A Randomised, Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacokinetics and Antiviral Activity of Multiple Doses of Orally Administered EDP-938 Against Respiratory Syncytial Virus Infection in the Virus Challenge Model.
Phase: PHASE2
Conditions: RSV Infection
Sponsor: Enanta Pharmaceuticals, Inc

Protocol Number:  EDP 938-101 
 
Official Title:  Randomised, Phase 2a, Double-Blind, Placebo-Controlled Study to 
Evaluate the Safety, Pharmacokinetics and Antiviral Activity of 
Multiple Doses of Orally Administered EDP-938 Against Respiratory 
Syncytial Virus Infection in the Virus Challenge Model 
 
NCT Number: NCT03691623 
 
Document Date:  07 NOV 2019 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019 
  
 
 
CLINICAL STUDY PROTOCOL 
 
 
 
 
Sponsor’s study number: EDP 938-101 
hVIVO Protocol No: ENA-CS-001 
A Randomised, Phase 2a, Double-Blind, Placebo-Controlled study to Evaluate the Safety, 
Pharmacokinetics and Antiviral Activity of Multiple Doses of Orally Administered EDP-938 
Against Respiratory Syncytial Virus Infection in the Virus Challenge Model. 
 
 
Short title:  
 
Safety, Pharmacokinetics and Antiviral Activity of Orally 
Administered EDP-938 Against RSV 
Version: 
Amendment 4.0 (version 5.0) Date 07NOV2019 
Sponsor: 
 
ENANTA Pharmaceuticals, Inc 
 
500 Arsenal Street 
Watertown, MA 02472 
United States of America (USA). 
Principal Investigator: 
 
  
hVIVO Services Limited (hVIVO), 
Queen Mary BioEnterprises Innovation Centre, 42 New 
Road, 
London E1 2AX, United Kingdom (UK).  
Study carried out at the facilities 
of: 
 
 
hVIVO Services Limited, 
Queen Mary BioEnterprises Innovation Centre, 42 New 
Road,  
London. E1 2AX. United Kingdom. 
 
EUDRACT Number:  
2018-001878-21 
 
Are any sub-studies in progress at the trial sites?  
 
Yes 
 
☐ 
 
No 
 
☒ 
 
 
 
 
 
 
 
 
 
 
 
 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019  
  
 
 
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afternoon of Day 5 post viral 
challenge. 
Appendix 7 footnote added to 
clarify the 72h PK plasma 
sample collection post last 
dose for Part 1. 
Clarification of rescreening 
process 
Section 
9.3.1 
clarified 
rescreening 
process 
for 
subjects who  are found 
ineligible based on review of 
eligibility criteria. 
Amendment 3.0 
(v4.0) 
11JUL2019 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirmation of the 
treatment groups for Part 2 
Section 
9.1 
updated 
to 
include a confirmation of the 
treatment groups for Part 2 
following the emerging data 
from Part 1. Due to the 
combination 
in 
dosing 
schedule (i.e OD and BD) all 
subjects will be treated Twice 
daily (similar to part 1) in 
order to maintain the blind 
between treatment groups. 
The duration of dosing for 
Part 2 clarified as a 5 days 
dosing regimen. 
The 
number 
of subjects 
enrolled in each of the 
treatment groups for Part 2 
confirmed as n=21 subjects 
per treatment group. 
Clarification of the 
randomisation ratio for Part 
2 
Section 10.1: randomisation 
ratio for Part 2 clarified as a 
1:1:1 ratio. 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019  
  
 
 
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Clarification of the PK 
blood sampling schedule 
for Part 2 
Appendix 
7: 
PK 
blood 
sampling schedule for Part 2 
clarified. 
Clarification of adverse 
events reporting for 15% 
drop in spirometry value  
Section 15 Adverse Events 
and Toxicity Management 
clarified for the reporting of 
adverse events related to a 
15% 
drop 
in 
spirometry 
value. 
Amendment 4.0 
(v5.0) 
07NOV2019 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019  
  
 
 
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TABLE OF CONTENTS 
1 
STUDY PERSONNEL CONTACT LIST ............................................................ 13 
2 
PROTOCOL SYNOPSIS .................................................................................. 15 
3 
GLOSSARY OF ABBREVIATIONS ................................................................. 25 
4 
DEFINITIONS ................................................................................................... 28 
4.1 
General ............................................................................................................................. 28 
4.2 
Study definitions of infection and illness ........................................................................... 29 
5 
BACKGROUND AND INTRODUCTION ........................................................... 31 
5.1 
Information about Respiratory Syncytial Virus (RSV) ....................................................... 31 
5.2 
Information about EDP-938 .............................................................................................. 31 
 
Product description .............................................................................................. 31 
 
Non-clinical studies .............................................................................................. 32 
5.2.2.1 Non-Clinical Pharmacology Studies ....................................................... 32 
5.2.2.2 Non-Clinical Pharmacokinetics ............................................................... 32 
5.2.2.3 Non-Clinical Toxicology in Animal Summary .......................................... 33 
 
