Clinical trial NCT04816721
Conditions: Respiratory Syncytial Virus (RSV)
Keywords: Respiratory Syncytial Virus, RSV, Pediatric study
Sponsor: Enanta Pharmaceuticals, Inc
Start date: 2022-04-26; Completion date: 2024-08-19
Enrollment: 99 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A 2-part study to evaluate the safety, pharmacokinetics and efficacy of EDP-938 in children with RSV infection.

Detailed description:
This is a randomized, double-blind, dose ranging, placebo-controlled study in respiratory syncytial virus (RSV) among hospitalized and non-hospitalized children aged from 28 days to 36 months, assessing the safety, tolerability, pharmacokinetics, clinical outcome and antiviral activity of a 5 day treatment with EDP-938.

Arms: arm 1: EDP-938, oral suspension, once daily for 5 days arm 2: Matching placebo, orally, once daily for 5 days
Interventions: intervention 1: EDP-938 intervention 2: Placebo
Intervention descriptions: intervention 1: Oral suspension intervention 2: Placebo oral suspension to match EDP-938

Protocol documents:
Prot_000.pdf: 
Clinical Study Protocol 
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Clinical Study Protocol 
A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 2-PART STUDY TO 
EVALUATE EDP-938 REGIMENS IN SUBJECTS AGED 28 DAYS TO 36 MONTHS INFECTED WITH 
RESPIRATORY SYNCYTIAL VIRUS (RSV)
Protocol Number: EDP 938-201 
Protocol Version:
Date:
09 July 2024
EudraCT-Number:
2020-001966-13
Study Sponsor:
Enanta Pharmaceuticals, Inc.
500 Arsenal St. 
Watertown, MA 02472
Sponsor Medical Monitor:
Enanta Pharmaceuticals, Inc.
500 Arsenal St. 
Watertown, MA 02472 
CONFIDENTIAL
Information and data in this protocol contain trade secrets and privileged or confidential 
information, which is the property of Enanta Pharmaceuticals, Inc. No person is authorized to 
make it public without the written permission of Enanta Pharmaceuticals, Inc.


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Protocol Document History 
Document
Date
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




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SIGNATURE PAGE
The signature below constitutes the approval of this protocol and the attachments and provides 
the necessary assurances that this study will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable US federal regulations and International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. 
Principal Investigator: 
___________________________________________________________________________ 
Signature:
____________________________
Date: 
_______________ 


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TABLE OF CONTENTS
1.
INTRODUCTION ......................................................................................................23
1.1. 
Overview .....................................................................................................................23
1.2. 
Background .................................................................................................................23 
1.3. 
Nonclinical Studies .....................................................................................................23
1.3.1. 
Pharmacology .............................................................................................................23 
1.3.2. 
Juvenile Toxicity Study ..............................................................................................24 
1.4. 
Clinical Studies ...........................................................................................................25
1.5. 
Potential Risks and Benefits .......................................................................................27
2.
OBJECTIVES AND ENDPOINTS ............................................................................29
2.1. 
Objectives ...................................................................................................................29
2.1.1. 
Part 1: Primary and Secondary Objectives .................................................................29
2.1.2. 
Part 2 and Pooled Population: Primary and Secondary Objectives ............................29 
2.1.3. 
Part 1, Part 2, and Pooled Population: Exploratory Objectives ..................................29 
2.2. 
Endpoints ....................................................................................................................30
2.2.1. 
Part 1: Primary and Secondary Endpoints ..................................................................30 
2.2.2. 
Part 2 and Pooled Population: Primary and Secondary Endpoints .............................30 
2.2.3. 
Part 1, Part 2, and Pooled Population: Exploratory Endpoints ...................................31 
3. 
SELECTION OF SUBJECTS ....................................................................................32
3.1. 
Subject Inclusion Criteria ...........................................................................................32
3.2.
Subject Exclusion Criteria ..........................................................................................32
4.
STUDY DESIGN .......................................................................................................34
4.1.
Dose and Treatment Schedule ....................................................................................34
4.2. 
Study Monitoring Committees ...................................................................................35 
4.2.1. 
Study Steering Committee ..........................................................................................35 
4.2.2. 
Independent Data Monitoring Committee ..................................................................36 
4.3. 
Alterations to Planned Doses and Cohort Progression Guidelines .............................36 
4.4. 
Rationale for Study Design .........................................................................................36 
4.4.1. 
Justification of Study Design, Endpoints, and Subject Population ............................37 
4.4.2. 
Justification of EDP-938 Dose ...................................................................................39 
5. 
STUDY DRUG AND TREATMENT OF SUBJECTS..............................................42 
5.1. 
Description of Study Drug ..........................................................................................42 


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5.2.
Packaging and Labeling ..............................................................................................42 
5.3.
Storage ........................................................................................................................42 
5.4.
Accountability .............................................................................................................42
5.5.
Handling and Disposal ................................................................................................43 
5.6.
Treatment Assignment/Randomization ......................................................................43
5.7. 
Study Drug Dose and Administration .........................................................................43 
5.7.1. 
Dispensing of Study Drug ..........................................................................................44 
5.7.2. 
Treatment Compliance ................................................................................................45
5.8. 
Prior and Concomitant Medication .............................................................................45 
5.9. 
Prohibited Medications and Therapies .......................................................................45 
6. 
BLINDING AND UNBLINDING .............................................................................46
6.1. 
Blinding ......................................................................................................................46 
6.2. 
Unblinding ..................................................................................................................46 
6.3. 
Access to Results for Individual Subjects ..................................................................47 
7. 
STUDY CONDUCT AND VISIT SCHEDULE ........................................................47 
7.1. 
Study Site Visits .........................................................................................................47 
7.1.1. 
Screening Period .........................................................................................................47 
7.1.2. 
Treatment Period (Day 1) ...........................................................................................48 
7.1.3. 
Treatment Period Days 2 to 5 .....................................................................................49 
7.1.4. 
Follow-up Period (Days 6 to 28) ................................................................................49
7.2. 
Addition or Replacement of Subjects .........................................................................49 
7.3. 
Subject Withdrawal/Early Termination ......................................................................50 
7.3.1. 
Withdrawal Criteria ....................................................................................................50 
7.3.2. 
Procedures for Early Discontinuation of Treatment or Early Discontinuation 
of Study .......................................................................................................................50
7.3.3. 
Documentation of Withdrawal of Subjects .................................................................51 
8. 
STUDY PROCEDURES/EVALUATIONS ...............................................................52 
8.1. 
Timing of Assessments ...............................................................................................52 
8.2. 
Demographics and Medical History ...........................................................................52 
8.3. 
Prior and Concomitant Treatment ..............................................................................52 
8.4. 
Vital Sign Measurements ............................................................................................52 
8.5. 
Electrocardiograms .....................................................................................................52 
8.6. 
Physical Examination .................................................................................................53


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8.7.
Body Weight and Length, and Head Circumference ..................................................53 
8.8.
Adverse Events ...........................................................................................................53
8.9.
Clinical Evaluation .....................................................................................................53
8.10.
Clinical Scoring Systems ............................................................................................54
8.10.1. 
Professional ReSVinet Clinical Scoring System ........................................................54 
8.10.2. 
Parent/Guardian ReSVinet Clinical Scoring System and Palatability 
Question ......................................................................................................................54 
8.10.3. 
Parent/Guardian
 Clinical Scoring System ............................................55 
8.11.
Laboratory and Diagnostic Procedures .......................................................................55 
8.12.
Virology Assessments ................................................................................................57 
8.12.1. 
Respiratory Syncytial Virus Rapid Diagnostic Test ...................................................58 
8.12.2. 
Confirmatory Respiratory Pathogen Testing ..............................................................58 
8.12.3. 
Respiratory Syncytial Virus Viral Load Quantification .............................................58
8.12.4. 
Respiratory Syncytial Virus Subgroup/Genotype Determination ..............................58 
8.12.5. 
Viral Resistance ..........................................................................................................58
8.13. 
Pharmacokinetic Samples ...........................................................................................59
8.14. 
Exploratory Biomarker Sample Collection ................................................................59 
9. 
SAFETY MONITORING AND REPORTING .........................................................60
9.1.
Definitions ..................................................................................................................60
9.1.1. 
Pretreatment Events ....................................................................................................60
9.1.2. 
Adverse Events ...........................................................................................................60
9.1.3. 
Serious Adverse Events ..............................................................................................60
9.2.
Documenting and Reporting of Adverse Events (Including Serious Adverse 
Events) ........................................................................................................................61 
9.2.1. 
Documenting and Reporting Adverse Events .............................................................61 
9.2.2. 
Assigning Attribution of Adverse Events ...................................................................62
9.2.3. 
Classifying Action Taken With Study Drug ...............................................................63
9.2.4. 
Classifying Adverse Event Outcome ..........................................................................63 
9.2.5. 
Documenting and Reporting Serious Pretreatment Events and Serious 
Adverse Events ...........................................................................................................64
9.3.
Follow-up of Adverse Events and Serious Adverse Events .......................................64 
9.4.
Sponsor’s Review of Adverse Events and Serious Adverse Events ...........................64 
10.
SUBJECT SAFETY MANAGEMENT/STUDY STOPPING RULES .....................65


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10.1.
Study Stopping Rules .................................................................................................65
10.2.
Individual Subject Discontinuation Criteria ...............................................................65
10.3.
Cohort Discontinuation Criteria .................................................................................65
10.4.
Site or Study Discontinuation .....................................................................................65
10.4.1. 
Study Discontinuation ................................................................................................65 
10.4.2. 
Site Termination .........................................................................................................66
10.4.3. 
Study Termination Procedures ...................................................................................66 
11.
STATISTICAL CONSIDERATIONS .......................................................................67
11.1. 
Sample Size Considerations .......................................................................................67
11.2. 
General Considerations ...............................................................................................67 
11.3. 
Analysis Populations ..................................................................................................67 
11.4. 
Subject Disposition and Demographic Data ...............................................................68 
11.5. 
Safety Analyses ..........................................................................................................68
11.5.1. 
Treatment Compliance ................................................................................................68
11.5.2. 
Study Drug Exposure ..................................................................................................68 
11.5.3. 
Adverse Events ...........................................................................................................68
11.5.4. 
Clinical Laboratory Data ............................................................................................69 
11.5.5. 
Vital Sign Measurements ............................................................................................69
11.5.6. 
Electrocardiograms .....................................................................................................69
11.5.7. 
Concomitant Medications and Therapies ...................................................................69 
11.5.8. 
Physical Examinations ................................................................................................70 
11.6. 
Pharmacokinetic Analyses ..........................................................................................70
11.7. 
Efficacy Analyses .......................................................................................................70
11.7.1. 
Antiviral Activity Analyses ........................................................................................70
11.8. 
Exploratory Analyses ..................................................................................................70 
11.8.1. 
Clinical Outcome ........................................................................................................70
11.8.2. 
Other Exploratory Analyses .......................................................................................70 
11.9. 
Interim Analyses .........................................................................................................71 
12. 
STUDY ADMINISTRATION ...................................................................................72 
12.1. 
Ethical Considerations ................................................................................................72 
12.1.1. 
Ethical Conduct of the Study ......................................................................................72 
12.1.2. 
Ethical Review ............................................................................................................72 




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LIST OF ABBREVIATIONS 
AE
adverse event
ALRI 
associated acute lower respiratory illness 
ATC
Anatomical Therapeutic Chemical
AUC 
area under the curve 
AUC0-24 
area under the curve from time zero to 24 hour 
BID
twice daily
BiPAP 
bilevel positive airway pressure 
C12
plasma concentration 24 hours after dosing
C24 
plasma concentration 12 hours after dosing 
Cmax
maximum observed concentration, occurring at Tmax
CPAP 
continuous positive airway pressure
CYP
cytochrome P450
EC
ethics committee 
EC50
50% maximal effective concentration
EC90 
90% maximal effective concentration
ECG 
electrocardiogram
eCOA
electronic clinical outcome assessment
eCRF 
electronic case report form 
EOS 
end-of-study 
EOT 
End-of-Treatment
FDA 
Food and Drug Administration
GCP
Good Clinical Practice
GLP 
Good Laboratory Practice 
IC50
half-maximal inhibitory concentration
ICF
informed consent form
ICH 
International Council for Harmonisation  
ICU 
intensive care unit
IDMC 
Independent Data Monitoring Committee
IRB
institutional review board
IRT
interactive response technology
IV
Intravenous
JAS
juvenile animal study
LD 
loading dose 
LLN 
lower limit of normal
LOD
limit of detection 
MAARI 
medically attended acute respiratory infection
NCI-CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
NOAEL 
no-observed-adverse-effect level
PE
physical examination
PK
pharmacokinetic(s)
PND 
postnatal day 
PT
post-treatment day
QD 
once daily 
RSV
respiratory syncytial virus 


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RT-qPCR
reverse transcription-quantitative polymerase chain reaction
SAE 
serious adverse event
SAP
statistical analysis plan
SoA 
Schedule of Assessments
SpO2
oxygen saturation
SSC 
Study Steering Committee
SUSAR
suspected, unexpected, serious adverse reactions
TBD 
to be determined
TEAE
treatment-emergent adverse event
TK 
toxicokinetic
Tmax
time to reach Cmax
ULN
upper limit of normal
US
United States 
WHO
World Health Organization






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Criteria for Evaluation
The primary efficacy endpoint is the daily change in RSV shedding in nasal swab samples 
determined using RT-qPCR from Baseline through the treatment phase in the pooled 
population (subjects from Part 1 and Part 2 together). 
Part 1 
Primary Endpoints
PK parameters of EDP-938 including area under the curve (AUC) and predose 
concentrations; 
Safety and tolerability of EDP-938 compared to placebo as assessed by, but not limited 
to, adverse events (AEs), vital signs, and clinical laboratory results. 
Secondary Endpoints
AUC for RSV RNA viral load measured in nasal swab samples by quantitative reverse 
transcription polymerase chain reaction (RT-qPCR); 
Daily change in RSV shedding in nasal swab samples determined using RT-qPCR from 
Baseline through the treatment phase; 
Proportion of subjects with RSV RNA viral load below the limit of detection (LOD) in 
subjects receiving EDP-938 compared to placebo; 
 Time to RSV RNA viral load being undetectable. 
Part 2 and Pooled Population 
Primary Endpoint
Daily change in RSV shedding in nasal swab samples determined using RT-qPCR from 
Baseline through the treatment phase. 
Secondary Endpoints 
 Safety and tolerability of EDP-938 compared to placebo as assessed by, but not limited 
to, AEs, vital signs, and clinical laboratory results; 
 AUC for RSV RNA viral load measured in nasal swab samples by RT-qPCR; 
 Proportion of subjects with RSV RNA viral load below the LOD in subjects receiving 
EDP-938 compared to placebo; 
 Time to RSV RNA viral load being undetectable; 
 PK parameters of EDP-938 including AUC and predose concentrations; 
 Time to discharge for hospitalized subjects; 
 Time to use of oxygen for hospitalized subjects who are not receiving oxygen at the 
time they receive the first dose of study drug; 
 Proportion of hospitalized subjects requiring oxygen supplementation or have an 
increased oxygen requirement; 
Time to mechanical ventilation for hospitalized subjects;






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SSC will review available blinded data, including at least safety and PK data, and will 
determine dosing for Part 1 Cohort 2 for each age group. The SSC will meet as required to 
review emerging safety and PK data to support dose decision and initiation of Cohort 2. 
Enrollment in Cohort 1 age groups will continue until 12 subjects have been enrolled. 
Cohort 1 Age Group 1 will include subjects who may be hospitalized or non-hospitalized at 
enrollment. Cohort 1 Age Group 2 will include subjects who are hospitalized at enrollment.    
Cohort 2 for both age groups will include subjects who may be hospitalized or non-hospitalized 
at enrollment.
Additional Part 1 cohorts may be added, as deemed necessary by the SSC.  
Part 2: Both age groups will include subjects who may be hospitalized or non-hospitalized at 
enrollment. The start of dosing for each age group will be contingent upon at least 6 subjects in 
that age group being exposed to EDP-938 in Part 1 Cohort 2 and will be based on SSC 
recommendations. After completion of dosing in the Part 2 cohort, the SSC will review 
available blinded data, including at least safety and PK data, in that age group. Twenty subjects 
are planned for each age group, but additional subjects may be enrolled based on SSC 
recommendations to allow a sufficient number of subjects to determine doses for both age 
ranges.  
Additional Part 2 cohorts may be added, as deemed necessary by the SSC.
In addition to the SSC responsible for dose escalation decisions based on blinded safety and PK 
data, to ensure that the safety of the subjects is thoroughly monitored, an Independent Data 
Monitoring Committee (IDMC) will review unblinded safety data. At a minimum, the IDMC 
will review data for each age group from Part 1 and subsequently from Part 2. Ad hoc meetings 
of the IDMC can be scheduled whenever deemed necessary. The IDMC will include 
2 clinicians and a statistician who are independent of study conduct, Enanta, and the Contract 
Research Organization. 
The study periods are summarized below. Study assessments are detailed in the Schedule of 
Assessments (SoA). For study assessments, a subject’s hospitalization status (hospitalized or 
non-hospitalized) will be based on their status on the day of the visit. 
Screening Period: At Screening, the subject’s legal representative (henceforth referred to as 
“caregiver”) must review and sign an informed consent form (ICF) before the subject 
undergoes any study-specific procedures. 
After the ICF is signed, screening assessments will be done, including physical examination, 
ECG, vital sign and body measurements. Some procedures performed as part of standard of 
care (such as an RSV diagnostic test or safety laboratory tests) may be used to determine study 
eligibility if they are performed within 72 hours of when the ICF is signed, as specified in the 
SoA. Screening safety laboratory test samples will be sent to the local laboratory for expedited 
testing. 
Subjects who have symptom onset, defined as the estimated onset of the first sign of respiratory 
infection, that does not exceed 7 days for Part 1 and 5 days for Part 2 before the signing of the 
ICF by their caregiver and whose swab sample tests positive for RSV will undergo further 
screening procedures to determine study eligibility. Screening should be completed as soon as 


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possible to ensure that subjects will be randomized and administered the first dose of study 
drug within 24 hours of signing the ICF. 
Treatment Period (Days 1 to 5): Subjects who are eligible for the study will be randomized 
2:1 (Part 1) or 4:1 (Part 2) to EDP-938:placebo. Subjects will be considered enrolled at the time 
of randomization. 
Nasal swab samples will be collected throughout the treatment period for RSV viral load 
assessments. At each scheduled visit, the site Investigator or designee will complete the 
Professional ReSVinet clinical scoring system. 
The subjects’ caregiver will receive an eCOA 
 
 handheld 
device. This device will be used to complete the Parent/Guardian ReSVinet clinical scoring 
system beginning after randomization but before the first dose and subsequently QD at 
approximately the same time each day ± 2 hours. The palatability question should be completed 
postdose. The device should be brought to each site study visit.   
The subjects’ caregivers will receive instructions on the proper use and care of the eCOA 
device. If a caregiver is unable to use the eDiary, a paper diary may be used.
In a subset of subjects, the subjects’ caregivers will also complete the 
clinical 
scoring system on paper after randomization but before the first dose and subsequently twice 
daily, approximately every 12 hours. 
Hospitalized Subjects 
Subjects will receive EDP-938 or placebo QD orally for 5 days at approximately the same time 
every day (± 1 hour). Hospitalization duration will not be extended solely for study purposes. 
Hospitalized subjects who are discharged before Day 3 should return to the study site for Day 3 
and Day 5 visits. Subjects who are discharged on or after Day 3 (but before Day 5), should 
return to the study site for the Day 5 visit. 
Non-hospitalized Subjects
Subjects will receive the first dose of EDP-938 or placebo orally at the study site on Day 1 and 
will be monitored at the site for safety assessments over the first 3 hours postdose. Subjects’ 
caregiver(s) will be instructed to administer EDP-938 or placebo QD at approximately the same 
time every day (± 1 hour) on Day 2 and Day 4. On Day 3 and Day 5 (End-of-Treatment visit; 
EOT), subjects should be dosed at the clinic. If a subject is unable to attend a study site visit, a 
home visit by study site personnel/home health staff may be arranged, if feasible. 
Follow-up Period (Days 6 to 28): Follow-up visits will occur 4, 9, and 23 days after the last 
dose of study drug (study Days 9, 14, and 28) for all subjects including those who discontinue 
treatment early (before completing 5 days of dosing). The end-of-study visit (EOS, Day 28) is a 
follow-up visit for posttreatment safety assessments and may be conducted as a telephone call.  
Early Termination 
Subjects who discontinue treatment early (before completing 5 days of dosing) should return to 
the study site within 24 hours after the last dose of study drug for an EOT visit. Subjects should 
then return to the site 4 and 9 days after discontinuation of study drug for post-treatment 
follow-up Visits 1 and 2 (PT1, PT2). A follow-up visit for post-treatment safety assessments 


