Clinical trial NCT04633187
Conditions: Respiratory Syncytial Virus Infections
Sponsor: Enanta Pharmaceuticals, Inc
Start date: 2021-07-07; Completion date: 2023-05-31
Enrollment: 9 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This was a Phase 2b, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of EDP-938 in HCT recipients with acute RSV infection and symptoms of URTI.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: EDP-938 intervention 2: Placebo
Intervention descriptions: intervention 1: EDP-938 800mg

Dose adjustments were made for subjects taking azole antifungals. intervention 2: Subjects took EDP-938 matching placebo tablets once a day orally for 21 days

Protocol documents:
Prot_000.pdf: 
 ______________________________________________________________________________________________________  
 
  
 
Clinical Study Protocol 
EudraCT Number: 2020-002213-18 
A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY EVALUATING 
THE EFFECTS OF EDP-938 IN HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS WITH ACUTE 
RESPIRATORY SYNCYTIAL VIRUS INFECTION OF THE UPPER RESPIRATORY TRACT 
Protocol Number: EDP 938-103 
 
IND number 
135874 
 
 
 
 
Date: 
07 March 2023 
 
 
Study Sponsor: 
Enanta Pharmaceuticals, Inc. 
500 Arsenal St. 
Watertown, MA 02472 
 
 
Sponsor Medical Officer: 
 
 
 
 
 
 
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.  
 
 
 


Clinical Study Protocol  
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Clinical Study Protocol  
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CONFIDENTIAL 
 
 
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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: 
_______________ 
 
 


Clinical Study Protocol  
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TABLE OF CONTENTS 
SIGNATURE PAGE ................................................................................................................................... 5 
TABLE OF CONTENTS ........................................................................................................................... 6 
LIST OF TABLES .................................................................................................................................... 10 
LIST OF FIGURES .................................................................................................................................. 10 
LIST OF ABBREVIATIONS .................................................................................................................. 11 
PROTOCOL SUMMARY ....................................................................................................................... 13 
1. 
INTRODUCTION........................................................................................................................ 20 
1.1 
OVERVIEW ....................................................................................................................................... 20 
1.2 
BACKGROUND ................................................................................................................................. 20 
1.3 
NONCLINICAL STUDIES .................................................................................................................... 21 
1.3.1 
Nonclinical Pharmacology ............................................................................................... 21 
1.3.2 
Nonclinical Pharmacokinetics .......................................................................................... 21 
1.3.3 
Safety Pharmacology ........................................................................................................ 22 
1.3.4 
Nonclinical Toxicology ..................................................................................................... 22 
1.4 
CLINICAL STUDIES ........................................................................................................................... 23 
1.5 
POTENTIAL RISKS AND BENEFITS .................................................................................................... 25 
2. 
OBJECTIVES AND ENDPOINTS ............................................................................................ 27 
2.1 
OBJECTIVES ..................................................................................................................................... 27 
2.1.1 
Primary Objective ............................................................................................................. 27 
2.1.2 
Secondary Objectives ........................................................................................................ 27 
 
2.2 
ENDPOINTS ...................................................................................................................................... 28 
2.2.1 
Primary Endpoint ............................................................................................................. 28 
2.2.2 
Secondary Endpoints ........................................................................................................ 28 
 
3. 
SELECTION OF SUBJECTS .................................................................................................... 30 
3.1 
SUBJECT INCLUSION CRITERIA ........................................................................................................ 30 
3.2 
SUBJECT EXCLUSION CRITERIA ....................................................................................................... 31 
4. 
STUDY DESIGN .......................................................................................................................... 33 
4.1 
DOSE AND TREATMENT SCHEDULE.................................................................................................. 33 
4.2 
RATIONALE FOR STUDY DESIGN ...................................................................................................... 34 
4.2.1 
Justification of Study Design, Endpoints, and Subject Population ................................... 34 
4.2.2 
Justification of EDP-938 Dose ......................................................................................... 36 
5. 
STUDY DRUG AND TREATMENT OF SUBJECTS ............................................................. 39 
5.1 
DESCRIPTION OF STUDY DRUG ........................................................................................................ 39 
5.2 
PACKAGING AND LABELING ............................................................................................................ 39 
5.3 
STORAGE ......................................................................................................................................... 39 
5.4 
ACCOUNTABILITY ............................................................................................................................ 39 
5.5 
HANDLING AND DISPOSAL ............................................................................................................... 40 


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5.6 
TREATMENT ASSIGNMENT/RANDOMIZATION .................................................................................. 40 
5.7 
STUDY DRUG DOSE AND ADMINISTRATION ..................................................................................... 40 
5.7.1 
Dispensing of Study Drug ................................................................................................. 41 
5.7.2 
Treatment Compliance ...................................................................................................... 41 
5.8 
PROHIBITED MEDICATIONS .............................................................................................................. 41 
6. 
BLINDING ................................................................................................................................... 43 
6.1 
MAINTAINING THE BLIND ................................................................................................................ 43 
6.2 
UNBLINDING .................................................................................................................................... 43 
7. 
STUDY CONDUCT AND VISIT SCHEDULE ........................................................................ 45 
7.1 
STUDY SITE VISITS .......................................................................................................................... 45 
7.1.1 
Screening Period (Day-1 to Day 1) .................................................................................. 45 
7.1.2 
Treatment Period (Days 1 to 21) ...................................................................................... 45 
7.1.3 
Follow-up Period (Days 22 to 49) .................................................................................... 46 
7.2 
SUBJECT WITHDRAWAL/EARLY TERMINATION/COMPLETION ......................................................... 46 
7.2.1 
Withdrawal Criteria .......................................................................................................... 47 
7.2.2 
Procedures for Early Discontinuation or Early Termination of Treatment ..................... 47 
7.2.3 
Documentation of Withdrawal of Subjects........................................................................ 47 
8. 
STUDY PROCEDURES/EVALUATIONS ............................................................................... 49 
8.1 
TIMING OF ASSESSMENTS ................................................................................................................ 49 
8.2 
DEMOGRAPHICS AND MEDICAL HISTORY ........................................................................................ 49 
8.2.1 
Prior and Concomitant Therapies .................................................................................... 49 
8.3 
CLINICAL EVALUATIONS ................................................................................................................. 49 
8.3.1 
Chest Imaging ................................................................................................................... 49 
8.3.2 
Vital Sign Measurements .................................................................................................. 50 
8.3.3 
Electrocardiograms .......................................................................................................... 50 
8.3.4 
Physical Examination ....................................................................................................... 50 
8.3.5 
Height, Weight, and Body Mass Index .............................................................................. 50 
8.3.6 
Adverse Events .................................................................................................................. 51 
8.3.7 
Lower Respiratory Tract Complications Clinical Source for Endpoint 
Adjudication Committee Review ....................................................................................... 51 
 
8.3.9 
Collection of Swabs and Blood Samples for Virology Assessments .................................. 52 
8.4 
LABORATORY PROCEDURES ............................................................................................................ 52 
8.4.1 
Safety Laboratory Panels.................................................................................................. 52 
8.4.2 
Pregnancy and Menopausal Laboratory Testing .............................................................. 53 
8.4.3 
Calcineurin Inhibitor and mTOR Inhibitor Levels ........................................................... 53 
8.5 
VIROLOGY ASSESSMENTS ................................................................................................................ 55 
8.5.1 
Respiratory Syncytial Virus Rapid Diagnostic Test .......................................................... 55 
8.5.2 
Confirmatory Respiratory Pathogen Panel ...................................................................... 55 
8.5.3 
Respiratory Syncytial Virus Viral Load Quantification .................................................... 55 
8.5.4 
Respiratory Syncytial Virus Subgroup/Genotype Determination ..................................... 55 
8.5.5 
Viral Resistance ................................................................................................................ 56 
8.5.6 
Respiratory Syncytial Virus Serology ............................................................................... 56 
8.6 
PHARMACOKINETIC SAMPLES .......................................................................................................... 56 
 
 
 
8.8 
ENDPOINT ADJUDICATION COMMITTEE ........................................................................................... 57 


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9. 
SAFETY MONITORING AND REPORTING ........................................................................ 59 
9.1 
DEFINITIONS .................................................................................................................................... 59 
9.1.1 
Pretreatment Events .......................................................................................................... 59 
9.1.2 
Adverse Events .................................................................................................................. 59 
9.1.3 
Serious Adverse Events ..................................................................................................... 59 
9.2 
DOCUMENTING AND REPORTING OF ADVERSE EVENTS (INCLUDING SERIOUS ADVERSE 
EVENTS) .......................................................................................................................................... 60 
9.2.1 
Documenting and Reporting Adverse Events .................................................................... 60 
9.2.2 
Assigning Attribution of Adverse Events ........................................................................... 61 
9.2.3 
Classifying Action Taken With Study Drug....................................................................... 62 
9.2.4 
Classifying Adverse Event Outcome ................................................................................. 62 
9.2.5 
Documenting and Reporting Serious Pretreatment Events and Serious Adverse 
Events................................................................................................................................ 63 
9.2.6 
Documenting and Reporting of Pregnancy ....................................................................... 64 
9.3 
FOLLOW-UP OF ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ............................................... 64 
9.4 
DATA MONITORING COMMITTEE ..................................................................................................... 65 
10. 
STUDY STOPPING AND DISCONTINUATION RULES ..................................................... 66 
10.1 
STUDY STOPPING RULES .................................................................................................................. 66 
10.2 
SITE OR STUDY DISCONTINUATION .................................................................................................. 66 
10.2.1 
Study Discontinuation ....................................................................................................... 66 
10.2.2 
Site Termination................................................................................................................ 66 
10.2.3 
Study Termination Procedures ......................................................................................... 67 
11. 
STATISTICAL CONSIDERATIONS ....................................................................................... 68 
11.1 
GENERAL CONSIDERATIONS ............................................................................................................ 68 
11.2 
SAMPLE SIZE CONSIDERATIONS ....................................................................................................... 68 
11.3 
ANALYSIS POPULATIONS ................................................................................................................. 68 
11.4 
SUBJECT DISPOSITION AND DEMOGRAPHIC DATA ........................................................................... 69 
11.5 
METHOD OF TREATMENT ASSIGNMENT ........................................................................................... 69 
11.6 
EFFICACY ANALYSES ....................................................................................................................... 69 
11.6.1 
Primary Efficacy Analyses ................................................................................................ 69 
11.6.2 
Secondary Efficacy Analyses ............................................................................................ 70 
11.7 
SAFETY ANALYSES .......................................................................................................................... 70 
11.7.1 
Adverse Events .................................................................................................................. 70 
11.7.2 
Clinical Laboratory Data ................................................................................................. 71 
11.7.3 
Vital Sign Measurements .................................................................................................. 71 
11.7.4 
Electrocardiograms .......................................................................................................... 71 
11.7.5 
Concomitant Medications ................................................................................................. 72 
11.7.6 
Physical Examinations ...................................................................................................... 72 
11.8 
PHARMACOKINETIC ANALYSES ....................................................................................................... 72 
11.9 
SUBGROUP AND COVARIATE ANALYSES .......................................................................................... 72 
 
 
11.11 
INTERIM ANALYSES ......................................................................................................................... 72 
12. 
STUDY ADMINISTRATION ..................................................................................................... 73 
12.1 
ETHICAL CONSIDERATIONS ............................................................................................................. 73 
12.1.1 
Ethical Conduct of the Study ............................................................................................ 73 


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12.1.2 
Ethical Review .................................................................................................................. 73 
12.1.3 
Written Informed Consent ................................................................................................. 73 
12.1.4 
Investigator Compliance ................................................................................................... 74 
12.2 
DATA COLLECTION .......................................................................................................................... 74 
12.3 
STUDY MONITORING ....................................................................................................................... 74 
12.4 
QUALITY ASSURANCE ..................................................................................................................... 75 
12.5 
RETENTION OF RECORDS ................................................................................................................. 75 
12.6 
INFORMATION DISCLOSURE ............................................................................................................. 75 
12.6.1 
Confidentiality .................................................................................................................. 75 
12.6.2 
Publication Policy ............................................................................................................ 76 
13. 
REFERENCES ............................................................................................................................. 77 
14. 
APPENDICES .............................................................................................................................. 79 
APPENDIX 1: 
SCHEDULE OF ASSESSMENTS ............................................................................................. 79 


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LIST OF TABLES 
Table 1: 
Clinical and Respiratory Syncytial Virus Laboratory Evaluations ................................... 54 
Table 2: 
Options for Action Taken With Study Drug ..................................................................... 62 
Table 3: 
Classification and Definition of Adverse Event Outcomes .............................................. 63 
LIST OF FIGURES 
Figure 1: Study Design ............................................................................................................................... 34 


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LIST OF ABBREVIATIONS 
AE 
adverse event 
ALC 
absolute lymphocyte count 
ANCOVA 
analysis of covariance 
ATC 
Anatomical Therapeutic Chemical 
AUC 
area under the curve 
AUC0-24 
area under the curve from 0 to 24 hours 
AUC0-inf 
area under the curve from 0 to infinity 
BCRP 
breast cancer resistance protein 
BID 
twice daily 
BMI 
body mass index 
CFR 
Code of Federal Regulations 
CNI 
calcineurin inhibitor 
CYP 
cytochrome P450 
DDI 
drug-drug interaction 
DMC 
Data Monitoring Committee 
EC 
ethics committee 
EC50 
half-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 
United States Food and Drug Administration 
FIH 
first-in-human 
 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HCT 
hematopoietic cell transplant 
HDPE 
high-density polyethylene 
HIV 
human immunodeficiency virus 
IC50 
half-maximal inhibitory concentration 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ICU 
intensive care unit 
IRB 
institutional review board 


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IRT 
interactive response technology 
ITT 
intent-to-treat 
IWRS 
Interactive Web Response System 
LD 
loading dose 
LLN 
lower limit of normal 
LRTC 
lower respiratory tract complication 
LRTI 
lower respiratory tract infection 
MAARI 
medically attended acute respiratory infection 
MDRD 
Modification of Diet in Renal Disease 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
PK 
pharmacokinetic(s) 
PND 
postnatal day 
QD 
once daily 
QTcF 
QT interval corrected for heart rate according to Fridericia 
RAV 
resistance-associated variant 
RSV 
respiratory syncytial virus 
RT-qPCR 
quantitative reverse transcription polymerase chain reaction 
SAE 
serious adverse event 
SAF 
safety (for the analysis population) 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SoA 
Schedule of Assessments 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
time to elimination half-life 
TEAE 
treatment-emergent adverse event 
TSS 
total symptom score 
ULN 
upper limit of normal 
URTI 
upper respiratory tract infection 
WHO 
World Health Organization 


Protocol Synopsis  
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PROTOCOL SUMMARY 
Name of Sponsor/Company: Enanta Pharmaceuticals, Inc. 
Name of Investigational Product: EDP-938 
Study Title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the 
Effects of EDP-938 in Hematopoietic Cell Transplant Recipients With Acute Respiratory 
Syncytial Virus Infection of the Upper Respiratory Tract 
Protocol Number: EDP 938-103 
Phase of Development: 2b 
Study Centers: This will be a multicenter global study and may include sites in North 
America, South America, Europe, and Asia-Pacific 
Number of Subjects Planned: Approximately 200 subjects will be enrolled. 
Planned Study Population: Male and female subjects aged between 16 and 75 years, 
inclusive, who have had a hematopoietic cell transplant (HCT) and have an acute respiratory 
syncytial virus (RSV) infection of the upper respiratory tract (URTI). 
Investigational Product, Dosage, and Mode of Administration: EDP-938 will be supplied as 
 tablets for oral administration. The total dose administered (once daily [QD]) 
will be either: 
• 
 EDP-938 or placebo (for subjects not taking azole antifungals that are 
moderate or strong cytochrome P450 [CYP] CYP3A4 inhibitors) 
• 
 EDP-938 or placebo (for subjects taking azole antifungals that are moderate 
CYP3A4 inhibitors) 
• 
 EDP-938 or placebo (for subjects taking azole antifungals that are strong 
CYP3A4 inhibitors) 
Duration of Treatment: 21 days 
Study Objectives: 
Primary Objective 
• To evaluate the effect of EDP-938 on the development of lower respiratory tract 
complication (LRTC) in HCT subjects with an acute RSV URTI 
 


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Secondary Objectives 
• To evaluate the effect of EDP-938 on RSV viral load as measured by quantitative 
reverse transcription polymerase chain reaction (RT-qPCR) of nasopharyngeal swab 
samples 
• To evaluate the effect of EDP-938 on progression to respiratory failure or all-cause 
mortality 
• To evaluate the progression of RSV infection using the InFLUenza Patient-Reported 
Outcome (FLU-PRO) questionnaire 
• To evaluate the pharmacokinetics (PK) of EDP-938 
 
• To evaluate the safety and tolerability of EDP-938 
 
 
 
 
 
 
 
 
 
 
Criteria for Evaluation: 
Primary Endpoint 
• Incidence of LRTC through Day 28 defined as at least one of the following as 
determined by the Endpoint Adjudication Committee 
o Lower respiratory tract infection (LRTI) by RSV 
o LRTI as secondary bacterial pneumonia 
o LRTI by unusual pathogens 
o LRTC of unknown etiology 
 
 


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Secondary Endpoints 
• Change in RSV RNA viral load from Baseline through Day 49 in nasopharyngeal swab 
samples by RT-qPCR 
• Incidence of subjects who develop respiratory failure of any cause requiring mechanical 
ventilation (invasive or noninvasive) or all-cause mortality through Day 49 
• Incidence of subjects with RSV RNA viral load below the limit of  detection in subjects 
receiving EDP-938 through Day 49 
• Time to RSV RNA viral load below the limit of detection 
• FLU-PRO questionnaire scores through Day 49 
• Plasma PK concentrations of EDP-938 and 
 
 
• Safety endpoints include, but are not limited to, adverse events (AEs), serious adverse 
events (SAEs), vital sign measurements, pulse oximetry measurements, and clinical 
laboratory test results (including chemistry, hematology, and urinalysis) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Design: 


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This is a Phase 2b, randomized, double-blind, placebo-controlled, multicenter study evaluating 
the efficacy and safety of EDP-938 in HCT recipients with acute RSV infection and symptoms 
of URTI. 
For each subject, the duration of study participation will be approximately 7 weeks and will 
consist of Screening, Treatment, and Follow-up Periods, as follows: 
Study Period 
Duration  
Screening 
1 day 
Treatment 
21 days 
Follow-up 
28 days  
Approximate total duration of participation 
Up to 50 days 
The design of the study is shown in Figure 1. All study procedures are detailed in the Schedule 
of Assessments (SoA; Appendix 1).  
Figure 1: Study Design 
 
Screening Period (Day -1 to Day 1): At Screening (Day -1 to Day 1), subjects must review 
and sign the informed consent form (ICF) before completing any study-specific procedures. 
After signing the ICF, screening assessments will be performed as soon as possible; the subject 
will be randomized and administered the first dose of study drug within 24 hours of signing the 
ICF. Subjects will be considered enrolled at the time of randomization. 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 performed up to 3 days before 
informed consent and chest imaging performed up to 2 days before informed consent. As 
required, screening safety laboratory test samples will be sent to the local laboratory for 
expedited testing.  
Treatment Period (Day 1 to 21): 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 to receive 
 EDP-938 or placebo administered orally for 21 days (see Section 4.1) . 
Subject randomization will be stratified by ribavirin treatment (presence or absence) and 
absolute lymphocyte count (ALC, <200 or ≥200 cells/µL). The treatment duration is 21 days, 
during which 6 study visits will be performed. 


