmetic mean of 4 items 
Daily score for 3 of 4 items 
must be present to calculate 
domain score 
Body/Systemic 
Felt dizzy 
Head congestion 
Headache
Lack of appetite 
Sleeping more than usual 
Body aches or pains 
Arithmetic mean of 11 items 
Daily score for 8 of 11 items 
must be present to calculate 
domain score 


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
80
Approved, Date: 27 September 2019
Domain 
Items 
Scoring and Minimum Data 
Requirement 
Weak or tired 
Chills or shivering 
Felt cold 
Felt hot 
Sweating 
Adult RSV additional questions
Additional Questions About Health and Functioning
1. Did you take any medicine for our respiratory infection 
symptoms today?
Yes
No
2. Did you use any rescue medicine today for asthma or 
COPD?
I do not take medicine for asthma or 
COPD
Yes
No
3. Since this time yesterday, how much of the time did you 
breathe oxygen from an oxygen tank?
None of the time
Less than an hour
1 to 4 hours
More than 4 hours
4. Overall, how severe were your respiratory infection 
symptoms today?
No respiratory infection symptoms 
today
Mild 
Moderate
Severe
Very Severe
5. Overall, how were your respiratory infection symptoms 
today compared to yesterday?
Much better
Somewhat better
A little better
About the same
A little worse
Somewhat worse
Much worse
6. How much did your respiratory infection symptoms 
interfere with your usual activities?
Not at all
A little bit
Somewhat
Quite a bit
Very Much


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
81
Approved, Date: 27 September 2019
7. Have you returned to your usual activities today?
Yes
No
8. In general, how would you rate your physical health 
today?
Excellent
Very good
Good
Fair
Poor
9. Have you returned to your usual health today?
Yes 
No
Respiratory Infection Intensity and Impact Questionnaire (RiiQ™)
CCI


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
82
Approved, Date: 27 September 2019
CCI


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
83
Approved, Date: 27 September 2019
CCI


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
84
Approved, Date: 27 September 2019
Attachment [4]:
EQ-5D-5L
EQ-5D-5L Dimensions
Dimension
Level
Interpretation
1
Mobility
1
No problems
I have no problems walking 
2
Slight problems
I have slight problems walking 
3
Moderate problems
I have moderate problems walking 
4
Severe problems
I have severe problems walking 
5
Extreme problems
I am unable to walk 
2
Self-care
1
No problems
I have no problems washing or dressing myself 
2
Slight problems
I have slight problems washing or dressing myself 
3
Moderate problems
I have moderate problems washing or dressing 
myself 
4
Severe problems
I have severe problems washing or dressing myself 
5
Extreme problems
I am unable to wash or dress myself 
3
Usual activities
1
No problems
I have no problems doing my usual activities
2
Slight problems
I have slight problems doing my usual activities
3
Moderate problems
I have moderate problems doing my usual activities
4
Severe problems
I have severe problems doing my usual activities
5
Extreme problems
I am unable to do my usual activities
4
Pain/discomfort
1
No problems
I have no pain or discomfort
2
Slight problems
I have slight pain or discomfort
3
Moderate problems
I have moderate pain or discomfort
4
Severe problems
I have severe pain or discomfort
5
Extreme problems
I have extreme pain or discomfort
5
Anxiety/depression
1
No problems
I am not anxious or depressed
2
Slight problems
I am slightly anxious or depressed
3
Moderate problems
I am moderately anxious or depressed
4
Severe problems
I am severely anxious or depressed
5
Extreme problems
I am extremely anxious or depressed


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
85
Approved, Date: 27 September 2019
EQ-5D-5L VAS

We would like to know how good or bad your health is 
TODAY.

This scale is numbered from 0 to 100.

100 means the best health you can imagine.
0 means the worst health you can imagine.

Mark an X on the scale to indicate how your health is TODAY.

Now, please write the number you marked on the scale in the box 
below.
YOUR HEALTH TODAY =
USA (English) © 2009 EuroQol Group. EQ-5D™ is a trade mark of the EuroQol Group
10
0
20
30
40
50
60
80
70
90
100
5
15
25
35
45
55
75
65
85
95
The best health       
you can imagine
The worst health
         you can imagine


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
86
Approved, Date: 27 September 2019
Valuation Index
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
11111
1
11242
0,498
11423
0,606
11554
0,018
11112
0,879
11243
0,484
11424
0,437
11555
-0,066
11113
0,848
11244
0,323
11425
0,26
12111
0,846
11114
0,635
11245
0,157
11431
0,653
12112
0,779
11115
0,414
11251
0,235
11432
0,596
12113
0,761
11121
0,837
11252
0,179
11433
0,582
12114
0,548
11122
0,768
11253
0,164
11434
0,412
12115
0,327
11123
0,75
11254
0,083
11435
0,236
12121
0,737
11124
0,537
11255
-0,001
11441
0,475
12122
0,678
11125
0,316
11311
0,883
11442
0,419
12123
0,663
11131
0,796
11312
0,827
11443
0,404
12124
0,45
11132
0,74
11313
0,812
11444
0,27
12125
0,229
11133
0,725
11314
0,599
11445
0,131
12131
0,709
11134
0,512
11315
0,378
11451
0,209
12132
0,653
11135
0,291
11321
0,785
11452
0,153
12133
0,638
11141
0,584
11322
0,728
11453
0,138
12134
0,425
11142
0,527
11323
0,714
11454
0,057
12135
0,204
11143
0,513
11324
0,501
11455
-0,027
12141
0,497
11144
0,352
11325
0,28
11511
0,556
12142
0,441
11145
0,186
11331
0,76
11512
0,5
12143
0,426
11151
0,264
11332
0,704
11513
0,485
12144
0,266
11152
0,208
11333
0,689
11514
0,404
12145
0,099
11153
0,193
11334
0,476
11515
0,32
12151
0,177
11154
0,112
11335
0,255
11521
0,458
12152
0,121
11155
0,028
11341
0,548
11522
0,401
12153
0,106
11211
0,906
11342
0,491
11523
0,387
12154
0,025
11212
0,837
11343
0,477
11524
0,306
12155
-0,059
11213
0,819
11344
0,316
11525
0,222
12211
0,806
11214
0,606
11345
0,15
11531
0,433
12212
0,748
11215
0,385
11351
0,228
11532
0,377
12213
0,733
11221
0,795
11352
0,172
11533
0,362
12214
0,52
11222
0,736
11353
0,157
11534
0,281
12215
0,299
11223
0,721
11354
0,076
11535
0,197
12221
0,706
11224
0,508
11355
-0,008
11541
0,328
12222
0,649
11225
0,287
11411
0,776
11542
0,272
12223
0,634
11231
0,767
11412
0,719
11543
0,257
12224
0,421
11232
0,711
11413
0,705
11544
0,176
12225
0,2
11233
0,696
11414
0,535
11545
0,092
12231
0,681
11234
0,483
11415
0,359
11551
0,17
12232
0,624
11235
0,262
11421
0,677
11552
0,114
12233
0,61
11241
0,555
11422
0,621
11553
0,099
12234
0,397
12235
0,176
12424
0,35
13113
0,744
13252
0,075