Clinical studies ..................................................................................................... 34 
5.2.3.1 Effects in Humans ................................................................................... 34 
5.3 
Rationale for the study ...................................................................................................... 34 
 
Study design ........................................................................................................ 35 
 
EDP-938 dose regimen ....................................................................................... 35 
5.4 
Potential risks and benefits to participants ....................................................................... 36 
 
Virus ..................................................................................................................... 36 
5.4.1.1 Vulnerable populations ........................................................................... 37 
 
EDP-938 .............................................................................................................. 37 
 
Study procedures ................................................................................................. 37 
6 
STUDY OBJECTIVES and ENDPOINTS ......................................................... 39 
6.1 
Primary Objective ............................................................................................................. 39 
 
Primary Endpoint ................................................................................................. 39 
6.2 
Secondary Objectives ....................................................................................................... 39 
 
Secondary Endpoints ........................................................................................... 39 
6.2.1.1 Efficacy.................................................................................................... 39 
6.2.1.2 Safety ...................................................................................................... 40 
6.2.1.3 Pharmacokinetics .................................................................................... 40 
6.3 
Exploratory Objectives ...................................................................................................... 40 
 
Exploratory Endpoints .......................................................................................... 41 
7 
STUDY POPULATION ..................................................................................... 42 
7.1 
Study Population............................................................................................................... 42 
7.2 
Number of subjects ........................................................................................................... 42 
7.3 
Inclusion criteria ................................................................................................................ 42 
7.4 
Exclusion criteria............................................................................................................... 45 
7.5 
Discontinuation of a subject’s participation ...................................................................... 48 
 
Subject withdrawal ............................................................................................... 48 
 
Subject discontinuation ........................................................................................ 49 
 
Replacements ...................................................................................................... 49 
 
Pregnancy ............................................................................................................ 49 
 
Arrangements for additional care if required ....................................................... 49 
7.6 
Reserve subjects .............................................................................................................. 50 
7.7 
Subject numbering ............................................................................................................ 50 
8 
PROCEDURES FOR MONITORING SUBJECT COMPLIANCE WITH 
TREATMENT AND RESTRICTIONS .................................................................................. 51 
8.1 
Concomitant therapies ...................................................................................................... 51 
 
Prohibited Medications: ....................................................................................... 52 
 
Permitted medications ......................................................................................... 53 
8.2 
Strenuous Exercise .......................................................................................................... 53 
8.3 
Alcohol, drugs of abuse and tobacco ............................................................................... 53 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019  
  
 
 
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8.4 
Restrictions related to study assessments ....................................................................... 53 
 
Spirometry............................................................................................................ 53 
9 
STUDY DESIGN ............................................................................................... 54 
9.1 
Summary .......................................................................................................................... 54 
 
Part 2 Progression and Additional Evaluation Guidelines ................................... 56 
9.2 
Screening Visit .................................................................................................................. 58 
 
Informed consent procedure ................................................................................ 58 
 
Screening Procedure ........................................................................................... 59 
9.3 
Quarantine Phase ............................................................................................................. 59 
 
Admission ............................................................................................................ 60 
 
Viral Challenge .................................................................................................... 60 
 
Discharge ............................................................................................................. 60 
9.4 
Follow-up phase ............................................................................................................... 61 
 
Study Day 13 to Day 18 ....................................................................................... 61 
 
Day 28 (±3 days) Follow-up Visit ......................................................................... 61 
9.5 
Duration of Subject Participation ...................................................................................... 62 
9.6 
Lost to follow-up................................................................................................................ 62 
9.7 
End of trial ......................................................................................................................... 62 
9.8 
Clinical Trial Summary Report .......................................................................................... 62 
10 
RANDOMISATION AND BLINDING ................................................................ 71 
10.1 
Randomisation .................................................................................................................. 71 
 Replacements ...................................................................................................... 72 
10.2 
Blinding ............................................................................................................................. 72 
10.3 
Unblinding ......................................................................................................................... 72 
11 
CHALLENGE VIRUS ........................................................................................ 74 
11.1 
Production ......................................................................................................................... 74 
11.2 
Supply and accountability ................................................................................................. 74 
11.3 
Preparation and administration ......................................................................................... 74 
11.4 
Disposal ............................................................................................................................ 75 
12 
INVESTIGATIONAL MEDICINAL PRODUCT .................................................. 76 
12.1 
Description ........................................................................................................................ 76 
12.2 
Dispensing and accountability .......................................................................................... 78 
12.3 
Packing and labelling ........................................................................................................ 78 
12.4 
Storage ............................................................................................................................. 79 
12.5 
Administration ................................................................................................................... 79 
 Fasting Schedule ................................................................................................. 80 
12.6 
Compliance ....................................................................................................................... 80 
12.7 
Overdose .......................................................................................................................... 80 
12.8 
Disposal ............................................................................................................................ 81 
13 
ASSESSMENTS AND PROCEDURES ............................................................ 82 
13.1 
Medical and medication history ........................................................................................ 82 
13.2 
Demographics ................................................................................................................... 82 
13.3 
Height, weight, and body mass index ............................................................................... 82 
13.4 
Complete physical examination ........................................................................................ 82 
13.5 
Directed physical examination .......................................................................................... 83 
13.6 
Vital signs ......................................................................................................................... 83 
13.7 
Tympanic Temperature .................................................................................................... 84 
13.8 
ECG .................................................................................................................................. 85 
13.9 
Spirometry ........................................................................................................................ 85 
13.10 hVIVO Symptom Diary Cards ........................................................................................... 86 
13.11 Nasal discharge collection from paper tissues ................................................................. 86 
13.12 Routine blood analysis ..................................................................................................... 87 
13.13 Challenge Virus serology .................................................................................................. 87 
13.14 Nasal samples .................................................................................................................. 87 
 Nasopharyngeal swab ......................................................................................... 87 
13.14.1.1 
Respiratory Pathogen Screen .......................................................... 88 
13.14.1.2 
Rapid Viral Screen ............................................................................ 88 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
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hVIVO Protocol No: ENA-CS-001 
 