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also needs to be scheduled (23 days after study drug discontinuation) and may be conducted as 
a telephone call. 
Subjects who discontinue the study early (before Day 28) should return to the study site within 
24 hours if possible and no more than 48 hours later to complete the EOS procedures. 
Addition or Replacement of Subjects 
If the objectives of the study are not met (due to subject dropout, lack of sufficient data points, 
or other reason) or based on recommendation from the SSC, additional subjects may be 
enrolled. Subjects who withdraw from the study before receiving the first dose of study drug 
may be replaced. Subjects who withdraw from the study after receiving the first dose of study 
drug will not be replaced, except as recommended by the SSC. 
Eligibility Criteria
Inclusion Criteria
Each subject must meet all of the following criteria to be enrolled into this study: 
Male or female who is either 
36 months (for Age Group 1) or 
 to
<6 months (for Age Group 2), defined at the time of randomization. Subjects in Age
Group 2 must have been born 29 weeks of gestation to be eligible. If a subject was born
<29 weeks of gestation, the subject can only be enrolled in Age Group 1;
Subjects diagnosed with RSV infection using an approved diagnostic assay, without
known and/or documented coinfection with SARS-CoV-2. If RSV infection is not
confirmed, caregivers may be asked to sign a RSV Diagnostic Test ICF allowing a rapid
antigen RSV test to be performed;
Subjects with signs of an acute respiratory illness (e.g., fever [or symptoms of fever],
cough, nasal congestion, runny nose, rapid breathing, shortness of breath, or wheezing)
7 days 
 days for Part 2 before the time of signing the ICF;
Note: Time of onset of signs is defined as the caregiver(s) estimated time of awareness of
the first sign of respiratory infection or worsening from the subject’s pre-existing
respiratory signs.
Have a calculated creatinine clearance rate not below the lower limit of normal (LLN) for
the subject’s age as determined by the Schwartz equation (Schwartz & Work, 2009) at
Screening;
In the Investigator’s opinion, the subject’s caregiver understands and is able to comply
with protocol requirements, instructions, and protocol-stated restrictions, and the subject is 
likely to complete the study as planned.
Additional inclusion criterion for Part 1 Cohort 1, Age Group 2 
6.
Subject is currently or is planned to be hospitalized as a consequence of RSV infection
and is not anticipated to be discharged in less than 24 hours after enrollment.
Exclusion Criteria 
Subjects will not be eligible to participate in the study if they meet any of the following criteria:


























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3.
SELECTION OF SUBJECTS
3.1.
Subject Inclusion Criteria
Each subject must meet all of the following criteria to be enrolled into this study: 
1.
Male or female who is either
<6 months (for Age Group 2), defined at the time of randomization. Subjects in Age Group 
<29 weeks of gestation, the subject can only be enrolled in Age Group 1; 
2.
Subjects diagnosed with RSV infection using an approved diagnostic assay, without known 
and/or documented coinfection with SARS-CoV-2. If RSV infection is not confirmed, 
caregivers may be asked to sign a RSV Diagnostic Test ICF allowing a rapid antigen RSV 
test to be performed;   
3. 
Subjects with signs of an acute respiratory illness (e.g., fever [or symptoms of fever], 
cough, nasal congestion, runny nose, rapid breathing, shortness of breath, or wheezing) 
7 days 
 days for Part 2 before the time of signing the informed 
consent form (ICF); 
Note: Time of onset of signs is defined as the caregiver(s) estimated time of awareness of 
the first sign of respiratory infection or worsening from the subject’s pre-existing 
respiratory signs. 
4. 
Have a calculated creatinine clearance rate not below the lower limit of normal (LLN) for 
the subject’s age as determined by the Schwartz equation (Schwartz & Work, 2009) at 
Screening; 
5. 
In the Investigator’s opinion, the subject’s caregiver understands and is able to comply with 
protocol requirements, instructions, and protocol-stated restrictions, and the subject is 
likely to complete the study as planned. 
Additional inclusion criterion for Part 1 Cohort 1, Age Group 2 
6. 
Subject is currently or is planned to be hospitalized as a consequence of RSV infection and 
is not anticipated to be discharged in less than 24 hours after enrollment. 
3.2. 
Subject Exclusion Criteria 
Subjects will not be eligible to participate in the study if they meet any of the following criteria: 
1. 
Use of, or anticipated need for, invasive mechanical ventilation, cardiopulmonary bypass, 
hemodialysis, or extracorporeal membrane oxygenation; or subjects who are not expected 
to survive the current illness; 
2.
Subjects who have a medical history or a concurrent illness 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. Examples include liver or renal insufficiency; significant 
cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, 
rheumatologic, or metabolic conditions; 








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representative, a biostatistician, a pediatrician with expertise in respiratory infections and who is 
independent of the study conduct, and the Contract Research Organization’s Medical Monitor. 
The SSC will not allow progression to the next cohort/part if there are two or more of the same 
study drug-related Grade 3 adverse events, one or more study drug-related Grade 4 adverse 
events, or one or more study drug-related serious adverse events. In order to proceed to the next 
cohort under these circumstances, the IDMC would be required to review the relevant data and 
agree with proceeding. 
4.2.2. 
Independent Data Monitoring Committee 
In addition to the SSC responsible for dose escalation decisions based on blinded safety and PK 
data, to ensure that the safety of the subjects is thoroughly monitored, an IDMC will review 
unblinded safety data. At a minimum, the IDMC will review data for each age group from Part 1 
and subsequently from Part 2. Ad hoc meetings of the IDMC can be scheduled whenever deemed 
necessary. The IDMC will include 2 clinicians and a statistician who are independent of study 
conduct, Enanta, and the Contract Research Organization. Further information about the IDMC 
will be provided in the IDMC Charter. 
4.3. 
Alterations to Planned Doses and Cohort Progression Guidelines 
The SSC may recommend modifications, such as if: 
 More subjects should be evaluated in any cohort to more fully characterize the safety 
and PK profile of EDP-938; 
 For each age group, enrollment into the Part 1 Cohort 2 can proceed at the proposed 
dose; 
 For each age group, enrollment into the Part 2 Cohort can proceed at the proposed 
dose. 
Additional cohort(s) may be enrolled based on recommendations from the SSC review of 
available blinded data to potentially evaluate different doses, dosing regimens, or additional 
subjects at the same dose. 
Once the SSC has reviewed the PK and safety data of the highest dose within each age group that 
will be used in Part 1, it may recommend that the protocol eligibility in Part 2 be expanded to 
include subjects with concurrent illness. 
A PK analysis will be conducted to support the dose for the next dose cohort in that same age 
group and dose selection will be guided by the totality of the safety, tolerability, and PK data. 
The SSC will make recommendations to determine which cohorts to initiate and which dose 
levels to administer. 
4.4. 
Rationale for Study Design 
This is the first study investigating the use of EDP-938 in pediatric patients. Based on current 
RSV guidance documents, the pathophysiology of RSV disease is believed to be different 
between adults and pediatric patients. Therefore, methods of efficacy extrapolation from adults 
to pediatric patients may not be appropriate. Thus, the goal of this first EDP-938 pediatric 
clinical trial is to evaluate the safety, tolerability, PK, clinical outcomes, and antiviral activity of 


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EDP-938 in pediatric patients 28 days to 36 months of age who are infected with RSV and 
who may be hospitalized or non-hospitalized. This study is designed to support dose selection 
within each age group/cohort and to provide data to support dose selection for future pediatric 
clinical trials. 
4.4.1. 
Justification of Study Design, Endpoints, and Subject Population
Despite the significant medical need, there is no vaccine or highly effective treatment currently 
available for RSV in children or adults. Currently, only 2 drugs are approved for treatment or 
prevention of RSV lower respiratory tract infection in pediatric patients: aerosolized ribavirin (a 
nucleoside analog) for treatment and palivizumab (a monoclonal antibody that targets the RSV 
fusion protein) for the prevention of serious lower respiratory tract disease caused by RSV in 
high risk children. However, analyses performed subsequent to the approval of aerosolized 
ribavirin suggest that it failed to impart any clinically significant benefits (Randolph & Wang, 
1996), and currently it is not recommended for routine treatment of RSV (Piedimonte & Perez, 
2014). There are also concerns about the toxicity, teratogenicity, and high cost of inhaled 
ribavirin (Chemaly, Aitken, Wolfe, Jain, & Boeckh, 2016). Current management of RSV 
bronchiolitis remains mostly supportive care such as oxygen for hypoxemia and intravenous 
fluids for dehydration. Consequently, clinicians have no safe and highly effective treatment for 
RSV infection, which is an issue of significant concern for those providing medical care for 
pediatric patients at risk of severe RSV disease. 
This Phase 2 study aims to evaluate the safety, tolerability, PK, and antiviral activity of EDP-938 
administered orally in pediatric patients 28 days to 36 months of age who are infected with 
RSV. The design of the study (randomized, double-blind, placebo-controlled, dose-ranging) is 
consistent with recent RSV guidance from regulatory agencies (EMA; FDA). 
While this initial Phase 2 trial should identify the optimal dose and treatment duration of 
EDP-938 with regard to PK, safety, and antiviral activity in children aged 28 days to 36 months, 
we will also be exploring the use of instruments for RSV signs and symptoms that may be 
relevant to a later stage of EDP-938 development in the pediatric population. 
The study will be conducted in 2 parts. In Part 1, the primary endpoints will be safety, 
tolerability, and PK. In Part 2, the primary endpoint will be antiviral activity. In Part 1, subjects 
will be randomized 2:1 to EDP-938:placebo. The SSC will make recommendations to determine 
dose selection and cohort progression in Part 1 and Part 2. 
Safety data on EDP-938 available to date supports the enrollment of both age groups, 6 months 
to 36 months and 28 days to less than 6 months. At least 2 dosing cohorts will be evaluated in 
Part 1. Part 1 Cohort 1 of both age groups will evaluate an initially selected dose of 
, 
which is anticipated to yield exposures that are safe and efficacious. As these exposures are 
predicted based on modeling and simulation using adult data (Section 4.4.2 for dose rationale), 
dose adjustments based on pediatric data may be needed. Therefore, a higher or lower dose will 
be explored in Cohort 2. If adequate exposures are achieved in Cohort 1 with no safety concerns, 
a higher dose that is not expected to exceed safe exposures in nonclinical studies and clinical 
studies may still be explored in Cohort 2 to evaluate the safety and PK of EDP-938 across a dose 
range. Additional cohorts in Part 1 may be added, as needed. Following completion of Part 1 for 
a specific age group and based on SSC review, enrollment in Part 2 for that same age group may 
begin. 












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5.5.
Handling and Disposal
All study drug bottles at the site 
 returned by subjects’ caregivers as well as those 
that have not been used or assigned to subjects will be retained at the site according to 
instructions provided by Enanta Pharmaceuticals, Inc. or designee until monitored by the Study 
Monitor. Full accountability of all study drug distributed to subjects will be documented per 
Section 5.4. 
Enanta Pharmaceuticals, Inc. will provide instructions for the return or destruction of any unused 
study drug. If Enanta Pharmaceuticals, Inc. authorizes destruction at the study site, the 
Investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by Enanta 
Pharmaceuticals, Inc., and, that the destruction was adequately documented. 
5.6. 
Treatment Assignment/Randomization 
Subjects will be randomized to a treatment group using an Interactive Web Response System. 
Subjects will be randomized to the initial EDP-938 or placebo treatment group as shown below: 
Part 1, Cohort 1, Age Group 1 and 2 (randomized 2:1) 
of EDP-938 orally QD for 5 days (8 subjects);
 placebo orally QD for 5 days (4 subjects).
The dose for Part 1 Cohort 2 for each age group will be determined based on review of Part 1 
Cohort 1 data.
Part 2 (randomized 4:1) 
EDP-938 orally QD for 5 days: dose to be determined
Oral EDP-938 QD for 5 days: dose to be determined (16 subjects);
Oral placebo QD for 5 days: dose to be determined (4 subjects).
The randomization code will be produced by Enanta Pharmaceuticals, Inc. (or designee). The 
Enanta Pharmaceuticals, Inc. unblinded biostatistician or designee will review and approve the 
final randomization list. 
During the Screening Period, subjects will be identified by a unique screening number. Subjects 
who have completed screening assessments and are eligible for participation in the study will be 
randomized before the first dose of study drug (Day 1). 
5.7. 
Study Drug Dose and Administration 
Complete instructions for dispensing and administering study drug are presented in the Pharmacy 
Manual. 
Hospitalized Subjects 
Following randomization, subjects will be administered EDP-938 or placebo QD orally 
 
for 5 days at approximately the same time every day 
(±1 hour) on each of the 4 subsequent days. 




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5.7.2. 
Treatment Compliance 
For non-hospitalized subjects, the subject’s caregiver will be instructed to bring all study drug 
to the site on Day 3, Day 5, or the End-of-Treatment (EOT) visit (for 
subjects who discontinue study drug). Both accountability and study drug compliance (via 
syringe counts) will be reviewed at each study site visit as indicated in the SoA (Appendix 1). 
 the site staff will ask the subject’s caregiver why 
any doses were missed, including administration of partial doses, if applicable. Repeated 
noncompliance of study drug dosing for any subject, despite continued educational efforts, 
should be discussed by the Investigator with 
 or the Sponsor’s Medical Monitor to 
consider possible discontinuation of the subject from the study. 
5.8.
Prior and Concomitant Medication
The subject’s caregiver will be instructed on the use of concomitant medications during the 
study. All subjects enrolled in the study must not be administered prohibited concomitant 
medications and therapies through the end-of-study. Details of prior and concomitant medication 
use will be recorded in the source documentation and the electronic case report form (eCRF) as 
indicated in the SoA (Appendix 1). 
Prior medications administered to the subjects up to 1 month before the first dose of study drug 
must be recorded at Screening. Only relevant medications and therapies should be recorded if 
they were discontinued more than 1 month before signing the ICF. All subjects will receive 
supportive care according to local institution standards and applicable guidelines. 
Concomitant medications and therapies are permitted as indicated for the management of study 
subjects with the exception of the medications and therapies noted in Section 5.9. 
5.9. 
Prohibited Medications and Therapies 
Systemic antiviral, antifungal, and antimycobacterial therapies are prohibited within 7 days of 
Screening and for the duration of the study. 
The following are also prohibited: 
Systemic medications other than corticosteroids (either chronically [more than
14 days] or within 21 days before randomization and for the duration of the study)
that are known to modulate the host’s immune response or increase viral shedding,
such as immunomodulatory therapies. In Part 2 only: Investigational or approved
medication that is intended to prevent or treat RSV infection is prohibited within the
following times before the first dose of study drug and for the duration of the study:
ribavirin: 35 days,
palivizumab: 100 days,
nirsevimab: 350 days,
other RSV specific monoclonal antibody: 5 half-lives of the specific antibody,
RSV vaccines: 12 months.




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Once a subject’s treatment assignment has been unblinded for a medical emergency or urgent 
clinical situation, the 
 and study coordinator should be notified within 
24 hours of unblinding of the treatment. Information relating to unblinding (e.g., the reason, 
date) should be clearly recorded in the subject’s study file. In addition, the Investigator should 
consider whether the clinical event that prompted unblinding should be considered an SAE, 
according to the regulatory definitions or criteria for SAEs and, if so, submit an SAE report as 
described in Section 9.2. 
The 
 will also unblind any SAE reports in compliance 
with regulatory reporting requirements. In addition, Enanta Pharmaceuticals, Inc. may unblind 
individual subjects at any time for matters relating to safety concerns. 
Note: Investigative sites will be provided country-specific toll-free telephone and fax numbers. 
6.3.
Access to Results for Individual Subjects
During the conduct of the study, Investigators, site personnel, and blinded Contract Research 
Organization/Sponsor staff will not have access to results for individual subjects that could 
impact clinician assessments, including results for RSV viral load, confirmatory respiratory 
pathogen panel testing, biomarkers, and PK. 
7. 
STUDY CONDUCT AND VISIT SCHEDULE 
7.1. 
Study Site Visits 
Key aspects of each part of the study (Screening, Treatment Period [Days 1 through 5]), and 
Follow-up) are summarized below. Assessments are presented in the SoA (Appendix 1). 
For study assessments, a subject’s hospitalization status (hospitalized or non-hospitalized) will 
be based on their status on the day of the visit.  
Study sites will be responsible for following up with subjects for any missed study site visits. 
Communication (such as telephone calls, emails, or other electronic communication methods) 
with parent(s)/subject’s caregiver(s) to facilitate compliance with study procedures between 
outpatient study visits are encouraged.  If a subject is unable to attend a study site visit, a home 
visit by study site personnel/home health staff may be arranged, if feasible. 
7.1.1. 
Screening Period 
All study assessments during the Screening Period are detailed in the SoA (Appendix 1). 
The subject’s legal representative (henceforth referred to as “caregiver”) must review and sign an 
institutional review board (IRB) or ethics committee (EC)-approved ICF and provide 
authorization to use protected health information (see Section 12.1.3) before the subject 
undergoes any study-specific procedures. By signing the ICF, the caregiver will indicate that he 
or she understands the purpose of, and procedures required for, the study and is willing for the 
subject to participate in the study. 
Some procedures performed as part of standard of care before Screening may be used in 
determining study eligibility, such as RSV diagnostic test or safety laboratory tests (as specified 
in the SoA) if they are performed within 72 hours before the ICF is signed. If any assessment is 


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anticipated to fall outside of that window, the Investigator should consult with the 
to determine if the subject can proceed. Screening safety laboratory test samples will be 
sent to the local laboratory for expedited testing. 
RSV diagnosis at Screening will be performed using an approved diagnostic assay locally. A 
nasal swab will be collected.
Subjects who have symptom onset, defined as the estimated onset of the first sign of respiratory 
infection and which does not exceed 7 days for Part 1 and 5 days for Part 2, before the signing of 
the ICF by their caregiver and whose swab sample tests positive for RSV will undergo further 
screening procedures to determine study eligibility. 
Subjects will be randomized after all screening activities that allow assessment of 
inclusion/exclusion criteria have been completed to the satisfaction of the Investigator. Subjects 
will be randomized 2:1 (Part 1) or 4:1 (Part 2) to EDP-938:placebo. 
7.1.2. 
Treatment Period (Day 1) 
All study assessments on Day 1 are detailed in the SoA (Appendix 1). 
All subjects (hospitalized and non-hospitalized) should undergo screening assessments, 
determined whether eligible, and be randomized and dosed within 24 hours of signing consent. If 
a subject needs to return the next day from Screening to complete Day 1 assessments, vital sign 
assessments should be repeated predose. 
The following assessments must be done between randomization and dosing: 
 Parent/Guardian ReSVinet clinical scoring system; 
 Parent/Guardian 
 clinical scoring system, in a subset of subjects; 
 Clinical evaluation (Section 8.9); 
 Vital signs. 
Subjects will be administered a dose of EDP-938/placebo on-site. Subjects will be monitored at 
the site for safety assessments over the first 3 hours postdose. Hospitalized subjects will have 
ongoing monitoring as a component of standard of care. The subjects’ caregivers will also 
receive instruction on the appropriate storage and transport of study drug (see Section 5.3). 
On Day 1, one nasal swab sample will be collected.
The subjects’ caregiver will receive an electronic data capture handheld device 
 
 
 to use for the duration of the study. This device will be used to complete the 
Parent/Guardian ReSVinet clinical scoring system (QD at approximately the same time each day 
±2 hours) beginning after randomization, prior to dose. The palatability question should be 
completed postdose. The subject’s caregiver will receive instructions on the proper use and care 
of the eCOA device, and the device should be brought to each study visit. If a caregiver is unable 
to use the eDiary, a paper diary may be used. 
In a subset of subjects, the subject’s caregiver will also complete the 
clinical 
scoring system on paper after randomization but before the first dose and subsequently twice 
daily, approximately every 12 hours. 


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7.1.3. 
Treatment Period Days 2 to 5
All study assessments during the Treatment Period are detailed in the SoA (Appendix 1). 
Hospitalized Subjects 
Subjects will receive EDP-938 or placebo QD at approximately the same time every day 
(±1 hour) on each of the 4 subsequent days after dosing on Day 1. Hospitalization duration will 
not be extended solely for study purposes. At discharge, the subject’s caregiver will be instructed 
to administer EDP-938 or placebo QD at approximately the same time every day (±1 hour) on 
each of the remaining dosing days. After discharge, subsequent assessments will follow the 
schedule for non-hospitalized subjects. 
Hospitalized subjects who are discharged before Day 3 should return to the study site for Day 3 
and Day 5 visits. Subjects who are discharged on or after Day 3 (but before Day 5), should return 
to the study site for the Day 5 visit. 
Non-hospitalized Subjects 
Subjects’ caregiver(s) will be instructed to administer EDP-938 or placebo to subjects QD at 
approximately the same time every day (±1 hour) on Day 2 and Day 4. On Day 3 and Day 5 
(EOT), subjects should be dosed at the clinic. It is recommended that the study visits on Day 3 
and Day 5 be scheduled close to the time that the subject normally takes the study drug so that 
dosing can occur at the site, when possible. If a subject is unable to attend a study site visit, a 
home visit by study site personnel may be arranged, if feasible. 
7.1.4. 
Follow-up Period (Days 6 to 28) 
All study assessments during the Follow-up Period are detailed in the SoA (Appendix 1). 
Follow-up visits will occur 4, 9, and 23 days (study Days 9, 14, and 28 [end-of-study; EOS]) 
after the last dose of study drug for all subjects including those who discontinue treatment early 
(before completing 5 days of dosing). The eCOA eDiary device should be returned to the site on 
or before Day 14 (or post-treatment visit 2 [PT2]). 
The Day 28 (EOS Visit) is a follow-up visit for post-treatment safety assessments and may be 
conducted as a telephone call. 
Any subject with ongoing AEs/SAEs at the EOS Visit should be followed up until resolution of 
their AE/SAE or until the Investigator has determined that the event has stabilized as discussed 
in Section 9.3. 
7.2. 
Addition or Replacement of Subjects 
If the objectives of the study are not met (due to subject dropout, lack of sufficient data points, or 
other reason) or based on recommendation from the SSC, additional subjects may be enrolled. 
Subjects who withdraw from the study before receiving the first dose of study drug may be 
replaced. Subjects who withdraw from the study after receiving the first dose of study drug will 
not be replaced, except as recommended by the SSC. 