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Randomized subjects will be assigned to an electronic device
 
. 
Following randomization on Day 1, subjects must complete baseline assessments before 
receiving the first dose of EDP-938 or placebo. Although prior local safety laboratory test 
results may have been used to determine eligibility, separate safety laboratory samples must be 
collected and sent to the central laboratory for baseline assessment. If Screening and 
randomization/first dose occur on the same day, then screening assessments for vital signs and 
pulse oximetry will be used as baseline values. If Screening and randomization/first dose occur 
on different calendar days within a 24-hour period, vital signs and pulse oximetry will be 
performed again on Day 1 (predose). 
Subjects will receive the first dose of study drug while at the study site. After the first dose, 
subjects will be instructed to take EDP-938 or placebo QD at approximately the same time 
every day (±1 hour) on each of the 20 subsequent days. The subject will also receive 
instructions on the appropriate storage and transport of study drug. At each study visit, subjects 
should bring their study drug with them as part of their study site visit for drug accountability 
and for dosing of study drug. If a subject is unable to attend a study site visit, a home visit by 
study site personnel may be arranged, if feasible. 
Safety evaluations will include assessment of clinical laboratory findings, physical examination 
findings (as applicable), vital sign measurements, pulse oximetry measurements, AEs, 
concomitant medications, hospitalizations, ICU admissions or utilization of ICU care for 
>24 hours, standard of care test results, and supplemental oxygen use (≥2 L/min for >24 hours). 
Except for Screening and Day 1, assessments may be completed at the study site or by study 
site personnel via a home visit, if feasible. 
Follow-up Period (Day 22 to 49): Follow-up visits will occur 1 and 4 (End-of-Study [EOS] 
visit) weeks after the last dose of study drug for all subjects including those who discontinue 
treatment early (ie, before completing 21 days of dosing). Visit assessments may be completed 
at the study site or by study site personnel via a home visit, if feasible. 
All study assessments during the Follow-up Period are detailed in the SoA (Appendix 1). 
Early Termination: Subjects who discontinue treatment before completing 21 days of dosing 
should return to the study site within 24 hours from the last dose of study treatment to complete 
an End-of-Treatment (EOT) visit. They should then return to the clinic for the Follow-up Visit 
1 (EOT +1 week) and the EOS visit 4 weeks following the last dose of study drug. 
Subjects who discontinue the study before Day 28 should return to the site within 48 hours to 
complete Follow-up Visit 1 (EOT +1 week) procedures. Subjects who discontinue the study 
early between Day 28 and Day 49 should return to the study site within 48 hours to complete 
the EOS procedures. 
Subject Eligibility Criteria: Males and females aged between 16 and 75 years, inclusive, who 
have received an autologous HCT (within 6 months of signing ICF) and have an ALC 
<300 cells/ µL OR received an allogeneic HCT (any time) and have an ALC <500 cells/µL, 


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and are diagnosed with RSV with new onset of respiratory symptom(s). This includes subjects 
who have oxygen saturation ≥95% on room air and body mass index (BMI) up to 40 kg/m2. 
Subjects with new abnormalities consistent with LRTI on chest imaging, hospital admission for 
a lower respiratory tract disease of any cause, positive for other respiratory viruses or having 
clinically significant viremia, bacteremia, or fungemia will be excluded from the study. Also 
excluded are subjects with known heart, liver, or kidney disease, or any historical or current 
medical condition that, in the opinion of the Investigator, deems the subject unsuitable for the 
study. 
Statistical Methods: Detailed statistical analysis will be outlined in the statistical analysis 
plan, which will be developed and finalized before database lock. 
Sample Size Considerations: Assuming an LRTC rate of 30% for placebo, then a 20% 
reduction with 90% power and a two-sided alpha at 0.05 using a unpooled z-test, with a ratio of 
2:1 would require approximately 160 subjects. Assuming a 15% dropout rate a total of 
190 subjects will be randomized.  
Statistical Analysis: The following analysis populations are planned:  
Intent-to-Treat (ITT) Population: All subjects who receive at least one dose of study drug. 
Subjects will be analyzed as treated. The ITT Population is designated as the primary efficacy 
population. 
Per Protocol Population: All subjects who are randomized and receive all planned doses of 
study drug and do not have major protocol deviations that may unduly influence outcome. 
Subjects will be analyzed in the treatment group that corresponds to the study drug received 
during the study. 
Safety (SAF) Population: All subjects who receive at least one dose of study drug. Subjects will 
be analyzed in the treatment group that corresponds to the study drug received during the study. 
Pharmacokinetic (PK) Population: All subjects receiving active study drug and having any 
measurable plasma concentration of study drug at any timepoint. 
Subject Disposition and Demographic Data: The number of subjects screened, randomized, and 
in the SAF and PK Populations will be summarized using frequencies and percentages. Subject 
demographics will be summarized by treatment group for all subjects in the SAF Population. 
Appropriate baseline characteristics will be included in addition to demographic characteristics. 
Efficacy Analyses: The proportion of LRTC between EDP-938 and placebo will be compared 
using a Cochran Mantel-Haenszel test with ribavirin use (presence or absence) and ALC 
(<200 or ≥200 cells/µL) as stratification factors. The primary analysis will be using the ITT 
Population based on the results of the Endpoint Adjudication Committee. A Fisher's exact test 
will be used to compare groups within each strata. The treatment difference in RSV RNA viral 
load area under the curve (AUC) will be analyzed using an analysis of covariance (ANCOVA) 
model with Baseline, treatment, and stratification factors in the model. FLU-PRO and TSS 
AUC overall score and individual components will be analyzed using an ANCOVA model with 
Baseline, treatment, and stratification factors in the model. 


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Safety Analyses: Statistical methods for the safety analyses will be primarily descriptive in 
nature. Safety data, including AEs, SAEs, vital sign measurements, concomitant medications, 
and laboratory values, will be summarized separately by treatment group. Change from 
Baseline will be included in summary tables for vital sign measurements and laboratory 
parameters. Shift tables will also be generated by laboratory analyte. All laboratory data will be 
included in the data listings, and all test values outside the normal range will be flagged. 
Pharmacokinetic Analyses: Summary of plasma concentration data will be descriptive in 
nature. Mean plasma concentration-time figures may be created for EDP-938 
 
, as allowed by the data. 
Subgroup and Covariate Analyses: Subgroup analyses will be performed on the primary and 
secondary endpoints, primarily. A logistic regression model will be planned when categorical 
endpoints are analyzed. For continuous endpoints, an ANCOVA model will be planned with 
treatment group and stratification factors as fixed effects in the model, and with subgroup and 
subgroup-by-treatment interaction. Various study populations may be used. Forest plots will be 
provided to visually describe the association. 
 
Data Monitoring Committee: The study data will be reviewed by a Data Monitoring 
Committee (DMC) throughout the study. The DMC will be headed by a DMC Chair and will 
include one or more physicians with expertise in transplant medicine. The DMC will consist of 
experts independent from the Sponsor. The DMC procedures will be governed by a separate 
DMC charter. 
 


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1. 
INTRODUCTION 
1.1 
Overview 
EDP-938 is a novel orally administered nonfusion replication inhibitor of respiratory syncytial 
virus (RSV) that is being developed as a potential treatment for RSV infection. This Phase 2b 
study, EDP-938-103, is a randomized, double-blind, placebo-controlled, multicenter study 
designed to assess the efficacy, safety, and tolerability of EDP-938 compared with placebo in 
adult hematopoietic cell transplant (HCT) recipients with an acute RSV infection and symptoms 
of an upper respiratory tract infection (URTI). 
1.2 
Background  
Respiratory syncytial virus is the leading cause of lower respiratory tract infection (LRTI) and 
presents a significant health challenge in small children, elderly, and immunocompromised 
patients, such as those who have received HCT (Falsey et al., 2005; Hall et al., 2009; Shook and 
Lin, 2017; Khawaja and Chemaly, 2019). Respiratory syncytial virus is one of the most common 
community respiratory viruses that may lead to death in HCT recipients, second only to 
influenza (Khawaja and Chemaly, 2019). The reported incidence of RSV infection in HCT 
recipients range from 5% to 49% depending on differing diagnostic methods, with 30% to 60% 
of RSV infections in HCT recipients causing LRTIs (Khawaja and Chemaly, 2019). The 
mortality rate of HCT recipients with LRTI ranges from 21% to 83% (Khawaja and Chemaly, 
2019). 
Currently, there is no vaccine or highly effective treatment available for RSV. At present, there 
are only two agents approved for the prevention or treatment of RSV infection, a prophylactic 
agent (palivizumab) and a therapeutic agent (aerosolized ribavirin), each having indications for 
use that are limited to the pediatric population. Aerosolized ribavirin, alone or in combination 
with palivizumab, has been used as a treatment of RSV in HCT recipients and retrospective 
studies show that the treatment may have some efficacy for preventing RSV-associated 
morbidity or mortality in this population (Shah and Chemaly, 2011). However, ribavirin-based 
treatments are controversial as aerosolized ribavirin is expensive, requires hospitalization, is 
considered to be potentially hazardous to health care workers, and does not have proven efficacy 
from randomized studies in HCT recipients (Boeckh et al., 2007). 
EDP-938 is active against all RSV-A and RSV-B laboratory strains and clinical isolates tested 
in vitro. EDP-938 appears to inhibit RSV replication by modulating viral nucleoprotein, based on 
in vitro resistance studies, although the exact mechanism of action is under further investigation. 
EDP-938 has demonstrated in vivo efficacy in the RSV-infected African green monkey model.  
To address the unmet medical need for more effective antiviral therapies for RSV and based on 
the promising early nonclinical safety and pharmacological profile, Enanta Pharmaceuticals, Inc. 
is investigating EDP-938 in humans as a potential treatment for RSV infection. 


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1.3 
Nonclinical Studies 
A summary of nonclinical studies is provided below. Additional information can be found in the 
Investigator’s Brochure. 
1.3.1 
Nonclinical Pharmacology 
EDP-938 is a novel nonfusion replication inhibitor of RSV. It is active in vitro against RSV-A 
and RSV-B laboratory strains and all clinical isolates tested. In primary human bronchial 
epithelial cells, EDP-938 has half-maximal effective concentration (EC50) values of 21 nM 
against RSV-A Long strain, 23 nM against RSV-A M37 strain, and 64 nM against RSV-B 
Washington strain. It is highly specific for RSV with no cross activity against other RNA or 
DNA viruses and no significant cytotoxicity. EDP--938 inhibits RSV at a post entry replication 
step of the viral life cycle as confirmed by the time-of-addition study, and the activity appears to 
be mediated by viral nucleoprotein. An in vitro resistance study suggests that EDP-938 presents 
a higher barrier to resistance compared with viral fusion or L polymerase inhibitor with no cross 
resistance observed. The combination of EDP-938 with other classes of RSV inhibitors led to 
additive synergist antiviral effects in vitro. The in vivo efficacy of EDP-938- was demonstrated 
in the RSV infected African green monkey model, with >4 log10 viral load reduction after 6 days 
of treatment. 
1.3.2 
Nonclinical Pharmacokinetics 
The pharmacokinetics (PK) of EDP-938 following single intravenous and oral doses were 
determined in mice, rats, dogs, and monkeys. Oral bioavailability of EDP-938 at a single oral 
dose
 was 
 in dogs,
 in mice, 
 in rats, and 
 in monkeys. An evaluation of membrane permeability of EDP-938 
performed using Caco2 cells showed 
in vitro permeability 
 
. 
Based on the outcome of these absorption studies, EDP-938 is projected to have a good oral 
absorption in humans. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




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1.4 
Clinical Studies 
Five Phase 1 clinical studies have been conducted:  
• EDP-938-001:  first-in-human (FIH) study in healthy adult subjects (n=68 treated with 
EDP-938),  
• EDP 938-002 and EDP 938-003: drug-drug interaction (DDI) studies in healthy adult 
subjects (n=48 and n=72 treated with EDP-938 for these two studies, respectively),  
• EDP 938-004: bioavailability study in healthy adult subjects (n=18 treated with EDP-938),  
• EDP 938-007: DDI study in healthy adult subjects (n= 24 treated with EDP-938), and 
• EDP 938-101: Phase 2a study in healthy adult subjects inoculated with RSV A Memphis 37b 
(virus challenge model) (n=118 treated with EDP-938).  
Results of these studies are summarized below; refer to the Investigator’s Brochure for further 
details. EDP-938 was administered as a suspension in all studies; it was also administered as a 
tablet formulation in Study EDP 938-004 (relative bioavailability study). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 


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Study EDP 938-101 was a Phase 2a study designed to assess the efficacy, safety, and PK of 
multiple doses of orally administered EDP-938 in the RSV healthy subject challenge model. The 
primary objective of this two-part study was to evaluate the antiviral activity of EDP-938 
compared with placebo in healthy adult subjects inoculated with RSV-A Memphis 37b.  
In Part 1, 115 subjects were randomized to one of three treatment groups for 5 days of oral 
suspension dosing as follows: EDP-938 
 
 for a total of 10 doses, n=38); EDP-938 
, for a total of 10 doses, n=39); placebo (n=38) every 12 hours. Both 
EDP-938 treatment regimens demonstrated robustly lowered RSV RNA levels measured as 
AUCs compared with placebo (p<0.001), with no significant difference between the 
 regimens. Additionally, both EDP-938 regimens demonstrated robustly lower 10-point RSV 
total symptom score (TSS) AUCs compared with placebo (p<0.001), with no significant 
difference between the QD and BID regimens. The number of subjects with any AE was similar 
among EDP-938 and placebo recipients, ranging 
. Only the treatment-emergent 
adverse events (TEAEs) of headache, diarrhea, dizziness, nausea, and URTI each occurred in at 
least 5 (4.4%) of the 114 subjects. Comparing the frequencies of these events in the EDP-938 
 and placebo treatment groups, only headache (
), dizziness 
(
), and diarrhea 
), respectively, were more common in one or 
both EDP-938 treatment groups compared with placebo. All TEAEs in EDP-938 recipients were 
mild except for a single event of moderate dyspepsia that was considered unrelated and resolved 
in follow-up. 
In Part 2 of the study, 63 subjects were randomized into one of three treatment groups for 5 days 
of EDP-938 oral suspension with doses being informed by Part 1 data and dosing as follows: 
EDP-938 
for a total of 10 doses, n=21); EDP-938 
 for a total of 
10 doses, n=21); placebo every 12 hours (n=21). Both EDP-938 treatment regimens 
demonstrated robustly lower RSV RNA AUCs compared with placebo (p<0.001), with no 
significant difference between the 
regimens. Additionally, both EDP-938 regimens 
demonstrated robustly lower 10-point RSV TSS AUCs compared with placebo (p=0.001 [QD 
regimen] and p=0.003 [BID regimen]), with no significant difference between the QD and BID 
regimens. The number of subjects with any AE was similar among EDP-938 and placebo 
recipients, ranging 
. Only the TEAEs of nausea, dizziness, headache, and URTI 
occurred in at least 3 (4.8%) of the 63 subjects in Part 2. Comparing the frequencies of these 
events in the EDP-938 
 and placebo treatment groups, only the frequencies of 
nausea (
), dizziness (
) and URTI (
), 
respectively, were more common in either EDP-938 arm compared with placebo. All TEAEs in 
EDP-938 recipients were mild except for a single event of vessel puncture site paraesthesia was 
considered moderate. All events resolved in follow-up. Therefore, both EDP-938 regimens were 
well tolerated with safety profiles that were comparable with placebo. 
The systemic EDP-938 exposures were generally comparable to those observed in the FIH study 
at similar doses. There was no correlation between efficacy endpoints (viral load AUC and TSS) 
and exposure to EDP-938 (AUC).  


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In this Phase 2a study of healthy adults inoculated with RSV, all four EDP-938 regimens were 
well tolerated and demonstrated robust reductions in both RSV RNA levels and TSSs which 
were superior to placebo, with favorable PK profiles and safety profiles that were comparable 
with placebo.  
1.5 
Potential Risks and Benefits 
EDP-938 is highly specific for RSV. In vitro, EDP-938 had no cross activity against other RNA 
or DNA viruses and no significant cytotoxicity. No safety pharmacology concerns have been 
identified following EDP-938 administration, and no secondary effects of toxicological concern 
were observed in the 28-day repeat-dose studies in mice, rats, or monkeys. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
It is possible that exposure to EDP-938 may lead to RSV resistance to EDP-938 as may occur 
with any study of an antiviral. However, the genetic barrier of EDP-938 to development of 
resistance is considered to be high and the risk of resistance is considered to be low. 
Additionally, to mitigate any risk to subjects, the following will be undertaken:  
• A Data Monitoring Committee (DMC) will ensure the continuing safety of subjects enrolled 
to the study through scheduled and as needed evaluations of safety data. The DMC will 
include one or more physicians with expertise in transplant medicine. 
• The EDP-938 dose selected for this study (
 administered as a tablet formulation for 
subjects not taking azole antifungals that are moderate or strong CYP3A4 inhibitors, 
 for subjects taking azole antifungals that are moderate CYP3A4 inhibitors, and 
 for subjects taking azole antifungals that are strong CYP3A4 inhibitors; QD for 
21 days) is expected to provide exposures within the range observed in the Phase 2a EDP 
938-101 study. These systemic EDP---938 exposures are expected to be generally safe and 
efficacious. See Section 4.2.2 for more information about the rationale for the EDP-938 dose. 
This is the first study that will evaluate the safety, PK, and efficacy of EDP-938 in HCT 
recipients, and consequently the efficacy and safety of EDP-938 in this population are not 


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known. Because EDP-938 has previously demonstrated clinical efficacy in the adult healthy 
subjects RSV challenge study, it is possible that subjects in the present study may have a more 
rapid clearance of RSV infection and a reduction in the symptoms associated with RSV infection 
compared with those who do not receive EDP-938. However, it is possible that no such effect 
will be observed. Additionally, subjects enrolled in the placebo treatment group will not be 
expected to derive any such benefit. Consequently, subjects enrolled to the study may experience 
no benefit with regard to impacting the rate of clearance of RSV or resolution of symptoms 
associated with RSV infection.  