 
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 Nasal wash .......................................................................................................... 88 
13.15 Breath alcohol ................................................................................................................... 88 
13.16 Adverse events and concomitant medications ................................................................. 88 
14 
LABORATORY ASSESSMENTS ..................................................................... 90 
14.1 
Blood volume .................................................................................................................... 90 
14.2 
Safety Blood Samples and Assessments ......................................................................... 90 
 Biochemistry ........................................................................................................ 91 
 Thyroid function test ............................................................................................ 91 
 Haematology ........................................................................................................ 91 
 Cardiac enzymes ................................................................................................. 92 
 Coagulation .......................................................................................................... 92 
 Human Immunodeficiency Virus and Hepatitis A, B, and C ................................ 92 
 Serum follicle stimulating hormone ...................................................................... 92 
 Serum pregnancy test .......................................................................................... 92 
14.3 
Urine Samples and Assessments..................................................................................... 92 
 Urinalysis ............................................................................................................. 92 
 Drugs of abuse and cotinine ................................................................................ 93 
 Pregnancy ............................................................................................................ 93 
14.4 
Virology Assessments ...................................................................................................... 93 
 Serum RSV neutralising antibody ........................................................................ 93 
 Respiratory Pathogen Screen ............................................................................. 93 
 Rapid Viral Screen ............................................................................................... 94 
 Viral load .............................................................................................................. 94 
14.4.4.1 
Quantitative Reverse Transcription Polymerase Chain Reaction (RT-
qPCR) ..................................................................................................... 94 
14.4.4.2 
Cell Based Infectivity Assay ............................................................... 94 
 Viral shedding for dosing ..................................................................................... 94 
14.4.5.1 
Qualitative Integrated Cycler Polymerase Chain Reaction (qicPCR) . 94 
 Replicative Strand PCR ....................................................................................... 94 
 Viral resistance .................................................................................................... 94 
14.5 
PK Assessments............................................................................................................... 95 
 Blood Plasma Samples ........................................................................................ 95 
 Nasal Wash samples ........................................................................................... 95 
15 
ADVERSE EVENTS AND TOXICITY MANAGEMENT ..................................... 96 
15.1 
Definitions ......................................................................................................................... 96 
 Adverse Event ..................................................................................................... 96 
 Adverse Drug Reaction ........................................................................................ 96 
 Unexpected Adverse (Drug) Reaction ................................................................. 97 
 Serious Adverse Event ........................................................................................ 97 
 Suspected Unexpected Serious Adverse Reaction ............................................. 98 
15.2 
Recording and reporting ................................................................................................... 98 
15.3 
Assessment ...................................................................................................................... 99 
 Description ........................................................................................................... 99 
 Onset and end ..................................................................................................... 99 
 Seriousness ......................................................................................................... 99 
 Intensity and severity ........................................................................................... 99 
 Adverse Events critical to the safety evaluation .................................................. 99 
 Challenge Virus symptoms ................................................................................ 100 
 Physical Examination ......................................................................................... 100 
 Directed Physical Examination .......................................................................... 100 
 Vital signs........................................................................................................... 100 
 Temperature ...................................................................................................... 100 
 Spirometry.......................................................................................................... 100 
 Laboratory values .............................................................................................. 101 
15.3.12.1 
C-reactive protein ........................................................................... 101 
15.4 
Classification of Adverse Events .................................................................................... 101 
 Severity .............................................................................................................. 101 
 Frequency .......................................................................................................... 102 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019  
  
 
 