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7.3.
Subject Withdrawal/Early Termination
Subjects may be withdrawn at any time at the request of their caregiver(s) or at the discretion of 
the Investigator or Enanta Pharmaceuticals, Inc. for safety, behavioral, or administrative reasons. 
However, the Investigator should consult with the 
 where possible before 
prematurely removing a subject. For any subject who is withdrawn by their caregiver, the 
Investigator should inquire about the reason for withdrawal, request that the subject’s caregiver
returns all unused investigational product(s), request that the subject returns for the EOT, PT1, 
and PT2 visits 
(if applicable) and the 
EOS Visit, and follow-up with the subject’s caregiver regarding any unresolved AEs. If a 
subject’s caregiver withdraws from the study and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected. Enanta Pharmaceuticals, Inc. may retain and continue to use any data collected before 
such withdrawal of consent. 
7.3.1. 
Withdrawal Criteria 
Subjects may be discontinued from the study at any time if the subject’s caregiver, Investigator, 
or Sponsor determines that it is not in the best interest of the subject to continue participation. 
Reasons for discontinuation include the following: 
 AE; 
 Lack of efficacy; 
 Lost to follow-up; 
 Withdrawal by subject; 
 Protocol deviation (including noncompliance with study drug or study procedures); 
 Study terminated by the Sponsor; 
 Other. 
7.3.2. 
Procedures for Early Discontinuation of Treatment or Early Discontinuation of 
Study 
Subjects who discontinue treatment early (before completing 5 days of dosing) should return to 
the study site within 24 hours after the last dose of study drug for an EOT visit. Subjects should 
then return to the site 4 and 9 days (PT1 and PT2 visits) after discontinuation of study drug for 
post-treatment follow-up visits. A follow-up visit for post-treatment safety assessments also 
needs to be scheduled (23 days after study drug discontinuation) and may be conducted as a 
telephone call. 
Subjects who discontinue the study early (before Day 28) should return to the study site within 
24 hours if possible and no more than 48 hours later to complete the EOS procedures and return 
eCOA handheld device per the SoA (Appendix 1). Any subject who withdraws with ongoing 
AEs/SAEs should be followed up until resolution of their AE(s) or until the Investigator has 
determined that the AE(s) has stabilized. 
Site staff will attempt to contact any subject’s caregiver who does not return to the site for the 
EOT or EOS Visit at least 3 times using the caregiver preferred method of communication, 


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followed by a letter requiring delivery notification if the 3 attempts were unsuccessful. Any 
subject who still cannot be reached following those attempts will be considered lost to follow-up. 
These subjects will be included in the PK and safety analysis as indicated in Section 11.2. 
7.3.3. 
Documentation of Withdrawal of Subjects 
The reason for early withdrawal/termination/lost to follow-up of any subject from the study must 
be documented on the appropriate eCRF. If the reason for early withdrawal is an AE or an 
abnormal laboratory value, the specific event or test result, if available, should be recorded on 
the AE eCRF and the subject should be monitored until the event is resolved or deemed stable by 
the Investigator. 


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8.
STUDY PROCEDURES/EVALUATIONS
8.1.
Timing of Assessments
The timing of assessments is shown in the SoA (Appendix 1). If multiple assessments are 
scheduled for the same timepoint, it is recommended that noninvasive procedures being done 
before more invasive procedures, eg, first complete
 and ReSVinet Scoring System 
(parent/guardian on ReSVinet eCoA and clinician scoring could be concurrent), then ECG, then 
vital signs/SpO2, then nasal swab, and finally blood draw. 
8.2. 
Demographics and Medical History
Demographics and baseline characteristics including age (months and days), gestational age (in 
weeks), gender or sex, race, ethnicity, and medical history will be obtained from each subject 
and entered in source documents and either interactive response technology (IRT) or eCRFs as 
reported during Screening. Significant medical history including surgeries will be obtained by 
consulting with the subject’s caregiver. As a rule, all medical events occurring within the last 
6 months should be recorded. For events that occurred more than 6 months before Screening
(and that are not ongoing), only significant or relevant events should be entered on the eCRF. 
Any items in the history that are still ongoing should be noted as such in the eCRF. 
If there is a question concerning a subject’s medical history, then medical records may be 
requested from the subject’s primary care physician, as appropriate. 
8.3. 
Prior and Concomitant Treatment 
Medications taken within 1 month of signing the ICF, blood products administered within 
6 months of study drug administration, and medications taken during the study will be recorded 
with indication, dosage, route of administration, and start and stop dates of administration. Only 
relevant medications and therapies should be recorded if they were discontinued more than 
1 month before signing the ICF (see Section 5.8). Subjects’ caregivers will be questioned about 
concomitant medication at each study site visit. Concomitant therapies will be collected from the 
time of consent. This will include requirement for hydration and feeding by intravenous (IV) 
catheter/nasogastric tube and requirement for and duration of oxygen 
supplementation/noninvasive mechanical ventilation support. 
8.4. 
Vital Sign Measurements 
Vital signs include heart rate, respiratory rate, systolic and diastolic blood pressure, body 
temperature, and pulse oximetry (to measure peripheral capillary oxygen saturation [SpO2]). 
8.5. 
Electrocardiograms 
ECGs will be performed locally. A standard bedside 12-lead ECG machine that calculates heart 
rate and measures PR, QRS, QT, RR, and QT interval corrected for heart rate according to 
Fridericia (QTcF) intervals is strongly preferred but in cases where a 12-lead ECG is not possible 
or feasible, a 6-lead ECG may be used. 


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During the collection of ECGs, subjects should be calm, resting quietly, or sleeping if possible. If 
blood sampling and a nasal swab are scheduled for the same timepoint as ECG recording, those 
assessments should be done after the ECG. 
The Investigator or designee should review the ECG for gross abnormalities and interval 
measurements of concern (absolute readings). The clinical interpretation by the Investigator or 
designee of the ECGs should be recorded on a hard copy of the ECG (ie, clinically significant or 
not clinically significant). 
An ECG may be repeated at the discretion of the Investigator to address suspected errors in 
performance. Before dosing, the screening ECG must be reviewed to confirm that no clinically 
significant cardiac abnormalities are present.
All subjects with new abnormal cardiac laboratory values or abnormal ECG results after 
receiving study drug should have echocardiograms. For echocardiogram results, only clinically 
significant abnormalities should be recorded as AEs. 
8.6. 
Physical Examination 
The Investigator or designee will perform the physical examination. A full physical examination 
will be conducted at Screening and will include examination of all pertinent body systems. Any 
subsequent physical examinations performed at the discretion of the Investigator will be targeted 
to new signs and symptoms including specific assessments of any changes from previous status. 
Only clinically significant abnormalities should be recorded as AEs. 
8.7. 
Body Weight and Length, and Head Circumference 
Body weight and length should be obtained with the subject unclothed, in a diaper only, or in 
light clothes and no shoes, as per standard of care. Body length and head circumference will be 
documented at Screening only. 
8.8. 
Adverse Events 
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE as provided in Section 9.1 of this protocol. All AEs and SAEs 
must be recorded in the source documents and eCRF as described in Section 9.2. At all study site 
visits, the Investigator or designee should inquire about the occurrence of AEs with the caregiver 
including well-being of the subject, if there were any medical problems recently or if any new 
medicines were taken since the last visit/assessment. Signs and symptoms that are part of the 
natural progression of RSV infection do not need to be captured as AEs. 
It is the Investigator’s responsibility to ensure all necessary information is documented in the 
subject source notes and eCRF. 
8.9. 
Clinical Evaluation 
Clinical evaluation will include but not be limited to the following evaluations of the clinical 
course of RSV infection: 
Vital signs (respiratory rate, heart rate, systolic blood pressure, diastolic blood
pressure, SpO2, and body temperature);


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Level of care (e.g., ICU, translational care unit, ward floor, home); 
Duration of hospitalization if hospitalized; 
Incidence of MAARI including hospitalizations, outpatient clinic visits, emergency 
department visits, and telephone visits due to acute respiratory infection; 
Requirement for and duration of oxygen supplementation/noninvasive mechanical 
ventilation support (e.g., nasal cannula, face mask, continuous positive airway 
pressure) and/or invasive mechanical ventilation support (e.g., endotracheal-
mechanical ventilation or mechanical ventilation via tracheostomy); 
 Requirement for hydration and feeding by IV catheter/nasogastric tube. 
On Day 1, these assessments must be done predose. 
8.10. 
Clinical Scoring Systems 
8.10.1. 
Professional ReSVinet Clinical Scoring System
The site Investigator or designee will perform ongoing clinical assessment scoring of the 
progression of RSV infection using the Professional ReSVinet clinical scoring system at 
scheduled time points through Day 14. Whenever possible, the same assessor should complete 
the scoring. A copy of the scoring system is provided in Appendix 2. 
8.10.2. 
Parent/Guardian ReSVinet Clinical Scoring System and Palatability Question 
During the study, subjects’ parent(s)/guardian(s) will assess the severity of RSV-related signs 
and symptoms and complete the required response in the Parent/Guardian ReSVinet clinical 
scoring system using a handheld eCOA eDiary. They will also assess the palatability of study 
drug. A copy of the scoring system and the palatability question is provided in Appendix 3. 
The eCOA eDiary will be provided to the parent(s)/guardian(s) on Day 1, and the 
Investigator/study site personnel will instruct the parent(s)/caregiver(s) on the completion of the 
eCOA eDiary. The eCOA eDiary should be returned to the study site at the Day 14 visit (or 
PT2). 
On Day 1, the ReSVinet Scoring System assessment should be completed before administration 
of the first dose of study drug. Subsequently the eCOA eDiary should be completed predose QD 
each day through Day 14 and at approximately the same time each day ±2 hours. The palatability 
question should be completed as soon as possible after each dose of study drug is administered. 
The eCOA eDiary will automatically record the date and time of the eCOA assessments. Entries 
should be recorded by the caregiver at approximately the same time each day. Whenever 
possible, the same parent/caregiver should complete the eCOA eDiary and should be the primary 
caregiver of the child who has sufficient opportunity to notice or observe the signs and 
symptoms being evaluated in the eCOA eDiary. Study site personnel will review the completion 
of the parent/caregiver eCOA on a regular basis to ensure that the eCOA eDiary is completed 
correctly and on schedule to avoid missing or incorrect data. If a caregiver is unable to use the 
eDiary, a paper diary may be used. 




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should have echocardiograms. Urinalysis will only be conducted in subjects who are either toilet 
trained and able to provide a specimen or are already catheterized or fitted with a urine collection 
bag. 
The subject’s estimated creatinine clearance will be calculated using the subject’s serum 
creatinine (Crserum) value, height, and the appropriate equation (Schwartz & Work, 2009): 
Glomerular filtration rate (mL/min per 1.73 m2) = 0.413 * height/Crserum 
A Laboratory Manual will be provided to the site detailing sample collection, and the kit 
contents, supply reordering process, sample handling, storage and shipping for samples 
processed at the central laboratory. 
Age-appropriate routine standard of care measures to reduce stress and pain, which may be 
associated with protocol-required procedures (e.g., venipuncture), are encouraged.




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8.12.1. 
Respiratory Syncytial Virus Rapid Diagnostic Test 
After the subject’s caregiver reviews and signs the ICF, subjects will undergo a screen for RSV 
using an approved diagnostic assay performed locally. If an RSV diagnostic test is performed as 
part of standard of care before screening, that test result may be used in determining study 
eligibility if the test was performed within 72 hours before the ICF is signed. 
Subjects who have symptom onset, defined as the estimated onset of the first sign of respiratory 
infection or worsening of pre-existing respiratory signs and which does not exceed 7 days for 
Part 1 or 5 days for Part 2 before the signing of the consent by their caregiver and whose swab 
sample tests positive for RSV at Screening (or previously, see following text) will undergo 
further screening procedures to determine study eligibility. Results will be recorded in the source 
documents. 
8.12.2. 
Confirmatory Respiratory Pathogen Testing 
Following randomization on Day 1, a nasal swab sample collected before taking the first dose of 
EDP-938 or placebo will be tested for other respiratory pathogens. This testing will be performed 
to identify other co-pathogens that may include adenovirus, coronaviruses including 
SARS-CoV-2, human metapneumovirus, human rhinovirus/enterovirus, influenza, parainfluenza 
virus, Chlamydophila pneumoniae, and/or Mycoplasma pneumoniae, which may impact the 
course of a subject’s illness. 
8.12.3. 
Respiratory Syncytial Virus Viral Load Quantification 
The RSV viral load will be measured in nasal swabs by infectious virus quantitative culture and
RT-qPCR assay. 
8.12.4. 
Respiratory Syncytial Virus Subgroup/Genotype Determination 
A nasal swab sample at Baseline (Day 1) will be analyzed to determine the subgroup (A or B) 
and genotype of RSV. 
8.12.5. 
Viral Resistance 
Nasal swab sample(s) may be analyzed for monitoring potential viral resistance. Resistance 
monitoring, if performed, will be conducted by population and/or deep sequencing of the RSV 
genes to assess the emergence of resistance-associated variants. Phenotypic analysis may also be 
performed to determine the susceptibility of the resistance variants to EDP-938. 


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8.13.
Pharmacokinetic Samples
Subjects will have blood (plasma) samples collected at the following time points for PK analysis: 
Hospitalized Subjects 
 Visit 1: 3 hours postdose; 
Visit 2: predose; 
Visit 5: predose.  
Non-hospitalized Subjects
Visit 1: 3 hours postdose; 
Visit 3: predose; 
Visit 5: predose. 
The predose samples should be collected at approximately the same time as the nasal swab 
sample(s). For the postdose sample collected on Day 1, a window of ±30 minutes for the 
sampling time is acceptable. Actual date and time of PK sample collection will be recorded in 
the eCRF. In addition, the site should record the date and time of last dose taken before the PK 
sample collection. It is important that the date and time of each of PK blood sample are 
accurately recorded in the source documents. 
The method of sampling for PK blood draws is at the discretion of the Investigator. Samples 
taken via peripherally inserted central catheter line, indwelling catheter access, individual 
peripheral phlebotomies, or an IV line (or comparable means of access) are preferred, however, 
in instances where samples are unable to be obtained from a second line, alternative methods 
(capillary blood sampling via heel sticks or finger sticks) are allowed. 
Blood samples will be collected and processed to measure plasma concentrations of EDP-938 
and its metabolites according to the procedures provided and/or approved by Enanta 
Pharmaceuticals, Inc. Additional details will be provided in the Laboratory Manual. 
EDP-938 and its metabolites
 in human 
plasma will be quantified by high-performance liquid chromatography with tandem mass 
spectrometric detection. The method will be fully validated by assessment of precision, accuracy, 
sensitivity, and specificity of EDP-938 and its major metabolites by the laboratory selected by 
Enanta Pharmaceuticals, Inc. 
Pharmacokinetic samples may be stored and used for future metabolite and/or further evaluation 
of the bioanalytical method. These data will be used for internal exploratory purposes and will 
not be included in the clinical study report. 
8.14. 
Exploratory Biomarker Sample Collection 
Residual nasal swab and PK sample volume will be stored and may be used for biomarker 
research, if warranted. This exploratory testing may include measures of host proteins and viral 
markers other than those previously described in the protocol. These samples will not be used for 
human genomic testing. The samples will be stored for up to 1 year after the finalization of the 
clinical study report. 


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Refer to the Laboratory Manual for further details for sample collection, processing, and storage. 
9.
SAFETY MONITORING AND REPORTING
9.1.
Definitions
9.1.1. 
Pretreatment Events 
A pretreatment event is any event that meets the criteria for an AE/SAE and occurs after the 
subject signs the ICF but before receiving the first administration of study drug. 
9.1.2. 
Adverse Events 
An AE is any event, side effect, or untoward medical occurrence in a subject enrolled in a 
clinical study whether or not it is considered to have a causal relationship to the study drug. An 
AE can therefore be any unfavorable and unintended sign, symptom, laboratory finding outside 
of normal range with associated clinical symptoms or suspected latent clinical symptoms in the 
opinion of the Investigator, including those requiring therapeutic intervention, physical 
examination finding, or disease temporally associated with the use of the study drug, whether or 
not the event is considered related to the study drug. 
The occurrence of AEs should be sought by nondirective questioning of the subject at each study 
site visit during the study. AEs also may be detected when they are volunteered by the subject 
during or between study site visits or through physical examination, laboratory test, or other 
assessments. 
Planned hospital admissions or surgical procedures for an illness or disease that existed before 
the subject was enrolled in the study are not to be considered AEs unless the condition 
deteriorated in an unexpected manner during the study (e.g., surgery was performed earlier than 
planned). 
9.1.3. 
Serious Adverse Events 
An SAE is any untoward medical occurrence at any dose that: 
Results in death: This includes deaths that appear to be completely unrelated to study
drug (e.g., a car accident);
Is a life-threatening event: An event that places the subject at immediate 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 prolonged hospitalization of an existing
hospitalization, unless hospitalization is for:
o
Routine treatment or monitoring of the studied indication;
o
RSV disease progression;
o
Elective or preplanned treatment for a pre-existing condition that is unrelated
to the indication under study and has not worsened since signing the ICF;


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o Treatment on an emergency outpatient basis for an event not fulfilling any of 
the definitions of an SAE given above and not resulting in hospital admission; 
o Social reasons and respite care in the absence of any deterioration in the 
subject’s general condition. 
 Results in permanent or prolonged (at least 28 days in duration) disability or 
incapacity 
 Is a congenital anomaly or birth defect in the offspring of a study subject 
 Medically important event: An event that may not be immediately life-threatening, or 
result in death or hospitalization, or require intervention to prevent one of the 
outcomes listed above but is considered medically significant for other reasons. An 
opportunistic or otherwise unusual infection for the Investigator’s practice, such as 
tuberculosis, will be considered medically significant. 
The term severe is used to describe the intensity of a specific event (as in mild, moderate, or 
severe); the event itself, however, may be of minor medical significance (such as severe 
headache). This is not the same as serious, which is based on outcome of the event, as described 
above. Seriousness, not intensity, serves as a guide for defining regulatory reporting obligations. 
9.2. 
Documenting and Reporting of Adverse Events (Including Serious 
Adverse Events) 
AEs will be evaluated and documented using the grading scales contained in the National Cancer 
Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. 
9.2.1. 
Documenting and Reporting Adverse Events
All AEs reported from the time of informed consent to the EOS Visit for each subject will be 
recorded in the subject’s source documents. For subjects who do not receive study drug (i.e., 
screen failures), AEs will only be recorded in the source documents. For subjects enrolled into 
the study (i.e., randomized), all AEs will be recorded in the subject’s AE eCRF and the SAE 
Form (if applicable). The site should record all AEs regardless of the intensity, seriousness, or 
relationship to study drug. 
AEs (serious and nonserious) will be graded in accordance with the NCI-CTCAE scale as 
follows: 
 Mild (Grade 1): asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated; 
 Moderate (Grade 2): minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living; 
 Severe (Grade 3): severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care activities of daily living; 
 Life-threatening (Grade 4): life-threatening consequences; urgent intervention 
indicated; 