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2. 
OBJECTIVES AND ENDPOINTS 
2.1 
Objectives 
2.1.1 
Primary Objective 
• To evaluate the effect of EDP-938 on the development of lower respiratory tract 
complication (LRTC) in HCT subjects with an acute RSV infection of the upper 
respiratory tract 
2.1.2 
Secondary Objectives 
• To evaluate the effect of EDP-938 on RSV viral load as measured by quantitative 
reverse transcription polymerase chain reaction (RT-qPCR) of nasopharyngeal swab 
samples 
• To evaluate the effect of EDP-938 on progression to respiratory failure or all-cause 
mortality 
• To evaluate the progression of RSV infection using the InFLUenza Patient-Reported 
Outcome (FLU-PRO) questionnaire 
• To evaluate the PK of EDP-938 
 
• To evaluate the safety and tolerability of EDP-938 
2.1.3 
 
 
 
 
 
 
 
 
 


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2.2 
Endpoints 
2.2.1 
Primary Endpoint 
• Incidence of LRTC through Day 28 defined as at least one of the following as determined 
by the Endpoint Adjudication Committee 
o LRTI by RSV 
o LRTI as secondary bacterial pneumonia 
o LRTI by unusual pathogens 
o LRTC of unknown etiology 
2.2.2 
Secondary Endpoints 
• Change in RSV RNA viral load from Baseline through Day 49 in nasopharyngeal 
swab samples by RT-qPCR 
• Incidence of subjects who develop respiratory failure of any cause requiring 
mechanical ventilation (invasive or noninvasive) or all-cause mortality through 
Day 49 
• Incidence of subjects with RSV RNA viral load below the limit of detection in 
subjects receiving EDP-938 through Day 49 
• Time to RSV RNA viral load below the limit of detection 
 
• Plasma PK concentrations of EDP-938 and 
  
 
• Safety endpoints include, but are not limited to, AEs, serious adverse events (SAEs), 
vital sign measurements, pulse oximetry measurements, and clinical laboratory test 
results (including chemistry, hematology, and urinalysis) 
2.2.3 
 
 
 
 
 
 
 
 
 


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3. 
SELECTION OF SUBJECTS 
A total of approximately 200 subjects are planned to be enrolled into this study. 
3.1 
Subject Inclusion Criteria 
Each subject must meet all of the following criteria to be enrolled into this study: 
1. An ICF signed and dated by the subject. 
2. Male or female individuals aged between 16 and 75 years, inclusive. 
3. Received an autologous HCT (within 6 months of signing ICF) or an allogeneic HCT 
(any time) using any conditioning regimen 
4. Absolute lymphocyte count (ALC) <500 cells/ µL in allogeneic HCT recipients. Absolute 
lymphocyte count (ALC) <300 cells/ µL in autologous HCT recipients. 
5. Laboratory confirmed RSV diagnosis from a respiratory sample within 3 days before 
signing the ICF. The RSV diagnosis can be determined by any validated laboratory 
method.  
6. New onset of at least one of the following respiratory symptoms within 3 days before 
signing the ICF: nasopharyngeal discharge, nasopharyngeal congestion, sneezing, sinus 
congestion, sore throat, hoarseness, earache, cough, shortness of breath, respiratory 
wheeze, or worsening of one of these symptoms if present chronically (associated with a 
previously existing diagnosis [eg, chronic rhinorrhea, chronic lung disease]) in the 3 days 
before signing the ICF or at Screening. 
7. No evidence of new abnormalities consistent with LRTI on chest imaging (chest x-ray 
and/or computed tomography) performed in the 2 days before signing the ICF. If there is 
no chest imaging available in the 2 days before signing the ICF, chest imaging (chest x-
ray and/or computed tomography) must be obtained at the Screening visit. 
8. Oxygen saturation ≥95% on room air. 
9. A body mass index (BMI) ≥18 kg/m2 and ≤40 kg/m2 and a body weight of ≥50 kg 
10. Negative urine pregnancy test for women of childbearing potential as defined in 
inclusion criterion 11. 
11. A woman of childbearing potential who is sexually active with a male must agree to use 
two effective methods of contraception from the date of Screening until 30 days after her 
last dose of study drug. Effective methods of contraception are defined as follows: 
A condom for the male partner and at least one of the following for the female subject: 
a. Intrauterine device 
b. Oral, injectable, implantable, transdermal, or intravaginal hormonal contraceptive 
(Note: hormonal contraception must be associated with the inhibition of ovulation) 


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The above does not apply to 1) a female subject who has a vasectomized male partner 
provided that partner is the sole sexual partner of the subject and the vasectomized 
partner has received medical assessment of surgical success or 2) a female subject   who 
is of nonchildbearing potential (ie, physiologically incapable of becoming pregnant) as 
defined below: 
a. Has had a complete hysterectomy ≥3 months before Screening,  
b. Has had a bilateral oophorectomy (ovariectomy),  
c. Has had a bilateral tubal ligation or fallopian tube inserts, or 
d. Is postmenopausal (a total cessation of menses for at least 2 years; subjects with a 
cessation of menses between 1 to 2 years and a follicle-stimulating hormone [FSH] 
level of >35 mIU/mL will also be considered to be postmenopausal.) 
12. A male subject who has not had a vasectomy and is sexually active with a woman of 
childbearing potential must agree to use effective contraception from the date of 
Screening to 90 days after his last dose of study drug. Effective contraception is defined 
as a condom and at least one of the following for a female partner: 
a. Intrauterine device 
b. Oral, injectable, implantable, transdermal, or intravaginal contraceptive 
(Note: hormonal contraception must be associated with the inhibition of ovulation). 
13. Male subjects must agree to refrain from sperm donation from the date of Screening until 
90 days after his last dose of study drug. 
14. Must be willing and able to adhere to the study assessments, visit schedules, prohibitions, 
and restrictions, as described in this protocol. 
3.2 
Subject Exclusion Criteria 
Subjects will not be eligible to participate in the study if they meet any of the following criteria: 
1. Admitted to the hospital primarily for a lower respiratory tract disease of any cause as 
determined by the Investigator. 
2. Known to be concurrently infected with other respiratory viruses (eg, severe acute 
respiratory syndrome coronavirus 2 [SARS-CoV-2] or other coronavirus, influenza, 
parainfluenza, human rhinovirus, adenovirus, human metapneumovirus) within 7 days 
before signing the ICF, as determined by local testing. 
3. Clinically significant viremia, bacteremia, or fungemia, or bacterial or fungal pneumonia 
within 2 weeks before signing the ICF that has not been adequately treated, as determined 
by the Investigator. 
4. Pregnant or nursing female subjects. 
5. History of drug and/or alcohol abuse that, in the opinion of the Investigator, may prevent 
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6. Known positive human immunodeficiency virus (HIV).  
7. Heart disease: any congenital heart disease, congenital long QT syndrome, or any clinical 
manifestation resulting in QT interval prolongation. Chronic heart failure or ischemic 
heart disease or cardiac disease occurring as a consequence of antineoplastic treatment 
and for which treatment medications have not added or increased in the last 3 months are 
not exclusionary. 
8. Known malignant tumor that may interfere with the aims of the study or a subject 
completing the study. 
9. Prior or planned ileal resection or bariatric surgery. Subjects who have undergone gastric 
surgeries that do not affect drug absorption (eg, gastric band or gastric sleeve procedures) 
will be allowed to participate if they are stable for at least 1 year before signing the ICF. 
Gastrectomy will be allowed if stable for at least 3 years before signing the ICF. 
10. Estimated glomerular filtration rate by Modification of Diet in Renal Disease (MDRD) 
<50 mL/min as measured in the 3 days before signing the ICF or at Screening. 
11. Alanine aminotransferase >5 × ULN as measured in the 3 days before signing the ICF or 
at Screening. 
12. Twelve-lead ECG demonstrating a QT interval corrected for heart rate according to 
Fridericia (QTcF) that is >470 milliseconds or other clinically relevant abnormalities as 
judged by the Investigator at Screening. 
13. Use of or intention to use any medication or supplement known to be a moderate or 
strong inducer or inhibitor of the CYP3A4 enzyme (Section 5.8) within 14 days before 
signing the ICF, with the exception of prophylactic azole antifungal therapies (e.g., 
fluconazole, itraconazole, ketoconazole, isavuconazole, posaconazole, and voriconazole), 
which are permitted with EDP-938 dose adjustment (Section 4.2.2).  
14. Use of nonmarketed (according to region) or investigational agents, vaccines, biological 
products within 30 days or five half-lives before signing the ICF, whichever is longer. 
15. Use of any investigational monoclonal anti-RSV antibodies within 4 months or 
five half-lives of signing the ICF, whichever is longer, or use of any investigational RSV 
vaccines after HCT. 
16. Known hypersensitivity or allergy to EDP-938 or placebo or their excipients. 
17. History of or currently experiencing a medical condition or any other finding (including 
laboratory test results) that, in the opinion of the Investigator, might confound the results 
of the study, pose an additional risk in administering study drug to the subject, could 
prevent, limit, or confound the protocol-specified assessments, or deems the subject 
unsuitable for the study. 


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4. 
STUDY DESIGN  
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study evaluating the 
efficacy and safety of EDP-938 in HCT recipients with acute RSV infection and symptoms of 
URTI. 
The study has 3 periods:  
• Screening Period will occur from Day -1 to Day 1. During this period, subjects will 
review and sign the ICF. Subjects will undergo screening assessments. Screening should 
be completed as soon as possible, and the subject will be randomized and administered 
the first dose of study drug within 24 hours of signing the ICF. A subject will be 
considered enrolled at the time of randomization. 
• Treatment Period will begin with the first dose of study drug on Day 1 and will conclude 
with the End-of-Treatment (EOT) Visit on Day 21. 
• Follow-up Period for safety will begin following the last dose of study drug and will 
conclude at the End-of-Study (EOS) visit on Day 49, 28 days following the last dose of 
study drug.  
The end of the study will be defined as the last visit of the last subject enrolled. 
4.1 
Dose and Treatment Schedule 
Subjects who meet all inclusion criteria and none of the exclusion criteria will be eligible to enter 
the study and will be randomly assigned (2:1 ratio) on Day 1 to receive EDP-938 or placebo 
administered orally QD for a total of 21 days. The total dose administered QD will be either: 
• 
EDP-938 or placebo (for subjects not taking azole antifungals that are 
moderate or strong CYP3A4 inhibitors) 
• 
EDP-938 or placebo (for subjects taking azole antifungals that are moderate 
CYP3A4 inhibitors) 
• 
 EDP-938 or placebo (for subjects taking azole antifungals that are strong 
CYP3A4 inhibitors) 
Eligibility will be determined at the time of randomization. An overview of the study design is 
shown Figure 1. Study site visits and assessments are detailed in the Schedule of Assessments 
(SoA; Appendix 1). 


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Figure 1: Study Design 
 
4.2 
Rationale for Study Design  
This proposed study will evaluate EDP-938 in adult subjects who have had an HCT and have an 
acute RSV infection of the upper respiratory tract. Subjects will be randomized to receive 
 EDP--938 or placebo in a 2:1 ratio (see Section 4.1). 
4.2.1 
Justification of Study Design, Endpoints, and Subject Population 
Respiratory syncytial virus is one of the most common community respiratory viruses that may 
lead to serious infection or death in HCT recipients and which is second only to influenza. 
Estimates of mortality rates associated with RSV LRTI range from 21% to 83%. It is estimated 
that approximately 1 to 2 out of every 3 HCT patients develop LRTI (Khawaja and Chemaly, 
2019). 
Despite the significant medical need, there is no vaccine or highly effective treatment currently 
available for RSV. At present, there are only two agents approved for the prevention or treatment 
of RSV infection, a prophylactic agent (palivizumab) and a therapeutic agent (aerosolized 
ribavirin), each having indications for use that are limited to the pediatric population. 
Consequently, physicians have no safe and highly effective treatment for RSV infection. This is 
an issue of significant concern for patients at risk of severe RSV disease, including the elderly, 
those with chronic lung and/or heart diseases, immunosuppressed individuals including HCT 
recipients, and pediatric patients. In these populations, RSV infection may be associated with 
significant morbidity and even mortality. 
This Phase 2b study aims to evaluate the efficacy and safety of EDP--938 in HCT recipients with 
acute RSV infection of the upper respiratory tract. In order to more fully investigate the efficacy 
of EDP--938, and noting the lack of an approved, safe and effective RSV therapy, a double-
blind, placebo-controlled study design was selected, where subjects will be randomized to 
receive
 EDP--938 or placebo in a 2:1 fashion (see Section 4.1). 
The study endpoints include efficacy and safety assessments. The primary endpoint is the 
incidence of LRTC. This endpoint will be based on an assessment of respiratory outcomes and 
will be adjudicated by an independent Endpoint Adjudication Committee blinded to treatment 
assignment. The secondary endpoint of RSV RNA viral load will be used to assess antiviral 
efficacy. RSV RNA viral load assessment was similarly employed in the Phase 2a EDP 938-101 
study. Clinical efficacy will be assessed using 
 and 


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other measures of disease progression, including incidences of respiratory failure and all-cause 
mortality. Safety and PK assessments will also be summarized in relation to study treatment 
group. 
Among HCT patients with an acute RSV URTI, those with lower lymphocyte counts, in 
particular, are considered at greater risk of progression to LTRI and were previously 
demonstrated to benefit from an investigational fusion inhibitor (Chemaly et al., 2019; Ison and 
Hirsch, 2019). Consequently, the eligible population will comprise adults who have received an 
HCT and are lymphopenic with an ALC <500 cells/µL and are diagnosed with RSV with new 
onset of respiratory symptom(s). This includes subjects who have oxygen saturation ≥95% on 
room air and a BMI up to 40 kg/m2. Subjects with new abnormalities consistent with LRTI on 
chest imaging and those who have been admitted to the hospital for a lower respiratory tract 
disease of any cause are excluded. Subjects known to be positive for other respiratory viruses, 
(eg, influenza, adenovirus, SARS CoV-2) or who have clinically significant viremia, bacteremia, 
fungemia, or bacterial or fungal pneumonia, are also excluded. Subjects with known HIV are 
excluded because the impact of HIV infection on the clearance of RSV in HCT patients is not 
known. Also excluded are subjects with defined renal, cardiac, and hepatic conditions, or any 
historical or current medical condition that, in the opinion of the Investigator, deems the subject 
unsuitable for the study. 
Previous data suggest that in HCT patients with acute RSV, the therapeutic window from 
symptom onset to initiation of treatment may be short (Chemaly et al. 2019; Marty et al. 2019). 
Because the window for optimal intervention for RSV infection may be limited, the screening 
process is optimized to allow rapid identification of subjects with RSV and who are otherwise 
appropriate for the study so that EDP-938 or placebo can be initiated at the earliest possible 
timepoint. The timeframe from onset of symptoms to signing the ICF is not more than 3 days and 
subjects are to be randomized and administered the first dose of study drug within 24 hours of 
signing the ICF. 
A dosing duration of 21 days has been selected as there is evidence that clearance of respiratory 
viruses may be slower in HCT patients than in healthy subjects (Chemaly et al., 2019; 
EDP 938-101). Although a 21-day treatment duration is longer than EDP-938 has been 
previously dosed, EDP-938 was demonstrated to be generally safe and efficacious in the 
Phase 2a EDP 938-101 study (see Section 1.4), in which healthy adult subjects were inoculated 
with RSV and received EDP-938 
 for up to 5 days and EDP-938 was observed 
to be generally safe and well tolerated in healthy adult subjects for up to 7 days of dosing in the 
FIH EDP-938-001 study (see Section 1.4). Also, EDP-938 was well-tolerated in preclinical 
repeat-dose general toxicology studies with no adverse effects observed in any species evaluated 
(mice, rats, monkeys) at up to the highest dose administered per species at up to 28-days dosing 
duration. 
The double-blind design utilizing a matched placebo for EDP-938 will allow for the most 
unbiased assessment of the clinical safety profile of EDP-938. Subject safety will be monitored 
through regularly scheduled assessments of AEs, safety laboratory tests, and the inclusion of a 
DMC whose activities will be defined in a separate DMC charter. 








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5. 
STUDY DRUG AND TREATMENT OF SUBJECTS 
5.1 
Description of Study Drug 
EDP-938 drug product tablets 
 
 
 
 
 
 
 
 
 
5.2 
Packaging and Labeling 
EDP-938- drug product tablets and the corresponding placebo tablets are supplied as 
 
tablets and
 tablets in 
 
 
 
All the drug product manufacturing, packaging, and release testing are conducted under Current 
Good Manufacturing Practice regulations. EDP-938- drug products are labeled according to the 
regulatory guidelines for labeling of investigational products. 
5.3 
Storage 
EDP-938 and placebo tablets will be shipped and stored at the site at 
 
 Additional information can be found in the in the Pharmacy Manual.  
Subjects will be instructed to store study drug in the original bottle at 
 
. 
5.4 
Accountability 
Site staff will maintain adequate records of the receipt and disposition of all study drug shipped 
to and/or procured by the site for this study. 
Site and/or pharmacy records (as appropriate for the site) must include dates, bottle numbers, lot 
numbers, quantities received, quantities dispensed, date and time of administration (Section 5.7), 
and the identification number of each subject who has received each lot of study drug.  
Unused study drug must not be discarded until the end of the study after full drug accountability 
is performed. Study drug that is dispensed to a subject, but not administered or completely 
ingested by the subject, must be returned to the pharmacy and the amount remaining recorded in 
the source documents. 
In addition, for drug accountability, subjects should bring study drug (including empty bottles) 
with them to the study site. 