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
87
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
12241
0,468
12425
0,174
13114
0,531
13253
0,06
12242
0,412
12431
0,566
13115
0,31
13254
-0,021
12243
0,397
12432
0,51
13121
0,717
13255
-0,105
12244
0,237
12433
0,495
13122
0,66
13311
0,779
12245
0,071
12434
0,325
13123
0,646
13312
0,723
12251
0,149
12435
0,149
13124
0,433
13313
0,708
12252
0,092
12441
0,389
13125
0,212
13314
0,495
12253
0,078
12442
0,332
13131
0,692
13315
0,274
12254
-0,003
12443
0,318
13132
0,636
13321
0,681
12255
-0,088
12444
0,184
13133
0,621
13322
0,624
12311
0,796
12445
0,044
13134
0,408
13323
0,61
12312
0,74
12451
0,122
13135
0,187
13324
0,397
12313
0,725
12452
0,066
13141
0,48
13325
0,176
12314
0,512
12453
0,051
13142
0,423
13331
0,656
12315
0,291
12454
-0,03
13143
0,409
13332
0,6
12321
0,698
12455
-0,114
13144
0,248
13333
0,585
12322
0,642
12511
0,469
13145
0,082
13334
0,372
12323
0,627
12512
0,413
13151
0,16
13335
0,151
12324
0,414
12513
0,398
13152
0,104
13341
0,444
12325
0,193
12514
0,317
13153
0,089
13342
0,387
12331
0,673
12515
0,233
13154
0,008
13343
0,373
12332
0,617
12521
0,371
13155
-0,076
13344
0,212
12333
0,602
12522
0,315
13211
0,786
13345
0,046
12334
0,389
12523
0,3
13212
0,73
13351
0,124
12335
0,168
12524
0,219
13213
0,715
13352
0,068
12341
0,461
12525
0,135
13214
0,502
13353
0,053
12342
0,405
12531
0,346
13215
0,281
13354
-0,028
12343
0,39
12532
0,29
13221
0,688
13355
-0,112
12344
0,23
12533
0,275
13222
0,631
13411
0,672
12345
0,063
12534
0,194
13223
0,617
13412
0,615
12351
0,141
12535
0,11
13224
0,404
13413
0,601
12352
0,085
12541
0,241
13225
0,183
13414
0,431
12353
0,07
12542
0,185
13231
0,663
13415
0,255
12354
-0,011
12543
0,17
13232
0,607
13421
0,573
12355
-0,095
12544
0,089
13233
0,592
13422
0,517
12411
0,689
12545
0,005
13234
0,379
13423
0,502
12412
0,633
12551
0,083
13235
0,158
13424
0,333
12413
0,618
12552
0,027
13241
0,451
13425
0,156
12414
0,448
12553
0,012
13242
0,394
13431
0,549
12415
0,272
12554
-0,069
13243
0,38
13432
0,492
12421
0,591
12555
-0,153
13244
0,219
13433
0,478
12422
0,534
13111
0,815
13245
0,053
13434
0,308
12423
0,52
13112
0,759
13251
0,131
13435
0,132
13441
0,371
14125
0,185
14314
0,435
14453
0,007
13442
0,315
14131
0,6
14315
0,247
14454
-0,074


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
88
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
13443
0,3
14132
0,544
14321
0,588
14455
-0,158
13444
0,166
14133
0,529
14322
0,532
14511
0,425
13445
0,027
14134
0,348
14323
0,517
14512
0,369
13451
0,105
14135
0,16
14324
0,337
14513
0,354
13452
0,049
14141
0,414
14325
0,149
14514
0,273
13453
0,034
14142
0,357
14331
0,564
14515
0,189
13454
-0,047
14143
0,343
14332
0,508
14521
0,327
13455
-0,131
14144
0,202
14333
0,493
14522
0,27
13511
0,452
14145
0,055
14334
0,312
14523
0,256
13512
0,396
14151
0,133
14335
0,124
14524
0,175
13513
0,381
14152
0,077
14341
0,378
14525
0,091
13514
0,3
14153
0,062
14342
0,321
14531
0,302
13515
0,216
14154
-0,019
14343
0,307
14532
0,246
13521
0,354
14155
-0,103
14344
0,166
14533
0,231
13522
0,297
14211
0,694
14345
0,019
14534
0,15
13523
0,283
14212
0,638
14351
0,097
14535
0,066
13524
0,202
14213
0,623
14352
0,041
14541
0,197
13525
0,118
14214
0,442
14353
0,026
14542
0,141
13531
0,329
14215
0,254
14354
-0,055
14543
0,126
13532
0,273
14221
0,596
14355
-0,139
14544
0,045
13533
0,258
14222
0,539
14411
0,601
14545
-0,039
13534
0,177
14223
0,525
14412
0,545
14551
0,039
13535
0,093
14224
0,344
14413
0,53
14552
-0,017
13541
0,224
14225
0,156
14414
0,382
14553
-0,032
13542
0,168
14231
0,571
14415
0,228
14554
-0,113
13543
0,153
14232
0,515
14421
0,502
14555
-0,197
13544
0,072
14233
0,5
14422
0,446
15111
0,436
13545
-0,012
14234
0,319
14423
0,431
15112
0,38
13551
0,066
14235
0,131
14424
0,283
15113
0,365
13552
0,01
14241
0,385
14425
0,13
15114
0,284
13553
-0,005
14242
0,328
14431
0,478
15115
0,2
13554
-0,086
14243
0,314
14432
0,422
15121
0,338
13555
-0,17
14244
0,173
14433
0,407
15122
0,281
14111
0,723
14245
0,026
14434
0,259
15123
0,267
14112
0,667
14251
0,104
14435
0,105
15124
0,186
14113
0,652
14252
0,048
14441
0,318
15125
0,102
14114
0,471
14253
0,033
14442
0,262
15131
0,313
14115
0,283
14254
-0,048
14443
0,247
15132
0,257
14121
0,624
14255
-0,132
14444
0,126
15133
0,242
14122
0,568
14311
0,687
14445
0
15134
0,161
14123
0,553
14312
0,631
14451
0,078
15135
0,077
14124
0,373
14313
0,616
14452
0,022
15141
0,208
15142
0,152
15331
0,277
21115
0,357
21254
0,026
15143
0,137
15332
0,221
21121
0,767
21255
-0,058
15144
0,056
15333
0,206
21122
0,708
21311
0,826


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
89
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
15145
-0,028
15334
0,125
21123
0,693
21312
0,77
15151
0,05
15335
0,041
21124
0,48
21313
0,755
15152
-0,006
15341
0,172
21125
0,259
21314
0,542
15153
-0,021
15342
0,116
21131
0,739
21315
0,321
15154
-0,102
15343
0,101
21132
0,683
21321
0,728
15155
-0,186
15344
0,02
21133
0,668
21322
0,671
15211
0,407
15345
-0,064
21134
0,455
21323
0,657
15212
0,351
15351
0,014
21135
0,234
21324
0,444
15213
0,336
15352
-0,042
21141
0,527
21325
0,223
15214
0,255
15353
-0,057
21142
0,47
21331
0,703
15215
0,171
15354
-0,138
21143
0,456
21332
0,647
15221
0,309
15355
-0,222
21144
0,296
21333
0,632
15222
0,252
15411
0,381
21145
0,129
21334
0,419
15223
0,238
15412
0,325
21151
0,207
21335
0,198
15224
0,157
15413
0,31
21152
0,151
21341
0,491
15225
0,073
15414
0,229
21153
0,136
21342
0,434
15231
0,284
15415
0,145
21154
0,055
21343
0,42
15232
0,228
15421
0,282
21155
-0,029
21344
0,26
15233
0,213
15422
0,226
21211
0,836
21345
0,093
15234
0,132
15423
0,211
21212
0,778
21351
0,171
15235
0,048
15424
0,13
21213
0,762
21352
0,115
15241
0,179
15425
0,046
21214
0,549
21353
0,1
15242
0,123
15431
0,258
21215
0,328
21354
0,019
15243
0,108
15432
0,202
21221
0,735
21355
-0,065
15244
0,027
15433
0,187
21222
0,679
21411
0,719
15245
-0,057
15434
0,106
21223
0,664
21412
0,663
15251
0,021
15435
0,022
21224
0,451
21413
0,648
15252
-0,035
15441
0,153
21225
0,23
21414
0,478
15253
-0,05
15442
0,097
21231
0,71
21415
0,302
15254
-0,131
15443
0,082
21232
0,654
21421
0,62
15255
-0,215
15544
-0,038
21233
0,639
21422
0,564
15311
0,4
15545
-0,122
21234
0,426
21423
0,549
15312
0,344
15551
-0,044
21235
0,205
21424
0,38
15313
0,329
15552
-0,1
21241
0,498
21425
0,204
15314
0,248
15553
-0,115
21242
0,442
21431
0,596
15315
0,164
15554
-0,196
21243
0,427
21432
0,54
15321
0,302
15555
-0,28
21244
0,267
21433
0,525
15322
0,245
21111
0,877
21245
0,1
21434
0,355
15323
0,231
21112
0,809
21251
0,178
21435
0,179
15324
0,15
21113
0,791
21252
0,122
21441
0,419
15325
0,066
21114
0,578
21253
0,107
21442
0,362
21443
0,348
22132
0,596
22321
0,641
22455
-0,17
21444
0,213
22133
0,582
22322
0,585
22511
0,413
21445
0,074
22134
0,369
22323
0,57
22512
0,356
21451
0,152
22135
0,148
22324
0,357
22513
0,342