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 Relationship ....................................................................................................... 102 
 Action taken ....................................................................................................... 103 
 Outcome ............................................................................................................ 103 
 Follow-up ........................................................................................................... 104 
15.5 
Serious Adverse Event reporting .................................................................................... 104 
 Reporting of SUSARs ........................................................................................ 106 
 Adverse Drug Reactions to non-IMPs ............................................................... 106 
 Post-study AEs and SAEs ................................................................................. 106 
 Pregnancy .......................................................................................................... 107 
16 
STATISTICAL METHODS AND PLANNED ANALYSES ............................... 108 
16.1 
Study analysis sets ......................................................................................................... 108 
 Subgroup analysis ............................................................................................. 109 
16.2 
Sample size .................................................................................................................... 109 
16.3 
Interim Analysis .............................................................................................................. 109 
16.4 
Statistical Analysis Plan .................................................................................................. 109 
 Clinical Study Report ......................................................................................... 110 
 Subject accountability ........................................................................................ 110 
 Protocol deviations ............................................................................................ 110 
 Demographic and baseline characteristics ........................................................ 110 
16.5 
Primary efficacy analysis ................................................................................................ 110 
16.6 
Secondary efficacy analysis ........................................................................................... 110 
 Safety analysis ................................................................................................... 111 
 Pharmacokinetic analysis .................................................................................. 111 
16.7 
Exploratory analysis ....................................................................................................... 112 
17 
STUDY FILES AND CLINICAL SOURCE DOCUMENTATION ...................... 113 
17.1 
Investigator’s Study File ................................................................................................. 113 
17.2 
Clinical source documentation ........................................................................................ 113 
17.3 
Data Capture .................................................................................................................. 113 
17.4 
Data quality assurance and quality control ..................................................................... 113 
17.5 
Data coding ..................................................................................................................... 114 
17.6 
Database lock ................................................................................................................. 114 
17.7 
Data protection ............................................................................................................... 114 
18 
STUDY MANAGEMENT AND ETHICAL RESPONSIBILITIES ...................... 115 
18.1 
Regulatory and Ethics Opinions and Good Clinical Practice ......................................... 115 
18.2 
Quality Assurance........................................................................................................... 115 
18.3 
Quality Control ................................................................................................................ 115 
18.4 
Deviations from the Protocol .......................................................................................... 115 
 Protocol Waivers ................................................................................................ 115 
 Protocol Deviations ............................................................................................ 115 
 Serious breach of the protocol or GCP .............................................................. 115 
 Protocol amendments ........................................................................................ 116 
 Urgent Safety Measures .................................................................................... 117 
18.4.5.1 
Pandemic .......................................................................................... 117 
18.5 
Discontinuation of the study ........................................................................................... 117 
 Stopping Criteria ................................................................................................ 118 
18.6 
Study records retention and direct access to source documents ................................... 119 
 Archiving ............................................................................................................ 120 
18.7 
Sponsor responsibilities .................................................................................................. 120 
 General .............................................................................................................. 120 
 No-fault compensation and indemnity ............................................................... 120 
 Monitoring .......................................................................................................... 120 
 Audits and inspections ....................................................................................... 121 
 Reports to the REC and MHRA ......................................................................... 121 
18.8 
Investigator responsibilities ............................................................................................ 121 
 Ethical considerations ........................................................................................ 121 
 Laboratory certification and normal values ........................................................ 122 
 Delegation of Investigator responsibilities ......................................................... 122 
 Informed Consent Process ................................................................................ 122 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019  
  
 
 
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 Information for General Practitioners ................................................................. 123 
 Compensation and Expenses ............................................................................ 123 
 Liability and insurance ....................................................................................... 123 
 Investigator’s Protocol Agreement ..................................................................... 123 
 Quality assurance .............................................................................................. 124 
18.9 
Study termination ............................................................................................................ 124 
18.10 GCP Compliance ............................................................................................................ 124 
19 
DISCLOSURE OF DATA................................................................................ 125 
19.1 
Subject confidentiality ..................................................................................................... 125 
19.2 
Sponsor confidentiality ................................................................................................... 125 
19.3 
Publication ...................................................................................................................... 125 
20 
REFERENCES AND BIBLIOGRAPHY ........................................................... 127 
21 
APPENDICES ................................................................................................ 132 
 
 
 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019  
  
 
 
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LIST OF APPENDICES 
Appendix 1: Patient Health Questionnaire (PHQ-9)40 ................................................................. 133 
Appendix 2: Generalised Anxiety Disorder Questionnaire (GAD-7)41 ........................................ 134 
Appendix 3: Normal ranges ........................................................................................................ 135 
Appendix 4: hVIVO Symptom Diary Card ................................................................................... 136 
Appendix 5: AE and Toxicity Grading Scales ............................................................................. 137 
Appendix 6: Assessment of Baseline by Investigator for Clinical Conduct ................................ 138 
Appendix 7: PK Blood Sampling Schedule ................................................................................. 140 
 
LIST OF TABLES  
Table 9-1: Time and events schedule ........................................................................................... 63 
Table 12-1: Physicochemical properties of EDP-938 Drug Substance ........................................ 76 
Table 12-2: Physical description of the Oral 
 ............................................................. 76 
Table 15-1: Classification of adverse event severity .................................................................. 102 
Table 15-2: Classification of Adverse Event relationship ........................................................... 102 
Table 15-3: Classification of adverse event outcome ................................................................. 103 
Table 15-4: Contact details for reporting all SAEs ...................................................................... 105 
Table 18-1: Study stopping criteria ............................................................................................. 118 
 
LIST OF FIGURES 
Figure 9-1: Study design ............................................................................................................... 57 
  

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
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hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019  
  
 
 
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OTHER PARTIES 
The Sponsor Trial Master File (TMF) / hVIVO TMF contains 
details of third party contractors, sub-investigators, 
laboratories, clinical monitors, data management suppliers, 
statisticians and all other service providers. 
 