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Death (Grade 5): death related to the AE. 
Any recurrence of an AE with similar causality to study drug will be reported as recurrence or 
exacerbation of the initial event, and not as a new event. Whenever possible, AEs will be 
reported as a specific diagnosis or syndrome (e.g., flu syndrome) rather than as individual signs 
or symptoms. If no specific diagnosis or syndrome is identified, AEs should be reported as 
separate and individual events. 
An AE includes the following: 
 Progression or exacerbation of the subject’s underlying disease. Clinical sequelae that 
result from disease progression, such as pleural effusion or small bowel obstruction, 
are reportable as AEs; 
 Pre-existing event that increases in frequency or intensity; 
 Condition detected or diagnosed during the study period, even though it may have 
been present, in retrospect, before the first dose of study drug; 
 Laboratory abnormalities outside of normal limits with associated clinical symptoms 
or suspected latent clinical symptoms in the opinion of the Investigator, including 
those requiring therapeutic intervention; 
 An overdose of the study drug without any signs or symptoms will be considered an 
AE. A calculated dose that exceeds its correct dose by 10% or more and is 
administered to the subject will be considered an overdose and documented as an AE. 
The following events will not be identified as AEs in this study: 
 Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, etc); 
however, the condition (the “triggering event”) that leads to the procedure may be an 
AE; 
 Pre-existing conditions present or detected before the first dose of study drug that do 
not worsen. 
9.2.2.
Assigning Attribution of Adverse Events
The Investigator must attempt to determine the cause of each event. Every effort will be made by 
the Investigator to assess the relationship of each AE to study drug. To ensure consistency of 
AE/SAE causality assessments, the Investigator should apply the following guidelines: 
 Related: There is an association between the event and the administration of study 
drug, a plausible mechanism for the event to be related to the study drug and causes 
other than the study drug has been ruled out, and/or the event reappeared on re-
exposure to the study drug; 
 Possibly related: There is an association between the event and the administration of 
the study drug and there is a plausible mechanism for the event to be related to study 
drug, but there may also be alternative etiology, such as characteristics of the 
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Unlikely related: The event is unlikely to be related to the study drug and likely to be 
related to factors other than study drug; 
 Not related: The event is related to an etiology other than the study drug (the 
alternative etiology must be documented in the study subject’s medical record). 
9.2.3. 
Classifying Action Taken With Study Drug 
In the case of an AE, the actions that can be taken with study drug are defined in Table 4. 
Table 4: 
Options for Action Taken With Study Drug 
Classification  
Definition  
Dose Not Changed 
Study drug dose not changed in response to the adverse event. 
Drug Interrupted 
Study drug administration interrupted in response to an adverse event. 
Drug Withdrawn 
Study drug administration permanently discontinued in response to an adverse 
event. 
Not Applicable 
Action taken regarding study drug administration does not apply. “Not applicable” 
should be used in circumstances when no opportunity to decide whether to 
continue, interrupt, or withdraw treatment was possible such as when the 
investigational treatment had been completed before the adverse event began.  
9.2.4. 
Classifying Adverse Event Outcome 
For every AE/SAE, the possible outcomes of the event and the definition of the outcome are 
shown in Table 5. One outcome must be entered into the appropriate field on the AE and (if 
appropriate) SAE Form for each event as discussed in the corresponding instructions. 
Table 5:  
Classification and Definition of Adverse Event Outcomes 
Classification  
Definition  
Recovered/Resolved
Resolution of an adverse event with no residual signs or symptoms. 
Recovered/Resolved with 
Sequelae 
Resolution of an adverse event with residual signs or symptom. 
Is Recovering/Is Resolving 
Incomplete improvement to date but adverse event continues to 
improve/resolve and complete resolution is expected over time. 
Not Recovered/Not Resolved 
Either incomplete improvement or no improvement of an adverse 
event, such that it remains ongoing. 
Fatal 
Outcome of an adverse event is death. “Fatal” should be used when 
death is at least possibly related to the AE. 
Unknown 
Outcome of an adverse event is not known (e.g., a subject lost to 
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10.
SUBJECT SAFETY MANAGEMENT/STUDY STOPPING RULES 
10.1.
Study Stopping Rules
If any of the following events occur, dosing will be placed on hold pending a full review of all 
available clinical safety data and discussion with the investigators and the SSC. 
Two or more subjects receiving study drug experience a similar Grade 3 study 
drug-related AE, including a confirmed treatment-emergent Grade 3 laboratory 
abnormality; 
 One or more subjects receiving study drug experience a study drug-related SAE; 
 One or more subjects receiving study drug experience Grade 4 or higher AE or a 
confirmed treatment-emergent laboratory abnormality regardless of causality 
attribution to study drug. 
10.2. 
Individual Subject Discontinuation Criteria 
If one (or more) of the following changes occur, the subject should discontinue study drug and 
should be followed until resolution (return to baseline) or stabilization of change (to be agreed 
upon with the Sponsor). The Sponsor should be informed even if the change occurs outside of 
the treatment period (but before the end of the study). 
 A TEAE which is considered clinically significant (e.g., meeting Grades 3 [severe] or 
4 [potentially life-threatening] criteria) and is attributed to study drug and/or which is 
thought to preclude further safe administration of study drug; 
 An AE/SAE, drug reaction, or complication, whether related or not to study drug, 
which precludes continuation of treatment with study drug; 
 The Principal Investigator’s opinion that it is not in the subject’s best interest to 
continue study participation. 
10.3.
Cohort Discontinuation Criteria
Further enrollment within a cohort or enrollment to subsequent cohorts will be discontinued once 
it has been established that safety risk(s) such as the following occur: 
 If any unacceptable toxicity (as determined by the Sponsor Medical Monitor) occurs; 
 If the SSC considers an event or multiple events to represent an unacceptable risk to 
the health and well-being of subjects at that or higher dose levels. 
10.4. 
Site or Study Discontinuation 
10.4.1. 
Study Discontinuation 
The Sponsor has the right to terminate this study at any time. Reasons for terminating the study 
may include, but are not limited to, the following: 
 The incidence or severity of AEs in this study indicates a potential health hazard to 
subjects; 


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Subject enrollment is unsatisfactory; 
Data recording is inaccurate or incomplete; 
Investigator does not adhere to the protocol or applicable regulatory guidelines in 
conducting the study; 
A decision from the IRB/EC or regulatory authority to terminate the study. 
If the study is suspended or terminated for safety reasons, Enanta Pharmaceuticals, Inc. will 
promptly notify the investigators and will also inform the regulatory authorities of the suspension 
or termination of the study and the reasons for the action. The Investigator is responsible for 
promptly informing the IRB/EC and providing the reasons for the suspension or termination of 
the study. 
10.4.2. 
Site Termination 
A single site may warrant termination under the following conditions: 
 Failure of the site to enroll subjects into the study at an acceptable rate; 
 Failure of the site to comply with pertinent governmental regulations as appropriate; 
 Submission of knowingly false information from the research facility to the Sponsor, 
Clinical Monitor, or governmental authority; 
 Failure to adhere to the protocol requirements; 
 Data recording is inaccurate or incomplete; 
 Investigator does not adhere to the protocol or applicable regulatory guidelines in 
conducting the study. 
10.4.3. 
Study Termination Procedures 
If the study is terminated by Enanta Pharmaceuticals, Inc. for one of the reasons listed 
previously, or upon completion of the study, the following activities must be conducted by the 
Study Monitor and/or site staff: 
 Return of all study data to Enanta Pharmaceuticals, Inc. or designee; 
 Respond to and complete all requests for data clarifications; 
 Accountability and final disposition of used and unused study drug; 
 Review of site records for completeness; 
 Shipment of all applicable biological samples (including PK samples) to the 
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11.4.
Subject Disposition and Demographic Data
The number of subjects screened, randomized, and in the safety, PK, clinical, and antiviral 
activity populations, will be summarized using frequencies and percentages. The denominator 
for the calculation of percentages will be from the number of subjects randomized. 
The following categories will also be summarized for subject disposition: 
 Completed study drug per the protocol; 
 Discontinued study drug early and the reason for discontinuation; 
 Completed the study; 
Discontinued from the study early and the reason for discontinuation. 
Subject demographics will be summarized by treatment group for all subjects in the safety 
population. Appropriate baseline characteristics will be included in addition to demographic 
characteristics. No statistical testing will be performed. 
11.5. 
Safety Analyses 
Statistical methods for the safety analyses will be primarily descriptive in nature. The safety 
population will be used for the respective analyses. Parts 1 and 2 may be pooled for AEs and 
laboratory analyses where appropriate. 
11.5.1. 
Treatment Compliance 
Listing of the randomization schedule and study drug dispensed with lot number will be 
provided. Treatment compliance for each subject will be calculated as the number of subjects 
receiving the amount of drug taken divided by the amount prescribed multiplied by 100. 
11.5.2. 
Study Drug Exposure 
Drug exposure will be summarized.  
11.5.3. 
Adverse Events 
AEs will be summarized by the Medical Dictionary for Regulatory Activities system organ class 
and preferred term by treatment group. All subjects in the safety population will be included in 
the summaries. Treatment-emergent AEs are defined as reported AEs that first occurred or 
worsened during the post-Baseline phase compared to Baseline (Day 1, Predose). The maximum 
severity at Baseline will be used as baseline severity. If the maximum severity during 
post-Baseline is greater than the maximum baseline severity, then the event is considered 
treatment-emergent. No statistical testing will be performed. 
Summaries of AEs will include the following at a minimum:
 An overall summary of AEs with a line for each of the categories provided below: 
o TEAEs; 
o Related TEAEs; 
o Maximum severity TEAE; 


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o TEAEs by severity; 
o TEAEs leading to study drug discontinuation; 
o AEs leading to death; 
o SAEs; 
o Related treatment-emergent SAEs. 
11.5.4. 
Clinical Laboratory Data 
Laboratory assessments will be reported as mean change from Baseline across scheduled visits, 
and as the incidence rate of shift change from Baseline. Shift from Baseline tables will be 
generated for each treatment group for selected analytes. Laboratory shifts will be displayed as 
treatment-emergent abnormal, high, or low results. The following details the summary types 
where LLN = lower limit of normal and ULN = upper limit of normal. 
For categorical tests: Treatment-emergent abnormal is defined as a change from normal at 
Baseline to abnormal at any post-Baseline visit. 
For continuous tests: 
 Treatment-emergent high is defined as a change from a result less than or equal to the 
high limit at Baseline to a value greater than the high limit at any time post-Baseline. 
Results will be reported according to any value greater than the high limit, any value 
greater than 2× ULN and 3× ULN. 
 Treatment-emergent low is defined as a change from a result greater than or equal to 
the low limit at Baseline to a value less than the low limit at any time post-Baseline. 
Results will be reported to any value less than the lower limit, any value less than 
2× LLN and 3× LLN. 
11.5.5. 
Vital Sign Measurements 
The incidence rate of subjects with treatment-emergent vital sign changes at any post-Baseline 
visit will be summarized. Specific criteria for the classification of treatment-emergent will be 
documented in the SAP. Vital sign observed, change, and percentage change will be summarized 
by treatment over visits. Oxygen saturation (SpO2) measurements will be summarized by visit 
and treatment. 
11.5.6. 
Electrocardiograms 
Screening and subsequent ECG data will be provided in data listings. 
11.5.7.
Concomitant Medications and Therapies
Concomitant medications will be coded according to the latest World Health Organization 
(WHO) Anatomical Therapeutic Chemical (ATC) Classification level 4 and WHO preferred 
term. Summaries will be provided by ATC Level 4 and preferred term. Subjects in the safety 
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12.
STUDY ADMINISTRATION
12.1.
Ethical Considerations
12.1.1.
Ethical Conduct of the Study
The study will be conducted in compliance with this protocol, principles of E6 Good Clinical 
Practice: Consolidated Guidance (ICH-GCP), Declaration of Helsinki, and all applicable local 
laws and regulations governing clinical studies. 
12.1.2. 
Ethical Review 
It is the Investigator’s responsibility to ensure that this protocol is reviewed and approved by an 
appropriate IRB/EC that conforms to the regulations set forth in FDA 21 Code of Federal 
Regulations Part 56 and other national, country, and regional regulations as applicable. The 
Investigator must also submit the ICF, any other written documentation provided to the subject’s 
caregiver, and all advertisements that may be used for study-specific recruitment to the IRB/EC 
for review and approval before commencing study-specific assessments. A copy of the ICF 
approved by the IRB/EC must be forwarded to Enanta Pharmaceuticals, Inc. for regulatory 
purposes. 
Changes that significantly affect the safety of the subjects, the scope of the investigation, or the 
scientific quality of the study (i.e., efficacy assessments) will require IRB/EC notification before 
implementation, except where the modification is necessary to eliminate an apparent immediate 
hazard to human subjects. 
12.1.3. 
Written Informed Consent 
The Investigator or designee must explain to each subject’s caregiver the purpose and nature of 
the study, the study procedures, the possible adverse effects, and all other elements of consent as 
defined in 21 Code of Federal Regulations Part 50, and other applicable national and local 
regulations governing informed consent. 
The subject’s caregiver must provide a signed and dated ICF before enrollment into this study. If 
RSV infection is not confirmed, caregivers may be asked to sign a RSV Diagnostic Test ICF 
allowing a rapid antigen RSV test to be performed. Signed consent forms must remain in each 
subject’s study file and be available for verification by study monitors at any time. In accordance 
with individual local and national subject privacy regulations, the Investigator or designee must 
explain to each subject’s caregiver before Screening that for the evaluation of study results, the 
subject’s protected health information obtained during the study may be shared with Enanta 
Pharmaceuticals, Inc. and its designees, regulatory agencies, and IRBs/ECs. As the study 
Sponsor, Enanta Pharmaceuticals, Inc. will not use the subject’s protected health information or 
disclose it to a third party without applicable subject’s caregiver authorization. It is the 
Investigator’s or designee’s responsibility to obtain written permission to use protected health 
information from each subject’s caregiver. If a subject’s caregiver withdraws permission to use 
protected health information, it is the Investigator’s responsibility to obtain the withdrawal 
request in writing from the subject’s caregiver and to ensure that no further data will be collected 
from the subject. Any data collected on the subject before withdrawal will be used in the analysis 
of study results. 


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12.1.4. 
Investigator Compliance 
No modifications to the protocol should be made without the approval of both the Investigator 
and Enanta Pharmaceuticals, Inc.
If it is necessary to amend the protocol during the study, it is the responsibility of the Investigator 
to ensure that IRB/EC approval is obtained before implementation of the amended procedures. It 
is also the responsibility of the Investigator to provide the IRB/EC with any SAE or 
Investigational New Drug safety reports.
If circumstances require an immediate departure from protocol procedures, the Investigator will 
contact Enanta Pharmaceuticals, Inc. and/or its designee to discuss the planned course of action. 
Contact should be made before the implementation of any changes when possible. Any 
departures from protocol must be fully documented in the source documents and reported to 
Enanta Pharmaceuticals, Inc. or its designee and the IRB/EC as required. 
12.2. 
Data Collection 
Initial subject screening data such as informed consent, age, inclusion/exclusion criteria met/not 
met, RSV symptoms, and limited demographics, will be collected in the IRT system. Data from 
screen failures will be collected in IRT only. 
Study data for each randomized subject will be entered into an eCRF by site staff. It is the 
Investigator’s responsibility to ensure the accuracy, completeness, clarity, and timeliness of the 
data reported in the subject’s eCRF. Source documentation supporting the eCRF data should 
indicate the subject’s participation in the study and should document the dates and details of 
study procedures, AEs, other observations, and subject status. The Investigator or designated 
representative should complete the eCRF as soon as possible after information is collected. An 
explanation should be provided for all missing data. 
After the subject has completed the study, the Investigator must review and sign the signature 
page of the eCRF indicating that he or she has reviewed the completed eCRF and pertinent 
clinical data for that subject and that, to the best of his or her knowledge, all data recorded in the 
eCRF accurately reflects the subject’s clinical performance in the study. 
Sites are responsible for abiding by the rules and regulations of their IRB/EC for recording and 
reporting protocol deviations. All deviations reported to the IRB/EC must be reported to Enanta 
Pharmaceuticals, Inc. and/or their designee and recorded as deviations as appropriate. 
12.3. 
Study Monitoring 
Representatives of Enanta Pharmaceuticals, Inc. or its designee will monitor this study until 
completion. Monitoring will be conducted through both on-site and remote visits with the
Investigator and site staff as well as any appropriate communications by mail, fax, email, or 
telephone. The purpose of monitoring is to ensure compliance with the protocol and the quality 
and integrity of the data. The Study Monitor will ensure that the investigation is conducted 
according to protocol and regulatory requirements, and as described in the Study Monitoring 
Plan.
Every effort will be made to maintain the anonymity and confidentiality of all subjects during 
this clinical study. However, because of the experimental nature of this treatment, the 


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Investigator agrees to allow the IRB/EC, representatives of Enanta Pharmaceuticals, Inc., its 
designated agent, and authorized employees of the appropriate regulatory agencies to inspect the 
facilities used in this study and, for purposes of verification, allow direct access to the hospital or 
study site records of all subjects enrolled into this study. A statement to this effect will be 
included in the ICF authorizing the use of protected health information. 
12.4.
Quality Assurance
At its discretion, Enanta Pharmaceuticals, Inc. or its designee may conduct a quality assurance 
audit of this study. If such an audit occurs, the Investigator will give the auditor direct access to 
all relevant documents and will allocate his or her time and the time of his or her site staff to the 
auditor as required. In addition, regulatory agencies may conduct an inspection of this study. If 
such an inspection occurs, the Investigator will notify the Sponsor and 
 and will allow the 
inspector direct access to all source documents, eCRFs, and other study documentation for 
source data check and/or on-site audit inspection.
12.5. 
Retention of Records 
The site will retain a copy of all study records in a safe, secure, and accessible location for at 
least 2 years after notification by Enanta Pharmaceuticals, Inc. that the investigations of 
EDP-938 have been discontinued or for 2 years following marketing approval of the drug, after 
which time, Enanta Pharmaceuticals, Inc. will be contacted for instructions on the disposition of 
study materials. Study records will contain all of the appropriate documents as detailed in 
Section 8.0 of the ICH-GCP E6. 
12.6. 
Information Disclosure 
12.6.1. 
Confidentiality 
Subject names will remain confidential and will not be supplied to Enanta Pharmaceuticals, Inc. 
or its designee. If the subject name appears on any other document collected (eg, unit discharge 
summary), it must be obliterated before the document is transmitted to Enanta Pharmaceuticals, 
Inc. or its designee. All study findings will be stored in electronic databases. Demographic data 
collected in eCRF are listed in Section 8.2. As indicated in the ICF, subject’s caregiver will give 
permission for representatives of the Sponsor, regulatory authorities, and the IRB/EC to inspect 
their medical records to verify the information collected. They will be informed that all personal 
information made available for inspection will be handled in the strictest confidence and in 
accordance with local data protection/privacy laws. 
Individual subject medical information obtained during this study is confidential and its 
disclosure to third parties other than those mentioned in the preceding paragraph is prohibited. 
Medical information obtained during this study may be provided to the subject’s personal 
physician or other appropriate medical personnel when required in connection with the subject’s 
continued health and welfare and with the subject’s caregiver’s prior knowledge and permission. 


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12.6.2. 
Publication Policy 
It is the intention of Enanta Pharmaceuticals, Inc. to publish the results of this study in their 
entirety within a reasonable period of time following conclusion of the study. The Sponsor will 
determine when and where data will be first disclosed. 
All information generated from this study is the proprietary property of Enanta Pharmaceuticals, 
Inc. Enanta Pharmaceuticals, Inc. reserves the right, among other things, to: 
 Modify or amend study material to ensure that no confidential or proprietary 
information is disclosed; 
 Ensure that the reported data are factually correct; 
 Utilize the information generated from or as a result of this study in any manner it 
deems appropriate, including but not limited to regulatory submissions, annual 
reports, and other scientific or business affairs of the company; 
 Modify the publication or disclosure or delay it a sufficient time to allow Enanta 
Pharmaceuticals, Inc.to seek patent protection of any invention contained therein. 
 


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13.
REFERENCES
Brint, M. E., Hughes, J. M., Shah, A., Miller, C. R., Harrison, L. G., Meals, E. A., . . . DeVincenzo, J. P. 
(2017). Prolonged viral replication and longitudinal viral dynamic differences among respiratory 
syncytial virus infected infants. Pediatr Res, 82(5), 872-880. doi:10.1038/pr.2017.173 
CDC. (2009). Clinical Growth Charts.  
Chemaly, R. F., Aitken, S. L., Wolfe, C. R., Jain, R., & Boeckh, M. J. (2016). Aerosolized ribavirin: the 
most expensive drug for pneumonia. Transpl Infect Dis, 18(4), 634-636. doi:10.1111/tid.12551 
EMA. Guideline on the clinical evaluation of medicinal products indicated for the prophylaxis or 
treatment of respiratory syncytial virus (RSV) disease. 18 October 2018. In 
EMA/CHMP/257022/2017. 
Falsey, A. R. (2005). Respiratory syncytial virus infection in elderly and high-risk adults. Exp Lung Res, 
31 Suppl 1, 77.  
FDA. Respiratory Syncytial Virus Infection: Developing Antiviral Drugs for Prophylaxis and 
Treatment. Draft Guidance October 2017. In. 
Hall, C. B., Weinberg, G. A., Iwane, M. K., Blumkin, A. K., Edwards, K. M., Staat, M. A., . . . Szilagyi, 
P. (2009). The burden of respiratory syncytial virus infection in young children. N Engl J Med, 
360(6), 588-598. doi:10.1056/NEJMoa0804877 
Guideline: Nonclinical Safety Testing in Support of Development of Paediatric Medicines S11,  (2018). 
Martinón-Torres, F., Rusch, S., Huntjens, D., Remmerie, B., Vingerhoets, J., McFadyen, K., . . . 
Stevens, M. (2020). Pharmacokinetics, safety, and antiviral effects of multiple doses of the 
respiratory syncytial virus (RSV) fusion protein inhibitor, JNJ-53718678, in infants hospitalized 
with RSV infection: A randomized Phase 1b study. Clin Infect Dis, 71(10), e594-e603. 
doi:10.1093/cid/ciaa283 
Nair, H., Nokes, D. J., Gessner, B. D., Dherani, M., Madhi, S. A., Singleton, R. J., . . . Campbell, H. 
(2010). Global burden of acute lower respiratory infections due to respiratory syncytial virus in 
young children: a systematic review and meta-analysis. Lancet, 375(9725), 1545-1555. 
doi:10.1016/S0140-6736(10)60206-1 
Piedimonte, G., & Perez, M. K. (2014). Respiratory syncytial virus infection and bronchiolitis. Pediatr 
Rev, 35(12), 519-530. doi:10.1542/pir.35-12-519 
Randolph, A. G., & Wang, E. E. (1996). Ribavirin for respiratory syncytial virus lower respiratory tract 
infection. A systematic overview. Arch Pediatr Adolesc Med, 150(9), 942-947. 
doi:10.1001/archpedi.1996.02170340056011 
Schwartz, G. J., & Work, D. F. (2009). Measurement and estimation of GFR in children and 
adolescents. Clin J Am Soc Nephrol, 4(11), 1832-1843. doi:10.2215/CJN.01640309 
Shi, T., McAllister, D. A., O'Brien, K. L., Simoes, E. A. F., Madhi, S. A., Gessner, B. D., . . . Network, 
R. S. V. G. E. (2017). Global, regional, and national disease burden estimates of acute lower 
respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic 
review and modelling study. Lancet, 390(10098), 946-958. doi:10.1016/S0140-6736(17)30938-8 