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
90
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
21452
0,096
22141
0,44
22325
0,136
22514
0,261
21453
0,081
22142
0,384
22331
0,617
22515
0,177
21454
0
22143
0,369
22332
0,56
22521
0,314
21455
-0,084
22144
0,209
22333
0,546
22522
0,258
21511
0,499
22145
0,043
22334
0,333
22523
0,243
21512
0,443
22151
0,121
22335
0,112
22524
0,162
21513
0,428
22152
0,064
22341
0,404
22525
0,078
21514
0,347
22153
0,05
22342
0,348
22531
0,29
21515
0,263
22154
-0,031
22343
0,333
22532
0,233
21521
0,401
22155
-0,115
22344
0,173
22533
0,219
21522
0,344
22211
0,747
22345
0,007
22534
0,138
21523
0,33
22212
0,691
22351
0,085
22535
0,054
21524
0,249
22213
0,676
22352
0,028
22541
0,185
21525
0,165
22214
0,463
22353
0,014
22542
0,128
21531
0,376
22215
0,242
22354
-0,067
22543
0,114
21532
0,32
22221
0,648
22355
-0,151
22544
0,033
21533
0,305
22222
0,592
22411
0,632
22545
-0,051
21534
0,224
22223
0,577
22412
0,576
22551
0,027
21535
0,14
22224
0,364
22413
0,561
22552
-0,03
21541
0,271
22225
0,143
22414
0,392
22553
-0,044
21542
0,215
22231
0,624
22415
0,216
22554
-0,125
21543
0,2
22232
0,567
22421
0,534
22555
-0,209
21544
0,119
22233
0,553
22422
0,477
23111
0,758
21545
0,035
22234
0,34
22423
0,463
23112
0,702
21551
0,113
22235
0,119
22424
0,293
23113
0,687
21552
0,057
22241
0,411
22425
0,117
23114
0,474
21553
0,042
22242
0,355
22431
0,509
23115
0,253
21554
-0,039
22243
0,34
22432
0,453
23121
0,66
21555
-0,123
22244
0,18
22433
0,438
23122
0,603
22111
0,778
22245
0,014
22434
0,269
23123
0,589
22112
0,72
22251
0,092
22435
0,093
23124
0,376
22113
0,705
22252
0,035
22441
0,332
23125
0,155
22114
0,492
22253
0,021
22442
0,276
23131
0,635
22115
0,271
22254
-0,06
22443
0,261
23132
0,579
22121
0,678
22255
-0,144
22444
0,127
23133
0,564
22122
0,621
22311
0,74
22445
-0,013
23134
0,351
22123
0,606
22312
0,683
22451
0,066
23135
0,13
22124
0,393
22313
0,669
22452
0,009
23141
0,423
22125
0,172
22314
0,456
22453
-0,005
23142
0,366
22131
0,653
22315
0,235
22454
-0,086
23143
0,352
23144
0,192
23333
0,528
23522
0,24
24155
-0,16
23145
0,025
23334
0,315
23523
0,226
24211
0,637
23151
0,103
23335
0,094
23524
0,145
24212
0,581
23152
0,047
23341
0,387
23525
0,061
24213
0,566
23153
0,032
23342
0,33
23531
0,272
24214
0,385


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
91
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
23154
-0,049
23343
0,316
23532
0,216
24215
0,198
23155
-0,133
23344
0,156
23533
0,201
24221
0,539
23211
0,729
23345
-0,011
23534
0,12
24222
0,482
23212
0,673
23351
0,067
23535
0,036
24223
0,468
23213
0,658
23352
0,011
23541
0,167
24224
0,287
23214
0,445
23353
-0,004
23542
0,111
24225
0,099
23215
0,224
23354
-0,085
23543
0,096
24231
0,514
23221
0,631
23355
-0,169
23544
0,015
24232
0,458
23222
0,575
23411
0,615
23545
-0,069
24233
0,443
23223
0,56
23412
0,559
23551
0,009
24234
0,262
23224
0,347
23413
0,544
23552
-0,047
24235
0,075
23225
0,126
23414
0,374
23553
-0,062
24241
0,328
23231
0,606
23415
0,198
23554
-0,143
24242
0,272
23232
0,55
23421
0,516
23555
-0,227
24243
0,257
23233
0,535
23422
0,46
24111
0,666
24244
0,116
23234
0,322
23423
0,445
24112
0,61
24245
-0,03
23235
0,101
23424
0,276
24113
0,595
24251
0,048
23241
0,394
23425
0,1
24114
0,414
24252
-0,009
23242
0,338
23431
0,492
24115
0,227
24253
-0,023
23243
0,323
23432
0,436
24121
0,568
24254
-0,104
23244
0,163
23433
0,421
24122
0,511
24255
-0,188
23245
-0,004
23434
0,251
24123
0,497
24311
0,63
23251
0,074
23435
0,075
24124
0,316
24312
0,574
23252
0,018
23441
0,315
24125
0,128
24313
0,559
23253
0,003
23442
0,258
24131
0,543
24314
0,378
23254
-0,078
23443
0,244
24132
0,487
24315
0,191
23255
-0,162
23444
0,109
24133
0,472
24321
0,532
23311
0,722
23445
-0,03
24134
0,291
24322
0,475
23312
0,666
23451
0,048
24135
0,104
24323
0,461
23313
0,651
23452
-0,008
24141
0,357
24324
0,28
23314
0,438
23453
-0,023
24142
0,3
24325
0,092
23315
0,217
23454
-0,104
24143
0,286
24331
0,507
23321
0,624
23455
-0,188
24144
0,145
24332
0,451
23322
0,567
23511
0,395
24145
-0,002
24333
0,436
23323
0,553
23512
0,339
24151
0,077
24334
0,255
23324
0,34
23513
0,324
24152
0,02
24335
0,068
23325
0,119
23514
0,243
24153
0,006
24341
0,321
23331
0,599
23515
0,159
24154
-0,076
24342
0,264
23332
0,543
23521
0,297
24155
-0,16
24343
0,25
24344
0,109
24533
0,175
25222
0,196
25411
0,324
24345
-0,038
24534
0,094
25223
0,181
25412
0,268
24351
0,041
24535
0,01
25224
0,1
25413
0,253
24352
-0,016
24541
0,14
25225
0,016
25414
0,172
24353
-0,031
24542
0,084
25231
0,227
25415
0,088
24354
-0,112
24543
0,069
25232
0,171
25421
0,226