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5.5 
Handling and Disposal 
Study drug must not be used for any purpose other than for administration to subjects enrolled 
into this clinical study. All study drug bottles that are opened and returned by subjects as well as 
those that are not opened or assigned to subjects will be retained at the site according to 
instructions provided by Enanta Pharmaceuticals, Inc. or designees 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 
(IWRS). Subjects will be randomized in a 2:1 ratio to the EDP-938 or placebo treatment group as 
shown below: 
• Treatment Group 1 (approximately 130 subjects): either 
 (see 
Section 4.1) of EDP-938 orally QD for 21 days 
• Treatment Group 2 (approximately 70 subjects): Placebo orally QD for 21 days 
In addition, subject randomization will be stratified based on ribavirin treatment (presence or 
absence) and ALC (<200 or ≥200 cells/µL) at Screening. 
During the Screening Period, subjects will be identified by a unique screening number assigned 
by the clinical site. 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) and 
assigned a unique four-digit subject number that will be used to identify the subject throughout 
the study. 
5.7 
Study Drug Dose and Administration 
Complete instructions for dispensing and administering study drug are presented in the 
study-specific Pharmacy Manual. 
Following randomization on Day 1, subjects will receive the first dose of EDP-938 or placebo 
orally while at the study site. After the first dose, subjects will be instructed to take the study 
drug orally QD on each of the 20 subsequent days. Subjects will be instructed to take the study 
drug at approximately the same time every day (±1 hour). 
Study site visits should be scheduled close to the time that the subject normally takes the study 
drug so that dosing can occur at the site. If a visit occurs within 4 hours of the scheduled dosing 
time, the subject should take the study drug at the site during the visit. If a visit occurs more than 
4 hours before or after the scheduled dosing time, the subject should take study drug at the 


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scheduled time at home. The time and date of doses of study drug taken at the study site should 
be recorded by site staff in source. 
If a subject forgets to take their study drug at the scheduled time, the dose should be taken as 
soon as the subject remembers; however, the following rules apply: 
• No more than one dose should be taken on any calendar day and 
• There must be a minimum of 16 hours between doses. 
Site staff will record the time and date of all study drug doses taken at the site. Subjects that took 
study drug at home on the day of a study visit should be asked for the time that dose was 
self-administered and record it in the electronic case report form (eCRF). 
5.7.1 
Dispensing of Study Drug 
EDP-938 and placebo must be dispensed by a licensed investigational pharmacist or other 
authorized site staff with appropriate training. Subjects will receive instructions on study drug 
storage (see Section 5.3) and dosing (see Section 5.7). 
5.7.2 
Treatment Compliance 
Both accountability and study drug compliance will be reviewed at each study site visit as 
indicated in the SoA (Appendix 1). The number of tablets will be counted, and the site staff will 
ask the subjects why any doses were missed, if applicable. Any potential reasons for lack of 
compliance with dosing will be monitored and followed up by the site staff. Compliance 
assessment may be completed at the study site or by a study site personnel via a home visit. 
For any subject considered to demonstrate continued noncompliance of study drug dosing 
despite continued educational efforts, the Investigator should contact
 the Sponsor’s 
Medical Monitor to discuss possible discontinuation of the subject from the study. 
5.8 
Prohibited Medications 
Following drugs, including over-the-counter medications and supplements with equivalent 
efficacy, will be prohibited before the study and from the first dose of study drug on Day 1 
through Day 49 or early termination: 
• Use of or intention to use any medication or supplement known to be a moderate or 
strong inducer or inhibitor of the 
enzyme within 14 days before signing the ICF 
and throughout the study, with the exception of prophylactic azole antifungal therapies 
(e.g., fluconazole, itraconazole, ketoconazole, isavuconazole, posaconazole, and 
voriconazole), which are permitted with EDP-938 dose adjustment (Section 4.2.2).  
• Treatment with azole antifungals that are weak inhibitors of 
 (e.g., clotrimazole) 
is allowed without EDP-938 dose adjustment. 


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• For HCT recipients on prophylactic antifungal therapy with azole antifungals, treatment 
with additional moderate or strong inhibitors of 
 outside the azole antifungal 
class is exclusionary within 14 days of signing the ICF and throughout the duration of the 
study. 
• For subjects not on prophylactic antifungal therapy with azole antifungals at screening, 
initiation of new azole antifungals that are moderate or strong inhibitors of 
 is 
prohibited. If treatment with these agents is considered medically necessary after Day 1, 
dosing with EDP-938 should be discontinued.    
• A comprehensive list of 
 inducers and inhibitors can be found at: 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-
interactions-table-substrates-inhibitors-and-inducers. 
• Cyclosporine, a moderate 
 inhibitor, has been shown 
in a Phase 1 DDI study (EDP 938-002) evaluating the effect of cyclosporine on EDP-938 
levels to have no apparent effect on the EDP-938 peak exposure and a weak effect on 
EDP-938 systemic exposures 
. In the same study, 
(EDP -938-002) coadministration with prednisone, a weak
 inducer, showed no 
apparent effect on EDP-938 exposure. Based on these results, no dose adjustments of 
EDP-938 when it is coadministered with cyclosporine or prednisone will be necessary. 
• Use of nonmarketed (according to region) or investigational agents, vaccines, biological 
products within 30 days or five half-lives before signing the ICF, whichever is longer, 
and throughout the study. 
• Use of any investigational monoclonal anti-RSV antibodies within 4 months or 
five half-lives of signing the ICF, whichever is longer, or use of any investigational RSV 
vaccines after HCT, and throughout the study. 




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the treatment and should inform the Sponsor's Medical Monitor. Information relating to 
unblinding (eg, 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 
 Safety and Risk Management group 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.  


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7. 
STUDY CONDUCT AND VISIT SCHEDULE  
7.1 
Study Site Visits 
Details of assessments at each study site visit are presented in the SoA (Appendix 1). Study sites 
will be responsible for following up with subjects for any missed study site visits. 
7.1.1 
Screening Period (Day-1 to Day 1) 
Screening procedures (from Day-1 to Day 1) will occur after the subject signs and dates an 
institutional review board (IRB)- or ethics committee (EC)-approved ICF and provides 
authorization to use protected health information (see Section 12.1.3). The ICFs will be 
completed before conduct of any study-specific procedures. 
After signing the ICF, screening assessments will be assessed within 24 hours before dosing. 
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 performed up 
to 3 days before informed consent and chest imaging performed within 2 days before informed 
consent, as specified in Section 8 and the SoA (Appendix 1). As required, screening safety 
laboratory test samples will be sent to the local laboratory for expedited testing.  
After signing the ICF, Screening should be completed as soon as possible, and the subject will be 
randomized and administered the first dose of study drug within 24 hours of signing the ICF. 
7.1.2 
Treatment Period (Days 1 to 21) 
Study Site Visits (Days 1, 4, 7, 11, 16, and 21):  
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 to receive 
 EDP-938 or 
placebo administered orally for 21 days. Subject randomization will be stratified by ribavirin 
treatment (presence or absence) and ALC (<200 or ≥200 cells/µL). Presence of ribavirin 
treatment will be defined as ≥1 dose of ribavirin (oral, intravenous, or aerosolized) before 
randomization or with written orders for the initiation of therapy at the time of randomization. 
The study drug treatment duration is 21 days, during which 6 study visits will be performed. 
Randomized subjects will be assigned to an electronic device
. 
Following randomization on Day 1, subjects must complete baseline assessments before 
receiving the first dose of EDP-938 or placebo. Although prior local safety laboratory test results 
may have been used to determine eligibility, separate safety laboratory samples must be collected 
and sent to the central laboratory for baseline assessment. If Screening and randomization/first 
dose occur on the same day (Day 1), then screening assessments for vital signs and pulse 
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(Day 1) occur on different calendar days within a 24-hour period, then vital signs and pulse 
oximetry will be performed again on Day 1 (predose). 
Subjects will receive the first dose of study drug while at the study site and will be instructed to 
take EDP-938 or placebo QD at approximately the same time every day (±1 hour) on each of the 
20 subsequent days. The subject will also receive instructions on the appropriate storage and 
transport of study drug. At each study visit, subjects should bring their study drug with them as 
part of their study site visit for drug accountability and for dosing of study drug. If a subject is 
unable to attend a study site visit, a home visit by study site personnel may be arranged, if 
feasible. 
Except for Screening and Day 1 visits, visit assessments for other visits may be completed at the 
study site or by study site personnel via a home visit, if feasible. 
During study visits throughout the Treatment Period, safety assessments, blood collections, and 
nasopharyngeal swab collections will be conducted as specified in the SoA (Appendix 1). Safety 
evaluations will include assessment of clinical laboratory findings, physical examination findings 
(as applicable), vital sign measurements, pulse oximetry measurements, AEs, and concomitant 
medications. Other assessments include incidences of hospitalization, ICU admissions or 
utilization of ICU care for >24 hours, incidences of MAARI, standard of care test results 
(eg, chest imaging reports, laboratory tests, ECGs), mechanical ventilation, and supplemental 
oxygen use (≥2 L/min for >24 hours).  
All study assessments during the Treatment Period are detailed in the SoA (Appendix 1). 
7.1.3 
Follow-up Period (Days 22 to 49)  
Study Site Visits (Days 28 and 49): 
Follow-up visits will occur 1 and 4 (EOS visit) weeks after the last dose of study drug for all 
subjects including those who discontinue treatment early (ie, before completing 21 days of 
dosing). Visit assessments may be completed at the study site or by study site personnel via a 
home visit, if feasible. 
All study assessments during the Follow-up Period are detailed in the SoA (Appendix 1). 
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 
Subject Withdrawal/Early Termination/Completion 
Subjects will be considered to have completed treatment if they did not permanently discontinue 
treatment before the EOT visit. Subjects will have completed the study if they completed the full 
Treatment Period and full Follow-up Period. 
If a subject 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 


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collected. Enanta Pharmaceuticals, Inc. may retain and continue to use any data collected before 
such withdrawal of consent. 
Any randomized subjects who withdraw or are withdrawn from the study will not be replaced. 
7.2.1 
Withdrawal Criteria 
Reasons for discontinuation include but are not limited to the following: 
• AE 
• Lack of efficacy 
• Lost to follow-up 
• Withdrawal by subject 
• Protocol deviation (including noncompliance with study drug or study procedures) 
• Pregnancy 
• Study terminated by the Sponsor 
• Other 
7.2.2 
Procedures for Early Discontinuation or Early Termination of Treatment 
Subjects who discontinue treatment before completing 21 days of dosing should return to the 
study site within 24 hours after the last dose of study treatment to complete an EOT visit, 
including EOT PK sample collection. Subjects should then return to the clinic for the Follow-up 
Visit 1 (EOT + 1 week) and the EOS visit 4 weeks following the last dose of the study drug. 
Subjects who discontinue the study before Day 28 should return to the site within 48 hours to 
complete Follow-up Visit 1 (EOT + 1 week) procedures. Subjects who discontinue the study 
early between Day 28 and Day 49 should return to the study site within 48 hours to complete the 
EOS procedures (see Appendix 1). Any subject who withdraws with ongoing AEs/SAEs should 
be followed 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 who does not return to the site for the EOS visit at 
least three times using the subject’s preferred method of communication, followed by a letter 
requiring delivery notification if the three 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 11.3. 
7.2.3 
Documentation of Withdrawal of Subjects 
The reason for early withdrawal/termination/lost to follow-up of any subject from the study must 
be documented in source and on the appropriate eCRF. If the reason for early withdrawal is an 


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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). 
8.2 
Demographics and Medical History 
Demographics and baseline characteristics including year of birth and age, gender or sex, race (if 
available), ethnicity (if available), medical history, and smoking history will be obtained from 
each subject and entered in the eCRF as reported at Screening. Significant medical history will 
be obtained by consulting with the subject. As a general rule, all medical events occurring within 
the last 6 months should be recorded. For events that occurred more than 6 months ago (and that 
are not ongoing), only significant or relevant events should be recorded on source and entered in 
the eCRF. Any items in the history that are still ongoing should be noted as such in the eCRF. 
All surgeries occurring in adulthood should be recorded in the eCRF, whereas surgical methods 
of contraception, if applicable, should only be documented in the source documents. 
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. 
8.2.1 
Prior and Concomitant Therapies 
Prior therapies will include medications and other therapies (including surgeries and other 
interventions) that end prior to the first dose of study drug. Concomitant therapies will include 
medications and other therapies (including surgeries and other interventions) ongoing at the first 
dose of study drug or started any time after the first dose of study drug.  
Any medication or therapy taken within 1 month of signing the ICF and during the study through 
the end of 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. Any therapies, including 
supplemental oxygen, administered while the subject is participating on the study will also be 
documented in source and reported on the eCRF. All subjects will be questioned about 
concomitant therapies at each study site visit. 
8.3 
Clinical Evaluations 
8.3.1 
Chest Imaging 
Chest imaging (CXR and/or CT) obtained within 2 days before signing the ICF may be used to 
determine a subject’s eligibility. If chest imaging is not available or was not obtained during 
standard care within 2 days before signing the ICF, it must be obtained at Screening.  


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8.3.2 
Vital Sign Measurements  
Vital signs include heart rate, respiratory rate, systolic and diastolic blood pressure, and body 
temperature. Vital signs will be measured at times shown in the SoA (Appendix 1) after the 
subject has been supine for a minimum of 5 minutes. Pulse oximetry will be performed to 
measure oxygen saturation as indicated in the SoA (Appendix 1). 
8.3.3 
Electrocardiograms  
A resting 12-lead ECG will be performed locally and recorded as specified in the SoA 
(Appendix 1) after the subject has been supine for 5 minutes and before dosing. A standard 
bedside 12-lead ECG machine that calculates heart rate and measures PR, QRS, QT, RR, and 
QTcF intervals will be used.  
At Screening on Day 1, 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 by the Investigator or 
designee to confirm that no clinically significant cardiac abnormalities are present. 
8.3.4 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. 
Clinically significant abnormalities should be recorded as AEs. 
The physical examination performed at Screening will be used as the baseline assessment. If 
Screening (Day -1) and Randomization/first dose (Day 1) occur on different calendar days within 
a 24-hour period, a subsequent physical examination will not be required unless it is deemed 
necessary by the Investigator due to new signs and symptoms or for specific assessments of 
changes from previous status. 
8.3.5 Height, Weight, and Body Mass Index 
Height and body weight should be obtained with the subject in light clothes and no shoes. Height 
will be documented at Screening only whereas weight will be measured at all visits.  
Body mass index will be calculated at Screening (to assess eligibility) and all other visits 
according to the following equation: 
BMI = weight (kg)/height (m)2 


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8.3.6 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. The following are 
examples of open-ended questions that may be used to obtain this information: “How are you 
feeling?”; “Have you had any medical problems recently?”; and “Have you taken any new 
medicines since your last visit/assessment?” 
It is the Investigator’s responsibility to ensure any necessary additional therapeutic measures and 
follow-up procedures are performed and documented in the subject source notes and eCRF.  
8.3.7 Lower Respiratory Tract Complications Clinical Source for Endpoint Adjudication 
Committee Review 
During the course of the study, it is anticipated that chest images, and other clinical evaluations 
and laboratory tests will be performed as part of standard of care if there is any concern of a 
LRTCs. In addition to eCRF data relevant to safety assessments, the following source will be 
submitted to adjudicators: 
• Chest images: Images and results for chest imaging used for Screening and eligibility, 
including the comparison chest imaging, and all scans done as part of the standard of care 
while subjects are on study, will be collected and stored electronically for review by the 
Endpoint Adjudication Committee. 
• Results of all local microbiological tests performed while on study (all bacterial, viral, 
fungal, parasitic, or other test results from samples obtained from any respiratory 
specimen [eg, bronchoalveolar lavage, sputum, pleural fluid, lung tissue] and from blood 
specimens, including bacterial culture, viral polymerase chain reaction, and serology 
studies). 
• Clinical notes with range of dates, including outpatient notes with vital signs, outpatient 
laboratory and hospital discharge summaries, as appropriate.  
• Autopsy reports (if performed). 
• Other supporting documentation, as requested, including by the Endpoint Adjudication 
Committee. 
8.3.8 
 
 
 
 
 


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8.3.9 Collection of Swabs and Blood Samples for Virology Assessments 
Refer to Section 8.5 for samples that will be collected for diagnosis and virology assessments. 
Nasopharyngeal swabs (one from each nostril) for virology assessments will be collected predose 
at visits specified in the SoA (Appendix 1). The RSV specific tests are indicated in Table 1. 
Residual volume from the nasopharyngeal swab sample collection may be stored 
 
. 
8.4 
Laboratory Procedures 
At Screening, clinical laboratory evaluations of blood samples will be performed at the local site 
laboratory for expedited testing and reporting if existing values collected in the 3 days before 
signing the ICF are not available to assess eligibility. Clinical laboratory evaluations to be 
assessed at Screening are noted in Table 1 with “a” and described in corresponding footnote a. 
On Day 1, randomized subjects will undergo the clinical laboratory evaluations of blood and 
urine samples specified in Table 1, which will be performed at the central laboratory(ies) as a 
baseline measurement. Subsequent clinical laboratory evaluations will be performed by the 
central laboratory(ies). Only central laboratory values will be collected for analysis.  
The Day 1 collection of blood and urine will be completed before administration of study drug.  
A Laboratory Manual will be provided to the site detailing kit contents, reordering supplies, 
sample collection, handling, storage, and shipment instructions. All unblinded laboratory values 
will be reviewed by the Investigator, documented, and the results maintained in the source 
documents. All out-of-range laboratory findings require an interpretation as to whether or not 
they are of clinical significance. Clinically significant laboratory findings in the opinion of the 
Investigator should be recorded as an AE (or SAE as appropriate) (see Section 9.1). 
8.4.1 Safety Laboratory Panels 
Safety laboratory tests include chemistry, hematology, and urinalysis. Blood samples will be 
collected for analysis of the analytes as shown in Table 1. Samples will be collected from all 
subjects randomized into the study.  
Blood and urine samples for clinical laboratory assessments will be collected according to the 
SoA (Appendix 1) and processed as indicated in the Laboratory Manual. Estimated glomerular 
filtration rate will be calculated using the MDRD equation. 