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Shook, B. C., & Lin, K. (2017). Recent Advances in Developing Antiviral Therapies for Respiratory 
Syncytial Virus. Top Curr Chem (Cham), 375(2), 40. doi:10.1007/s41061-017-0129-4 
Toback, S., Lewis, S., DeMuro, C., Chien, J., Schwartz, R., Wolynn, T., . . . Williams, V. (2015). 
Psychometric evaluation of a novel observer-reported outcome tool for the assessment of 
respiratory syncytial virus infection symptoms in infants. Paper presented at the IDWeek 2015, 
San Diego, CA.  
Ujiie, M., Tsuzuki, S., Nakamoto, T., & Iwamoto, N. (2021). Resurgence of respiratory syncytial virus 
infections during COVID-19 pandemic, Tokyo, Japan. Emerg Infect Dis, 27(11), 2969-2970. 
doi:10.3201/eid2711.211565 
 


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14.
APPENDICES 


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APPENDIX 1. SCHEDULE OF ASSESSMENTS 
Study Period
Screening1,2 Treatment
Follow-Up
For non-hospitalized subjects, V2 and V4 assessments will be done at 
home. (X) is for V2 and V4 assessments for hospitalized subjects.
Visit
Screening V1 V2 V3 V4
V5
PT1
PT2
PT33
Day 
Day-1 to 
Day 1 
1 
2 
3
(±1)4 4
5 (±1)
EOT5 
9 
(±1) 
14 
(±2) 
28 (±4)
EOS5 Notes6; Protocol Section 
Screening/Administrative 
Study site visit 
X 
X 
 
X 
 
X 
X 
X 
X 
 
RSV diagnostic test 
and informed consent 
form
X 
 
 
 
 
 
 
 
 
If RSV infection has not been confirmed using an approved diagnostic 
assay, caregivers may be asked to sign a RSV Diagnostic Test ICF to 
allow a rapid antigen RSV test to be performed.
Informed consent 
form 
X 
 
 
 
 
 
 
 
Section 12.1.3
Demographics 
X 
 
 
 
 
 
 
 
Section 8.2 
Medical history 
X 
 
 
 
 
 
 
 
Section 8.2 
Inclusion/Exclusion  
X 
 
 
 
 
 
 
 
Section 3 
Body weight 
X 
 
 
 
X 
 
 
 
Section 8.7 
Body length/head 
circumference
X 
Section 8.7
Study Drug Administration
Subjects will be randomized and administered the first dose of study drug within 24 hours of signing the ICF.
Randomization
X 
Subjects will be randomized 2:1 in Part 1 and 4:1 in Part 2 to 
EDP 938:placebo. Parent/Guardian ReSVinet clinical scoring system 
Day 1 assessment, clinical evaluation, and vital signs must be done 
between randomization and dosing. Section 5.6
Dispense/
Administer study drug
X X 
X 
X 
X 
Study drug should be administered QD from D1 through D5 at
approximately the same time (±1 hr) every day. Section 5.7
Study drug 
accountability 
 
X 
 
X 
 
X* 
 
 
on D3 and D5 for non-hospitalized patients. If 
V5 is conducted before D5 due to the visit window, caregivers should be 
contacted as soon as possible after D5 dosing to collect the date and time 
of dosing. Section 5.4
Clinical Efficacy Evaluations
Professional ReSVinet 
clinical scoring 
system
X 
X 
X 
X 
X 
The visit assessment will be completed by the Site Investigator (or 
designee). The ReSVinet D1 assessment must be predose. Section 8.10.1


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Study Period
Screening1,2 Treatment
Follow-Up
For non-hospitalized subjects, V2 and V4 assessments will be done at 
home. (X) is for V2 and V4 assessments for hospitalized subjects.
Visit
Screening V1 V2 V3 V4
V5
PT1
PT2
PT33
Day
Day-1 to 
Day 1
1
2
3
(±1)4 4
5 (±1)
EOT5
9 
(±1)
14 
(±2)
28 (±4)
EOS5 Notes6; Protocol Section
Parent/Guardian 
ReSVinet clinical 
scoring system and 
palatability question 
 
Once daily from predose on D1 through 
D14 
 
 
Caregiver(s) should complete the Parent/Guardian ReSVinet clinical 
scoring system using the eCOA handheld eDiary for both hospitalized 
and non-hospitalized subjects. The ReSVinet D1 assessment must be 
predose, and subsequent assessments should be completed predose at the 
same time daily (±2 hr) for 14 days. The palatability assessment should 
be completed after each dose of study drug is administered. If a caregiver 
is unable to use the eDiary, a paper diary may be used. Section 8.10.2
Parent/Guardian 
clinical 
scoring system) 
 
Twice daily on D1 through D14 
 
Caregiver(s) should complete the Parent/Guardian 
clinical 
scoring system on paper for both hospitalized and non-hospitalized 
subjects. The D1 assessment must be completed predose, and subsequent 
assessments should be completed twice daily, approximately every 
12 hours, for 14 days. If D1 assessment is completed in the afternoon, 
only one assessment is expected for that day. 
 will be 
completed in a subset of subjects. Section 8.10.3
Clinical Safety Evaluations
Vital sign 
measurements 
(including SpO2) 
X 
X 
 
X 
 
X 
X 
X 
 
If Screening and V1 occur on the same calendar day, vital signs 
measurements do not need to be repeated and the Screening 
measurements will be used as baseline values. If Screening and V1 occur 
on different calendar days, V1 measurements should be taken pre-dose 
as baseline values. Starting on D1, vital signs should be performed QD
on marked study site visit days. Section 8.4
Physical examination
X 
X 
X 
X 
X 
Full PE at Screening. Subsequent PEs done at discretion of Investigator 
will be targeted to new signs and symptoms, including specific 
assessments of changes from previous status. Section 8.6
ECG
X 
X 
12-lead ECG strongly preferred but where not possible, 6-lead ECG may 
be performed. If blood sampling and/or a nasal swab are scheduled for 
the same timepoint as ECG recording, those assessments should be done 
after the ECG. Section 8.5
Procedures
Residual samples from blood and/or nasal swab volume may be used for 
exploratory biomarker analyses. Section 8.14
Nasal swab
X 
X 
X 
X 
X 
Swab samples should be taken at approx. same time before study drug 
administration. One swab will be collected at each visit. Section 8.12


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Study Period
Screening1,2 Treatment
Follow-Up
For non-hospitalized subjects, V2 and V4 assessments will be done at 
home. (X) is for V2 and V4 assessments for hospitalized subjects.
Visit
Screening V1 V2 V3 V4
V5
PT1
PT2
PT33
Day
Day-1 to 
Day 1
1
2
3
(±1)4 4
5 (±1)
EOT5
9 
(±1)
14 
(±2)
28 (±4)
EOS5 Notes6; Protocol Section
Blood sampling for 
clinical laboratory 
tests 
X 
X*
 
X 
 
X 
 
 
 
Clinical laboratory tests include biochemistry, hematology, and cardiac 
biomarkers. All clinical laboratory tests that will be evaluated in the 
study are specified in Table 3. Evaluations will be conducted by local 
laboratories. 
*For subjects who have screening and randomization separated by more 
than 24 hours, blood sampling for clinical laboratory tests should be 
done predose on Day 1 for baseline values. This blood sampling does not 
need to be done for subjects who have randomization within 24 hours 
after screening because the screening clinical laboratory test results will 
be used as the baseline values. Section 8.11 
Urinalysis 
X 
 
 
 
 
X 
 
 
 
Urine will be collected only from subjects who are either toilet trained 
and able to provide a specimen or are already catheterized or fitted with 
a urine collection bag, Section 8.11
Blood sampling for 
PK 
 
X (X) X 
 
X 
 
 
 
Hospitalized subjects
Visit 1: 3 hours postdose
 Visit 2: predose 
 Visit 5: predose  
Non-hospitalized subjects
 Visit 1: 3 hours postdose 
 Visit 3: predose 
 Visit 5: predose 
All subjects: Predose samples should be collected at approximately the 
same time as the nasal swab sample(s). For the postdose collection on 
Day 1, a window of ±30 minutes for the sampling time is acceptable. The 
time and date of PK sample collection will be recorded in source and 
eCRF. Section 8.13


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Study Period
Screening1,2 Treatment
Follow-Up
For non-hospitalized subjects, V2 and V4 assessments will be done at 
home. (X) is for V2 and V4 assessments for hospitalized subjects.
Visit
Screening V1 V2 V3 V4
V5
PT1
PT2
PT33
Day
Day-1 to 
Day 1
1
2
3
(±1)4 4
5 (±1)
EOT5
9 
(±1)
14 
(±2)
28 (±4)
EOS5 Notes6; Protocol Section
Ongoing Subject Review
Concomitant 
treatment 
X 
X (X) X (X)
X 
X 
X 
X 
Section 8.3
Healthcare resource 
utilization 
 
X (X) X (X)
X 
X 
X 
X 
Evaluate level of care (e.g., ICU, translational care unit, ward floor, 
home), duration of hospitalization if hospitalized, incidence of MAARI, 
requirement for and duration of oxygen supplementation/noninvasive 
mechanical ventilation support and/or invasive mechanical ventilation 
support and requirement for hydration and feeding by IV 
catheter/nasogastric tube. Section 8.9
Adverse events
X 
X (X)
X (X)
X 
X 
X 
X 
If V5 is conducted before D5 due to the visit window, caregivers should 
be contacted as soon as possible after D5 dosing to assess AEs, 
concomitant treatments, and healthcare utilization. Section 8.8 
Abbreviations: approx. = approximately, D = day; ECG = electrocardiogram; eCOA = electronic clinical outcome assessment; eCRF = electronic case report 
form; EOS = end-of-study; MAARI = medically attended acute respiratory infection; EOT = End-of-Treatment; ICF = informed consent form; ICU = intensive 
care unit; PE = physical examination; PK = pharmacokinetics; PT = post-treatment visit; QD = once daily; RSV = respiratory syncytial virus; SpO2 = peripheral 
capillary oxygen saturation; V = visit
 
1 Procedures performed as part of standard of care within 72 hours before the informed consent is signed may be used in determining study eligibility and/or as
baseline values.  
2 Screening should be completed as soon as possible to ensure that subjects will be randomized and administered the first dose of study drug within 24 hours of 
signing the ICF. 
3 PT3 assessment may be conducted as a telephone call. 
4 If Visit 3 occurs on Day 4 due to the visit window, Visit 5 should occur on Day 5 or Day 6.
5 Subjects who discontinue treatment early (before completing 5 days of dosing) should return to the study site within 24 hours following the last dose of study 
drug for an EOT visit. Follow-up visits will be scheduled 4 days (PT1, Day 9), 9 days (PT2, Day 14), and 23 days (PT3), Day 28 [EOS]) after the last dose of 
study drug was administered. Assessments should be performed as indicated, respectively for the Day 9 (PT1), Day 14 (PT2), and Day 28 (EOS/PT3) visit. 
Subjects who discontinue the study early (before Day 28) should return to the study site within 24 hours and no more than 48 hours later to complete the EOS 
procedures. 
6 If multiple assessments are scheduled for the same timepoint, it is recommended that noninvasive procedures being done before more invasive procedures, e.g., 
first complete questionnaires (parent/guardian and clinician questionnaires could be concurrent), then ECG, then vital signs/SpO2, then nasal swab and finally 
blood draw. 










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The facial expression suggested that he/she did not like the taste; 
Cried after tasting it; 
Would not open mouth or turned head away to avoid it; 
Spit out or coughed it out; 
Gagged or vomited (within 2 minutes of swallowing medicine). 


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SAP_001.pdf: 










 
Statistical Analysis Plan, 
 
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TABLE OF CONTENTS 
 
LIST OF ABBREVIATIONS .................................................................................................................... 4 
 
TABLE OF CONTENTS ........................................................................................................................... 6 
 
1.          INTRODUCTION.......................................................................................................................... 8 
 
2.          STUDY DESIGN............................................................................................................................ 9 
 
2.1         DOSE AND TREATMENT SCHEDULE....................................................................................................9 
2.2         TREATMENT ASSIGNMENT/RANDOMIZATION AND BLINDING ..........................................................11 
 
3.          OBJECTIVES AND ENDPOINTS ............................................................................................ 12 
 
3.1         OBJECTIVES .....................................................................................................................................12 
3.1.1      Part 1: Primary and Secondary Objectives ......................................................................12 
3.1.2      Part 2 and Pooled Population: Primary and Secondary Objectives ................................12 
 
3.2         ENDPOINTS ......................................................................................................................................13 
3.2.1      Part 1: Primary and Secondary Endpoints.......................................................................13 
3.2.2      Part 2 and Pooled Population: Primary and Secondary Endpoints .................................13 
 
 
4.          STATISTICAL CONSIDERATIONS ....................................................................................... 16 
 
4.1         GENERAL CONSIDERATIONS ............................................................................................................16 
4.2         SAMPLE SIZE CONSIDERATIONS.......................................................................................................17 
4.3         HANDLING OF DROPOUTS OR MISSING DATA ..................................................................................17 
4.3.1      Missing Dates ...................................................................................................................17 
4.4         ANALYSIS POPULATIONS .................................................................................................................19 
4.4.1      Full or Partial Dose..........................................................................................................20 
4.5         ANALYSIS VISIT WINDOWS .............................................................................................................20 
4.6         SUBJECT DISPOSITION......................................................................................................................22 
4.7         PROTOCOL DEVIATIONS...................................................................................................................22 
4.8         DEMOGRAPHIC AND BASELINE CHARACTERISTICS ..........................................................................23 
4.9         MEDICAL HISTORY ..........................................................................................................................23 
4.10       PRIOR AND CONCOMITANT MEDICATIONS.......................................................................................23 
4.11       EXTENT OF EXPOSURE .....................................................................................................................23 
4.12       TREATMENT COMPLIANCE...............................................................................................................24 
4.13       EFFICACY ANALYSES.......................................................................................................................24 
4.13.1    Primary Efficacy Analysis Part 1 .....................................................................................24 
4.13.2    Secondary Efficacy Analysis Part 1 ..................................................................................24 
4.13.3    Primary Efficacy Analysis Part 2 .....................................................................................26


 
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4.13.4    Secondary Efficacy Analysis Part 2 ..................................................................................26 
4.13.5    Efficacy Analysis for Pooled Population ..........................................................................29 
4.13.6    Sensitivity Analysis ...........................................................................................................31 
 
4.14       SAFETY ANALYSES ..........................................................................................................................37 
4.14.1    Adverse Events..................................................................................................................37 
4.14.2    Clinical Laboratory Data .................................................................................................38 
4.14.3    Vital Sign Measurements ..................................................................................................39 
4.14.4    Electrocardiograms ..........................................................................................................39 
4.14.5    Physical Examinations......................................................................................................39 
4.15       PHARMACOKINETIC ANALYSES .......................................................................................................39 
4.15.1    PK Analysis.......................................................................................................................40 
4.15.2    PKPD (Pharmacokinetic-Pharmacodynamic)..................................................................40 
4.16       RESPIRATORY SYNCYTIAL VIRUS SUBGROUP/GENOTYPE DETERMINATION ....................................41 
4.17       INTERIM ANALYSES .........................................................................................................................41 
 
 
 
6.          REFERENCES............................................................................................................................. 43 
 
7.          APPENDICES .............................................................................................................................. 44 
 
7.1         SCHEDULE OF ASSESSMENTS ...........................................................................................................44 
7.2         PROFESSIONAL RESVINET CLINICAL SCORING SYSTEM ..................................................................49 
7.3         PARENT/GUARDIAN RESVINET CLINICAL SCORING SYSTEM AND PALATABILITY 
QUESTION ........................................................................................................................................51 
 
7.4         RESPIRATORY OBSERVABLE REPORTED OUTCOME -PEDIATRIC (RESOLVE-P) .............................53 
7.5         CAREGIVER GLOBAL IMPRESSION OF SEVERITY (CAGI-S) ..............................................................55 
7.6         CAREGIVER GLOBAL IMPRESSION OF CHANGE (CAGI-C)................................................................55


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Statistical Analysis Plan, 
 
EDP 938-201 
Enanta Pharmaceuticals, Inc. 
CONFIDENTIAL 
 
 
 
 
1.   INTRODUCTION 
 
EDP-938 (also known as EPC-3938, EPS-3938, and EP-023938) is a novel, orally administered, non- 
fusion replication inhibitor of respiratory syncytial virus (RSV) that is being developed as a potential 
treatment for RSV infection. This Phase 2 study, EDP 938-201, is a randomized double-blind, placebo- 
controlled, 2-part study to evaluate the safety, tolerability, pharmacokinetics (PK), clinical outcome, and 
antiviral activity of orally administered EDP-938 regimens in hospitalized or non-hospitalized infants 
and children aged 28 days to 36 months infected with RSV. 
 
The preparation of this Statistical Analysis Plan (SAP) is based on the International Conference on 
Harmonization (ICH) E9 guidelines [1] and study protocol Version 18.0 dated 09 July 2024. The SAP 
outlines the statistical analyses of the efficacy and safety data to support the clinical study report (CSR) 
and will be finalized prior to the database lock. Any changes to the SAP after finalization will be 
documented in the CSR. The table of contents and shells for the tables, figures, and listings (TFLs) will 
be produced in a separate document.


 
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2.   STUDY DESIGN 
 
This is a Phase 2, dose-ranging, randomized, double-blind, placebo-controlled, 2-part study to evaluate 
the safety, tolerability, PK, clinical outcome, and antiviral activity of orally administered EDP-938 
regimens in infants and children aged 28 days to 36 months with RSV-associated respiratory tract 
infection, who are hospitalized or non-hospitalized. 
 
Each part of the study has 3 periods: Screening, Treatment, and Follow-up. For each subject, the 
duration of study will be approximately 29 days (Table 1). Study site visits and assessments are detailed 
in the Schedule of Assessments (SoA; Appendix 7.1). 
 
The end of the study will be defined as the last visit of the last subject enrolled. 
 
Table 1 
 
Study Period 
Duration 
Screening (Day -1 to Day 1) 
Up to 24 hours 
(note: some assessments done as part of 
standard of care can be used as screening 
assessments if they are done within 72 
hours) 
Treatment (Day 1 to Day 5) 
5 days 
Follow-up (Day 6 to Day 28) 
23 days 
Approximate total duration of participation 
29 days maximum 
 
 
2.1    Dose and Treatment Schedule 
 
Approximately 90 subjects are planned to be enrolled. Oral doses of EDP-938 or placebo will be 
administered once daily (QD). Initial doses are planned to be 
 in each age group: 
 
Group 1 (Ages ≥6 to ≤36 months) 
Group 2 (Ages ≥28 days to <6 months) 
Varying age-appropriate volumes of a fixed concentration (
) of EDP-938 or placebo will be 
administered to achieve the intended dose in each pediatric patient. 
 
Subjects who meet all of the inclusion criteria and none of the exclusion criteria will be eligible to enter 
the study and will be randomized 2:1 (Part 1) or 4:1 (Part 2) to EDP-938:placebo. 
 
The study design is shown in Figure 1. 
 
Part 1 
 
Enrollment will begin simultaneously with Cohort 1 Age Group 1 and Cohort 1 Age Group 2. When at 
least 9 subjects have been randomized in Cohort 1, for each age group, the Study Steering Committee




 
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** SSC will review available blinded data when at least 6 subjects have been randomized in Cohort 2 for each age group. 
 
 
 
2.2    Treatment Assignment/Randomization and Blinding 
 
The study will be double-blinded, meaning that the subjects and their caregivers, investigators, and site 
staff will be blinded to treatment assignment until the completion of the study. 
 
Subjects will be randomized to a treatment group using an Interactive Web Response System. 
Subjects will be randomized to the initial EDP-938 or placebo treatment group as shown below: 
Part 1, Cohort 1, Age Group 1 and 2 (randomized 2:1) 
•  
of EDP-938 orally QD for 5 days (8 subjects); 
•  
 placebo orally QD for 5 days (4 subjects). 
 
The dose for Part 1 Cohort 2 for each age group will be determined based on review of Part 1 Cohort 1 
data. 
Part 2, Age Group 1 and 2 (randomized 4:1) 
 
EDP-938 orally QD for 5 days: dose to be determined 
•  Oral EDP-938 QD for 5 days: dose to be determined (16 subjects); 
•  Oral placebo QD for 5 days: dose to be determined (4 subjects).


 
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3.   OBJECTIVES AND ENDPOINTS 
 
 
3.1        Objectives 
 
The primary efficacy objective is to evaluate the antiviral activity of EDP-938 in the pooled population 
(subjects from Part 1 and Part 2 together). 
 
 
3.1.1    Part 1: Primary and Secondary Objectives 
 
Primary Objectives 
 
•  To evaluate the PK of EDP-938 
 
•  To assess the safety and tolerability of EDP-938 
 
Secondary Objective 
 
•  To evaluate the antiviral activity of EDP-938 
 
 
3.1.2    Part 2 and Pooled Population: Primary and Secondary Objectives 
 
Primary Objective 
 
•  To evaluate the antiviral activity of EDP-938 
 
Secondary Objectives 
 
•  To assess the safety and tolerability of EDP-938 
 
•  To evaluate the PK of EDP-938 
 
•  To evaluate additional antiviral activity measures of EDP-938 
 
•  To evaluate clinical outcomes of EDP-938 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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3.2        Endpoints 
 
The primary efficacy endpoint is the daily change in RSV shedding in nasal swab samples determined 
using RT-qPCR from Baseline through the treatment phase in the pooled population (subjects from Part 
1 and Part 2 together). 
 