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
92
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
24355
-0,196
24544
-0,012
25233
0,156
25422
0,169
24411
0,544
24545
-0,096
25234
0,075
25423
0,155
24412
0,488
24551
-0,018
25235
-0,009
25424
0,074
24413
0,473
24552
-0,074
25241
0,122
25425
-0,01
24414
0,325
24553
-0,089
25242
0,066
25431
0,201
24415
0,172
24554
-0,17
25243
0,051
25432
0,145
24421
0,446
24555
-0,254
25244
-0,03
25433
0,13
24422
0,389
25111
0,379
25245
-0,114
25434
0,049
24423
0,375
25112
0,323
25251
-0,036
25435
-0,035
24424
0,227
25113
0,308
25252
-0,092
25441
0,096
24425
0,073
25114
0,227
25253
-0,107
25442
0,04
24431
0,421
25115
0,143
25254
-0,188
25443
0,025
24432
0,365
25121
0,281
25255
-0,272
25444
-0,056
24433
0,35
25122
0,224
25311
0,343
25445
-0,14
24434
0,202
25123
0,21
25312
0,287
25451
-0,062
24435
0,049
25124
0,129
25313
0,272
25452
-0,118
24441
0,262
25125
0,045
25314
0,191
25453
-0,133
24442
0,205
25131
0,256
25315
0,107
25454
-0,214
24443
0,191
25132
0,2
25321
0,245
25455
-0,298
24444
0,069
25133
0,185
25322
0,188
25511
0,285
24445
-0,057
25134
0,104
25323
0,174
25512
0,229
24451
0,022
25135
0,02
25324
0,093
25513
0,214
24452
-0,035
25141
0,151
25325
0,009
25514
0,133
24453
-0,05
25142
0,095
25331
0,22
25515
0,049
24454
-0,131
25143
0,08
25332
0,164
25521
0,187
24455
-0,215
25144
-0,001
25333
0,149
25522
0,13
24511
0,369
25145
-0,085
25334
0,068
25523
0,116
24512
0,312
25151
-0,007
25335
-0,016
25524
0,035
24513
0,298
25152
-0,063
25341
0,115
25525
-0,049
24514
0,217
25153
-0,078
25342
0,059
25531
0,162
24515
0,133
25154
-0,159
25343
0,044
25532
0,106
24521
0,27
25155
-0,243
25344
-0,037
25533
0,091
24522
0,214
25211
0,35
25345
-0,121
25534
0,01
24523
0,199
25212
0,294
25351
-0,043
25535
-0,074
24524
0,118
25213
0,279
25352
-0,099
25541
0,057
24525
0,034
25214
0,198
25353
-0,114
25542
0,001
24531
0,246
25215
0,114
25354
-0,195
25543
-0,014
24532
0,189
25221
0,252
25355
-0,279
25544
-0,095
25545
-0,179
31234
0,414
31423
0,537
32112
0,707
25551
-0,101
31235
0,193
31424
0,368
32113
0,692
25552
-0,157
31241
0,486
31425
0,191
32114
0,479
25553
-0,172
31242
0,429
31431
0,584
32115
0,258
25554
-0,253
31243
0,415
31432
0,527
32121
0,665
25555
-0,337
31244
0,254
31433
0,513
32122
0,609
31111
0,85
31245
0,088
31434
0,343
32123
0,594


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
93
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
31112
0,794
31251
0,166
31435
0,167
32124
0,381
31113
0,779
31252
0,11
31441
0,406
32125
0,16
31114
0,566
31253
0,095
31442
0,35
32131
0,64
31115
0,345
31254
0,014
31443
0,335
32132
0,584
31121
0,752
31255
-0,07
31444
0,201
32133
0,569
31122
0,695
31311
0,814
31445
0,062
32134
0,356
31123
0,681
31312
0,758
31451
0,14
32135
0,135
31124
0,468
31313
0,743
31452
0,084
32141
0,428
31125
0,247
31314
0,53
31453
0,069
32142
0,372
31131
0,727
31315
0,309
31454
-0,012
32143
0,357
31132
0,671
31321
0,716
31455
-0,096
32144
0,197
31133
0,656
31322
0,659
31511
0,487
32145
0,03
31134
0,443
31323
0,645
31512
0,431
32151
0,108
31135
0,222
31324
0,432
31513
0,416
32152
0,052
31141
0,515
31325
0,211
31514
0,335
32153
0,037
31142
0,458
31331
0,691
31515
0,251
32154
-0,044
31143
0,444
31332
0,635
31521
0,389
32155
-0,128
31144
0,283
31333
0,62
31522
0,332
32211
0,735
31145
0,117
31334
0,407
31523
0,318
32212
0,678
31151
0,195
31335
0,186
31524
0,237
32213
0,664
31152
0,139
31341
0,479
31525
0,153
32214
0,451
31153
0,124
31342
0,422
31531
0,364
32215
0,23
31154
0,043
31343
0,408
31532
0,308
32221
0,636
31155
-0,041
31344
0,247
31533
0,293
32222
0,58
31211
0,821
31345
0,081
31534
0,212
32223
0,565
31212
0,765
31351
0,159
31535
0,128
32224
0,352
31213
0,75
31352
0,103
31541
0,259
32225
0,131
31214
0,537
31353
0,088
31542
0,203
32231
0,612
31215
0,316
31354
0,007
31543
0,188
32232
0,555
31221
0,723
31355
-0,077
31544
0,107
32233
0,541
31222
0,666
31411
0,707
31545
0,023
32234
0,328
31223
0,652
31412
0,65
31551
0,101
32235
0,107
31224
0,439
31413
0,636
31552
0,045
32241
0,399
31225
0,218
31414
0,466
31553
0,03
32242
0,343
31231
0,698
31415
0,29
31554
-0,051
32243
0,328
31232
0,642
31421
0,608
31555
-0,135
32244
0,168
31233
0,627
31422
0,552
32111
0,763
32245
0,002
32251
0,08
32435
0,08
33124
0,364
33313
0,639
32252
0,023
32441
0,32
33125
0,143
33314
0,426
32253
0,009
32442
0,263
33131
0,623
33315
0,205
32254
-0,072
32443
0,249
33132
0,567
33321
0,612
32255
-0,157
32444
0,115
33133
0,552
33322
0,555
32311
0,727
32445
-0,025
33134
0,339
33323
0,541
32312
0,671
32451
0,053
33135
0,118
33324
0,328
32313
0,656
32452
-0,003
33141
0,411
33325
0,107