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8.4.2 Pregnancy and Menopausal Laboratory Testing 
All female subjects of childbearing potential will undergo a urine pregnancy test at Screening, 
Day 28 (EOT + 1 week), and at the EOS (EOT + 4 weeks) visit. In addition, on Day 1, a blood 
sample will be collected for a serum pregnancy test to be performed by the central laboratory. 
The screening urine pregnancy test results will be used to qualify subjects at study entry. 
To confirm nonsurgical postmenopausal status for women stating that they are amenorrhoeic for 
1 to 2 years, documentation of FSH levels >35 mIU/mL will be required. Where such 
documentation is not available, FSH levels will be measured on Day 1. In such subjects, urine 
and serum pregnancy testing should also be performed at Screening, and these subjects will be 
required to follow appropriate contraceptive practices for women of childbearing potential until a 
confirming FSH level is available. 
8.4.3 Calcineurin Inhibitor and mTOR Inhibitor Levels 
For subjects taking a calcineurin inhibitor (CNI) and/or mTOR inhibitor, blood samples will be 
harvested at timepoints indicated in the SoA (Appendix 1) and sent to both the central and local 
laboratories where the CNI and mTOR inhibitor levels will be measured. Management of CNI 
and mTOR inhibitor levels (including obtaining additional CNI or mTOR inhibitor levels as 
clinically indicated) will be at the Investigator’s discretion based on levels reported by the local 
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Table 1: 
Clinical and Respiratory Syncytial Virus Laboratory Evaluations 
CHEMISTRY PANEL 
Alanine aminotransferasea 
Albumin, seruma 
Alkaline phosphatase, serum a 
Amylasea 
Aspartate aminotransferasea 
Bilirubin, total and directa 
BUNa 
BUN/creatinine ratio (calculation) 
Calcium, serum 
Creatine kinase 
Creatinine, seruma 
Glomerular filtration rate, estimated 
Uric acid 
Electrolyte panel (sodium, potassium, 
chloride, bicarbonate)a 
Phosphorus 
Gamma glutamyl transferase 
Globulin, total 
Glucose, seruma 
Cholesterol 
Triglycerides 
Lactate dehydrogenase 
Lipase 
Protein, total serum 
Calcineurin and mTOR inhibitorsb 
HEMATOLOGY PANEL 
Hemoglobina 
Hematocrita 
Differential white blood cell count, percentage and 
absolute (basophils, eosinophils, lymphocytes, 
monocytes, neutrophils)a 
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin concentration 
Mean corpuscular volume 
Platelet counta 
Red blood cell count 
White blood cell counta 
International normalized ratioa 
Prothrombin timea 
Activated thromboplastin timea 
RSV-SPECIFIC TESTS  
RSV diagnostic test (nasopharyngeal or other 
appropriate secretions), if necessary 
Confirmatory respiratory pathogen panel  
RSV RNA quantitation of viral load (nasopharyngeal 
secretions) 
RSV RNA quantitation of live viral load using cell-
based infectivity assay (nasopharyngeal secretions) 
RSV subgroup/genotype determination 
(nasopharyngeal secretions) 
Viral resistance (nasopharyngeal secretions, archived) 
RSV serology (neutralizing antibodies, serum, 
archived) 
URINALYSIS  
Routine urinalysis to include: color and 
appearance, pH, specific gravity, bilirubin, 
glucose, ketones, leukocytes, nitrite, occult 
blood, protein, urobilinogen, microscopic 
examination (including red blood cells and 
white blood cells) 
PREGNANCY AND OTHER TESTS  
Urine pregnancy test  
Serum pregnancy test (only Day 1 and to the central 
laboratory) 
Follicle-stimulating hormone 
Abbreviations: BUN = blood urea nitrogen; mTOR = mammalian target of rapamycin; RSV = respiratory syncytial virus. 
a 
If existing values collecting in the 3 days before signing the ICF are not available for these identified tests to 
assess eligibility at Screening, blood and urine samples for these tests should be taken and sent to the local 
laboratory for testing and reporting in an expedited manner. 
b 
Samples will be collected and analyzed only for subjects taking calcineurin and mTOR inhibitor(s).  


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8.5 
Virology Assessments 
Virology assessments and tests (Table 1) will be performed using nasopharyngeal or other 
appropriate swab (rapid diagnostic screen) or nasopharyngeal swab samples (other virology 
assessments) and serology samples collected at Screening and at timepoints indicated in the SoA 
(Appendix 1). The tests are further described in the Laboratory Manual, including swab 
collection, sampling, and handling procedures. Multiple nasopharyngeal swab samples may be 
collected at each timepoint. With the exception of the rapid diagnostic screen for RSV that will 
be performed at the local site laboratory, all other virology/RSV assessments will be analyzed at 
the central laboratory(ies). 
8.5.1 Respiratory Syncytial Virus Rapid Diagnostic Test 
RSV diagnostic testing determined in the 3 days before signing the ICF or at Screening may be 
used to assess eligibility. Subjects who were not tested for RSV as standard of care in the 3 days 
before signing the ICF may consent to the study and be tested for RSV during the Screening 
visit. A nasopharyngeal or other appropriate swab sample will be collected to obtain respiratory 
secretions. Subjects whose swab sample tests positive for RSV may proceed for further screening 
assessments. Results will be recorded in the source documents.  
8.5.2 Confirmatory Respiratory Pathogen Panel  
Following randomization on Day 1, a nasopharyngeal swab sample(s) will be obtained before 
taking the first dose of EDP-938 or placebo for central laboratory analysis and confirmation of 
respiratory pathogens recovered. This testing will be performed to identify other nasopharyngeal 
co-pathogens that may include adenovirus, coronavirus including SARS-CoV-2, human 
metapneumovirus, human rhinovirus/enterovirus, parainfluenza virus, Chlamydophila 
pneumoniae, and/or Mycoplasma pneumoniae, which may impact the course of a subject’s 
illness. Refer to the Laboratory Manual for further details. 
8.5.3 Respiratory Syncytial Virus Viral Load Quantification 
The RSV viral load will be measured in nasopharyngeal swabs by an infectious virus cell-based 
infectivity assay and RT-qPCR assay at the timepoints specified in the SoA (Appendix 1). The 
RT-qPCR will also be used to determine viral dynamics (eg, peak viral load and time to peak). 
Refer to the Laboratory Manual for further details. 
8.5.4 Respiratory Syncytial Virus Subgroup/Genotype Determination 
Nasopharyngeal swab sample(s) at Baseline (Day 1) will be analyzed to determine the subgroup 
(A or B) and genotype of RSV. 


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8.5.5 Viral Resistance 
Nasopharyngeal swab sample(s) may be analyzed for potential viral resistance monitoring 
assessment. Resistance monitoring assessment, if performed, will be conducted by population 
and/or deep sequencing of the RSV gene to monitor for treatment-emergent RAVs. Phenotypic 
analysis using reverse genetics system may also be performed to determine the susceptibility of 
the RAVs to EDP-938. Refer to the Laboratory Manual for further details. 
8.5.6 Respiratory Syncytial Virus Serology 
At the timepoints specified in the SoA (Appendix 1), samples will be collected for RSV serology 
assessment using the RSV neutralization antibody assay. Refer to the Laboratory Manual for 
further details. 
8.6 
Pharmacokinetic Samples 
Blood (plasma) samples for PK analysis will be collected as outlined in the SoA (Appendix 1). 
On Day 1, Day 7, and Day 21, two samples will be collected: one predose, collected within 
1 hour before dosing (preferably within 30 minutes of dosing if possible) and at the same 
approximate time as that of the nasopharyngeal swab collection; and one postdose sample 
collected 1 to 3 hour post dose.  
At all other visits, one predose plasma PK sample will be collected at the same approximate time 
as that of the nasopharyngeal swab collection. Subjects who discontinue treatment before 
completing 21 days of dosing should return to the study site within 24 hours from the last dose of 
study treatment to complete an EOT visit. One plasma PK sample will be collected at the same 
approximate time as that of the nasopharyngeal swab collection. 
The time and date of PK sample collection should be recorded in source and in the eCRF. Study 
drug (EDP-938 or placebo) should be administered during the study visit on days when clinic 
visits occur. Study visits should be scheduled close to the time that the subject normally takes the 
study drug so that dosing expected on the day of the visit can occur during the visit. In addition, 
the site should record the date and time of last dose taken before the PK sample collection. See 
Section 5.7 for additional dosing details. 
Blood samples will be collected and processed to measure plasma concentrations of EDP-938 
 according to the procedures provided and/or approved by Enanta 
Pharmaceuticals, Inc. Additional details will be provided in the Laboratory Manual. 
EDP-938 
 
 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 
 by the laboratory selected by 
Enanta Pharmaceuticals, Inc. 


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Pharmacokinetic samples may be stored and used for 
 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 (CSR). 
8.7 
 
 
 
 
 
8.8 
Endpoint Adjudication Committee 
Blinded reviewers will review relevant clinical data and source documentation to determine 
whether a LRTC has developed. These relevant clinical data and documentation (ie, clinical 
notes, radiology reports, and microbiology results) will be used to determine if one of the 
following has occurred: 


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• Primary RSV LRTI  
o New findings on chest imaging compared with screening baseline chest image 
consistent with a viral LRTI AND 
o Positive RSV test from lower respiratory tract within ±7 days of new chest image 
findings 
• Secondary bacterial LRTI  
o New findings on chest imaging compared with screening baseline chest image 
consistent with a bacterial LRTI AND 
o Evidence of a significant bacterial infection in lower respiratory tract within ±7 
days of new chest image findings 
• LRTI due to unusual pathogen 
o New findings on chest imaging compared with screening baseline chest image 
consistent with a lower respiratory tract infection AND 
o Positive microbiologic test for atypical bacteria, fungus, or other respiratory 
viruses within ±7 days of new chest image findings 
• LRTC due to unknown etiology 
o New findings on chest imaging compared with screening baseline chest image 
consistent with an LRTI, inflammatory process or some other clinically 
significant pulmonary process AND 
o No organisms documented from lower respiratory tract 
 
Detailed definitions for each of the above diagnoses will be provided to the adjudication 
committee in the Endpoint Adjudication Committee Charter. 
 


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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. Adverse events 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 (eg, 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 (eg, 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 


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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 
o Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a 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) 
Adverse events 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. 
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 
(ie, alternates or screen failures), AEs will only be recorded in the source documents. For 
subjects enrolled into the study (ie, 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. 
Adverse events (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 


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• 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  
• 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 (eg, 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 
The following events will not be identified as AEs in this study:  
• Medical or surgical procedures (eg, 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 have been ruled out, and/or the event reappeared on re-exposure to the 
study drug.  


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• 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 subject’s clinical 
status or underlying disease.  
• 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 by the Investigator or 
designee are defined in Table 2. 
Table 2: 
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 3. One outcome must be entered into the appropriate field on the AE and (if 
appropriate) SAE form for each event. 


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Table 3:  
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 symptoms  
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 adverse event 
Unknown  
Outcome of an adverse event is not known (eg, a subject lost to 
follow-up)  
9.2.5 
Documenting and Reporting Serious Pretreatment Events and Serious Adverse 
Events 
All SAEs that occur after obtaining informed consent through the EOS visit, regardless of 
causality, must be reported by the Investigator or designee to 
 
and Enanta Pharmaceuticals, Inc. In addition, all SAEs, including those that result in death, that 
occur after the EOS visit and that are considered related to study drug must be reported to 
 and Enanta Pharmaceuticals, Inc. within 24 hours of learning of its 
occurrence. Additional details are provided in the Safety Management Plan. The SAE form 
should be sent to
. 
 
Serious Adverse Event and Pregnancy Reporting 
 
 
Email at 
 
Faxed to
 
Phone contact is 
 
 
All SAEs will be recorded on the SAE form using a recognized medical term or diagnosis that 
accurately reflects the event. All SAEs will be assessed by the Investigator for severity, 
relationship to the investigational study drug, and possible etiologies. On the SAE form, 
relationship to study drug will be assessed only as related or not related. For the purposes of 
study analysis, if the event has not resolved at the end of the study reporting period, it will be 
documented as ongoing.  


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For purposes of regulatory safety monitoring, the Investigator is required to follow up the event 
to resolution and report the outcome of the event to 
, and Enanta Pharmaceuticals, Inc. using the SAE form.  
The Investigator or designee is responsible for notifying the Sponsor within 24 hours of 
identifying an SAE, regardless of the presumed relationship to the investigational study drug. 
The SAE form should be completed for new/initial events as well as to report follow-up 
information on previously reported events. The Investigator or designee is asked to report 
follow-up information as it becomes available.  
Enanta Pharmaceuticals, Inc. or its designee, as study Sponsor, is responsible for reporting 
suspected, unexpected, serious adverse reactions (ie, SUSARs) involving the study drug to all 
regulatory authorities, and participating investigators, in accordance with United States Food and 
Drug Administration (FDA), International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use (ICH) guidelines, and/or local regulatory requirements, as 
applicable. 
9.2.6 
Documenting and Reporting of Pregnancy 
Subjects will be counseled to inform the Investigator of any pregnancy that occurs during study 
drug and for 90 days after the last dose of study drug. 
If a female subject or the female partner of a male subject becomes pregnant while participating 
in the study, study drug must be permanently discontinued immediately. The Investigator or 
designee must notify 
 (Section 9.2.5), the Sponsor’s Medical 
Monitor, and
 within 1 business day of the sites’ knowledge of the 
subject’s (or partner’s) pregnancy, by utilizing the study-specified pregnancy report form.  
If confirmed to be on active drug, the subject or partner will be followed up until the end of the 
pregnancy and the infant will be followed up for 3 months after the birth, provided informed 
consent is obtained. A separate ICF will be provided to explain these follow-up activities. 
Pregnancy itself does not constitute an AE. 
9.3 
Follow-up of Adverse Events and Serious Adverse Events 
All AEs (serious and nonserious) will be followed up until resolution or otherwise explained (see 
Table 3), the subject dies, the event stabilizes and is not expected to further resolve with the 
maximum time limit for stabilization defined as 30 days after the occurrence of the event, or 
when alternative therapy is instituted, whichever occurs first. If alternative therapy is instituted, it 
should be documented. Enanta Pharmaceuticals, Inc. may request that the Investigator perform 
or arrange for supplemental measurements or evaluations to further clarify the nature of the 
event. 


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9.4 
Data Monitoring Committee 
Safety data from this study will be reviewed by a DMC throughout the study. The DMC will be 
headed by a DMC Chair and will include one or more physicians with expertise in transplant 
medicine, consisting of expert(s) independent from the Sponsor. Procedures for data review, 
including timing and potential outcomes, roles and responsibilities, and interactions with the 
Sponsor and PPD, will be governed by a separate DMC charter. 


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10. 
STUDY STOPPING AND DISCONTINUATION RULES  
10.1 Study Stopping Rules 
If either of the following events occur, enrollment will be paused pending a full review of all 
available clinical safety data and discussion with the DMC: 
• One subject has a Grade 4 AE or SAE that is judged as possibly related to study drug 
• Two subjects experience the same Grade 3 AE that is judged as possibly related to study 
drug 
Unless the subject’s randomization code is unblinded by the Sponsor for clinical reasons, only 
the DMC will have access to unblinded data. 
10.2 Site or Study Discontinuation 
10.2.1 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: 
• Incidence or severity of AEs in this study indicates a potential health hazard to subjects 
• 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 
• 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. 
10.2.2 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 


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• 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 
10.2.3 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 designated 
laboratory 
 


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11. 
STATISTICAL CONSIDERATIONS 
11.1 General Considerations 
Statistical analysis of this study will be the responsibility of Enanta Pharmaceuticals, Inc. or its 
designee. Details of the statistical analysis methods will be described in the statistical analysis 
plan (SAP) document.  
Continuous endpoints will be summarized using n, mean, standard deviation, median, 
25th quartile, 75th quartile, minimum, and maximum values. Categorical endpoints will be 
summarized by the number of subjects meeting the endpoint and the percentage of subjects out 
of the appropriate population. The denominator will be displayed when needed. Statistical 
inference will be performed as appropriate. Inferential testing will be conducted using a 
two-sided alpha of 0.05, unless stated otherwise. Reference to stratification factors will include 
ribavirin treatment (presence or absence) and ALC (<200 or ≥200 cells/µL) at Screening. 
Any change to the data analysis methods described in the protocol will require an amendment if 
it changes a principal feature of the protocol. Any other change to the data analysis methods 
described in the protocol, and the justification for making the change, will be described in the 
CSR or SAP. The SAP will be developed and finalized before database lock. Changes to the SAP 
may not be made after unblinding of treatment assignments (after database lock). 
11.2 Sample Size Considerations 
Assuming an LRTC rate of 30% for placebo, then a 20% reduction with 90% power and a 
two-sided alpha at 0.05 using a unpooled z-test, with a ratio of 2:1 would require approximately 
160 subjects. Assuming a 15% dropout rate a total of 190 subjects will be randomized. 
11.3 Analysis Populations 
The following analysis populations are planned:  
• Intent-to-Treat (ITT) Population: All subjects who receive at least one dose of study 
drug. Subjects will be analyzed as treated. The ITT Population is designated as the 
primary efficacy population. 
• Per Protocol Population: All subjects who are randomized and receive all planned doses 
of study drug and do not have major protocol deviations that may unduly influence 
outcome. Subjects will be analyzed in the treatment group that corresponds to the study 
drug received during the study. 
• Safety (SAF) Population: All subjects who receive at least one dose of study drug. 
Subjects will be analyzed in the treatment group that corresponds to the study drug 
received during the study. 
• Pharmacokinetic (PK) Population: All subjects receiving active study drug and having 
any measurable plasma concentration of study drug at any timepoint. 


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11.4 Subject Disposition and Demographic Data 
The number of subjects screened, randomized, and in the SAF and PK 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 SAF 
Population. Appropriate baseline characteristics will be included in addition to demographic 
characteristics. No statistical testing will be performed. 
11.5 Method of Treatment Assignment 
Subjects who meet all criteria for enrollment will be randomized to blinded treatment on Day 1 
in a 2:1 ratio to 
 EDP-938 or placebo. Assignment to treatment groups 
will be determined by a computer-generated random sequence using an IWRS. The IWRS will 
be used to assign investigational product to each subject. To achieve between group 
comparability, the randomization will be stratified by presence or absence of ribavirin treatment. 
11.6 Efficacy Analyses  
11.6.1 Primary Efficacy Analyses 
The proportion of LRTC between EDP-938 and placebo will be compared using a Cochran 
Mantel-Haenszel test with ribavirin treatment (presence or absence) and ALC (<200 or 
≥200 cells/µL) as stratification factors. The primary analysis will be using the ITT Population 
based on the results of the Endpoint Adjudication Committee. Subjects with missing LRTC data 
will be treated as a nonresponse. A Fisher’s exact test will be used to compare groups within 
each strata. A two-sided 95% confidence intervals for the odds ratio between groups based on 
stratum adjusted Mantel Haenszel proportions. Frequency and proportion of subjects who 
develop LRTC will be provided using 95% confidence intervals based on the normal 
approximation method. If stratification leads to small cell sizes a modification of the strata may 
be performed. This will be described in detail in the SAP. 