 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
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hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019 
  
 
 
  
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5 
BACKGROUND AND INTRODUCTION  
5.1 
Information about Respiratory Syncytial Virus (RSV)   
RSV Virus Challenge strain Memphis-37b strain has been utilised in over 900 healthy subjects 
in at least 17 clinical studies. RSV inoculation of healthy subjects was shown to infect 
approximately 65 - 85% of placebo subjects and produced mild to moderate upper respiratory 
tract illness24. 
 
Additionally, another sub-batch of live RSV (Memphis 37c) has been used as a challenge 
agent and was shown to be safe in over 77 healthy young adults across three studies. RSV 
infection was not associated with any serious adverse side effects7-9. 
 
The study virus, like many viruses, can cause more substantial health issues such as 
myocarditis (inflammation or damage to the heart muscle). However, the chance of this 
resulting in serious or permanent changes is rare, as most cases are minor and resolve without 
any lasting changes. In our virus challenge studies, uncommonly blood tests have shown a 
change suggestive of myocarditis, although in these few subjects the blood tests returned to 
normal without treatment and were not associated with specific symptoms or ECG changes. 
 
Human RSV is an enveloped, single-stranded ribonucleic acid (ssRNA) virus, which infects all 
human age groups, but causes the most severe disease burden in the paediatric population. 
RSV infects over half of all infants within their first year of life10, and is the single most common 
cause of hospitalisation of infants11, 12, representing more than 126,000 childhood 
hospitalisations per year in the United States (US) and a similar number in the European Union 
(EU)13. Furthermore, the development of childhood asthma and other post-acute sequelae is 
also known to occur after severe childhood RSV infections14-16.  
Childhood infection is not associated with life-long immunity to RSV and infections in 
adulthood occur periodically with an acute, mild rhinitis10, 14, 17. In susceptible adult populations 
(e.g., the elderly, those with co-existing heart or lung disease, individuals receiving 
chemotherapy or who are immuno-compromised), RSV can produce more severe and 
potentially life-threatening lower respiratory tract infections18-22.  
No vaccine to treat or prevent RSV mediated disease is available. The only approved antiviral 
therapy for RSV, ribavirin, is rarely used in the US or European paediatric population due to 
its unfavourable toxicity, its poor antiviral effect, and its controversial and limited efficacy23-25. 
Existing prevention strategies rely on monoclonal antibodies which are only partially effective 
and which are administered to only a small fraction of the at-risk population26. Thus, an 
effective therapy for RSV infection represents a major unmet medical need. 
5.2 
Information about EDP-938 
 
Product description 
The study drug is EDP-938, is a novel, orally administered, non-fusion replication inhibitor of 
RSV that is being developed as a potential treatment for RSV infection.  
 
EDP-938 is a small molecule, with a molecular formula C27H22F3N7O3. The drug product is  
 
 
 
  
 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019 
  
 
 
  
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Non-clinical studies 
5.2.2.1 Non-Clinical Pharmacology Studies 
The principal findings from the non-clinical pharmacology studies are summarised below: 
• 
EDP-938 is a novel non-fusion replication inhibitor of RSV with in vitro resistance 
studies suggesting that the compound targets RSV nucleoprotein (N) 48-49. 
 
• 
It is specific for RSV with no cross-activity against two unrelated viruses, HBV and 
HCV, and the antiviral effect is not due to cytotoxicity. 
 
• 
In vitro resistance study revealed that mutations selected with EDP-938 are mainly 
located in the P-binding pocket of RSV N protein, which is consistent with previous 
reports with other inhibitors of the same class48. 
 
• 
RSV N protein is an essential component of viral RNA-dependent RNA polymerase 
(RdRp), which is responsible for viral replication and transcription. In vitro time-of-
addition study confirms that EDP-938 works at a post-entry, replication step of RSV. 
 
• 
 
 
 
 
 
• 
Taken together, these data suggest that the anti-RSV effect of EDP-938 is likely 
mediated through viral N protein, although the exact mechanism of action remains to 
be further elucidated. 
 
5.2.2.2 Non-Clinical Pharmacokinetics  
The PK properties of EDP-938 were investigated in non-clinical studies conducted 
 
 The PK of EDP-938 
following single intravenous (IV) and oral (PO) doses were determined in each of these animal 
species. In addition, multiple-dose oral pharmacokinetic studies were conducted as 
components 
 Good Laboratory Practice (GLP) toxicology studies in mice and 
monkeys. The mouse and the monkey comprised the primary species used to evaluate the 
safety of the compound. 
• 
 
 
 
 
 
 
• 
 
 
 
 
 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
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hVIVO Protocol No: ENA-CS-001 
 
 
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• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.2.2.3 Non-Clinical Toxicology in Animal Summary 
Key findings from these studies are summarised below: 
 
• 
Oral EDP-938 treatment in single and repeat dose general toxicity studies at up to 
 of once-daily dosing across species was well-tolerated.  
 