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
94
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
32314
0,443
32453
-0,018
33142
0,354
33331
0,587
32315
0,222
32454
-0,099
33143
0,34
33332
0,531
32321
0,629
32455
-0,183
33144
0,179
33333
0,516
32322
0,573
32511
0,4
33145
0,013
33334
0,303
32323
0,558
32512
0,344
33151
0,091
33335
0,082
32324
0,345
32513
0,329
33152
0,035
33341
0,375
32325
0,124
32514
0,248
33153
0,02
33342
0,318
32331
0,604
32515
0,164
33154
-0,061
33343
0,304
32332
0,548
32521
0,302
33155
-0,145
33344
0,143
32333
0,533
32522
0,246
33211
0,717
33345
-0,023
32334
0,32
32523
0,231
33212
0,661
33351
0,055
32335
0,099
32524
0,15
33213
0,646
33352
-0,001
32341
0,392
32525
0,066
33214
0,433
33353
-0,016
32342
0,336
32531
0,277
33215
0,212
33354
-0,097
32343
0,321
32532
0,221
33221
0,619
33355
-0,181
32344
0,161
32533
0,206
33222
0,562
33411
0,603
32345
-0,006
32534
0,125
33223
0,548
33412
0,546
32351
0,072
32535
0,041
33224
0,335
33413
0,532
32352
0,016
32541
0,172
33225
0,114
33414
0,362
32353
0,001
32542
0,116
33231
0,594
33415
0,186
32354
-0,08
32543
0,101
33232
0,538
33421
0,504
32355
-0,164
32544
0,02
33233
0,523
33422
0,448
32411
0,62
32545
-0,064
33234
0,31
33423
0,433
32412
0,564
32551
0,014
33235
0,089
33424
0,264
32413
0,549
32552
-0,042
33241
0,382
33425
0,087
32414
0,379
32553
-0,057
33242
0,325
33431
0,48
32415
0,203
32554
-0,138
33243
0,311
33432
0,423
32421
0,522
32555
-0,222
33244
0,15
33433
0,409
32422
0,465
33111
0,746
33245
-0,016
33434
0,239
32423
0,451
33112
0,69
33251
0,062
33435
0,063
32424
0,281
33113
0,675
33252
0,006
33441
0,302
32425
0,105
33114
0,462
33253
-0,009
33442
0,246
32431
0,497
33115
0,241
33254
-0,09
33443
0,231
32432
0,441
33121
0,648
33255
-0,174
33444
0,097
32433
0,426
33122
0,591
33311
0,71
33445
-0,042
32434
0,256
33123
0,577
33312
0,654
33451
0,036
33452
-0,02
34141
0,345
34325
0,08
34514
0,204
33453
-0,035
34142
0,288
34331
0,495
34515
0,12
33454
-0,116
34143
0,274
34332
0,439
34521
0,258
33455
-0,2
34144
0,133
34333
0,424
34522
0,201
33511
0,383
34145
-0,014
34334
0,243
34523
0,187
33512
0,327
34151
0,064
34335
0,055
34524
0,106
33513
0,312
34152
0,008
34341
0,309
34525
0,022
33514
0,231
34153
-0,007
34342
0,252
34531
0,233
33515
0,147
34154
-0,088
34343
0,238
34532
0,177


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
95
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
33521
0,285
34155
-0,172
34344
0,097
34533
0,162
33522
0,228
34211
0,625
34345
-0,05
34534
0,081
33523
0,214
34212
0,569
34351
0,028
34535
-0,003
33524
0,133
34213
0,554
34352
-0,028
34541
0,128
33525
0,049
34214
0,373
34353
-0,043
34542
0,072
33531
0,26
34215
0,185
34354
-0,124
34543
0,057
33532
0,204
34221
0,527
34355
-0,208
34544
-0,024
33533
0,189
34222
0,47
34411
0,532
34545
-0,108
33534
0,108
34223
0,456
34412
0,476
34551
-0,03
33535
0,024
34224
0,275
34413
0,461
34552
-0,086
33541
0,155
34225
0,087
34414
0,313
34553
-0,101
33542
0,099
34231
0,502
34415
0,159
34554
-0,182
33543
0,084
34232
0,446
34421
0,433
34555
-0,266
33544
0,003
34233
0,431
34422
0,377
35111
0,367
33545
-0,081
34234
0,25
34423
0,362
35112
0,311
33551
-0,003
34235
0,062
34424
0,214
35113
0,296
33552
-0,059
34241
0,316
34425
0,061
35114
0,215
33553
-0,074
34242
0,259
34431
0,409
35115
0,131
33554
-0,155
34243
0,245
34432
0,353
35121
0,269
33555
-0,239
34244
0,104
34433
0,338
35122
0,212
34111
0,654
34245
-0,043
34434
0,19
35123
0,198
34112
0,598
34251
0,035
34435
0,036
35124
0,117
34113
0,583
34252
-0,021
34441
0,249
35125
0,033
34114
0,402
34253
-0,036
34442
0,193
35131
0,244
34115
0,214
34254
-0,117
34443
0,178
35132
0,188
34121
0,555
34255
-0,201
34444
0,057
35133
0,173
34122
0,499
34311
0,618
34445
-0,069
35134
0,092
34123
0,484
34312
0,562
34451
0,009
35135
0,008
34124
0,304
34313
0,547
34452
-0,047
35141
0,139
34125
0,116
34314
0,366
34453
-0,062
35142
0,083
34131
0,531
34315
0,178
34454
-0,143
35143
0,068
34132
0,475
34321
0,519
34455
-0,227
35144
-0,013
34133
0,46
34322
0,463
34511
0,356
35145
-0,097
34134
0,279
34323
0,448
34512
0,3
35151
-0,019
34135
0,091
34324
0,268
34513
0,285
35152
-0,075
35153
-0,09
35342
0,047
35531
0,15
41215
0,299
35154
-0,171
35343
0,032
35532
0,094
41221
0,686
35155
-0,255
35344
-0,049
35533
0,079
41222
0,629
35211
0,338
35345
-0,133
35534
-0,002
41223
0,615
35212
0,282
35351
-0,055
35535
-0,086
41224
0,411
35213
0,267
35352
-0,111
35541
0,045
41225
0,2
35214
0,186
35353
-0,126
35542
-0,011
41231
0,661
35215
0,102
35354
-0,207
35543
-0,026
41232
0,605
35221
0,24
35355
-0,291
35544
-0,107
41233
0,59
35222
0,183
35411
0,312
35545
-0,191
41234
0,387


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
96
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
35223
0,169
35412
0,256
35551
-0,113
41235
0,176
35224
0,088
35413
0,241
35552
-0,169
41241
0,456
35225
0,004
35414
0,16
35553
-0,184
41242
0,4
35231
0,215
35415
0,076
35554
-0,265
41243
0,385
35232
0,159
35421
0,213
35555
-0,349
41244
0,231
35233
0,144
35422
0,157
41111
0,813
41245
0,07
35234
0,063
35423
0,142
41112
0,757
41251
0,149
35235
-0,021
35424
0,061
41113
0,742
41252
0,092
35241
0,11
35425
-0,023
41114
0,539
41253
0,078
35242
0,054
35431
0,189
41115
0,327
41254
-0,004
35243
0,039
35432
0,133
41121
0,714
41255
-0,088
35244
-0,042
35433
0,118
41122
0,658
41311
0,777
35245
-0,126
35434
0,037
41123
0,643
41312
0,721
35251
-0,048
35435
-0,047
41124
0,44
41313
0,706
35252
-0,104
35441
0,084
41125
0,229
41314
0,503
35253
-0,119
35442
0,028
41131
0,69
41315
0,291
35254
-0,2
35443
0,013
41132
0,634
41321
0,678
35255
-0,284
35444
-0,068
41133
0,619
41322
0,622
35311
0,331
35445
-0,152
41134
0,416
41323
0,607
35312
0,275
35451
-0,074
41135
0,204
41324
0,404
35313
0,26
35452
-0,13
41141
0,485
41325
0,193
35314
0,179
35453
-0,145
41142
0,429
41331
0,654
35315
0,095
35454
-0,226
41143
0,414
41332
0,598
35321
0,233
35455
-0,31
41144
0,26
41333
0,583
35322
0,176
35511
0,273
41145
0,099
41334
0,38
35323
0,162
35512
0,217
41151
0,177
41335
0,168
35324
0,081
35513
0,202
41152
0,121
41341
0,449
35325
-0,004
35514
0,121
41153
0,106
41342
0,393
35331
0,208
35515
0,037
41154
0,025
41343
0,378
35332
0,152
35521
0,175
41155
-0,059
41344
0,224
35333
0,137
35522
0,118
41211
0,784
41345
0,063
35334
0,056
35523
0,104
41212
0,728
41351
0,141
35335
-0,028
35524
0,023
41213
0,713
41352
0,085
35341
0,103
35525
-0,062
41214
0,51
41353
0,07
41354
-0,011
41543
0,17
42232
0,518
42421
0,491
41355
-0,095
41544
0,089
42233
0,504
42422
0,434
41411
0,676
41545
0,005
42234
0,3
42423
0,42
41412
0,62
41551
0,083
42235
0,089
42424
0,257
41413
0,605
41552
0,027
42241
0,37
42425
0,087
41414
0,442
41553
0,012
42242
0,313
42431
0,466
41415
0,272
41554
-0,069
42243
0,299
42432
0,41
41421
0,577
41555
-0,153
42244
0,144
42433
0,395
41422
0,521
42111
0,726
42245
-0,016
42434
0,232
41423
0,506
42112
0,67
42251
0,062
42435
0,063
41424
0,343
42113
0,655
42252
0,006
42441
0,294