 
3.2.1    Part 1: Primary and Secondary Endpoints 
 
Primary Endpoints 
 
• PK parameters of EDP-938 including area under the curve (AUC) and predose 
concentrations 
 
• Safety and tolerability of EDP-938 compared to placebo as assessed by, but not limited to, 
adverse events (AEs), vital signs, and clinical laboratory results 
 
Secondary Endpoints 
 
• AUC for RSV RNA viral load measured in nasal swab samples by quantitative reverse 
transcription polymerase chain reaction (RT-qPCR) 
 
•  Daily change in RSV shedding in nasal swab samples determined using RT-qPCR from 
Baseline through the treatment phase 
 
• Proportion of subjects with RSV RNA viral load below the limit of detection (LOD) in 
subjects receiving EDP-938 compared to placebo 
 
•  Time to RSV RNA viral load being undetectable 
 
 
3.2.2    Part 2 and Pooled Population: Primary and Secondary Endpoints 
 
Primary Endpoint 
 
Daily change in RSV shedding in nasal swab samples determined using RT-qPCR from Baseline 
through the treatment phase. 
 
Secondary Endpoints 
 
• Safety and tolerability of EDP-938 compared to placebo as assessed by, but not limited to, 
AEs, vital signs, and clinical laboratory results;


 
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•  AUC for RSV RNA viral load measured in nasal swab samples by RT-qPCR; 
 
•  Proportion of subjects with RSV RNA viral load below the LOD in subjects receiving EDP- 
938 compared to placebo; 
 
•  Time to RSV RNA viral load being undetectable; 
 
•  PK parameters of EDP-938 including AUC and predose concentrations; 
 
•  Time to discharge for hospitalized subjects; 
 
• Time to use of oxygen for hospitalized subjects who are not receiving oxygen at the time 
they receive the first dose of study drug; 
 
• Proportion of hospitalized subjects requiring oxygen supplementation or have an increased 
oxygen requirement; 
 
•  Time to mechanical ventilation for hospitalized subjects; 
 
•  Proportion of hospitalized subjects requiring mechanical ventilation; 
 
•  Deaths among hospitalized subjects; 
 
•  Time to hospitalization for initial outpatients who are subsequently hospitalized; 
 
•  Proportion of outpatients who are subsequently hospitalized or died; 
 
•  Time to resolution of symptoms for outpatients who are not hospitalized. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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4.   STATISTICAL CONSIDERATIONS 
 
 
4.1    General Considerations 
 
All statistical procedures will be completed using SAS version 9.4 or higher. 
 
Continuous variables will be summarized using descriptive statistics (i.e., n, mean, standard deviation 
(SD), median, 25th percentile, 75th percentile, minimum and maximum values). The mean, median and 
the percentiles will be rounded to one decimal place beyond the precision of the values being 
summarized; the SD will be rounded to 2 additional decimal places beyond this precision and the 
minimum and maximum values will be displayed in the same precision. If n=0, then display n and leave 
all other statistics blank. If n=1, display “N/A” for SD. 
 
Categorical variables will be summarized using frequency counts and percentages. The denominator for 
the percentages will be the number of subjects in the appropriate age group and treatment group within 
the analysis set of interest, unless otherwise specified. The denominator will be displayed when needed 
and the percentage will be rounded to one decimal place. If the frequency is 0, the percentage will not be 
displayed. A row denoted “Missing” will be included in count tabulations where specified on the shells 
to account for dropouts and missing values where applicable. 
 
All subject data, including those derived, will be presented in individual subject data listings. Unless 
otherwise stated, unscheduled visit results will be included in date/time chronological order, within 
subject listings. All listings will be sorted by study part, treatment group, subject number, date/time and 
visit. The treatment group (randomized) as well as subject’s sex, race, age and age group will be stated 
on each listing. Unless otherwise stated, data listings will be based on all subjects randomized. 
 
Baseline, unless otherwise specified, will be defined as the last non-missing assessment collected before 
or on the date of first dose of study drug. For analyses of nasal swab data and analyses of RSV-related 
signs and symptoms, if assessments before the first dose of study drug are not available, a post treatment 
assessment collected no more than 60 minutes after the first dose of study drug will be used as the 
baseline value. 
 
Efficacy summary tables and figures will be presented by randomized treatment group and age group for 
Part 1 and Part 2 separately and will be labelled as follows. Additionally, efficacy summary tables and 
figures for efficacy endpoints for the pooled population will be summarized using pooled data (subjects 
from Parts 1 and 2) as appropriate. Other summaries including disposition, analysis populations, 
demographics, and baseline data will be displayed by treatment group, age group for Parts 1 and 2 
separately. Parts 1 and 2 will also be pooled for these summaries. 
 
Age Group: 
 
•  “≥6 to ≤36 months” 
 
o “≥6 to <12 months” 
 
o “≥12 to ≤36 months” 
•  “≥28 days to <6 months” 
 
o “≥28 days to <3 months”


 
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Treatment: 
o “≥3 to <6 months”
 
•  “EDP-938” 
 
•  “Placebo” 
 
Study Part: 
 
•  “Part 1” 
 
•  “Part 2” 
 
•  “Parts 1 and 2” 
 
Safety summary tables and figures will be summarized separately for Part 1 and Part 2 as well as pooled 
Parts 1 and 2 data by the actual treatment group. In addition, pooled Parts 1 and 2 data will be 
summarized by age group. 
 
For the reporting of this study both CDISC SDTM (SDTM Implementation Guide version 3.3 or later) 
and ADaM (ADaM Implementation Guide version 1.1 or later) standards will be applied. A subject will 
be considered to have completed the study after his/her attendance at the last planned study visit (Day 28 
± 4 day), or the last unscheduled visit (if any occur), as applicable. For each subject his or her study 
completion status (Yes/No) is recorded on the End of Study CRF. 
 
 
4.2    Sample Size Considerations 
 
No formal hypothesis testing is planned for Parts 1 or 2 of this study. Therefore, no formal sample size 
justification is provided. Approximately 90 subjects will participate in this study: 12 subjects are 
planned in each cohort of the age groups in Part 1 (24 subjects in each age group). In Part 2, 20 subjects 
are planned in each of the age groups. Additional subjects may be added based on SSC 
recommendations. 
 
 
4.3    Handling of Dropouts or Missing Data 
 
In general, missing data will not be imputed and all summary statistics will be reported based upon 
observed data. In particular, incomplete dates for adverse events and concomitant medication use 
(Section 4.3.1) are presented. For any other data which has partial dates, which are required for use in 
time related calculations, these dates will be completed using a suitably conservative approach. Dates 
will be shown in subject listings as they have been recorded. 
 
 
4.3.1    Missing Dates 
 
Imputation rules for missing or partial AE start/end dates are defined as: 
 
•  Only Day of AE start date is missing: 
 
o If the AE start year and month are the same as that for the first dose date, then:


 
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▪ If the full (or partial) AE end date is NOT before the first dose date or AE end 
date is missing, then impute the AE start day as the day of first dose date. 
 
o Otherwise, impute the AE start day as 1. 
•  If Day and Month of AE start date are missing: 
 
o If AE start year = first dose year, then: 
 
▪   If the full (or partial) AE end date is NOT before the first dose date or AE end 
date is missing, then impute the AE start Month and Day as the Month and Day of 
first dose date. 
 
▪   If the full (or partial) AE end date is before the first dose date, then impute the AE 
start Month and Day as the Month and Day of AE end date after imputation. 
 
o If AE start date > first dose year, impute the AE start MONTH as January and the DAY 
as 1. 
 
o If AE start year < first dose year, then: 
▪ If the full (or partial) AE end date is NOT before the 31st of December of AE start 
year, or AE end date is missing, then impute the AE start MONTH as December 
and the DAY as 31. 
 
▪ Otherwise, if the full (or partial) AE end date is before the 31st of December and 
AE start year, then impute the AE start Month and Day as the Month and Day of 
AE end date after imputation. 
 
•  If Year of AE start date is missing: 
 
o If the year of AE start is missing or AE start date is completely missing, then query site 
and leave as missing. 
 
•  For missing and partial adverse event end dates, imputation will be performed as follows: 
 
o If only the day of the month is missing, the last day of the month will be used to replace 
the missing day. 
 
o If the day and month are missing or a date is completely missing, it will be considered as 
missing. 
 
Imputation rules for missing or partial medication start/stop dates are defined below: 
 
•  If only Day of CM start date is missing: 
 
o If the CM start year and month are the same as that for the first dose date, then: 
 
▪ If the full (or partial) CM end date is NOT before the first dose date or CM end 
date is missing, then impute the CM start day as the day of first dose date. 
 
o Otherwise, impute the CM start day as 1. 
•  If Day and Month of CM start date are missing: 
 
o If CM start year = first dose year, then:


 
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▪ If the full (or partial) CM end date is NOT before the first dose date or CM end 
date is missing, then impute the CM start Month and Day as the Month and Day 
of first dose date. 
 
▪   If the full (or partial) CM end date is before the first dose date, then impute the 
CM start Month and Day as the Month and Day of CM end date after imputation. 
 
o If CM start date > first dose year, impute the CM start MONTH as January and the DAY 
as 1. 
 
o If CM start year < first dose year, then: 
▪ If the full (or partial) CM end date is NOT before the 31st of December of CM 
start year, or CM end date is missing, then impute the CM start MONTH as 
December and the DAY as 31. 
 
▪ Otherwise, if the full (or partial) CM end date is before the 31st of December and 
CM start year, then impute the CM start Month and Day as the Month and Day of 
CM end date after imputation. 
 
•  If Year of CM start date is missing: 
 
o If the year of CM start is missing or CM start date is completely missing, then query site 
and leave as missing. 
 
•  For missing and partial CM end dates, imputation will be performed as follows: 
 
o If only the day of the month is missing, the last day of the month will be used to replace 
the missing day. 
 
o If the day and month are missing or a date is completely missing, it will be considered as 
missing. 
 
 
4.4    Analysis Populations 
 
• Safety (SAF) Population: All subjects who receive any dose (including partial doses) of any 
study drug; 
 
• PK Population: All subjects who receive one full dose of study drug and have blood samples 
with quantifiable plasma levels to allow estimation of PK parameters; 
 
•  Efficacy Population: All subjects who receive one full dose of study drug. 
 
• Modified Intention to Treat 3 (mITT-3) population: All subjects who receive one full dose of 
study drug and have onset of the first sign of respiratory infection within 3 days before 
randomization. 
 
• Modified Intention to Treat 5 (mITT-5) population: All subjects who receive one full dose of 
study drug and have onset of the first sign of respiratory infection within 5 days before 
randomization.


 
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4.4.1    Full or Partial Dose 
 
A full or partial dose is determined by clinical pharmacology and medical teams. If all treated subjects 
receive at least one full dose of study drug, then the Efficacy Population and the Safety Population will 
be the same. 
 
A full dose of study drug is defined as a dose taken on a given day as confirmed by Dose Admin Form 
with the following criteria from the palatability questionnaire: 
 
• A “Yes” answer to “Successfully swallowed the medicine without vomiting within 2 minutes of 
swallowing” 
 
AND 
 
•  Absence of a “Yes” answer to “Spit out or coughed it out” 
 
AND 
 
•  Absence of a “Yes” answer to Gagged or vomited (within 2 minutes of swallowing medicine) 
 
 
 
A partial dose of study drug is defined as a dose taken on a given day with the following criteria from 
the palatability questionnaire: 
 
• A “No” answer to “Successfully swallowed the medicine without vomiting within 2 minutes of 
swallowing” 
 
OR 
 
•  A “Yes” answer to “Spit it out or coughed it out” 
 
OR 
 
•  A “Yes” answer to “Gagged or vomited (within 2 minutes of swallowing medicine” 
 
 
4.5    Analysis Visit Windows 
 
Study day is defined as the number of days from the date of first dose. Day 1 is the date of first dose. For 
assessments or events after the first dose date, study day is calculated as the date of interest minus first 
dose date plus 1 day. For assessments/events before the first dose date, study day is calculated as the 
date of interest minus first dose date. 
 
Analysis visit windows are described in the tables below. 
 
For vital signs, safety laboratory tests, Professional ReSVinet, and RSV RNA quantitation of viral load: 
 
Analysis 
Visit # 
Analysis Visit Label 
Target 
Day 
Derivation 
Visit Window 
1 
Day 1 
1 
Based on nominal visit 
3 
Day 3 
3 
Based on date of assessment 
2 to 4* 


 
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5 
Day 5 
5 
Based on date of assessment 
4 to 6* 
9 
Day 9 
9 
Based on date of assessment 
8 to 11 
14 
Day 14 
14 
Based on date of assessment 
12 to 16 
 
*The visit on Day 4 should be mapped to analysis Visit #3 unless there is an earlier analysis Visit #3. 
 
For eCOA eDiary (Parent/Guardian ReSVinet, Palatability Questionnaire), RESOLVE-P: 
 
Analysis 
Visit # 
Analysis Visit Label 
Target 
Day 
Timepoint* 
Assessment 
Derivation 
1 
Day 1 
1 
AM 
Study day =1 
1 
Day 1 
1 
PM 
Study day =1 
2 
Day 2 
2 
AM 
Study day =2 
2 
Day 2 
2 
PM 
Study day =2 
3 
Day 3 
3 
AM 
Study day =3 
3 
Day 3 
3 
PM 
Study day =3 
4 
Day 4 
4 
AM 
Study day =4 
4 
Day 4 
4 
PM 
Study day =4 
5 
Day 5 
5 
AM 
Study day =5 
5 
Day 5 
5 
PM 
Study day =5 
6 
Day 6 
6 
AM 
Study day =6 
6 
Day 6 
6 
PM 
Study day =6 
7 
Day 7 
7 
AM 
Study day =7 
7 
Day 7 
7 
PM 
Study day =7 
8 
Day 8 
8 
AM 
Study day =8 
8 
Day 8 
8 
PM 
Study day =8 
9 
Day 9 
9 
AM 
Study day =9 
9 
Day 9 
9 
PM 
Study day =9 
10 
Day 10 
10 
AM 
Study day =10 
10 
Day 10 
10 
PM 
Study day =10 
11 
Day 11 
11 
AM 
Study day =11 


 
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11 
Day 11 
11 
PM 
Study day =11 
12 
Day 12 
12 
AM 
Study day =12 
12 
Day 12 
12 
PM 
Study day =12 
13 
Day 13 
13 
AM 
Study day =13 
13 
Day 13 
13 
PM 
Study day =13 
14 
Day 14 
14 
AM 
Study day =14 
14 
Day 14 
14 
PM 
Study day =14 
* The ReSVinet assessments will be completed predose QD each day, by subjects’ parent(s)/guardian(s), through Day 
14 and at approximately the same time each day ±2 hours. The palatability question will be completed as soon as 
possible after each dose of study drug is administered. The RESOLVE-P assessments will be completed twice daily 
(AM and PM), approximately every 12 hours for 14 days. The D1 assessment must be completed pre-dose. Only one 
D1 assessment is expected if completed in the afternoon. 
 
 
4.6    Subject Disposition 
 
All subjects who provided informed consent will be included in a summary of subject accountability. 
The number and percentage of randomized, treated, randomized and not treated, as well as the number 
and percentage of subjects in each analysis population will be summarized using all subjects 
randomized. The denominator for the calculation of percentages will be from the number of subjects 
randomized. 
 
The following categories will also be summarized by all randomized subjects: 
 
•  Completed study drug per protocol 
 
•  Discontinued study drug early and the primary reason for discontinuation 
 
•  Completed the study per protocol 
 
•  Discontinued from the study early and the primary reason for discontinuation 
 
The number of subjects excluded from analysis sets and reasons for exclusion will be summarized. 
A separate listing will be also provided for subject disposition. 
 
4.7    Protocol Deviations 
 
All protocol deviations (PDs) will be entered and tracked in
 Clinical Trial Management System 
(CTMS) by the study steam throughout the conduct of the study in accordance with 
 Protocol 
Deviation Guidance document. Protocol deviations that adversely affect the risk/benefit ratio of the study, 
the rights, safety, or welfare of the participants or others, or the integrity of the study must be reported to 
the medical monitoring team. 
 
The PDs will be reviewed prior to closure of the database and unblinding the study to ensure all significant 
deviations (classified as “Important” in the PD Guidance document) are captured and categorised.


 
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Significant protocol deviations will be summarized. Separate listings will also be provided for 
significant and non-significant protocol deviations. Summaries will be conducted on all subjects who 
were randomized. 
 
 
4.8    Demographic and Baseline Characteristics 
 
No statistical testing will be performed for the comparison between treatment groups on demographics 
and baseline characteristics. Subject demographics and baseline characteristics will be summarized 
descriptively using the Safety Population. 
 
Age, Gestational Age, Body Length, Head Circumference, and Weight, RSV viral load measured by 
RT-qPCR (log10 copies/mL), professional and parent/guardian ReSVinet total scores, RESOLVE-P 
domain and composite scores, CaGI-S total score collected at baseline, and duration of RSV symptom 
onset (from the first sign of respiratory infection to randomization) will be summarized. 
 
Qualitative variables such as sex, ethnicity, race, RSV type (RSV-A, RSV-B), and pathogen will be 
summarized using descriptive statistics. A by-subject listing will be provided. 
 
 
4.9    Medical History 
 
Medical history will be coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 
26.1 or higher. The number and percentage of subjects with relevant medical history will be summarized 
by system organ class (SOC) and preferred term (PT). The percentage will be calculated based on the 
Safety Population. A by-subject listing will be provided. 
 
 
4.10  Prior and Concomitant Medications 
 
Medications used in this study will be coded using the latest available version of the World Health 
Organization Drug Dictionary Global B3 September 2020 or higher. Prior medications are defined as 
those medications with a start date prior to the first dose of study drug. Concomitant medications are 
defined as those medications with a start date on or after the first dose of study drug. A medication 
which started prior to dosing and continued after dosing will also be considered as concomitant 
medications. Concomitant medications will be summarized descriptively using frequency tables by 
Anatomical Therapeutic Chemical (ATC) level 2 (therapeutic main group) and ATC level 4 
(chemical/therapeutic subgroup) and PT using the Safety Population. A by-subject listing will be 
provided for prior and concomitant medications. Details for imputing missing or partial start and/or stop 
dates of medication are described in Section 4.3.1. 
 
 
4.11  Extent of Exposure 
 
Duration of study drug (in days) will be calculated as: last dose date – first dose date + 1 day, regardless 
of study drug interruption. Study drug exposure will be summarized using the Safety Population and the 
Efficacy Population. Only the summaries of Safety Population will be provided if the Safety Population 
and the Efficacy Population are identical.


 
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4.12  Treatment Compliance 
 
Study drug compliance based on the number of syringes taken will be calculated as: 100 x (total number 
of days dosed)/ (number of days of treatment planned per protocol) except for subjects who discontinued 
study during the treatment period. The number of days dosed (for subjects who were lost to follow-up) 
or the number of days since first dose to the day of drug refusal (for subjects who refused to take study 
drug) is used as the denominator. Study drug compliance will be summarized using the Safety 
Population and the Efficacy Population. Only the summaries of Safety Population will be provided if the 
Safety Population and the Efficacy Population are identical. 
 
 
4.13  Efficacy Analyses 
 
All efficacy analyses will be based on the Efficacy Population. Selected efficacy endpoints will also be 
based on the mITT-3 and mITT-5 populations. Part 1 data and Part 2 data will be summarized separately 
using descriptive statistics. In addition, all secondary efficacy endpoints in Part 2 as well as all 
exploratory endpoints will be summarized based on pooled data from both Parts 1 and 2. Inferential 
statistical analysis will be performed to these pooled analyses, as appropriate. 
 
 
4.13.1  Primary Efficacy Analysis Part 1 
 
Not applicable because the primary endpoint for this part of the study is the PK analysis (please refer to 
Section 4.15.1) 
 
 
4.13.2  Secondary Efficacy Analysis Part 1 
 
The following secondary endpoints will be analyzed descriptively using the Efficacy, mITT-3, mITT-5 
Populations. 
 
• AUC for RSV RNA viral load measured in nasal swab samples by quantitative reverse 
transcription polymerase chain reaction (RT-qPCR) 
 
RSV RNA viral load will be measured in nasal swab samples by RT-qPCR on Days 1, 3, 5, 9 
and 14. Viral load values reported as TD (Target Detected, but below LLOQ) will be set to the 
average of LOD (limit of detection) and LLOQ (lower limit of quantification). Viral load values 
reported as TND (Target Not Detected, below LOD) will be set to zero. Viral load data will be 
transformed using a log10 scale before analyses. In case of zero value, the log transformed value 
will be also set as zero. For the RT-qPCR assay used for detection and quantification of RSV A 
and RSV B, the LLOQ is 1000 copies/mL for RSV A and 250 copies/mL for RSV B; the LOD is 
620 copies/mL for RSV A and 80 copies/mL for RSV B. 
 
The RSV type of each subject will be decided at baseline based on the RT-qPCR test. The 
baseline RSV viral load result is from the nasopharyngeal swab sample taken after 
randomization and prior to first dose on Day 1. After the imputation of TD, TND, and log10 
transformation, if the baseline RSV A viral load is greater than RSV B viral load, the baseline


 
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RSV type is classified as RSV A. Further, if the baseline RSV B viral load is greater than RSV A 
viral load, the baseline RSV type is classified as RSV B. 
 