• 
 
 
 
 
 
 
 
• 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
It was concluded that the toxicology studies support progression into clinical trials in healthy 
subjects. 
 
 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
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hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019 
  
 
 
  
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Clinical studies 
5.2.3.1 Effects in Humans 
EDP- 938 is being evaluated in an ongoing Phase 1, randomized, double-blind, placebo-
controlled, first-in-human (FIH) study in which the safety, tolerability, and PK is being assessed 
in healthy adult subjects. The Phase 1 study included a SAD phase enrolling a total of 6 dose 
cohorts of which, one was a two-part Food Effect (FE) cohort, and a MAD phase enrolling 5 
dose cohorts.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
In summary: 
• 
 
 
 
 
 
 
These results support further clinical evaluation of EDP-938 in patients with RSV. 
For a detailed description of available clinical data, please refer to the EDP-938 IB addendum. 
5.3 
Rationale for the study 
EDP-938 is an investigational drug substance being developed for the treatment of RSV 
infection.  
 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
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hVIVO Protocol No: ENA-CS-001 
 
 
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EDP-938 is a novel non-fusion replication inhibitor of RSV, and it is against all RSV A and B 
laboratory strains and clinical isolates tested in vitro. In the primary human bronchial epithelial 
cells, EDP-938 had an EC50 of 21nM, 23nM and 64nM, against RSV-A Long, M37 and RSV-
B Washington strains, respectively. EDP-938 appears to inhibit RSV replication by modulating 
viral nucleoprotein (N), 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.  
The rationale for taking EDP-938 into further development is the expectation that this 
compound could be effective for the treatment of RSV, to address the unmet medical need for 
more effective antiviral therapies for RSV. 
 
Study design 
The study will be conducted by hVIVO Services Limited, which has extensive experience with 
viral challenge studies. Numerous studies have been performed using experimental RSV-A 
Memphis 37b infection in human subjects. To date, in hVIVO’s studies, more than 900 subjects 
have been successfully and safely inoculated with RSV-A Memphis 37b. These studies42-47 
demonstrated that adults could be infected by nasal inoculation. This strain has been shown 
to cause symptoms and virus shedding that closely match natural infection. 
Administration of study drug and challenge with RSV-A Memphis 37b will take place in 
hVIVO’s specialised Unit. Standard study procedures (including collection of blood, urine, and 
nasopharyngeal secretions for assessment of safety and efficacy) have been employed in 
previous studies conducted by hVIVO. 
 
EDP-938 dose regimen 
Doses selected for Part 1 of the Study are: 
▪ 
600mg OD every 24 hours (+/- 1hr) for 5 days  
▪ 
A single Loading Dose (LD) of 500mg followed by a 300mg dose every 12 hours (+/-
1hr) for 5 days.  
These doses are expected to provide exposures in the anticipated therapeutic range.  
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
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Based on in vitro testing, an EC90 value for EDP-938 of 20 ng/ml was determined in human 
bronchial epithelial cells (HBEC). The EDP-938 doses selected for Part 1 (600mg OD or a 
single LD of 500mg followed by 300mg dose every 12 hours) are expected to result in mean 
Ctrough concentrations at steady state of approximately 600ng/ml. These values are expected 
to provide mean exposures of approximately 30x compared to the EC90 in HBEC (based on 
total EDP-938 concentrations). As EDP-938 is 95% plasma protein bound, the corresponding 
multiple corrected for plasma protein binding is approximately 1.5x for both dosing regimens.  
Doses and regimens for Part 2 of the Study will be determined based on emerging PK, 
virology, clinical symptom score and safety data from Part 1. However, the maximum individual 
dose in any treatment regimen will not exceed a loading dose followed by maintenance doses 
which are projected to deliver mean IMP exposure of 28745 ng.hr/mL (AUC).  
5.4 
Potential risks and benefits to participants 
There are no expected benefits to study participants, although subjects may develop some 
immunity to RSV-A Memphis 37b and benefit from a general health check at screening.  
The known risks to participants are detailed below. However, there may also be risks that are 
unforeseen and not anticipated (e.g., unknown allergies). Every effort will be made to monitor 
the health of the subjects to ensure that such risks are minimised. Trained medical personnel 
and facilities will be available to provide medical emergency care. 
 
Virus  
Subjects have approximately 65% to 85% chance of becoming infected with RSV following 
the administration of the virus6. Typical RSV illness is characterised by an abrupt onset of 
rhinitis, nasal stuffiness, fever, malaise, myalgia (muscle aches), and sore throat. In healthy 
adults, the illness usually resolves without any treatment, with relief of symptoms occurring 
naturally within 7 to 10 days. Qualified doctors and nurses in the Quarantine Unit will manage 
any symptoms. 
 
The study virus, like many viruses, can cause more substantial health issues such as 
myocarditis (inflammation or damage to the heart muscle). However, the chance of this 
resulting in serious or permanent changes is rare, as most cases are minor and resolve without 
any lasting changes. In hVIVO’s virus challenge studies, uncommonly blood tests have shown 
a change suggestive of myocarditis, although in these few subjects the blood tests returned 
to normal without treatment and were not associated with specific symptoms or ECG changes. 
Severe complications of naturally occurring RSV infection tend to occur almost exclusively in 
infants, the elderly, and persons of any age with chronic co-morbidities and significant immune 
compromise.  
 