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
97
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
41425
0,174
42114
0,452
42253
-0,009
42442
0,238
41431
0,553
42115
0,241
42254
-0,09
42443
0,223
41432
0,497
42121
0,628
42255
-0,174
42444
0,093
41433
0,482
42122
0,572
42311
0,69
42445
-0,042
41434
0,319
42123
0,557
42312
0,634
42451
0,036
41435
0,149
42124
0,353
42313
0,619
42452
-0,021
41441
0,381
42125
0,142
42314
0,416
42453
-0,035
41442
0,325
42131
0,603
42315
0,205
42454
-0,116
41443
0,31
42132
0,547
42321
0,592
42455
-0,2
41444
0,18
42133
0,532
42322
0,536
42511
0,383
41445
0,044
42134
0,329
42323
0,521
42512
0,326
41451
0,122
42135
0,118
42324
0,317
42513
0,312
41452
0,066
42141
0,399
42325
0,106
42514
0,231
41453
0,051
42142
0,342
42331
0,567
42515
0,147
41454
-0,03
42143
0,328
42332
0,511
42521
0,284
41455
-0,114
42144
0,173
42333
0,496
42522
0,228
41511
0,469
42145
0,013
42334
0,293
42523
0,213
41512
0,413
42151
0,091
42335
0,082
42524
0,132
41513
0,398
42152
0,034
42341
0,363
42525
0,048
41514
0,317
42153
0,02
42342
0,306
42531
0,26
41515
0,233
42154
-0,061
42343
0,292
42532
0,203
41521
0,371
42155
-0,145
42344
0,137
42533
0,189
41522
0,315
42211
0,698
42345
-0,023
42534
0,108
41523
0,3
42212
0,641
42351
0,055
42535
0,024
41524
0,219
42213
0,627
42352
-0,002
42541
0,155
41525
0,135
42214
0,423
42353
-0,016
42542
0,098
41531
0,346
42215
0,212
42354
-0,097
42543
0,084
41532
0,29
42221
0,599
42355
-0,181
42544
0,003
41533
0,275
42222
0,543
42411
0,589
42545
-0,081
41534
0,194
42223
0,528
42412
0,533
42551
-0,003
41535
0,11
42224
0,325
42413
0,518
42552
-0,06
41541
0,241
42225
0,113
42414
0,355
42553
-0,074
41542
0,185
42231
0,575
42415
0,186
42554
-0,155
42555
-0,239
43244
0,127
43433
0,378
44122
0,467
43111
0,709
43245
-0,034
43434
0,215
44123
0,452
43112
0,653
43251
0,045
43435
0,045
44124
0,278
43113
0,638
43252
-0,012
43441
0,277
44125
0,098
43114
0,435
43253
-0,027
43442
0,221
44131
0,499
43115
0,223
43254
-0,108
43443
0,206
44132
0,442
43121
0,61
43255
-0,192
43444
0,076
44133
0,428
43122
0,554
43311
0,673
43445
-0,06
44134
0,254
43123
0,539
43312
0,617
43451
0,018
44135
0,074
43124
0,336
43313
0,602
43452
-0,038
44141
0,318
43125
0,125
43314
0,399
43453
-0,053
44142
0,262
43131
0,586
43315
0,187
43454
-0,134
44143
0,247


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
98
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
43132
0,53
43321
0,574
43455
-0,218
44144
0,11
43133
0,515
43322
0,518
43511
0,365
44145
-0,032
43134
0,312
43323
0,503
43512
0,309
44151
0,047
43135
0,1
43324
0,3
43513
0,294
44152
-0,01
43141
0,381
43325
0,089
43514
0,213
44153
-0,024
43142
0,325
43331
0,55
43515
0,129
44154
-0,105
43143
0,31
43332
0,494
43521
0,267
44155
-0,189
43144
0,156
43333
0,479
43522
0,211
44211
0,593
43145
-0,005
43334
0,276
43523
0,196
44212
0,536
43151
0,073
43335
0,064
43524
0,115
44213
0,522
43152
0,017
43341
0,345
43525
0,031
44214
0,348
43153
0,002
43342
0,289
43531
0,242
44215
0,168
43154
-0,079
43343
0,274
43532
0,186
44221
0,494
43155
-0,163
43344
0,12
43533
0,171
44222
0,438
43211
0,68
43345
-0,041
43534
0,09
44223
0,423
43212
0,624
43351
0,037
43535
0,006
44224
0,249
43213
0,609
43352
-0,019
43541
0,137
44225
0,069
43214
0,406
43353
-0,034
43542
0,081
44231
0,47
43215
0,195
43354
-0,115
43543
0,066
44232
0,413
43221
0,582
43355
-0,199
43544
-0,015
44233
0,399
43222
0,525
43411
0,572
43545
-0,099
44234
0,225
43223
0,511
43412
0,516
43551
-0,021
44235
0,045
43224
0,307
43413
0,501
43552
-0,077
44241
0,289
43225
0,096
43414
0,338
43553
-0,092
44242
0,233
43231
0,557
43415
0,168
43554
-0,173
44243
0,218
43232
0,501
43421
0,473
43555
-0,257
44244
0,082
43233
0,486
43422
0,417
44111
0,622
44245
-0,06
43234
0,283
43423
0,402
44112
0,565
44251
0,018
43235
0,072
43424
0,239
44113
0,551
44252
-0,039
43241
0,352
43425
0,07
44114
0,377
44253
-0,053
43242
0,296
43431
0,449
44115
0,197
44254
-0,134
43243
0,281
43432
0,393
44121
0,523
44255
-0,218
44311
0,586
44445
-0,087
45134
0,074
45323
0,144
44312
0,529
44451
-0,009
45135
-0,01
45324
0,063
44313
0,515
44452
-0,065
45141
0,121
45325
-0,021
44314
0,341
44453
-0,08
45142
0,065
45331
0,19
44315
0,161
44454
-0,16
45143
0,05
45332
0,134
44321
0,487
44455
-0,245
45144
-0,031
45333
0,119
44322
0,431
44511
0,339
45145
-0,115
45334
0,038
44323
0,416
44512
0,282
45151
-0,037
45335
-0,046
44324
0,242
44513
0,268
45152
-0,093
45341
0,085
44325
0,062
44514
0,187
45153
-0,108
45342
0,029
44331
0,463
44515
0,103
45154
-0,189
45343
0,014
44332
0,406
44521
0,24
45155
-0,273
45344
-0,067
44333
0,392
44522
0,184
45211
0,321
45345
-0,151