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11.6.2 Secondary Efficacy Analyses 
 TSS AUC will be calculated for overall and individual components. All 
parameters will be analyzed using an analysis of covariance (ANCOVA) model with treatment 
group and stratification factors as fixed effects and the baseline TSS as a covariate. Treatment 
groups will be compared using a type III sum-of-squares. Other sensitivity analysis may include 
a mixed model repeated measures analysis on the change from Baseline over all visits. 
The RSV RNA viral load AUC measured in nasopharyngeal swab samples by RT-qPCR will be 
measured. The trapezoid rule will be used to calculate the AUC of the RSV RNA viral load. An 
ANCOVA model with treatment group and stratification factors as fixed effects, and the baseline 
RSV RNA viral load as a covariate will be performed. Treatment groups will be compared using 
a type III sum-of-squares. The proportion of subjects with RSV RNA below the limit of 
detection will be analyzed on days collected. Treatment groups will be compared using a 
Cochran-Mantel-Haenszel test controlling for the stratification factors 
11.7 Safety Analyses 
Statistical methods for the safety analyses will be primarily descriptive in nature. Safety data, 
including AEs, SAEs, vital sign measurements, concomitant medications, and laboratory values, 
will be summarized separately by treatment group. Change from Baseline will be included in 
summary tables for vital sign measurements and laboratory parameters. Shift tables will also be 
generated by laboratory analyte. All laboratory data will be included in the data listings, and all 
test values outside the normal range will be flagged. 
11.7.1 Adverse Events 
Adverse events will be summarized by the Medical Dictionary for Regulatory Activities system 
organ class and preferred term by treatment group. All subjects in the SAF Population will be 
included in the summaries. Treatment-emergent AEs (TEAEs) are defined as reported AEs that 
first occurred or worsened during the post-Baseline phase compared with Baseline. 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  
o TEAEs by severity  
o TEAEs leading to study drug discontinuation  


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o AEs leading to death  
o SAEs  
o Related treatment-emergent SAEs  
11.7.2 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. 
11.7.3 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. Pulse oximetry measurements will be summarized by visit and 
treatment. 
11.7.4 Electrocardiograms 
Screening ECG data will be provided in data listings. 


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11.7.5 Concomitant Medications 
The number and percentage of subjects taking 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 SAF Population will be summarized by treatment group. 
11.7.6 Physical Examinations 
Physical examination data will be provided in data listings. 
11.8 Pharmacokinetic Analyses 
Summary of plasma PK concentration data will be descriptive in nature. Mean plasma 
concentration-time figures may be created for EDP-938 
, as allowed by the 
data. Additional details will be provided in the SAP. 
11.9 Subgroup and Covariate Analyses 
Subgroup analyses will be performed on the primary and secondary endpoints, primarily. A 
logistic regression model will be planned when categorical endpoints are analyzed. For 
continuous endpoints, an ANCOVA model with treatment group and stratification factor as fixed 
effects in the model, with subgroup and subgroup-by-treatment interaction. Various study 
populations may be used. Forest plots will be provided to visually describe the association. 
11.10
 
 
 
 
11.11 Interim Analyses 
An interim analysis may be conducted, if deemed necessary by the Sponsor. 


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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 (CFR) 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, and all advertisements that may be used for study-specific recruitment to the IRB/EC for 
review and approval before commencing study-specific assessments. If it is necessary to amend 
the protocol during the study, then 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. A copy of the ICF approved by the IRB/EC must be forwarded to Enanta 
Pharmaceuticals, Inc. for regulatory purposes. 
12.1.3 Written Informed Consent 
The Investigator or designee must explain to each subject the purpose and nature of the study, 
the study procedures, the possible adverse effects, and all other elements of consent as defined in 
21 CFR Part 50, and other applicable national and local regulations governing informed consent.  
Each subject must provide a signed and dated ICF before enrollment into this study. 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 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 designee, 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 
authorization. It is the Investigator’s or designee’s responsibility to obtain written permission to 
use protected health information from each subject, or if appropriate, the subject’s legal 
guardian. If a subject or subject’s legal guardian withdraws permission to use protected health 
information, it is the Investigator’s responsibility to obtain the withdrawal request in writing 


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from the subject or subject’s legal guardian 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.  
12.1.4 Investigator Compliance 
No modifications to the protocol should be made without the approval of both the Investigator 
and Enanta Pharmaceuticals, Inc. Changes that significantly affect the safety of the subjects, the 
scope of the investigation, or the scientific quality of the study (ie, efficacy assessments) will 
require IRB/EC notification before implementation, except where the modification is necessary 
to eliminate an apparent immediate hazard to human subjects.  
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 
Study data 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. Subjects who did not randomize will not be entered into the clinical database. Reasons for 
screen failure will be collected in the interactive response technology (IRT) system. In addition, 
criteria for confirming RSV eligibility will be collected in IRT.  
Source documentation supporting the clinical 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 designees 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 


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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 
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 designees 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 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 a 
minimum of 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 or any other identifiers will remain confidential and will not be supplied to Enanta 
Pharmaceuticals, Inc. or its designees. Only subject number and year of birth with age will be 
recorded on the eCRF. 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 designees. All study findings will be stored in electronic databases. 
As indicated in the ICF, subjects will give permission for representatives of the Sponsor, 
regulatory authorities, and the IRB/EC to inspect their medical records to verify the information 
collected. Subjects will be informed that all personal information made available for inspection 


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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 prior knowledge and permission. 
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. The Sponsor, Enanta Pharmaceuticals, Inc. reserves the right, among other things, to the 
following: 
• 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 
Ahmad A, Sanderson K, Dickerson D, et al. EDP-938, a novel, non-fusion replication inhibitor of 
respiratory syncytial virus: final results of a Phase 1 study in healthy subjects (HS). Poster session 
presented at: 11th International Respiratory Syncytial Virus Symposium; 2018 Oct 31-Nov 4, Asheville, 
NC. 
Boeckh M, Enlgud J, Li Y, et al. Randomized controlled multicenter trial of aerosolized ribavirin for 
respiratory syncytial virus upper respiratory tract infection in hematopoietic cell transplant recipients. 
Clin Infect Dis. 2007;44 (2):245–249. 
Busca A, Pagano L. Antifungal Therapy in Hematopoietic Stem Cell Transplant Recipients. Mediterr J 
Hematol Infect Dis. 2016;8(1):e2016039. Published 2016 Sep 1. doi:10.4084/MJHID.2016.039. 
Casey J, Morris K, Narayana M, Nakagaki M, & Kennedy GA. Oral ribavirin for treatment of 
respiratory syncitial virus and parainfluenza 3 virus infections post allogeneic haematopoietic stem cell 
transplantation. Bone Marrow Transplant 2013; 48(12):1558-61. doi:10.1038/bmt.2013.112. 
Chemaly RF, Dadwal SS, Bergeron A, et al. A phase 2, randomized, double-blind, placebo-controlled 
trial of presatovir for the treatment of respiratory syncytial virus upper respiratory tract infection in 
hematopoietic-cell transplant recipients. Clin Infect Dis. 2019;ciz1166. 
Falsey AR, Hennessey PA, Formica MA, et al. Respiratory syncytial virus infection in elderly and 
high-risk adults. N Engl J Med. 2005;352(17):1749-59. 
Foolad F, Aitken, SL, Shigle TL Prayag A, Ghantoji S, Ariza-Heredia E, & Chemaly RF. Oral Versus 
Aerosolized Ribavirin for the Treatment of Respiratory Syncytial Virus Infections in Hematopoietic Cell 
Transplant Recipients. Clin Infect Dis 2019; 68(10):1641-49. doi:10.1093/cid/ciy760 
Ghosh S, Champlin RE, Englund J, Giralt SA, Rolston K, Raad I, et al. Respiratory syncytial virus upper 
respiratory tract illnesses in adult blood and marrow transplant recipients: combination therapy with 
aerosolized ribavirin and intravenous immunoglobulin. Bone Marrow Transplant 2000; 25(7):751-55. 
doi:10.1038/sj.bmt.1702228 
Gorcea CM, Tholouli E, Turner A, Saif M, Davies E, Battersby E, & Dignan FL. Effective use of oral 
ribavirin for respiratory syncytial viral infections in allogeneic haematopoietic stem cell transplant 
recipients. J Hosp Infect 2017; 95(2):214-17. doi:10.1016/j.jhin.2016.11.012 
Gueller S, Duenzinger U, Wolf T, Ajib S, Mousset S, Berger A. et al. Successful systemic high-dose 
ribavirin treatment of respiratory syncytial virus-induced infections occurring pre-engraftment in 
allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 2013; 15(4):435-40. 
doi:10.1111/tid.12092 
Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young 
children. N Engl J Med. 2009;360(6):588-98. 
Ison MG and Hirsch HH. Community-acquired respiratory viruses in transplant patients: diversity, 
impact, unmet clinical needs. Clin Microbiol Rev. 2019;32(4):e00042-19. 
Khawaja F and Chemaly RR. Respiratory syncytial virus in hematopoietic cell transplant recipients and 
patients with hematologic malignancies. Haematologica 2019; 104(7):1322-1331. 


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Kontoyiannis, D. Antifungal prophylaxis in hematopoietic stem cell transplant recipients: the unfinished 
tale of imperfect success. Bone Marrow Transplant 2011; 46:165–73.  
Ljungman P, Ward, KN, Crooks BN, et al. Respiratory virus infections after stem cell transplantation: a 
prospective study from the Infectious Diseases Working Party of the European Group for Blood and 
Marrow Transplantation. Bone Marrow Transplant 2001; 28(5):479-84. doi:10.1038/sj.bmt.1703139 
Marty FM, Chemaly RF, Mullane KM, et al. A phase 2b, randomized, double-blind, placebo-controlled 
multicenter study evaluating antiviral effects, pharmacokinetics, safety, and tolerability of presatovir in 
hematopoietic cell transplant recipients with respiratory syncytial virus (RSV) infection of the lower 
respiratory tract. Clin Infect Dis. 2019;ciz1167.  
McColl MD, Corser RB, Bremner J, & Chopra R. Respiratory syncytial virus infection in adult BMT 
recipients: effective therapy with short duration nebulised ribavirin. Bone Marrow Transplant 1998; 
21(4):423-25. doi:10.1038/sj.bmt.1701091 
 
 
 
 
Shah, DP, Ghantoji SS, Shah JN, et al. Impact of aerosolized ribavirin on mortality in 280 allogeneic 
haematopoietic stem cell transplant recipients with respiratory syncytial virus infections. J Antimicrob 
Chemother 2013; 68(8):1872-80. doi:10.1093/jac/dkt111 
Shah JN and Chemaly RF. Management of RSV infections in adult recipients of hematopoietic stem cell 
transplantation. Blood. 2011;117(10):2755-63. 
Shook BC and Lin K. Recent advances in developing antiviral therapies for respiratory syncytial virus. 
Top Curr Chem (Cham). 2017:375(2):40. 
Whimbey, E., Champlin, R. E., Englund, J. A., et al. Combination therapy with aerosolized ribavirin and 
intravenous immunoglobulin for respiratory syncytial virus disease in adult bone marrow transplant 
recipients. Bone Marrow Transplant 1995;16(3):393-399. 






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l 
Height will be documented at Screening only. The BMI will be calculated at Screening (to assess eligibility) and other visits according to the following equation: 
BMI = (weight in kg)/(height in m2). 
m 
Pregnancy testing will be performed in female subjects of childbearing potential. A urine pregnancy test will be performed at Screening, Day 28, and at the EOS visit. In 
addition, on Day 1, blood will be collected for a serum pregnancy test to be performed by the central laboratory. The screening urine pregnancy test results will be used to 
qualify subjects at study entry. Refer to Section 8.4.2 of the protocol for pregnancy testing requirements for postmenopausal females. 
n 
FSH should be tested in postmenopausal females. Refer to Section 8.4.2 of the protocol. 
o 
Subjects who meet all inclusion criteria and none of the exclusion criteria will be eligible to enter the study and will be randomized 2:1 to receive 
 800 mg of 
EDP-938 or placebo. Subject randomization will be stratified by ribavirin treatment (presence or absence) and absolute lymphocyte count (<200 or ≥200 cells/µL) at 
Screening. 
 
 
q 
Two nasal/nasopharyngeal swabs, one from each nostril, will be collected predose at each visit. 
 
. 
r 
Subject participation is optional. Subjects will be required to review and sign a separate ICF for this assessment. Day 1 and 21 samples should be collected predose. 
s 
Study drug (EDP-938 or placebo) should be administered during the study visit on days when clinic visits occur. Study visits should be scheduled close to the time that the 
subject normally takes the study drug so that dosing can occur during the visit. See Section 5.7 for additional dosing details. 
t 
Subjects should bring their study drug with them as part of their study site visit for drug accountability and for dosing of study drug. Study drug accountability will occur 
through a tablet count at each visit during Treatment and up through the Day 21 EOT visit. 
u 
On Day 1, Day 7, and Day 21, two samples will be collected: one predose, collected within 1 hour before dosing (preferably within 30 minutes of dosing if possible) and at 
the same approximate time as that of the nasopharyngeal swab collection; and one postdose, collected 1-3 hours postdose. At all other visits, one predose plasma PK sample 
will be collected at the same approximate time as that of the nasopharyngeal swab collection. Time and date of collection should be recorded in source and in the eCRF. 
Subjects who discontinue treatment early (before completing 21 days of dosing) should return to the study site within 24 hours after the last dose of study treatment to 
complete an EOT visit. One plasma PK sample will be collected at the same approximate time as that of the nasopharyngeal swab collection.  
v 
For subjects taking CNI and/or mTOR inhibitor, a blood sample will be collected to be analyzed at the local laboratory for CNI and/or mTOR inhibitor blood levels and a 
separate sample will be collected for analysis at the central laboratory. 
w 
Standard of care test results may include chest imaging reports, laboratory tests, electrocardiogram , or other assessments.  
x 
Prior therapies will include medications and other therapies (including surgeries and other interventions) that end prior to the first dose of study drug. Concomitant therapies 
will include medications and other therapies (including surgeries and other interventions) ongoing at the first dose of study drug or started any time after the first dose of study 
drug. Any medication or therapy (including surgeries and other interventions) taken within 1 month of signing the ICF (Screening) and during the study through the end of the 
study will be recorded. 
 

SAP_001.pdf: 
Enanta Pharmaceuticals 
EDP 938-103 
A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY
EVALUATING THE EFFECTS OF EDP-938 IN HEMATOPOIETIC CELL TRANSPLANT
RECIPIENTS WITH ACUTE RESPIRATORY SYNCYTIAL VIRUS INFECTION OF THE
UPPER RESPIRATORY TRACT 
January 8th, 2024 
 Statistical Analysis Plan 
Version: Final 1.0 
Prepared by: 
Enanta Pharmaceuticals, Inc. 
500 Arsenal St. 
Watertown, MA 02472 
Page 2


Enanta Pharmaceuticals 
 Statistical Analysis Plan, Version: Final 1.0 
EDP 938-103  
      Date Issued: 8Jan2024 
Page 2 of 33 
Table of Contents 
TABLE OF CONTENTS ............................................................................................................. 2 
LIST OF ABBREVIATIONS ...................................................................................................... 4 
1 
INTRODUCTION ............................................................................................................ 6 
2 
OBJECTIVES ................................................................................................................... 6 
2.1 
PRIMARY OBJECTIVE .......................................................................................................... 6 
2.2 
SECONDARY OBJECTIVES ................................................................................................... 6 
 
 
 
3 
INVESTIGATIONAL PLAN .......................................................................................... 7 
3.1 
OVERALL STUDY DESIGN AND PLAN .................................................................................. 7 
3.2 
STUDY ENDPOINTS ............................................................................................................. 8 
3.2.1 
Primary Endpoint........................................................................................................ 8 
3.2.2 
Secondary Endpoints .................................................................................................. 8 
3.3 
TREATMENTS ...................................................................................................................... 8 
4 
GENERAL STATISTICAL CONSIDERATIONS ....................................................... 9 
4.1 
SAMPLE SIZE .................................................................................................................... 10 
4.2 
RANDOMIZATION, STRATIFICATION, AND BLINDING ........................................................ 10 
4.3 
ANALYSIS POPULATIONS .................................................................................................. 11 
4.3.1 
Intent-to-Treat (ITT) ................................................................................................. 11 
4.3.2 
Modified Intent-to-Treat by RT-qPCR (mITT by RT-qPCR) .................................... 11 
4.3.3 
Modified Intent-to-Treat by CBIA (mITT by CBIA) .................................................. 11 
4.3.4 
Safety (SAF) .............................................................................................................. 11 
4.3.5 
Pharmacokinetic (PK) .............................................................................................. 12 
4.4 
DATA HANDLING STRATEGY ............................................................................................ 12 
4.4.1 
Study Days and Visit Windows ................................................................................. 12 
4.4.2 
Missing Date Imputation........................................................................................... 15 
5 
SUBJECT DISPOSITION ............................................................................................. 16 
5.1 
DISPOSITION ..................................................................................................................... 16 
5.2 
PROTOCOL DEVIATIONS ................................................................................................... 17 
6 
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .................................. 17 
6.1 
DEMOGRAPHICS ................................................................................................................ 17 
6.2 
MEDICAL HISTORY ........................................................................................................... 18 
6.2.1 
General Medical History .......................................................................................... 18 
6.2.2 
Hematopoietic Cell Transplant History .................................................................... 18 
7 
TREATMENTS AND MEDICATIONS ....................................................................... 18 
7.1 
PRIOR AND CONCOMITANT MEDICATIONS ........................................................................ 18 
7.2 
PRIOR AND CONCOMITANT THERAPIES ............................................................................. 19 
7.3 
STUDY TREATMENTS ........................................................................................................ 19 
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8 
EFFICACY AND PHARMACOKINETICS ANALYSIS .......................................... 19 
8.1 
PRIMARY EFFICACY ENDPOINT ......................................................................................... 19 
8.1.1 
Primary Analysis ....................................................................................................... 20 
8.2 
SECONDARY EFFICACY ENDPOINTS .................................................................................. 20 
8.2.1 
RSV viral load AUC by RT-qPCR from Baseline (Day 1) through Day 49 .............. 20 
8.2.2 
Change from Baseline in RSV viral load by RT-qPCR over time ............................. 21 
8.2.3 
Proportion of subjects with RSV viral load by RT-qPCR below the LOD over time 21 
 