The RSV RNA viral load AUC will be calculated using the trapezoid rule [2]. The AUC will 
require at least 2 non-missing data points. Subjects with missing or undetectable RSV RNA viral 
load at baseline will be excluded from the analysis. The AUC will be calculated based on all 
available assessments collected on Days 1/Baseline, 3, 5, 9, and 14 and the actual date/time of 
each assessment will be used for the calculation. For the baseline viral load (Day 1), time is set 
as 0. For each assessment post first dose, the actual time in days is computed as difference 
between the date/time of the assessment and the date/time of the first dose. The AUC is also 
standardized for 14 days by multiplying 14/tlast where tlast is the actual time in days of the last 
available assessment. Additionally, the AUC from Day 1 through Day 3, the AUC from Day 1 
through Day 5, and the AUC from Day 1 through Day 9 will be also derived and standardized 
similarly as for AUC from Day 1 though Day 14. 
 
Descriptive statistics for RSV RNA viral load AUC will include, at a minimum, the number of 
non-missing measurements, mean, standard deviation, median, minimum, 25th percentile, 75th 
percentile, maximum, and 95% CI for the mean. 
 
• Daily change in RSV shedding in nasal swab samples determined using RT-qPCR from baseline 
through the treatment phase 
o RSV RNA viral load observed and change from baseline will be summarized by visit 
(Baseline, Days 3, 5, 9 and 14). The summary statistics will include, at a minimum, the 
number of non-missing measurements, mean, standard deviation, median, minimum, 25th 
percentile, 75th percentile, maximum, and 95% CI for the mean. 
 
Line graph of RSV RNA viral load will be produced: 
 
(1) Observed mean viral load ± 95% confidence interval by days (1, 3, 5, 9 and 14) 
for each treatment group and age group. 
 
•  Time to RSV RNA viral load being undetectable 
 
Time to RSV RNA viral load being undetectable (TND) will be analyzed using two approaches 
as defined below: 
 
o Time to RSV RNA viral load being undetectable (days) is defined as the time between 
the date of first dose to the first date during post-dose period of achieving RSV RNA 
viral load TND after which no further samples have detectable RSV RNA viral load. 
Subjects with baseline RSV viral load TND will be excluded from the analysis. 
 
o Time to confirmed undetectable RSV RNA viral load (days) is defined as the time 
between the date of first dose to the first of 2 consecutive post-baseline time points of 
achieving RSV RNA viral load TND. Subjects with baseline RSV viral load TND will be 
excluded from the analysis. 
 
• Proportion of subjects with RSV RNA viral load below the LOD in subjects receiving EDP-938 
compared to placebo


 
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o Frequency counts and percentages of subjects with RSV RNA viral load below the LOD 
will be summarized by Day 14. The respective 95% CIs will be reported using Clopper 
Pearson CI methods. 
 
 
4.13.3  Primary Efficacy Analysis Part 2 
 
• Daily change in RSV shedding in nasal swab samples determined using RT-qPCR from baseline 
through the treatment phase 
o RSV RNA viral load observed and change from baseline will be summarized 
descriptively by visit (Baseline, Days 3, 5, 9 and 14) using the efficacy, mIIT-3 and 
mITT-5 populations. The summary statistics will include, at a minimum, the number of 
non-missing measurements, mean, standard deviation, median, minimum, 25th percentile, 
75th percentile, maximum, and 95% CI for the mean. 
 
Line graph of RSV RNA viral load will be produced: 
 
(1) Observed mean viral load ± 95% confidence interval by Days (1, 3, 5, 9 and 14) 
for each treatment group and age group. 
 
 
4.13.4  Secondary Efficacy Analysis Part 2 
 
The following efficacy analyses will be summarized using the Efficacy, mITT-3, and mITT-5 
populations. 
 
• AUC for RSV RNA viral load measured in nasal swab samples by quantitative reverse 
transcription polymerase chain reaction (RT-qPCR) 
 
o The RSV RNA viral load AUC will be summarized as described in Section 4.13.2. 
• Proportion of subjects with RSV RNA viral load below the LOD in subjects receiving EDP-938 
compared to placebo 
 
o Frequency counts and percentages of subjects with RSV RNA viral load below LOD will 
be summarized by Day 14. The respective 95% CIs will be reported using Clopper 
Pearson CI methods. 
 
•  Time to RSV RNA viral load being undetectable 
 
Time to RSV RNA viral load being undetectable (TND) will be analyzed using two approaches 
as defined below: 
 
o Time to RSV RNA viral load being undetectable (days) is defined as the time between 
the date of first dose to the first date during the post-dose period of achieving viral load 
TND after which no further samples have detectable RSV RNA viral load. Subjects with 
baseline RSV viral load TND will be excluded from the analysis. 
 
o Time to confirmed undetectable RSV RNA viral load (days) is defined as the time 
between the date of first dose to the first 2 consecutive post-baseline time points of


 
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achieving RSV RNA viral load TND. Subjects with baseline RSV viral load TND will be 
excluded from the analysis. 
 
Frequency counts and percentages of subjects by end of study (Day 28 ±4), and their respective 95% CIs 
will be reported using Clopper Pearson CI methods for the following endpoints summarized using the 
Efficacy Population. 
 
• Proportion of hospitalized subjects requiring oxygen supplementation or have an increased 
oxygen requirement. 
 
o Subjects who are hospitalized at randomization and/or during study are included.  The 
proportion will be defined by the number of subjects who develop a new requirement for 
oxygen supplementation or new increase(s) in oxygen requirements after the first dose of 
study drug, based on the response of “yes” to the “is this an increase of oxygen 
supplementation compared to previous use?” question on the Oxygen Supplementation 
CRF. 
 
•  Proportion of hospitalized subjects requiring mechanical ventilation 
 
o Subjects who are hospitalized at randomization and/or during study are included. The 
proportion will be defined by the number of subjects who developed a new requirement 
for mechanical ventilation after the first dose of study drug.  Subjects on mechanical 
ventilation prior to the first dose of study drug are excluded from analysis. 
 
•  Deaths among hospitalized subjects 
 
o Subjects who are hospitalized at randomization and/or during study are included. 
 
•  Proportion of outpatients who are subsequently hospitalized or died 
 
o Subjects who are not hospitalized at randomization are included. 
 
•  Proportion of outpatients who died 
 
o Subjects who are not hospitalized at randomization are included. 
 
The following endpoints will be summarized using the Efficacy Population. The summary statistics will 
include, at a minimum, the number of non-missing measurements, mean, standard deviation, median, 
minimum, 25th percentile, 75th percentile, and maximum. 
 
•  Time to discharge for hospitalized subjects 
 
o Time to first hospital discharge for subjects who are hospitalized at randomization will be 
defined as the time between the first dose of study drug and the first date of discharge. 
For subjects with continuous hospitalization, the last date of discharge from the 
continuous hospitalization will be used. 
 
• Time to use of oxygen for hospitalized subjects who are not receiving oxygen at the time they 
receive the first dose of study drug 
 
o For subjects who are hospitalized at randomization, time to use of oxygen for 
hospitalized subjects not receiving oxygen at the time they receive the first dose, is


 
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defined as the time between the date/time of first dose of study drug to the first date/time 
of receiving oxygen. 
 
•  Duration of oxygen use for hospitalized subjects 
 
o This analysis will include subjects who are hospitalized at randomization and received 
oxygen supplementation at any time after the first dose of study drug. The duration of 
oxygen use (days) is defined as the sum of each duration of oxygen use (days) that 
occurred from the first dose of study drug to the end of study.  The duration of oxygen 
use for the initial hospitalization is calculated as date/time of the end of oxygen use – 
date/time of first dose of study drug. The duration of oxygen use for subsequent 
rehospitalization(s) is calculated as date/time of the end of oxygen use – date/time of the 
start of oxygen use for the rehospitalization. Missing start times will be imputed to 00:01. 
Missing end times will be imputed to 23:59. 
 
•  Time to mechanical ventilation for hospitalized subjects 
 
o This analysis will include subjects who are hospitalized at randomization and required 
mechanical ventilation at any time after the first dose of study drug. Subjects on 
mechanical ventilation before their first dose of study drug are excluded from analysis. 
Time to mechanical ventilation is defined as the date/time from the first dose of study 
drug to the first use of mechanical ventilation. 
 
•  Duration of mechanical ventilation for hospitalized subjects 
 
o This analysis includes subjects who are hospitalized at randomization and required 
mechanical ventilation at any time after the first dose of study drug.  The duration of 
mechanical ventilation (days) is defined as the sum of each duration of mechanical 
ventilation (days) that occurred from the first dose of study drug to the end of study.  The 
duration of mechanical ventilation for the initial hospitalization is calculated as date/time 
of the end of mechanical ventilation – date/time of first dose of study drug. The duration 
of mechanical ventilation for subsequent rehospitalization(s) is calculated as date/time of 
the end of mechanical ventilation – date/time of the start of mechanical ventilation. 
Missing start times will be imputed to 00:01.  Missing end times will be imputed to 
23:59. 
 
•  Time to hospitalization for initial outpatients who are subsequently hospitalized 
 
o Time to hospitalization for initial outpatients who are subsequently hospitalized will be 
calculated, defined as the time between the date/time of first dose to the first date of 
hospitalization. 
 
•  Time to resolution of symptoms for outpatients who are not hospitalized 
 
o Time to resolution of symptoms for outpatients at randomization who are not hospitalized 
during study, is defined as the time between the date/time of first dose to the first of 2 
consecutive time points where each of the seven symptoms assessed by the 
Parent/Caregiver ReSVinet clinical scoring is 0 or 1. If a subject meets the resolution


 
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definition (0 or 1 score for 2 consecutive timepoints) at baseline and Day 2, then this 
subject will be excluded from the analysis. 
 
 
4.13.5  Efficacy Analysis for Pooled Population 
 
The primary endpoint is the daily change in RSV shedding in nasal swab samples determined using RT- 
qPCR from baseline through the treatment phase in the pooled population (subjects from Parts 1 and 2 
together). 
 
All secondary efficacy endpoints described in Section 4.13.4, as well as all exploratory endpoints 
described in Section 4.13.7 are also the secondary and exploratory endpoints for the pooled population 
and will be analyzed with the pooled data from both Parts 1 and 2. 
 
All pooled efficacy data will be summarized descriptively by EDP 938 and Placebo for each age group 
and combined EDP 938 and Placebo, as described in Section 4.13.4 and Section 4.13.7. 
 
Inferential statistics analysis will be performed to detect treatment effects of EDP 938 and Placebo using 
the Efficacy Population, mITT-3 and mITT-5 for the following RSV RNA viral endpoints as well as 
RSV symptom related endpoints described in Section 4.13.7 (except for RESOLVE-P where Efficacy 
Population is used) 
• Daily change in RSV shedding in nasal swab samples determined using RT-qPCR from baseline 
through treatment phase 
o Absolute change from baseline in RSV RNA viral load (outcome variable) will also be 
analyzed using MMRM as described below. 
 
o AUC for RSV RNA viral load measured in nasal swab samples by quantitative reverse 
transcription polymerase chain reaction (RT-qPCR) will be estimated via MMRM. 
 
•  Time to RSV RNA viral load being undetectable 
 
Time to RSV RNA viral load being undetectable (TND) will be analyzed using two approaches 
as defined below: 
 
o Time to RSV RNA viral load being undetectable (days) is defined as the time between 
the date of first dose to the first date during post-dose period of achieving RSV RNA 
viral load TND after which no further samples have detectable RSV RNA viral load. 
Subjects with baseline RSV viral load TND will be excluded from the analysis. 
 
o Time to confirmed undetectable RSV RNA viral load (days) is defined as the time 
between the date of first dose to the first of 2 consecutive post-baseline time points of 
achieving RSV RNA viral load TND. Subjects with baseline RSV viral load TND will be 
excluded from the analysis.


 
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Inferential statistics analysis approaches are as follows: 
 
For continuous endpoints with multiple timepoints: 
 
Absolute change from baseline in the outcome of interest (outcome variable) will be analyzed using a 
mixed-effect model for repeated measures (MMRM) to compare EDP-938 and Placebo. 
 
The model includes treatment group (EDP-938, placebo) and Day (all scheduled post-baseline 
timepoints available) as fixed effect, associated baseline (as appropriate), and treatment group-by-Day 
interaction term as factors. Treatment groups will be compared at scheduled post-baseline timepoints of 
interest. An unstructured covariance matrix will be imposed. If the unstructured covariance matrix fails 
to converge, then the following covariance structure will be assessed in this order: autoregressive, 
compound symmetry, Toeplitz. The Satterthwaite approximation will be used to estimate the 
denominator degrees of freedom. The least-squares means and two-sided 95% CIs of absolute change 
from baseline at each post-baseline timepoint will be presented for individual groups and the difference 
between groups. AUC of change from baseline will be derived via this model.  The least-squares means 
and two-sided 95% CIs of AUC through Days 3, 5, 9 and 14 will be presented for individual groups and 
the difference between groups. The p-value will be presented for the difference between treatment 
groups at each post-baseline timepoint. 
 
For time to event endpoints: 
 
Kaplan-Meier estimates will be provided including at least median survival and its 95% CI on the 
combined EDP-938 and placebo for Parts 1 and 2. Kaplan-Meier plots will also be provided. 
Generalized Wilcoxon test will be performed to compare the EDP-938 vs Placebo. If appropriate, log- 
rank test will be performed as well. If required, a Cox proportional hazards model, adjusting for 
associated baseline assessment (if appropriate), would be considered. Subjects who did not achieve the 
specified event will be censored as follows: 
 
RSV RNA viral load: 
 
• Subjects who have not been followed through the Day 14 visit (discontinued from the study or 
incomplete follow-up) or completed Day 14 visit will be censored at Day 14 visit date. 
 
Parent/Guardian ReSVinet, Professional ReSVinet, Parent/Guardian RESOLVE-P, Caregiver Global 
Impression of Severity (CaGI-S), Caregiver Global Impression of Change (CaGI-C): 
 
• Subjects who have not been followed through the Day 14 visit (discontinued from the study or 
incomplete follow-up) or completed Day 14 questionnaire will be censored at Day 14.


 
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4.13.6  Sensitivity Analysis 
 
Sensitivity analyses will be based on the Efficacy Population. 
 
Final dosing regimen: 
 
Subjects who received the final selected doses (7.5 mg/kg in subjects in 12 to ≤36 months and 5 mg/kg 
in subjects <12 months) will be included in the following analyses. 
• Daily change in RSV shedding in nasal swab samples determined using RT-qPCR from baseline 
through the treatment phase 
o Absolute change from baseline in RSV RNA viral load (outcome variable) will also be 
analyzed using MMRM as described in Section 4.13.5. 
 
o AUC for RSV RNA viral load measured in nasal swab samples by quantitative reverse 
transcription polymerase chain reaction (RT-qPCR) will be estimated via MMRM. 
 
•  Time to RSV RNA viral load being undetectable 
 
o The analyses are outlined in the time to event analyses as described in Section 4.13.5. 
 
 
Steroid Use: 
 
The populations for analysis of steroid use are defined as follows: 
 
• Subjects who received systemic corticosteroids at any time between 21 days prior to 
randomization and the PT 2 visit (Day 14). 
 
• Subjects who did not receive systemic corticosteroids at any time between 21 days prior to 
randomization and the PT 2 visit (Day 14). 
 
The following analyses will be analyzed descriptively for each of the above populations. 
 
• Daily change in RSV shedding in nasal swab samples determined using RT-qPCR from baseline 
through the treatment phase 
• AUC for RSV RNA viral load measured in nasal swab samples by quantitative reverse 
transcription polymerase chain reaction (RT-qPCR) 
•  Time to RSV RNA viral load being undetectable 
 
Time to RSV RNA viral load being undetectable (TND) will be analyzed using two approaches 
as defined below: 
 
o Time to RSV RNA viral load being undetectable (days) is defined as the time between 
the date of first dose to the first date during post-dose period of achieving RSV RNA 
viral load TND after which no further samples have detectable RSV RNA viral load. 
Subjects with baseline RSV viral load TND will be excluded from the analysis. 
 
o Time to confirmed undetectable RSV RNA viral load (days) is defined as the time 
between the date of first dose to the first of 2 consecutive post-baseline time points of


 
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achieving RSV RNA viral load TND. Subjects with baseline RSV viral load TND will be 
excluded from the analysis. 
 
• Change from baseline of the Parent/Guardian ReSVinet total score which is defined as a sum 
of the score from each of the 7 parameters 
 
• Parent/Guardian ReSVinet total score AUC will be calculated and summarized as described 
in Section 4.13.2. 
 
• Time to resolution of RSV infection symptoms is defined as the time between the date of first 
dose to the first of 2 consecutive time points where each of the seven symptoms assessed by 
the Parent/Caregiver ReSVinet clinical scoring is 0 or 1. If a subject meets the resolution 
definition (0 or 1 score for 2 consecutive timepoints) at baseline and Day 2, then this subject 
will be excluded from the analysis. 
 
 
 
Coinfection: 
 
The populations for analysis of viral coinfection are defined as follows: 
 
• Subjects who had a viral coinfection at baseline. Viral coinfection is defined as subjects who 
were infected with RSV and other pathogens at baseline. 
 
•  Subjects who were infected with RSV only (did not have a viral coinfection) at baseline. 
The following analyses will be analyzed descriptively for each of the above populations. 
• Daily change in RSV shedding in nasal swab samples determined using RT-qPCR from baseline 
through the treatment phase 
• AUC for RSV RNA viral load measured in nasal swab samples by quantitative reverse 
transcription polymerase chain reaction (RT-qPCR) 
•  Time to RSV RNA viral load being undetectable 
 
Time to RSV RNA viral load being undetectable (TND) will be analyzed using two approaches 
as defined below: 
 
o Time to RSV RNA viral load being undetectable (days) is defined as the time between 
the date of first dose to the first date during post-dose period of achieving RSV RNA 
viral load TND after which no further samples have detectable RSV RNA viral load. 
Subjects with baseline RSV viral load TND will be excluded from the analysis. 
 
o Time to confirmed undetectable RSV RNA viral load (days) is defined as the time 
between the date of first dose to the first of 2 consecutive post-baseline time points of 
achieving RSV RNA viral load TND. Subjects with baseline RSV viral load TND will be 
excluded from the analysis. 
 
• Change from baseline of the Parent/Guardian ReSVinet total score which is defined as a sum 
of the score from each of the 7 parameters.


 
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• Parent/Guardian ReSVinet total score AUC will be calculated and summarized as described 
in Section 4.13.2. 
 
• Time to resolution of RSV infection symptoms is defined as the time between the date of first 
dose to the first of 2 consecutive time points where each of the seven symptoms assessed by 
the Parent/Caregiver ReSVinet clinical scoring is 0 or 1. If a subject meets the resolution 
definition (0 or 1 score for 2 consecutive timepoints) at baseline and Day 2, then this subject 
will be excluded from the analysis. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 








 
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4.14  Safety Analyses 
 
Statistical methods for the safety analyses will be primarily descriptive in nature. The SAF will be used 
for all safety analyses, unless stated otherwise. Part 1 and Part 2 will be summarized separately and 
pooled. In addition, pooling of Parts 1 and 2 will be summarized by age group. 
 
 
4.14.1  Adverse Events 
 
Adverse events will be summarized by the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 26.1 or higher, using the SOC and PT. All subjects in the SAF Population will be included in 
the summaries. AEs will be classified as pre-treatment AEs and treatment emergent adverse events 
(TEAEs) and are defined as follows: 
 
▪ Pre-treatment AE: A pre-treatment event is any event that meets the criteria for an AE/SAE and 
occurs after the subject signs the ICF but before receiving the first administration of study drug. 
 
▪ TEAE: A TEAE is defined as an AE occurring or worsening on or after the first dose of study 
drug. 
 
▪ Treatment-Related TEAEs: TEAE will be defined as related if causality is related or possibly 
related. TEAEs where the causality is missing will be assumed to be related for table summary. 
However, it is displayed as missing in the listing. 
 
▪   Grade AEs: Grade AEs in accordance with the NCI/CTCAE Version 5.0 scale as follows: Mild 
(Grade 1), Moderate (Grade 2), Severe (Grade 3), Life-threatening (Grade 4), Fatal (Grade 5).


 
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Where a subject has the same adverse event, based on PT, reported multiple times, the subject will only 
be counted once at the PT level in adverse event frequency tables. Where a subject has multiple adverse 
events within the same SOC, the subject will only be counted once at the SOC level in adverse event 
frequency tables. When reporting adverse events by severity, in addition to providing a summary table 
based on the event selection criteria detailed above, summary table will also be provided based on the 
most severe event - independent of relationship to study treatment. Missing severity will be presented as 
severe for table summary. However, it is displayed as missing in the listing. All AEs will be presented in 
tables in descending order from the SOC with the highest total incidence (across all treatment groups) to 
the SOC with the lowest total incidence. Within each SOC, AEs will be sorted in alphabetical order of 
PT. 
 
Summaries of TEAEs will include the following at a minimum: 
 
•  Overall summary of subjects with any TEAEs with a line for each of the following categories 
 
o TEAEs 
 
o Study Drug-Related TEAEs 
 
o TEAEs of Grade 3 or Higher 
 
o TEAEs by Maximum Severity (Grades 1 to 5) 
o TEAEs leading to study drug discontinuation 
o TEAEs leading to study discontinuation 
o AEs leading to death 
 
o Serious TEAEs 
 
o Study Drug-Related Serious TEAEs 
 
The above categories will also be summarized by SOC and PT. 
 
 
4.14.2  Clinical Laboratory Data 
 
Laboratory assessments will be reported as observed and change from baseline across scheduled visits, 
and as the incidence rate of shift change from baseline. ‘Shift from baseline’ tables will be generated for 
selected analytes. Laboratory shifts will be displayed as treatment-emergent abnormal, high, or low 
results. The following details the summary types where LLN = lower limit of normal and ULN = upper 
limit of normal. 
 