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
99
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
44334
0,218
44523
0,169
45212
0,264
45351
-0,073
44335
0,038
44524
0,088
45213
0,25
45352
-0,129
44341
0,282
44525
0,004
45214
0,169
45353
-0,144
44342
0,226
44531
0,216
45215
0,085
45354
-0,225
44343
0,211
44532
0,159
45221
0,222
45355
-0,309
44344
0,074
44533
0,145
45222
0,166
45411
0,294
44345
-0,068
44534
0,064
45223
0,151
45412
0,238
44351
0,011
44535
-0,02
45224
0,07
45413
0,223
44352
-0,046
44541
0,111
45225
-0,014
45414
0,142
44353
-0,06
44542
0,054
45231
0,198
45415
0,058
44354
-0,141
44543
0,04
45232
0,141
45421
0,196
44355
-0,225
44544
-0,041
45233
0,127
45422
0,139
44411
0,504
44545
-0,126
45234
0,046
45423
0,125
44412
0,448
44551
-0,047
45235
-0,039
45424
0,044
44413
0,433
44552
-0,104
45241
0,092
45425
-0,04
44414
0,29
44553
-0,118
45242
0,036
45431
0,171
44415
0,142
44554
-0,199
45243
0,021
45432
0,115
44421
0,406
44555
-0,283
45244
-0,06
45433
0,1
44422
0,35
45111
0,349
45245
-0,144
45434
0,019
44423
0,335
45112
0,293
45251
-0,066
45435
-0,065
44424
0,192
45113
0,278
45252
-0,122
45441
0,066
44425
0,043
45114
0,197
45253
-0,137
45442
0,01
44431
0,381
45115
0,113
45254
-0,218
45443
-0,005
44432
0,325
45121
0,251
45255
-0,302
45444
-0,086
44433
0,31
45122
0,195
45311
0,313
45445
-0,17
44434
0,167
45123
0,18
45312
0,257
45451
-0,092
44435
0,019
45124
0,099
45313
0,242
45452
-0,148
44441
0,226
45125
0,015
45314
0,161
45453
-0,163
44442
0,169
45131
0,226
45315
0,077
45454
-0,244
44443
0,155
45132
0,17
45321
0,215
45455
-0,328
44444
0,036
45133
0,155
45322
0,159
45511
0,255
45512
0,199
51151
-0,05
51335
-0,059
51524
-0,009
45513
0,184
51152
-0,106
51341
0,072
51525
-0,093
45514
0,103
51153
-0,121
51342
0,016
51531
0,119
45515
0,019
51154
-0,202
51343
0,001
51532
0,063
45521
0,157
51155
-0,286
51344
-0,08
51533
0,048
45522
0,101
51211
0,307
51345
-0,164
51534
-0,033
45523
0,086
51212
0,251
51351
-0,086
51535
-0,117
45524
0,005
51213
0,236
51352
-0,142
51541
0,014
45525
-0,079
51214
0,155
51353
-0,157
51542
-0,042
45531
0,132
51215
0,071
51354
-0,238
51543
-0,057
45532
0,076
51221
0,209
51355
-0,322
51544
-0,138
45533
0,061
51222
0,152
51411
0,281
51545
-0,222
45534
-0,02
51223
0,138
51412
0,225
51551
-0,144
45535
-0,104
51224
0,057
51413
0,21
51552
-0,2


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
100
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
45541
0,027
51225
-0,027
51414
0,129
51553
-0,215
45542
-0,029
51231
0,184
51415
0,045
51554
-0,296
45543
-0,044
51232
0,128
51421
0,182
51555
-0,38
45544
-0,125
51233
0,113
51422
0,126
52111
0,249
45545
-0,209
51234
0,032
51423
0,111
52112
0,193
45551
-0,131
51235
-0,052
51424
0,03
52113
0,178
45552
-0,187
51241
0,079
51425
-0,054
52114
0,097
45553
-0,202
51242
0,023
51431
0,158
52115
0,013
45554
-0,283
51243
0,008
51432
0,102
52121
0,151
45555
-0,367
51244
-0,073
51433
0,087
52122
0,095
51111
0,336
51245
-0,157
51434
0,006
52123
0,08
51112
0,28
51251
-0,079
51435
-0,078
52124
-0,001
51113
0,265
51252
-0,135
51441
0,053
52125
-0,085
51114
0,184
51253
-0,15
51442
-0,003
52131
0,126
51115
0,1
51254
-0,231
51443
-0,018
52132
0,07
51121
0,238
51255
-0,315
51444
-0,099
52133
0,055
51122
0,181
51311
0,3
51445
-0,183
52134
-0,026
51123
0,167
51312
0,244
51451
-0,105
52135
-0,11
51124
0,086
51313
0,229
51452
-0,161
52141
0,021
51125
0,002
51314
0,148
51453
-0,176
52142
-0,035
51131
0,213
51315
0,064
51454
-0,257
52143
-0,05
51132
0,157
51321
0,202
51455
-0,341
52144
-0,131
51133
0,142
51322
0,145
51511
0,242
52145
-0,215
51134
0,061
51323
0,131
51512
0,186
52151
-0,137
51135
-0,023
51324
0,05
51513
0,171
52152
-0,193
51141
0,108
51325
-0,035
51514
0,09
52153
-0,208
51142
0,052
51331
0,177
51515
0,006
52154
-0,289
51143
0,037
51332
0,121
51521
0,144
52155
-0,373
51144
-0,044
51333
0,106
51522
0,087
52211
0,221
51145
-0,128
51334
0,025
51523
0,073
52212
0,164
52213
0,15
52352
-0,229
52541
-0,073
53225
-0,131
52214
0,069
52353
-0,244
52542
-0,129
53231
0,08
52215
-0,016
52354
-0,325
52543
-0,144
53232
0,024
52221
0,122
52355
-0,409
52544
-0,225
53233
0,009
52222
0,066
52411
0,194
52545
-0,309
53234
-0,072
52223
0,051
52412
0,138
52551
-0,231
53235
-0,156
52224
-0,03
52413
0,123
52552
-0,287
53241
-0,025
52225
-0,114
52414
0,042
52553
-0,302
53242
-0,081
52231
0,098
52415
-0,042
52554
-0,383
53243
-0,096
52232
0,041
52421
0,096
52555
-0,467
53244
-0,177
52233
0,027
52422
0,04
53111
0,232
53245
-0,261
52234
-0,054
52423
0,025
53112
0,176
53251
-0,183
52235
-0,139
52424
-0,056
53113
0,161
53252
-0,239
52241
-0,008
52425
-0,14
53114
0,08
53253
-0,254
52242
-0,064
52431
0,071
53115
-0,004
53254
-0,335