8.4 
PK ENDPOINTS ................................................................................................................. 22 
8.4.1 
Plasma PK concentrations of EDP-938 
 ................................................................................... 22 
9 
SAFETY ANALYSIS ..................................................................................................... 22 
9.1 
ADVERSE EVENTS ............................................................................................................. 22 
9.2 
CLINICAL LABORATORY EVALUATIONS ........................................................................... 24 
9.2.1 
Hematology ............................................................................................................... 24 
9.2.2 
Serum Chemistry ....................................................................................................... 24 
9.2.3 
Urinalysis .................................................................................................................. 24 
9.3 
VITAL SIGN MEASUREMENTS ........................................................................................... 24 
9.4 
PHYSICAL EXAMINATION ................................................................................................. 25 
9.5 
ELECTROCARDIOGRAM ..................................................................................................... 25 
10 
INTERIM ANALYSIS ................................................................................................... 25 
11 
DATA MONITORING COMMITTEE (DMC) ........................................................... 25 
12 
CHANGES IN THE PLANNED ANALYSIS .............................................................. 25 
13 
REFERENCES ................................................................................................................ 27 
14
APPENDICES................................................................................................................. 28
14.1 
SCHEDULE OF STUDY PROCEDURES .............................................................................. 28 
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List of Abbreviations 
AE 
adverse event 
ALC 
absolute lymphocyte count 
ANC 
absolute neutrophil count 
ATC 
Anatomical Therapeutic Chemical 
AUC 
area under the curve 
BLQ 
below the limit of quantitation 
BMI 
body mass index 
BUN 
blood urea nitrogen
CBIA 
cell-based infectivity assay 
CMH 
Cochran Mantel-Haenszel 
CI 
confidence interval 
CNI 
calcineurin inhibitor 
CTMS 
Clinical Trial Management System 
CYP 
cytochrome P450 
DMC 
Data Monitoring Committee 
EAC 
Endpoint Adjudication Committee 
ECG 
electrocardiogram 
eCOA 
electronic clinical outcome assessment 
eCRF 
electronic case report form 
eGRF 
estimated Glomerular Filtration Rate 
EOS 
End-of-Study 
EOT 
End-of-Treatment 
FSH 
follicle-stimulating hormone 
HCT 
hematopoietic cell transplant 
HDPE 
high-density polyethylene 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ICU 
intensive care unit 
IRT 
interactive response technology 
ITT 
intent-to-treat 
IWRS 
Interactive Web Response System 
LLOQ 
lower limit of quantitation 
LOD 
lower limit of detection 
LRTC 
lower respiratory tract complication 
LRTI 
lower respiratory tract infection 
MAARI 
medically attended acute respiratory infection 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat 
mTOR 
mammalian target of rapamycin 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events 
NRR 
Not reportable result 
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PK 
pharmacokinetic(s) 
PP 
per protocol 
PT 
preferred term 
QD 
once daily 
QTcF 
QT interval corrected for heart rate according to Fridericia 
RAV 
resistance-associated variant 
RBC 
red blood cell count 
RSV 
respiratory syncytial virus 
RT-qPCR 
quantitative reverse transcription polymerase chain reaction 
SAE 
serious adverse event 
SAF 
safety  
SAP 
statistical analysis plan 
SD 
standard deviation 
SE 
standard error 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
TD 
Target detected 
TND 
Target not detected 
TSS 
total symptom score 
ULN 
upper limit of normal 
URTI 
upper respiratory tract infection 
WBC 
white blood cell count 
WHO 
World Health Organization 
 
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      Date Issued: 8Jan2024 
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1 Introduction 
Respiratory syncytial virus is the leading cause of lower respiratory tract infection (LRTI) and 
presents a significant health challenge in infants, small children, elderly, and 
immunocompromised patients, such as those who have received HCT (Falsey et al., 2005; Hall 
et al., 2009; Shook and Lin, 2017; Khawaja and Chemaly, 2019). Respiratory syncytial virus is 
one of the most common community acquired respiratory viruses that may lead to death in HCT 
recipients, second only to influenza (Khawaja and Chemaly, 2019). The use of ribavirin has been 
associated with clinical benefit (e.g., reduced rates of progression from upper to lower 
respiratory tract infection and decreased mortality) in observational studies and case series. 
Currently, there is no vaccine or highly effective treatment available for RSV.  
To address the unmet medical need for more effective antiviral therapies for RSV and based on 
the promising early nonclinical safety and pharmacological profile, Enanta Pharmaceuticals, Inc. 
is investigating EDP-938 in humans as a potential treatment for RSV infection. This Phase 2b 
study, EDP-938-103, is a randomized, double-blind, placebo-controlled, multicenter study 
designed to assess the efficacy, safety, and tolerability of EDP-938 compared with placebo in 
adult hematopoietic cell transplant (HCT) recipients with an acute RSV infection and symptoms 
of an upper respiratory tract infection (URTI). 
This statistical analysis plan (SAP) is based upon the protocol (version 8.0, dated 7 March 2023) 
for this Phase 2b clinical study, and is prepared in compliance with International Conference on 
Harmonisation (ICH) E3, E6 and E9. Furthermore, this SAP contains definitions for analysis 
sets, derived variables, and statistical methods and data presentations for the analysis of efficacy 
and safety endpoints.  
The study was terminated on September 12, 2023, due to slow enrollment. The decision was 
made by the sponsor. This statistical analysis plan describes the analyses that will be conducted 
based on the data collected up until the study terminated. The changes from the originally 
planned analyses in the protocol is described in Section 12.  
2 Objectives 
2.1 Primary Objective 
To evaluate the effect of EDP-938 on the development of lower respiratory tract 
complication (LRTC) in HCT subjects with an acute RSV infection of the upper 
respiratory tract 
2.2 Secondary Objectives 
To evaluate the effect of EDP-938 on RSV viral load as measured by quantitative 
reverse transcription polymerase chain reaction (RT-qPCR) of nasopharyngeal swab 
samples 
To evaluate the effect of EDP-938 on progression to respiratory failure or all-cause 
mortality 
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 To evaluate the pharmacokinetics (PK) of EDP-938 
 
 To evaluate the safety and tolerability of EDP-938 
 
3 Investigational Plan 
3.1 Overall Study Design and Plan 
 
This is a Phase 2b, randomized, double-blind, placebo-controlled, multicenter study evaluating 
the efficacy and safety of EDP-938 in HCT recipients with acute RSV infection and symptoms 
of URTI.  
 
The study has 3 periods:  
 Screening Period will occur from Day -1 to Day 1. During this period, subjects will 
review and sign the ICF. Subjects will undergo screening assessments. Screening should 
be completed as soon as possible, and the subject will be randomized and administered 
the first dose of study drug within 24 hours of signing the ICF. A subject will be 
considered enrolled at the time of randomization. 
 Treatment Period will begin with the first dose of study drug on Day 1 and will conclude 
with the End-of-Treatment (EOT) Visit on Day 21. 
 Follow-up Period for safety will begin following the last dose of study drug and will 
conclude at the End-of-Study (EOS) visit on Day 49, 28 days following the last dose of 
study drug.  
 
An overview of the study design is shown in Figure 1. Study site visits and assessments are 
detailed in the Schedule of Study Procedures (Appendix 14.1). 
Figure 1: Study Design 
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EDP-938 drug product tablets and the corresponding placebo tablets are supplied as 150 mg 
tablets and 200 mg tablets in 
 
 
 
Following randomization on Day 1, subjects will receive the first dose of EDP-938 or placebo 
orally while at the study site. After the first dose, subjects will be instructed to take the study 
drug orally once daily (QD) on each of the 20 subsequent days. 
 
  
 
 
 
 
 
 
Subjects will be instructed to take the study drug at approximately the same time every day 
(±1 hour). 
 
 
 
 
 
 
 
 
4 General Statistical Considerations 
All analyses will be conducted using SAS Version 9.4 or higher. 
Continuous data will be described using descriptive statistics (i.e. n, mean, standard deviation 
(SD), median, 25th percentile, 75th percentile, minimum, and maximum). For the summary 
statistics of all numerical variables unless otherwise specified, minimum and maximum will be 
displayed to the same level of precision as reported. Mean and median will be displayed to one 
level of precision greater than the data collected. Standard deviation / standard error (SE) will be 
displayed to two levels of precision greater than the data collected. If the precision of the values 
being summarized are too large (e.g. 3 or more decimal places), then limit the precision to two 
decimal places and follow the rules previously stated above. For derived data, the precision of 
values will be determined on a case-by-case basis. If n=0, then display n and leave all other 
 
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Categorical data will be described using the subject count and percentage in each category. 
When count data are presented, the percentage will be suppressed when the count is zero. A row 
for dropouts and missing values where applicable. The denominator for all percentages will be 
the number of subjects in that treatment within the analysis set of interest, unless otherwise 
specified. Non-zero percentages will be rounded to one decimal place, except 100% will be 
displayed without any decimal places. 
 
Summary Tables will be presented by treatment group. Tables values for treatment group will be 
-
, ribavirin 
treatment (present or absent
unless an insufficient amount of 
data exists where convergence or the analysis cannot be performed. 
 
All subject data, including those derived, will be presented in individual subject data listings. 
Dates will be shown in subject listings as they have been recorded. Unless otherwise stated, 
unscheduled visit results will be included in date/time chronological order, within subject listings 
only. All listings will be sorted by subject number, date/time and visit. The treatment group 
stated, data listings will be based on all subjects randomized.  
 
When no data are available for a table or listing, an empty page with the title will be produced 
 For analyses where 
will be presented in 
summary tables. 
 
Unless otherwise specified, baseline will be defined as the last non-missing measurement 
collected on or before the date of the first dose of study treatment. For subjects who are 
randomized, but not treated, the baseline will be defined as the last non-missing measurement on 
or before the date of randomization. The date of first dose will be collected on the Day 1 Study 
Drug eCRF and the date of last dose will be the date collected on the End of Treatment eCRF. 
  
For the reporting of this study both CDISC SDTM (SDTM Implementation Guide version 3.2) 
and ADaM (ADaM Implementation Guide version 1.1) 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 49 ± 2 days), 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.  
4.1 Sample Size 
 
When the study was terminated, there were 9 subjects randomized. 
4.2 Randomization, Stratification, and Blinding 
 
Subjects who had completed screening assessments and were eligible for participation in the 
study were randomized to blinded treatment before the first dose of study drug (Day 1) in a 2:1 
ratio to 
 EDP-938 or placebo administered orally for 21 days. Subject 
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The safety (SAF) population will include all subjects who received at least one dose of study 
drug. All subjects in the safety population will be analyzed according to the treatment actually 
received. 
4.3.5 Pharmacokinetic (PK) 
The pharmacokinetic (PK) population will include all subjects receiving active study drug and 
having any measurable plasma concentration of study drug at any timepoint. 
4.4 Data Handling Strategy 
4.4.1 Study Days and Visit Windows 
Study day is defined as the number of days from the date of first dose. Day 1 is the date of the 
first dose. For assessments or events that occur after the first dose date, study day is calculated as 
the date of interest minus first dose date plus 1 day. For assessments or events that occur before 
the first dose date, study day is calculated as the date of interest minus the first dose date. 
Analysis visit windows are described in the tables below. Analysis visits are based on nominal 
scheduled visits and will be used for by-visit analyses or summaries unless otherwise specified in 
the respective analysis sections. Unscheduled visits and visits performed for early 
discontinuation will not be included in the by-visit summary or analyses. 
Unscheduled visits including repeat central laboratory assessments for the EOS visit to 
follow an AE for resolution will not be included in the by-visit analyses/ summaries, but 
will be included in the listings and other types of analyses/summaries as applicable (e.g. 
AUC, time to event and treatment emergent safety abnormalities any time post-baseline). 
For subjects who discontinues study treatment, they should complete a EOT visit and this 
d also complete 
FU1 visit and FU2 visit, 
 
For subjects who completes study treatment and discontinues study before Day 28, they 
should complete FU1 visit and this visit will be label
who discontinues study between Day 28 and Day 49, they should complete FU2 visit and 
 
Vital signs and safety laboratory tests: 
Analysis Visit # 
Analysis Visit Label 
Target Day 
Derivation 
1 
Day 1 
1 
Based on nominal visit of V1 
4 
Day 4 
4 
Based on nominal visit of V2 
7 
Day 7 
7 
Based on nominal visit of V3 
11 
Day 11 
11 
Based on nominal visit of V4 
16 
Day 16 
16 
Based on nominal visit of V5 
21 
Day 21 
21 
Based on nominal visit of V6 if 
subject completes treatment 
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28 
Day 28 
28 
Based on nominal visit of FU V1 if 
subject completes treatment and last 
visit is FU V2. 
97 
Early Disc/EOT 
NA 
Based on nominal visit of V6 if 
subject discontinues treatment 
98 
Early Disc/FU1 
NA 
Based on nominal visit of FU V1 if 
subject discontinues treatment or last 
visit is FU V1. 
 
RSV viral load by both RT-qPCR and CBIA: 
Analysis Visit # 
Analysis Visit Label 
Target Day 
Derivation 
1 
Day 1 
1 
Based on nominal visit of V1 
4 
Day 4 
4 
Based on nominal visit of V2 
7 
Day 7 
7 
Based on nominal visit of V3 
11 
Day 11 
11 
Based on nominal visit of V4 
16 
Day 16 
16 
Based on nominal visit of V5 
21 
Day 21 
21 
Based on nominal visit of V6 if 
subject completes treatment 
28 
Day 28 
28 
Based on nominal visit of FU V1 if 
subject completes treatment and last 
visit is FU V2. 
49 
Day 49 
49 
Based on nominal visit of FU V2 if 
subject completes treatment and 
study 
97 
Early Disc/EOT 
NA 
Based on nominal visit of V6 if 
subject discontinues treatment 
98 
Early Disc/FU1 
NA 
Based on nominal visit of FU V1 if 
subject discontinues treatment or last 
visit is FU V1. 
99 
Early Disc/FU2 
NA 
Based on nominal visit of FU V2 if 
subject discontinues treatment or 
study. 
 
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ECG: 
Analysis Visit # 
Analysis Visit Label 
Target Day 
Derivation 
-1
Screening 
-1
Based on nominal visit of Screening 
4 
Day 4 
4 
Based on nominal visit of V2 
11 
Day 11 
11 
Based on nominal visit of V4 
21 
Day 21 
21 
Based on nominal visit of V6 if 
subject completes treatment. 
28 
Day 28 
28 
Based on nominal visit of FU V1 if 
subject completes treatment and last 
visit is FU V2. 
97 
Early Disc/EOT 
NA 
Based on nominal visit of V6 if 
subject discontinues treatment 
98 
Early Disc/FU1 
NA 
Based on nominal visit of FU V1 if 
subject discontinues treatment or last 
visit is FU V1. 
PK: 
Analysis Visit # 
Analysis Visit Label 
Target Day Timepoint* 
Assessment 
Derivation 
1 
Day 1 
1 
1 
Based on nominal visit 
of V1 
1 
Day 1 
1 
2 
Same as above 
4 
Day 4 
4 
1 
Based on nominal visit 
of V2 
7 
Day 7 
7 
1 
Based on nominal visit 
of V3 
7 
Day 7 
7 
2 
Same as above 
11 
Day 11 
11 
1 
Based on nominal visit 
of V4 
16 
Day 16 
16 
1 
Based on nominal visit 
of V5 
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21 
Day 21 
21 
1 
Based on nominal visit 
of V6 if subject 
completes treatment 
21 
Day 21 
21 
2 
Same as above 
97 
Early Disc/EOT 
NA 
 
Based on nominal visit 
of V6 if subject 
discontinues treatment 
* On Day 1, Day 7, and Day 21, two plasma PK samples will be collected (one predose and one postdose) 
and thus are assigned as Timepoint 1 and 2. At all other visits, only predose samples will be collected. 
 
4.4.2 Missing Date Imputation 
 
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: 
 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. 
o Otherwise, impute the AE start MONTH as January and the DAY as 1.  
 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/therapy 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: 
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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 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: 
 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. 
o Otherwise, impute the CM start MONTH as January and the DAY as 1.  
 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. 
5 Subject Disposition 
5.1 Disposition 
 
A summary of the analysis populations includes the number and percentage of subjects in each 
analysis population (ITT, mITT by RT-qPCR, mITT by CBIA, SAF, and PK) by treatment group 
and overall. The number and percentage of subjects excluded from each analysis population and 
the reasons for exclusion will also be presented. All percentages will be based on the number of 
subjects randomized.  
 
Subject disposition will be summarized by treatment group and overall for all subjects who 
provided informed consent. A disposition of subjects includes the number and percentage of 
subjects for the following categories: subjects who were randomized, subjects who completed 
study treatment, subjects who discontinued study treatment, subjects who completed the study, 
subjects who discontinued from the study. All percentages will be based on the number of 
subjects randomized. The reasons for discontinuation of study treatment and study participation 
will also be summarized in this table.  
 
The reason for discontinuation of study treatment or study participation may include any of the 
following: adverse event, lack of efficacy, lost to follow-up, pregnancy, protocol deviation, study 
terminated by sponsor, withdrawal by subject, physician decision, COVID-19, or other reason. 
 
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Subject disposition data and exclusions from analysis populations will also be presented in a 
listing. 
5.2 Protocol Deviations 
 
All protocol deviations (both significant and non-significant) were entered and tracked in 
Clinical Trial Management System (CTMS) by the study team throughout the conduct of the 
deviation that may affect primary efficacy and safety assessments (as applicable), the safety or 
mental integrity of a subject, or the scientific value of the trial. 
 
Data will be reviewed by the study team prior to unblinding and closure of the database to ensure 
all significant deviations are captured and properly categorized.  
 
Significant protocol deviations will be summarized by treatment group and overall based on 
randomized subjects. A separate listing will be provided for significant protocol deviations and 
non-significant protocol deviations.  
6 Demographics and Baseline Characteristics 
6.1 Demographics 
 
A summary of demographics and baseline information will be presented by treatment group and 
overall for all subjects in the safety population.  
 
The demographic characteristics consist of age, sex, race, and ethnicity.  
 
The baseline characteristics consist of baseline height, baseline weight, baseline body mass 
index, smoking history, ribavirin treatment at screening (stratification factor), absolute 
lymphocyte count (ALC) at screening (stratification factor), absolute neutrophil count (ANC) on 
Day 1, RSV subgroup,
RSV viral load by RT-qPCR and 
CBIA, co-pathogens detected on Day 1, hospitalization status on Day 1 
 
. Body mass index is calculated as (body weight in 
kilograms) / (height in centimeters / 100)2. RSV subgroup is determined by an RSV A/B 
RT-qPCR assay and co-pathogens are determined by a respiratory pathogen panel at the central 
laboratory.  The baseline RSV type category is derived by algorithm described in Section 8.2.1. 
 
Age (years), baseline height (cm), baseline weight (kg), baseline BMI (kg/m2), 
 
RSV viral load as measured by RT-qPCR (log10 copies/mL) and CBIA (log10 PFU/mL) will be 
summarized using descriptive statistics. The number and percentage of subjects by age group (< 
65,  65 years), sex (Male, Female), race (White, African American, Asian, American Indian or 
Alaska Native, Native Hawaiian or Other Pacific Islander, Other), ethnicity (Hispanic or Latino, 
Not Hispanic or Latino), smoking history (Current, Previous, Never), ribavirin treatment at 
screening (Present, Absent), ALC at screening (<200, 
 cells/µL), ANC on Day 1 (<500, 
500 cells/µL), RSV subgroup (RSV A, RSV B, Undetectable, Missing), co-pathogens detected 
on Day 1 (e.g., Adenovirus, Parainfluenza virus, SARS-CoV-2), hospitalized on Day 1 (Yes, 
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No), 
, and 
subjects with any medical conditions will also be reported. Percentages will be based on the total 
number of subjects in the safety population. 
 