It is unlikely for the subjects to transmit RSV to their close contacts. After infection with RSV, 
the virus will be present in the subjects’ noses for several days; although it is not expected 
that infectious RSV will be present in the respiratory tract at the time of discharge from the 
isolation facility (quarantine). This is because the usual duration of time that RSV infection 
remains in adults is several days shorter than the time subjects spend in the isolation facility 
(quarantine). A nasal swab sample will also be tested for RSV prior to discharge using a 
qualitative RSV Rapid Viral Antigen Test (RVAT) to determine subjects’ suitability for 
departure. If a subject is still positive for RSV (using RVAT) on Day 12, he/she may be asked 
to remain in quarantine. A further test will be carried out on Day 12 evening, if negative the 

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subject can be discharged. If the test is still positive on Day 12 or 13 and following review by 
the Investigator, the subject may be asked to remain in quarantine for further observation.  
If symptoms are present, but no virus is detected (negative RVAT), discharge will be at the 
investigator’s discretion. If appropriate, subjects may reside in quarantine for extra days if 
required. 
 
5.4.1.1 Vulnerable populations  
To reduce the risk of passing the Challenge Virus to others, subjects will be asked to avoid 
contact (have close contact or share the same apartment or house) with vulnerable people for 
2 weeks after they leave quarantine. For the purposes of this protocol, a vulnerable individual 
includes but not limited to the following:   
• 
Persons ≥65 years of age. 
• 
Children ≤2 years of age. 
• 
Residents of nursing homes. 
• 
Persons of any age with significant chronic medical conditions such as:  
o Chronic pulmonary disease (e.g., severe asthma, COPD).  
o Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, 
cardiac surgery, ischemic heart disease, known anatomic defects). 
o Contacts that required medical follow-up or hospitalization during the past 5 years 
because of chronic metabolic disease (e.g., insulin dependent diabetes mellitus, 
renal dysfunction, hemoglobinopathies). 
o Immunosuppression or cancer.  
o Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, 
stroke, seizures).  
• 
Individuals who are receiving long-term aspirin therapy. 
• 
Women who are pregnant or who are trying to become pregnant. 
 
 
EDP-938 
Based on pre-clinical data and final unblinded data for the SAD part and preliminary blinded 
data for the MAD part of the ongoing FIH Study EDP- 938-001, EDP-938 is expected to be 
safe and well tolerated in subjects inoculated with RSV.  
 
 
  
 
Study procedures 
Some of the study procedures may cause discomfort to the subject, however these normally 
resolve without further problems. The discomforts due to study procedures are described in 
the Volunteer Information Sheet (VIS). 
The blood tests performed to address the health of the subjects at screening and during the 
study may indicate that a subject has an infection that he/she was not previously aware of 
(such as HIV or hepatitis) or an unexpected illness. The hVIVO doctor will provide the subject’s 
general practitioner (GP), or doctor with a referral letter if the subject agrees. There may also 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
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be circumstances in which disclosing information without consent is justified in the public 
interest for important public benefits as required by local regulations. 
Should any new information relevant to the subjects’ participation in the study and their safety 
become available, a member of the hVIVO medical staff will notify subjects in a timely manner. 
If appropriate, subjects will be asked to reconfirm their consent to their participation in the 
study. 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
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6 
STUDY OBJECTIVES AND ENDPOINTS 
6.1 
Primary Objective 
To evaluate the antiviral activity of EDP-938 compared to placebo in healthy adult subjects 
inoculated with RSV-A Memphis 37b. 
 
Primary Endpoint 
The area under the curve (AUC) for RSV viral load measured in nasal washes by quantitative 
reverse transcription polymerase chain reaction (RT-qPCR), in subjects inoculated with RSV-
A Memphis 37b. 
6.2 
Secondary Objectives 
• 
To evaluate EDP-938 compared to placebo in healthy adult subjects inoculated with 
RSV-A Memphis 37b in terms of: 
 
o Clinical symptoms 
o Viral load 
o Safety and Tolerability 
 
• 
To characterise the PK profile of multiple doses of EDP-938 and metabolites in healthy 
adult subjects inoculated with RSV-A Memphis 37b. 
 