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
101
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
52243
-0,079
52432
0,015
53121
0,134
53255
-0,419
52244
-0,16
52433
0
53122
0,077
53311
0,196
52245
-0,244
52434
-0,081
53123
0,063
53312
0,14
52251
-0,166
52435
-0,165
53124
-0,019
53313
0,125
52252
-0,222
52441
-0,034
53125
-0,103
53314
0,044
52253
-0,237
52442
-0,09
53131
0,109
53315
-0,04
52254
-0,317
52443
-0,105
53132
0,053
53321
0,098
52255
-0,402
52444
-0,186
53133
0,038
53322
0,041
52311
0,213
52445
-0,27
53134
-0,043
53323
0,027
52312
0,157
52451
-0,192
53135
-0,127
53324
-0,055
52313
0,142
52452
-0,248
53141
0,004
53325
-0,139
52314
0,061
52453
-0,263
53142
-0,052
53331
0,073
52315
-0,023
52454
-0,344
53143
-0,067
53332
0,017
52321
0,115
52455
-0,428
53144
-0,148
53333
0,002
52322
0,059
52511
0,155
53145
-0,232
53334
-0,079
52323
0,044
52512
0,099
53151
-0,154
53335
-0,163
52324
-0,037
52513
0,084
53152
-0,21
53341
-0,032
52325
-0,121
52514
0,003
53153
-0,225
53342
-0,088
52331
0,09
52515
-0,081
53154
-0,306
53343
-0,103
52332
0,034
52521
0,057
53155
-0,39
53344
-0,184
52333
0,019
52522
0,001
53211
0,203
53345
-0,268
52334
-0,062
52523
-0,014
53212
0,147
53351
-0,19
52335
-0,146
52524
-0,095
53213
0,132
53352
-0,246
52341
-0,015
52525
-0,179
53214
0,051
53353
-0,261
52342
-0,071
52531
0,032
53215
-0,033
53354
-0,342
52343
-0,086
52532
-0,024
53221
0,105
53355
-0,426
52344
-0,167
52533
-0,039
53222
0,048
53411
0,177
52345
-0,251
52534
-0,12
53223
0,034
53412
0,121
52351
-0,173
52535
-0,204
53224
-0,047
53413
0,106
53414
0,025
53553
-0,319
54242
-0,108
54431
0,027
53415
-0,059
53554
-0,4
54243
-0,123
54432
-0,029
53421
0,078
53555
-0,484
54244
-0,204
54433
-0,044
53422
0,022
54111
0,205
54245
-0,288
54434
-0,125
53423
0,007
54112
0,149
54251
-0,21
54435
-0,209
53424
-0,074
54113
0,134
54252
-0,266
54441
-0,078
53425
-0,158
54114
0,053
54253
-0,281
54442
-0,134
53431
0,054
54115
-0,031
54254
-0,362
54443
-0,149
53432
-0,002
54121
0,107
54255
-0,446
54444
-0,23
53433
-0,017
54122
0,05
54311
0,169
54445
-0,314
53434
-0,098
54123
0,036
54312
0,113
54451
-0,236
53435
-0,182
54124
-0,045
54313
0,098
54452
-0,292
53441
-0,051
54125
-0,129
54314
0,017
54453
-0,307
53442
-0,107
54131
0,082
54315
-0,067
54454
-0,388
53443
-0,122
54132
0,026
54321
0,071
54455
-0,472
53444
-0,203
54133
0,011
54322
0,014
54511
0,111


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
102
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
53445
-0,287
54134
-0,07
54323
0
54512
0,055
53451
-0,209
54135
-0,154
54324
-0,081
54513
0,04
53452
-0,265
54141
-0,023
54325
-0,165
54514
-0,041
53453
-0,28
54142
-0,079
54331
0,046
54515
-0,125
53454
-0,361
54143
-0,094
54332
-0,01
54521
0,013
53455
-0,445
54144
-0,175
54333
-0,025
54522
-0,044
53511
0,138
54145
-0,259
54334
-0,106
54523
-0,058
53512
0,082
54151
-0,181
54335
-0,19
54524
-0,139
53513
0,067
54152
-0,237
54341
-0,059
54525
-0,223
53514
-0,014
54153
-0,252
54342
-0,115
54531
-0,012
53515
-0,098
54154
-0,333
54343
-0,13
54532
-0,068
53521
0,04
54155
-0,417
54344
-0,211
54533
-0,083
53522
-0,017
54211
0,176
54345
-0,295
54534
-0,164
53523
-0,032
54212
0,12
54351
-0,217
54535
-0,248
53524
-0,113
54213
0,105
54352
-0,273
54541
-0,117
53525
-0,197
54214
0,024
54353
-0,288
54542
-0,173
53531
0,015
54215
-0,06
54354
-0,369
54543
-0,188
53532
-0,041
54221
0,078
54355
-0,453
54544
-0,269
53533
-0,056
54222
0,022
54411
0,15
54545
-0,353
53534
-0,137
54223
0,007
54412
0,094
54551
-0,275
53535
-0,221
54224
-0,074
54413
0,079
54552
-0,331
53541
-0,09
54225
-0,158
54414
-0,002
54553
-0,346
53542
-0,146
54231
0,053
54415
-0,086
54554
-0,427
53543
-0,161
54232
-0,003
54421
0,052
54555
-0,511
53544
-0,242
54233
-0,018
54422
-0,005
55111
0,122
53545
-0,326
54234
-0,099
54423
-0,019
55112
0,066
53551
-0,248
54235
-0,183
54424
-0,1
55113
0,051
53552
-0,304
54241
-0,052
54425
-0,184
55114
-0,03
55115
-0,114
55254
-0,445
55443
-0,232
55121
0,024
55255
-0,529
55444
-0,313
55122
-0,033
55311
0,086
55445
-0,397
55123
-0,048
55312
0,03
55451
-0,319
55124
-0,129
55313
0,015
55452
-0,375
55125
-0,213
55314
-0,066
55453
-0,39
55131
-0,001
55315
-0,15
55454
-0,471
55132
-0,057
55321
-0,013
55455
-0,555
55133
-0,072
55322
-0,069
55511
0,028
55134
-0,153
55323
-0,084
55512
-0,028
55135
-0,237
55324
-0,165
55513
-0,043
55141
-0,106
55325
-0,249
55514
-0,124
55142
-0,162
55331
-0,037
55515
-0,208
55143
-0,177
55332
-0,093
55521
-0,071
55144
-0,258
55333
-0,108
55522
-0,127
55145
-0,342
55334
-0,189
55523
-0,142
55151
-0,264
55335
-0,273
55524
-0,223


JNJ-53718678
Statistical Analysis Plan 53718678RSV2004
103
Approved, Date: 27 September 2019
Health state
Index Value
Health state
Index Value
Health state
Index Value
Health state
Index Value
55152
-0,32
55341
-0,142
55525
-0,307
55153
-0,335
55342
-0,198
55531
-0,095
55154
-0,416
55343
-0,213
55532
-0,151
55155
-0,5
55344
-0,294
55533
-0,166
55211
0,093
55345
-0,378
55534
-0,247
55212
0,037
55351
-0,3
55535
-0,331
55213
0,022
55352
-0,356
55541
-0,2
55214
-0,059
55353
-0,371
55542
-0,256
55215
-0,143
55354
-0,452
55543
-0,271
55221
-0,005
55355
-0,536
55544
-0,352
55222
-0,062
55411
0,067
55545
-0,436
55223
-0,076
55412
0,011
55551
-0,358
55224
-0,157
55413
-0,004
55552
-0,414
55225
-0,241
55414
-0,085
55553
-0,429
55231
-0,03
55415
-0,169
55554
-0,51
55232
-0,086
55421
-0,032
55555
-0,594
55233
-0,101
55422
-0,088
55234
-0,182
55423
-0,103
55235
-0,266
55424
-0,184
55241
-0,135
55425
-0,268
55242
-0,191
55431
-0,056
55243
-0,206
55432
-0,112
55244
-0,287
55433
-0,127
55245
-0,371
55434
-0,208
55251
-0,293
55435
-0,292
55252
-0,349
55441
-0,161
55253
-0,364
55442
-0,217