Subject demographic and baseline characteristics will also be presented in a listing. Additionally, 
the RSV test information collected at screening (i.e. RSV test date, RSV test type, manufacturer 
name of RSV test, RSV test result, number of days between RSV test and first dose) will be 
presented in a separate listing.   
6.2 Medical History 
6.2.1 General Medical History 
 
Medical history will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 23.1 or higher. The number and percentage of subjects with any medical history will be 
summarized overall and for each system organ class and preferred term. Percentages will be 
calculated based on number of subjects in the safety population. 
 
Subject medical history data including specific details, will also be presented in a listing.  
6.2.2  Hematopoietic Cell Transplant History 
 
Hematopoietic cell transplant (HCT) history will be collected at screening and will consist of 
donor type, cell source, date of transplant, conditioning regimen prior to HCT, diagnosis for 
which HCT was received, CMV seropositive status, and acute or chronic graft-vs-host disease. 
HCT history will be summarized in a table by treatment group and overall. Percentages will be 
based on the number of subjects in the safety population.  
 
HCT history data will also be presented in a listing. 
7 Treatments and Medications 
7.1 Prior and Concomitant Medications 
 
All medications taken within 1 month of signing informed consent and during the study 
throughout the end of the study will be collected on the CRF. All medications will be coded 
according to the World Health Organization (WHO) Drug Dictionary (WHODrug Global-B3 
202009 or later). 
 
Prior medications are defined as those medications with a start date prior to the date of first dose 
of study drug. Concomitant medications are defined as any medications with a start date on or 
after the date of first dose of study drug or any medications with a start date prior to the date of 
first dose and a stop date after the date of first dose. Furthermore, a medication could be labeled 
as both a prior and concomitant medication if it was started prior to the first dose of study drug 
and continued after the first dose of study drug. 
 
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The number and percentages of subjects with at least one prior medication will be summarized 
by treatment group and overall. The number and percentages of all prior medications will be 
summarized by treatment group and overall and listed by Anatomical Therapeutic Chemical 
(ATC) level 2 and preferred term. All summaries will be performed using the safety population. 
The number and percentages of subjects with at least one concomitant medication will be 
summarized by treatment group and overall. The number and percentages of all concomitant 
medications will be summarized by treatment group and overall and listed by Anatomical 
Therapeutic Chemical (ATC) level 2 and preferred term. All summaries will be performed using 
the safety population. 
Prior and concomitant medications, including prohibited medication, will also be presented in a 
listing. Details for imputing missing or partial start and/or stop dates of medications are 
described in Section 4.4.2. 
7.2 Prior and Concomitant Therapies 
Prior and concomitant therapies include surgical interventions, procedures, or non-medication 
treatments (e.g. supplemental oxygen). All reported therapies will be coded using the MedDRA 
Version 23.1 or higher and classified by system organ class (SOC) and preferred term (PT). 
Prior therapies are defined as those therapies with a start date prior to the date of first dose of 
study drug. Concomitant therapies are defined as any therapies with a start date on or after the 
date of first dose of study drug or any therapies with a start date prior to the date of first dose and 
a stop date after the date of first dose.  
Both prior and concomitant therapies will be presented in a listing. Details for imputing missing 
or partial start and/or stop dates of medications are described in Section 4.4.2. 
7.3 Study Treatments 
The study drug administration data collected from eCRF will be listed. 
8 Efficacy and Pharmacokinetics Analysis 
Efficacy analysis on LRTC 
 will be based on ITT population. The efficacy 
analysis on RSV viral load by RT-qPCR will be based on mITT by RT-qPCR population, The 
efficacy analysis on RSV viral load by CBIA will be based on mITT by CBIA population. 
Missing data will not be imputed unless otherwise specified. Relevant subject data listings will 
be provided to support all efficacy analyses.  
8.1 Primary Efficacy Endpoint 
The primary endpoint is the proportion of LRTC through Day 28, defined as one of the 
following, as determined by the Endpoint Adjudication Committee (EAC): 
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LRTI by RSV 
LRTI as secondary bacterial pneumonia 
LRTI by unusual pathogens 
LRTC of unknown etiology 
The EAC reviewed relevant clinical data and source documentation to determine whether a 
LRTC occurred, the type and date of onset of any LRTC. Details of the adjudication process 
were provided to the EAC in an EAC charter. This EAC charter defined the EAC membership, 
decision, meeting logistics, and meeting frequency.  
8.1.1 Primary Analysis 
The number and proportion of subjects who developed LRTC through Day 28 will be 
summarized for each treatment group for ITT population. Subjects with missing LRTC data will 
be considered having no LRTC event. The LRTC data will also be listed.  
8.2 Secondary Efficacy Endpoints 
8.2.1 RSV viral load AUC by RT-qPCR from Baseline (Day 1) through Day 49 
The RSV viral load will be measured in nasopharyngeal swabs by quantitative RT-qPCR at the 
following scheduled visits: Days 1, 4, 7, 11, 16, 21, 28, and 49. Viral load values reported as TD 
(Target  detected) are samples with viral RNA concentrations equal and above the LOD (limit of 
detection) (TD 
LOD) and below the LLOQ (lower limit of quantification). (TD < LLOQ). For 
analysis purpose, TD will be set to the average of LOD  and LLOQ Viral load values reported as 
TND (Target Not Detected, value below LOD) will be set to zero. Viral load data will be 
transformed using a log10 scale before analyses. If zero values are observed, the log transformed 
value will be set to 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 and 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 by RT-qPCR 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 
RSV type is classified as RSV A. And if the baseline RSV B viral load is greater than RSV A 
viral load, the baseline RSV type is classified as RSV B.  
After the categorization of baseline RSV type, only RSV values from the same baseline RSV 
type will be selected for postbaseline values to be used for analyses. 
The AUC of RSV viral load by RT-qPCR will be calculated using the trapezoid rule (Matthews 
et al., 1990). To calculate AUC, at least two non-missing data points on the RSV by RT-qPCR 
curve are needed. The AUC will be calculated based on available individual assessments of viral 
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load collected at each visit (Days 1, 4, 7, 11, 16, 21, 28, and 49) 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 
to 49 days by multiplying 49/tlast where tlast is the actual time in days of the last available 
assessment up to Day 49 visit.  
 
The descriptive statistics for the RSV viral load AUC by RT-qPCR from Day 1 to Day 49 will be 
presented by treatment group based on the mITT by RT-qPCR population. The RSV viral load 
by RT-qPCR data will be listed.  
8.2.2 Change from Baseline in RSV viral load by RT-qPCR over time 
 
Observed and change from baseline values for RSV viral load by RT-qPCR will be summarized 
with descriptive statistics by visit (Days 1, 4, 7, 11, 16, 21, 28, and 49) for each treatment group 
based on mITT by RT-qPCR population and will include the number of non-missing 
measurements, mean, standard deviation, median, minimum, 25th percentile, 75th percentile, and 
maximum.  
8.2.3 Proportion of subjects with RSV viral load by RT-qPCR below the LOD over 
time 
 
The proportion of subjects with RSV viral load by RT-qPCR below the limit of detection (LOD) 
will be summarized by visit (Days 4, 7, 11, 16, 21, 28, and 49) for each treatment group based on 
mITT by RT-qPCR population.  
 
 
 
 
 
 
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8.4 PK Endpoints 
8.4.1 Plasma PK concentrations of EDP-938 
 
 
On Day 1, Day 7, and Day 21, two samples will be collected: one predose, collected within 
1 hour before dosing (preferably within 30 minutes of dosing if possible); and at the same 
approximate time as that of the nasopharyngeal swab collection and one postdose, collected 1 to 
3 hours postdose. At all other visits (Days 4, 11, and 16), one predose plasma PK sample will be 
collected at the same approximate time as that of the nasopharyngeal swab collection. Time and 
date of collection will be recorded on the Plasma PK Sample Collection eCRF. 
For subjects in the PK analysis set, the concentration data for EDP-938 and each 
 will be summarized by visit (Days 1, 4, 7, 11, 
16, and 21) and timepoint (predose or postdose). 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 below BLQ, descriptive statistics will not be 
presented except for maximum and BLQ will be displayed for mean and minimum. The number 
of observations, arithmetic mean, SD, % coefficient of variation (%CV), median, minimum, 
maximum, geometric mean, and %CV of the geometric mean (%GCV) will be displayed. 
 
Individual data will be presented in a listing. 
9 Safety Analysis 
 
All safety analyses will be conducted using the Safety (SAF) population, where subjects will be 
analyzed according to the treatment actually received. 
9.1 Adverse Events 
 
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Adverse events (AEs) will be coded using the MedDRA Version 23.1 or higher and classified by 
SOC and PT. 
AEs will be classified as pre-treatment AEs and treatment emergent adverse events (TEAEs) and 
are defined as follows:  
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.  
A TEAE is defined as an AE occurring or worsening on or after the date of first dose of 
study drug.  
A treatment-related AE will be defined as related if causality is related or possibly related. AEs 
where the causality is missing will be assumed to be related in table summaries.  
TEAEs leading to study drug discontinuation will be identified as TEAEs with a study drug 
with 
Adverse events (serious and non-serious) will be graded in accordance with the NCI-CTCAE 
scale as follows: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 
4), and Death (Grade 5). AEs with missing severity will be assumed to be severe in table 
summaries. 
Details for imputing missing or partial start and/or stop dates of AEs are described in Section 
4.4.2. 
All summaries of AEs will be based on treatment-emergent adverse events (TEAEs) in the safety 
population. The following summaries of TEAEs will be provided by treatment group: 
An overall summary of TEAEs including the number of TEAEs and the number and 
percentage of subjects with any of the following: TEAEs, study drug related TEAEs, 
TEAEs of grade 3 or higher, TEAEs by maximum grade, TEAEs leading to study drug 
discontinuation, TEAEs leading to death, serious TEAEs, and study drug related serious 
TEAEs. 
TEAEs  by PT and SOC 
Study Drug-Related TEAEs - by PT and SOC 
TEAEs of Grade 3 or Higher - by PT and SOC 
TEAEs by Maximum Grade  by PT and SOC 
TEAEs leading to study drug discontinuation  by PT and SOC 
AEs leading to death  by PT and SOC 
Serious TEAEs  by PT and SOC  
Study Drug-Related Serious TEAEs  by PT and SOC 
For the above summaries by SOC and PT, each subject is counted once within each unique 
category. For the summary by maximum severity, subjects who experience the same event 
several times, with different severity levels, will only be counted with the maximum severity. 
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AEs will be sorted in descending order of frequency of SOC based on the total of all treatment 
groups.  Within each SOC, AEs will be sorted in alphabetical order of preferred terms.  
 
Subject AEs will also be presented in a listing. 
9.2 Clinical Laboratory Evaluations 
 
Safety laboratory tests include chemistry, hematology, and urinalysis will be performed by a 
central laboratory on Days 1, 4, 7, 11, 16, 21, and 28. Estimated glomerular filtration rate 
(eGRF) will be calculated using the Modification of Diet in Renal Disease (MDRD) equation.  
 
Summary tables for observed values and changes from baseline will be presented for clinical 
laboratory tests with numeric values by treatment group and visit for subjects in the safety 
population.  
 
All safety laboratory data will be included in separate listings and all test values outside the 
normal range will be flagged. 
9.2.1 Hematology 
 
The following laboratory tests will be included:  Hemoglobin, Hematocrit, Differential white 
blood cell count, percentage and absolute (basophils, eosinophils, lymphocytes, monocytes, 
neutrophils), Mean corpuscular hemoglobin, Mean corpuscular hemoglobin concentration, Mean 
corpuscular volume, Platelet count, Red blood cell count, White blood cell count, International 
normalized ratio, Prothrombin time, and Activated thromboplastin time.  
9.2.2 Serum Chemistry 
 
The following laboratory tests will be included: Alanine aminotransferase, Albumin, Alkaline 
phosphatase, Amylase, Aspartate aminotransferase, total and direct bilirubin, BUN, 
BUN/creatinine ratio, Calcium, Creatine kinase, Creatinine, Estimated glomerular filtration rate, 
Uric acid, Sodium, Potassium, Chloride, Bicarbonate, Phosphorus, Gamma glutamyl transferase, 
Total globulin, Glucose, Cholesterol, Triglycerides, Lactate dehydrogenase, Lipase, Total 
protein, Calcineurin and mTOR inhibitors. 
9.2.3 Urinalysis 
 
The following laboratory tests will be included: color and appearance, pH, specific gravity, 
bilirubin, glucose, ketones, leukocytes, nitrite, occult blood, protein, urobilinogen, microscopic 
examination (including red blood cells and white blood cells).  
9.3 Vital Sign Measurements 
 
Vital signs include heart rate (beats/min), respiratory rate (breaths/min), systolic and diastolic 
blood pressure (mmHg), body temperature ( C), weight (kg), and BMI (kg/m2). Pulse oximetry 
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will be performed to measure oxygen saturation (%). Vital signs and pulse oximetry will be 
measured at Days 1, 4, 7, 11, 16, 21, and 28. 
All vital sign and pulse oximetry data will be presented in a listing. 
9.4 Physical Examination 
A full physical examination will be performed at Screening and any subsequent examinations 
performed at the discretion of the investigator will be targeted to new signs and symptoms. Any 
abnormal findings should be captured directly on the medical history or AE pages directly as 
appropriate.  
9.5 Electrocardiogram 
All subjects will have a standard 12-lead electrocardiogram (ECG) performed locally during the 
study at Screening, Day 4, Day 11, Day 21, and Day 28.  
ECG data includes heart rate, RR interval, PR interval, QRS duration, QT interval, and QT 
interval corrected for heart rate according to Fridericia (QTcF), etc.  
ECG data for subjects will be presented in a listing. 
10 Interim Analysis 
No interim analysis was conducted. 
11 Data Monitoring Committee (DMC) 
An independent Data Monitoring Committee (DMC) was established to review the safety data 
throughout the study to ensure the safety of study subjects, the ethical continuation of the study, 
and provide recommendations regarding continuation or termination of the study. The DMC was 
headed by a DMC Chair and will include one or more physicians with expertise in transplant 
medicine. The DMC consisted of experts independent from the Sponsor.  
The roles, responsibilities and rules governing operation of the DMC were discussed in full in 
the DMC charter, which was finalized prior to the administration of investigational product. The 
DMC charter defined the primary responsibilities of the DMC; guide its activities, its 
relationship with other study components, its membership, and the purpose and timings of its 
meetings. It provided the procedures for ensuring confidentiality, formal communication, and 
outline of the content of reports that will be provided by the DMC. 
12 Changes in the Planned Analysis 
The study was terminated early by sponsor on September 12, 2023. Due to the small number of 
subjects randomized into the study, it was decided a reduced data analysis will be provided. The 
statistical tests or large sample-based estimates defined in the protocol, such as Cochran Mantel-
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Haenszel (CMH) test p-value, 95% CI for proportions, treatment difference estimates in 
proportions and its 95% CI, Cox proportional model estimate for hazard ratio and its 95% CI, 
Kaplan-Meier estimates will not be provided for treatment comparison purpose. The study 
exposure duration and compliance will not be calculated. The incidence of treatment-emergent 
laboratory tests, vital signs, or ECG will not be summarized. The summary of observed and 
change from baseline in vital sign and ECG will not be provided.
 
In addition, the following endpoints defined in the protocol are deleted from this analysis plan. If 
the related raw data will still be listed, some details are provided as needed:  
Incidence of subjects who develop respiratory failure of any cause requiring mechanical 
ventilation (invasive or noninvasive) or all-cause mortality through Day 49 
o
Respiratory failure events requiring mechanical ventilation can be identified
based on the Concomitant Therapy eCRF where the response to the respiratory
failure therapy question is Yes. Death events can be identified based on the
listed in AE listing.
Time to RSV RNA viral load below the limit of detection   
Plasma PK concentrations of EDP-938 in relation to the following: 
o
RSV RNA viral loads from Baseline through Day 49
Incidence of subjects hospitalized or rehospitalized through Day 49 
o
Hospitalization data will be listed. A subject will be considered being hospitalized
or re-hospitalized if the subject has any hospitalization or re-hospitalization that
starts or restarts on or after the first dose date.
Incidence of  medically attended acute respiratory infection (MAARI) through Day 49  
o
The MAARI data will be listed. A subject will be considered as developing
MAARI if the subject has any hospitalizations, home health visits, non-
hospitalization visits, or receives any concomitant therapies related to MAARI
that occur on or after the first dose date. The dates of the medical visits and
therapy use related to MAARI were collected on the Hospitalization eCRF, Home
Health Care Visit eCRF, MAARI Non-Hospitalization Visit eCRF, and the
Concomitant Therapy eCRF, respectively.
Incidence, duration and number of days free of supplemental oxygen requirement through 
Day 49  
o
A subject will be considered as requiring supplemental oxygen if the subject was
administered any supplemental oxygen on or after the first dose date. Dates of
supplemental oxygen use were reported on the Concomitant Therapy eCRF. The
available supplemental oxygen data will be listed.
Duration of time of hospital stay and time in the ICU through Day 49 
Incidence of use of certain therapeutics including antibiotics, ribavirin, corticosteroids, 
and/or immunoglobulin through Day 49 
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o
The data for individual subjects who use certain therapeutics through Day 49 will
be included in the concomitant medication listing.
Emergence of EDP-938 resistance-associated variants (RAVs) in RSV obtained from 
nasopharyngeal swab samples 
RSV subgroup/genotype obtained from nasopharyngeal swab samples in relation to the 
following: 
o
RSV viral load from Baseline through Day 49
13 References 
Falsey AR, Hennessey PA, Formica MA, et al. Respiratory syncytial virus infection in elderly 
and high-risk adults. N Engl J Med. 2005;352(17):1749-59. 
Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in 
young children. N Engl J Med. 2009;360(6):588-98. 
Khawaja F and Chemaly RR. Respiratory syncytial virus in hematopoietic cell transplant 
recipients and patients with hematologic malignancies. Haematologica 2019; 104(7):1322-1331. 
Matthews JN, Altman DG, Campbell MJ, et al. Analysis of serial measurements in medical 
research. BMJ. 1990; 300(6719): 230-5. 
Shook BC and Lin K. Recent advances in developing antiviral therapies for respiratory syncytial 
virus. Top Curr Chem (Cham). 2017:375(2):40. 
United States Food and Drug Administration Guidance Document. International Conference on 
Harmonization E6 Good Clinical Practice. May 1996. 
United States Food and Drug Administration Guidance Document. International Conference on 
Harmonization E3 Structure and Content of Clinical Study Reports. July 1996. 
United States Food and Drug Administration Guidance Document. International Conference on 
Harmonization E9 Statistical Principles for Clinical Trials. September 1998. 
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