For categorical tests: Treatment-emergent abnormal is defined as a change from normal at baseline to 
abnormal at any post-baseline visit. 
 
Laboratory assessment grading is to be based on National Institute of Allergy and Infectious 
Diseases Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric 
Adverse Events Version 2.1 dated July 2017. Lab grading will be coded as follows: 
 
Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-threatening.


 
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Shift from baseline by DAIDS Grading will be summarized for selected chemistry and hematology 
parameters. Also, DAIDS Grading will be included in the chemistry and hematology listings. 
 
 
In addition to DAIDS grading, selected laboratory parameters that are not graded by DAIDS will be 
displayed using the following custom laboratory shift reports: 
 
• Treatment-emergent high is defined as a change from a result less than or equal to the high limit 
at baseline to a value greater than the high limit at any time post-baseline. 
 
Results will be reported according to any value greater than the high limit, any value greater than 
2× ULN and 3× ULN. 
 
• Treatment-emergent low is defined as a change from a result greater than or equal to the low 
limit at baseline to a value less than the low limit at any time post-baseline. 
 
Results will be reported to any value less than the LLN, less than (½)× LLN and (1/3)× LLN. 
 
 
4.14.3  Vital Sign Measurements 
 
Vital signs will include systolic blood pressure (mmHg), diastolic blood pressure (mmHg), respiratory 
rate (breaths/min), heart rate (beats/min), and body temperature (°C). Pulse oximetry (to measure 
peripheral capillary oxygen saturation [SpO2] (%) will also be summarized. Vital sign observed and 
change from baseline will be summarized over scheduled visits. 
 
 
4.14.4  Electrocardiograms 
 
Screening and Day 5 ECG data will be provided in data listings. 
 
 
4.14.5  Physical Examinations 
 
Physical examination data will be provided in data listings. 
 
 
4.15  Pharmacokinetic Analyses 
 
During the study, PK samples will be collected for hospitalized subjects on Visit 1 (3 hours postdose), 
Visit 2 (predose), and Visit 5 (predose), and for non-hospitalized subjects on Visit 1 (3 hours postdose), 
Visit 3 (predose), and Visit 5 (predose). Predose samples will be collected at approximately the same 
time as the nasal swab sample(s). For the postdose collection on Day 1, a window of ±30 minutes for the 
sampling time is acceptable. 
 
Actual date and time of PK sample collection will be recorded in the eCRF. In addition, the date and 
time of last dose taken before the PK sample collection will be recorded by the site.


 
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4.15.1  PK Analysis 
 
Concentration-Time Data 
 
For subjects in the PK population, descriptive statistics (number of subjects, arithmetic mean, geometric 
mean, standard deviation (SD), % coefficient of variation (%CV), %CV of the geometric mean 
(%GCV), median, min, and max) will be used to summarize the concentration data for EDP-938 and 
each metabolite by dose, age group, visit, and nominal time for Part 1 and Part 2 separately and pooled 
data from Parts 1 and 2. For predose samples, nominal time will be set to 0. For postdose samples, 
nominal time will be assigned based on the closest postdose integer hour. Concentrations that are below 
the limit of quantitation (BLQ) will be treated as zero for the computation of descriptive statistics. If 
more than 50% of subjects have concentration values BLQ, descriptive statistics will not be presented 
except for maximum (unless also BLQ, then BLQ will be presented), and BLQ will be displayed for 
mean and minimum. 
 
Individual and mean (+/-SD) EDP-938 plasma PK concentrations will be plotted over time. Listing for 
the PK sampling time and concentrations of EDP-938 and each metabolite will be provided. 
 
PK Parameters 
 
Plasma concentration of EDP-938 will be used to estimate the PK parameters of EDP-938 (including 
area under the curve (AUC, Ctrough, and others as deemed appropriate) using a population PK model, as 
allowed by the data. The analysis will be described in a separate plan and results reported separately. 
 
 
4.15.2  PKPD (Pharmacokinetic-Pharmacodynamic) 
 
Scatter plots of EDP-938 plasma concentrations (Visit 5 predose for all subjects, Visit 2 predose for 
hospitalized subjects) in relation to RSV RNA viral load, clinical symptoms (ReSVinet 
[Parent/Guardian and Professional], RESOLVE-P), and AEs will be presented by Part 1 and Part 2 
separately and pooled data from Parts 1 and 2. 
 
PKPD will be presented as scatter plots using actual values. Both absolute change from baseline and 
percent change from baseline (for viral load and clinical symptoms) versus PK concentration on a linear 
scale figure will be presented as follows: 
 
For all subjects: 
 
•  RSV RNA Viral Load and EDP-938 Plasma Concentration Predose at Visit 5 
 
•  RSV RNA Viral Load Change from Baseline and EDP-938 Plasma Concentration Predose at 
Visit 5 
 
•  RSV RNA Viral Load AUC Days 1-5 and EDP-938 Plasma Concentration Predose at Visit 5 
 
•  RSV RNA Viral Load AUC Days 1-14 and EDP-938 Plasma Concentration Predose at Visit 5 
 
•  Parent/Guardian ReSVinet Total Score and EDP-938 Plasma Concentration Predose at Visit 5 
 
•  Parent/Guardian ReSVinet Total Score Change from Baseline and EDP-938 Plasma 
Concentration Predose at Visit 5


 
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•  Professional ReSVinet Total Score and EDP-938 Plasma Concentration Predose at Visit 5 
 
•  Professional ReSVinet Total Score Change from Baseline and EDP-938 Plasma Concentration 
Predose at Visit 5 
 
•  Parent/Guardian RESOLVE-P Total Score and EDP-938 Plasma Concentration Predose at Visit 
5 
 
•  Parent/Guardian RESOLVE-P Total Score Change from Baseline and EDP-938 Plasma 
Concentration Predose at Visit 5 
 
•  Total number of TEAEs and EDP-938 Plasma Concentration Predose at Visit 5 (by severity) 
For hospitalized subjects: 
•  RSV RNA Viral Load at Day 5 and EDP-938 Plasma Concentration Predose at Visit 2 
 
•  RSV RNA Viral Load Change from Baseline at Day 5 and EDP-938 Plasma Concentration 
Predose at Visit 2 
 
 
4.16  Respiratory Syncytial Virus Subgroup/Genotype Determination 
 
A nasal swab sample at Baseline (Day 1) will be analyzed to determine the subgroup (A or B) and 
genotype of RSV. If data from Baseline (Day 1) are not available, then subgroup (A or B) will be 
determined from another nasal swab sample. Other subgroup analyses may be explored as allowed by 
data. 
 
 
4.17  Interim Analyses 
 
An interim analysis may be conducted as deemed necessary by the Sponsor.


 
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6.   REFERENCES 
 
[1] United States Food and Drug Administration Guidance Document. International Conference on 
Harmonization E9 Statistical Principles for Clinical Trials. September 1998. 
 
[2] Matthews JN, Altman DG, Campbell MJ, et al. Analysis of serial measurements in medical 
research. BMJ. 1990; 300(6719): 230-5.


 
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7.   APPENDICES 
 
 
7.1    Schedule of Assessments 
 
Study Period 
Screening1,2 Treatment 
Follow-Up 
For non-hospitalized subjects, V2 
and V4 assessments will be done at 
home. (X) is for V2 and V4 
assessments for hospitalized 
subjects. 
Visit 
Screening 
V1 V2 V3 V4 
V5 
PT1 
PT2 
PT33 
Day 
Day-1 to 
1 
2 
3 
4 
5 (±1) 
9 
14 
28 (±4) 
Notes6; Protocol Section 
Day 1 
(±1)4 
EOT5 
(±1) 
(±2) 
EOS5 
Screening/Administrative 
Study site visit 
X 
X 
X 
X 
X 
X 
X 
RSV diagnostic test 
X 
If RSV infection has not been 
confirmed using an approved 
diagnostic assay, caregivers may be 
asked to sign a RSV Diagnostic Test 
ICF to allow a rapid antigen RSV 
test to be performed. 
and informed 
consent form 
Informed consent 
X 
Section 12.1.3 
form 
Demographics 
X 
Section 8.2 
Medical history 
X 
Section 8.2 
Inclusion/Exclusion 
X 
Section 3 
Body weight 
X 
X 
Section 8.7 
Body length/head 
X 
Section 8.7 
circumference 
Study Drug Administration 
Subjects will be randomized and administered the first dose of study drug within 24 hours of signing the ICF. 
Randomization 
X 
Subjects will be randomized 2:1 in 
Part 1 and 4:1 in Part 2 to 
EDP 938:placebo. Parent/Guardian 
ReSVinet clinical scoring system 
Day 1 assessment, clinical 
evaluation, and vital signs must be 
done between randomization and 
dosing. Section 5.6 
Dispense/ 
X 
X 
X 
X 
X 
Study drug should be administered 
QD from D1 through D5 at 
approximately the same time (±1 hr) 
every day. Section 5.7 
Administer study 
drug 
Study drug 
X 
X 
X* 
Assess return of syringes on D3 and 
D5 for non-hospitalized patients. If 
V5 is conducted before D5 due to the 
visit window, caregivers should be 
contacted as soon as possible after 
D5 dosing to collect the date and 
time of dosing. Section 5.4 
accountability 
Clinical Efficacy Evaluations 
Professional 
X 
X 
X 
X 
X 
The visit assessment will be 
completed by the Site Investigator 
(or designee). The ReSVinet D1 
ReSVinet clinical 
scoring system 


 
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Study Period 
Screening1,2 Treatment 
Follow-Up 
For non-hospitalized subjects, V2 
and V4 assessments will be done at 
home. (X) is for V2 and V4 
assessments for hospitalized 
subjects. 
Visit 
Screening 
V1 V2 V3 V4 
V5 
PT1 
PT2 
PT33 
Day 
Day-1 to 
1 
2 
3 
4 
5 (±1) 
9 
14 
28 (±4) 
Notes6; Protocol Section 
Day 1 
(±1)4 
EOT5 
(±1) 
(±2) 
EOS5 
assessment must be predose. 
Section 8.10.1 
Parent/Guardian 
Once daily from predose on D1 through 
D14 
Caregiver(s) should complete the 
Parent/Guardian ReSVinet clinical 
scoring system using the eCOA 
handheld eDiary for both 
hospitalized and non-hospitalized 
subjects. The ReSVinet D1 
assessment must be predose, and 
subsequent assessments should be 
completed predose at the same time 
daily (±2 hr) for 14 days. The 
palatability assessment should be 
completed after each dose of study 
drug is administered. If a caregiver is 
unable to use the eDiary, a paper 
diary may be used. Section 8.10.2 
ReSVinet clinical 
scoring system and 
palatability question 
Parent/Guardian 
Twice daily on D1 through D14 
Caregiver(s) should complete the 
Parent/Guardian RESOLVE-P 
clinical scoring system on paper for 
both hospitalized and non- 
hospitalized subjects. The D1 
assessment must be completed 
predose, and subsequent assessments 
should be completed twice daily, 
approximately every 12 hours, for 14 
days. If D1 assessment is completed 
in the afternoon, only one 
assessment is expected for that day. 
RESOLVE-P will be completed in a 
subset of subjects. Section 8.10.3 
RESOLVE-P 
clinical scoring 
system) 
Clinical Safety Evaluations 
Vital sign 
X 
X 
X 
X 
X 
X 
If Screening and V1 occur on the 
same calendar day, vital signs 
measurements do not need to be 
repeated and the Screening 
measurements will be used as 
baseline values. If Screening and 
V1 occur on different calendar 
days, V1 measurements should 
be taken pre-dose as baseline 
values. Starting on D1, vital signs 
should be performed QD on marked 
study site visit days. Section 8.4 
measurements 
(including SpO2) 


 
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Study Period 
Screening1,2 Treatment 
Follow-Up 
For non-hospitalized subjects, V2 
and V4 assessments will be done at 
home. (X) is for V2 and V4 
assessments for hospitalized 
subjects. 
Visit 
Screening 
V1 V2 V3 V4 
V5 
PT1 
PT2 
PT33 
Day 
Day-1 to 
1 
2 
3 
4 
5 (±1) 
9 
14 
28 (±4) 
Notes6; Protocol Section 
Day 1 
(±1)4 
EOT5 
(±1) 
(±2) 
EOS5 
Physical 
X 
X 
X 
X 
X 
Full PE at Screening. Subsequent 
PEs done at discretion of 
Investigator will be targeted to new 
signs and symptoms, including 
specific assessments of changes from 
previous status. Section 8.6 
examination 
ECG 
X 
X 
12-lead ECG strongly preferred but 
where not possible, 6-lead ECG may 
be performed. If blood sampling 
and/or a nasal swab are scheduled 
for the same timepoint as ECG 
recording, those assessments should 
be done after the ECG. Section 8.5 
Procedures 
Residual samples from blood and/or 
nasal swab volume may be used for 
exploratory biomarker analyses. 
Section 8.14 
Nasal swab 
X 
X 
X 
X 
X 
Swab samples should be taken at 
approx. same time before study drug 
administration. One swab will be 
collected at each visit. Section 8.12 
Blood sampling for 
X 
X* 
X 
X 
Clinical laboratory tests include 
biochemistry, hematology, and 
cardiac biomarkers. All clinical 
laboratory tests that will be evaluated 
in the study are specified in Table 3. 
Evaluations will be conducted by 
local laboratories. 
*For subjects who have screening 
and randomization separated by 
more than 24 hours, blood sampling 
for clinical laboratory tests should be 
done predose on Day 1 for baseline 
values. This blood sampling does not 
need to be done for subjects who 
have randomization within 24 hours 
after screening because the screening 
clinical laboratory test results will be 
used as the baseline values. 
Section 8.11 
clinical laboratory 
tests 
Urinalysis 
X 
X 
Urine will be collected only from 
subjects who are either toilet trained 
and able to provide a specimen or are 
already catheterized or fitted with a 
urine collection bag, Section 8.11 


 
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Study Period 
Screening1,2 Treatment 
Follow-Up 
For non-hospitalized subjects, V2 
and V4 assessments will be done at 
home. (X) is for V2 and V4 
assessments for hospitalized 
subjects. 
Visit 
Screening 
V1 V2 V3 V4 
V5 
PT1 
PT2 
PT33 
Day 
Day-1 to 
1 
2 
3 
4 
5 (±1) 
9 
14 
28 (±4) 
Notes6; Protocol Section 
Day 1 
(±1)4 
EOT5 
(±1) 
(±2) 
EOS5 
Blood sampling for 
PK 
X (X) X 
X 
Hospitalized subjects 
•  Visit 1: 3 hours postdose 
•  Visit 2: predose 
•  Visit 5: predose 
Non-hospitalized subjects 
•  Visit 1: 3 hours postdose 
•  Visit 3: predose 
•  Visit 5: predose 
All subjects: Predose samples should 
be collected at approximately the 
same time as the nasal swab 
sample(s). For the postdose 
collection on Day 1, a window of 
±30 minutes for the sampling time is 
acceptable. The time and date of PK 
sample collection will be recorded in 
source and eCRF. Section 8.13 
Ongoing Subject Review 
Concomitant 
X 
X (X) X (X) 
X 
X 
X 
X 
Section 8.3 
treatment 
Healthcare resource 
X (X) X (X) 
X 
X 
X 
X 
Evaluate level of care (e.g., ICU, 
translational care unit, ward floor, 
home), duration of hospitalization if 
hospitalized, incidence of MAARI, 
requirement for and duration of 
oxygen supplementation/noninvasive 
mechanical ventilation support 
and/or invasive mechanical 
ventilation support and requirement 
for hydration and feeding by IV 
catheter/nasogastric tube. Section 8.9 
utilization 
Adverse events 
X 
X (X) X (X) 
X 
X 
X 
X 
If V5 is conducted before D5 due to 
the visit window, caregivers should 
be contacted as soon as possible after 
D5 dosing to assess AEs, 
concomitant treatments, and 
healthcare utilization. Section 8.8 
Abbreviations: approx. = approximately, D = day; ECG = electrocardiogram; eCOA = electronic clinical outcome 
assessment; eCRF = electronic case report form; EOS = end-of-study; MAARI=medically attended acute respiratory 
infection; EOT = end-of-treatment; ICF = informed consent form; ICU = intensive care unit; PE = physical examination; PK 
= pharmacokinetics; PT = post-treatment visit; QD = once daily; RSV = respiratory syncytial virus; SpO2 = peripheral 
capillary oxygen saturation; V = visit 
 
1  Procedures performed as part of standard of care within 72 hours before the informed consent is signed may be used in 
determining study eligibility and/or as baseline values.


 
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2 Screening should be completed as soon as possible to ensure that subjects will be randomized and administered the first 
dose of study drug within 24 hours of signing the ICF. 
3 PT3 assessment may be conducted as a telephone call. 
4 If Visit 3 occurs on Day 4 due to the visit window, Visit 5 should occur on Day 5 or Day 6. 
5 Subjects who discontinue treatment early (before completing 5 days of dosing) should return to the study site within 24 
hours following the last dose of study drug for an EOT visit. Follow-up visits will be scheduled 4 days (PT1, Day 9), 9 days 
(PT2, Day 14), and 23 days (PT3), Day 28 [EOS]) after the last dose of study drug was administered. Assessments should be 
performed as indicated, respectively for the Day 9 (PT1), Day 14 (PT2), and Day 28 (EOS/PT3) visit. Subjects who 
discontinue the study early (before Day 28) should return to the study site within 24 hours and no more than 48 hours later to 
complete the EOS procedures. 
6 If multiple assessments are scheduled for the same timepoint, it is recommended that noninvasive procedures being done 
before more invasive procedures, e.g., first complete eCOA (parent/guardian and clinician eCOAs could be concurrent), then 
ECG, then vital signs/SpO2, then nasal swab and finally blood draw.










 
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7.4    Respiratory Observable Reported Outcome -Pediatric (RESOLVE-P) 
Instructions 
Please answer the following questions thinking about the past 12 hours. Please complete this twice per 
day (once in the morning and once in the evening) around the same times each day. An [alarm/text] 
reminder will notify you when you can complete the survey. 
 
Items 
 
 
 
1.   How bad was the child’s difficulty breathing (e.g., shortness of breath, labored breathing, unable 
to breathe normally, rapid breathing) at its worst over the past 12 hours? 
 
☐ 0 None 
☐ 1 Mild 
☐ 2 Moderate 
☐ 3 Severe 
 
 
2.   How bad was the child’s wheezing (a high-pitched whistling sound when breathing) at its worst 
over the past 12 hours? 
 
☐ 0 None 
☐ 1 Mild 
☐ 2 Moderate 
☐ 3 Severe 
 
 
3.   How bad was the child’s cough at its worst over the past 12 hours? 
 
☐ 0 None 
☐ 1 Mild 
☐ 2 Moderate 
☐ 3 Severe 
 
 
4.   How bad was the child’s stuffy nose at its worst over the past 12 hours? 
 
☐ 0 None 
☐ 1 Mild 
☐ 2 Moderate 
☐ 3 Severe 
 
 
5.   How bad was the child’s runny nose at its worst over the past 12 hours?


 
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☐ 0 None 
☐ 1 Mild 
☐ 2 Moderate 
☐ 3 Severe 
 
 
 
6.   How bad was the child’s sneezing at its worst over the past 12 hours? 
 
☐ 0 None 
☐ 1 Mild 
☐ 2 Moderate 
☐ 3 Severe 
 
 
7.   Did the child have a fever (a lot warmer to the touch) over the past 12 hours? 
 
☐ 0 No 
☐ 3 Yes 
 
 
8.   How was the child’s appetite over the past 12 hours? 
 
☐ 0 Usual appetite 
☐ 1 Ate/nursed a little less than usual 
☐ 2 Ate/nursed a lot less than usual 
☐ 3 Did not eat/nurse at all 
 
 
9.   How was the child’s activity level over the past 12 hours? 
 
☐ 0 Usual activity level 
☐ 1 A little less active than usual 
☐ 2 A lot less active than usual 
☐ 3 Not active at all 
 
 
10. How was the child’s alertness/responsiveness over the past 12 hours? 
 
☐ 0 Usual alertness/responsiveness level 
☐ 1 A little less alert/responsive than usual 
☐ 2 A lot less alert/responsive than usual 
☐ 3 Not alert/responsive at all 
 
 
11. How was the child’s crying over the past 12 hours? 
 
☐ 0 Usual crying


 
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☐ 1 A little more crying than usual 
☐ 2 More crying than usual 
☐ 3 A lot more crying than usual 
 
 
 
 
 
7.5    Caregiver Global Impression of Severity (CaGI-S) 
Please choose the response that best describes the severity of the child’s Respiratory Syncytial Virus (RSV) 
symptoms in the past 12 hours. 
☐ 0 None 
☐ 1 Mild 
☐ 2 Moderate 
☐ 3 Severe 
 
 
 
 
 
7.6    Caregiver Global Impression of Change (CaGI-C) 
Compared to pre-treatment 
Please choose the response that best describes the overall change in the child’s Respiratory Syncytial Virus 
(RSV) symptoms since the child started taking the study medication. 
☐ 2 Much better 
☐ 1 A little better 
☐ 0 No change 
☐ -1 A little worse 
☐ -2 Much worse 
 
 
Compared to the previous assessment (continuation) 
Please choose the response that best describes the overall change in the child’s Respiratory Syncytial Virus 
(RSV) symptoms in the past 12 hours compared to the previous assessment. 
☐ 2 Much better 
☐ 1 A little better 
☐ 0 No change 
☐ 1 A little worse 
☐ 2 Much worse