• 
To characterise the relationship between Plasma PK of EDP-938 and viral load AUC 
(RT-PCR) and total symptom score AUC  
 
 
Secondary Endpoints 
Secondary endpoints relating to efficacy include, but not limited to: 
6.2.1.1 Efficacy 
• 
Clinical Symptoms: 
o Effect of EDP-938 compared to placebo on RSV symptoms (using the 10- item diary 
card), with endpoints including: 
 
▪ 
AUC of total symptom score 
▪ 
Peak total symptom score over the duration of quarantine 
▪ 
Total symptom score  
▪ 
Time to peak symptom score after IMP dosing.  
▪ 
Time to resolution from peak symptom. 
 
o Total weight of nasal mucus produced (via weighed paper tissues).  
• 
Viral Load: 
o Additional viral load endpoints calculated separately using data from RT-qPCR of 
nasal wash comparing placebo and EDP-938 treated including: 

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▪ 
Peak viral load 
▪ 
Time to peak viral load 
▪ 
Time to resolution from peak 
▪ 
Time to cessation of virus quantifiable post first dosing 
 
6.2.1.2 Safety 
Secondary endpoints relating to safety include, but are not limited to: 
• 
AEs 
• 
Physical Examinations 
• 
Vital signs 
• 
12-lead ECGs 
• 
Spirometry 
• 
Clinical laboratory results (including biochemistry, haematology, coagulation (if 
required), cardiac enzymes and urine analysis 
 
6.2.1.3 Pharmacokinetics 
Secondary endpoints related to PK include, but are not limited to: 
• 
Plasma PK parameters of EDP-938 (and metabolites) following repeat dose 
administration in healthy adult subjects inoculated with RSV-A Memphis 37b: Cmax, 
Tmax, t1/2, CL/F, λz, Vd/F, C12, C24, AUClast, AUC0-tau, or AUC0-inf (as applicable). 
• 
Plasma PK (AUC) correlations with viral load AUC (e.g. RT-PCR) and TSS AUC 
 
6.3 
Exploratory Objectives 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
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Exploratory Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 

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Subjects will be counselled that early withdrawal from the viral challenge phase of the study 
is strongly discouraged, as it may pose a risk both to the subject and his/her contacts. In the 
event of a subject insisting on early withdrawal during the challenge isolation period, the 
subject will be encouraged to stay and would be advised of the potential risks of carrying RSV-
A Memphis 37b infection into the community, and to vulnerable groups (5.4.1.1) in particular.  
 
 
Subject discontinuation 
A subject's participation may be stopped (early discontinuation) for any of the following 
reasons: 
• 
Non-compliance with the study requirements and restrictions. 
• 
Clinically significant abnormal laboratory findings, which in the opinion of the 
Investigator(s) and/or Sponsor, precludes further participation in the study. 
• 
Development of inter-current illness which, in the opinion of the Investigator would 
compromise the health of the subject or the study objectives. 
• 
The Investigator’s decision that withdrawal from further participation would be in the 
subject’s best interest.  
• 
Termination of the study at the discretion of the Investigator(s) or Sponsor for safety, 
behavioural, or administrative reasons. 
• 
The wish of the subject. 
Subjects who are withdrawn from the study, will be requested to attend an Early Withdrawal 
Visit, with assessments as detailed in Table 9-1. 
 
Replacements 
Subjects that have been inoculated but not dosed will be replaced. 
Subjects who have been dosed with IMP (i.e. subject has received at least one IMP dose) and 
end participation early will not be replaced. 
 
Pregnancy 
In the event of a subject discontinuing the study prematurely due to pregnancy, or if pregnancy 
in a study subject’s partner becomes known, please refer to section 15 for pregnancy reporting 
requirements.  
 
Arrangements for additional care if required 
Subjects who still have significant worsening of their clinical signs compared to baseline may 
be required to stay in quarantine for additional observation and medical management longer 
than the scheduled Day 12 discharge date. Assessments will be conducted as clinically 
indicated by the Investigator. Such subjects upon discharge may be asked to return for a follow 
-up visit whether that be at the scheduled day 28 or an unscheduled visit.  

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7.6 
Reserve subjects 
Reserve subjects may remain available to replace any subjects who become ineligible for the 
study between the day of admission to quarantine and the final assessment of eligibility prior 
to Viral Challenge.  
Reserve subjects who are not needed for a particular quarantine group may be discharged 
from the planned quarantine before or on the day of Viral Challenge (Day 0) at the latest. 
A reserve subject who was not enrolled into a quarantine group may be enrolled into a later 
quarantine group within 56 days of screening with no re-screening required if the Day - 2 (or 
Day -1) clinical assessments meet the eligibility criteria, and provided sero-susceptibility 
results are within the 90 days (inclusive) window from the planned inoculation date (Day 0).  
7.7 
Subject numbering 
hVIVO assigns a unique subject number to each subject in the hVIVO subject database. This 
subject number will be used to identify a subject up to the point of randomisation (Section 
10.1), on source documents, on all study correspondence and in the study database. 
A separate randomisation number will be allocated to the subjects at randomisation and will 
be used for allocation of IMP. 
For subjects who subsequently do not enter the study, a reason will be documented in the 
source documentation and the subject’s medical notes.  
For subjects who are subsequently enrolled into the study, the Investigator will maintain an 
enrolment log, listing the identifiers for each subject alongside the subject number assigned 
and the date enrolled. A copy of the log will be filed in the hVIVO TMF at the study site. 
 

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8 
PROCEDURES FOR MONITORING SUBJECT COMPLIANCE WITH 
TREATMENT AND RESTRICTIONS 
8.1 
Concomitant therapies 
All medications taken from the time the subject consents to participation in the study will be 
recorded. Concomitant medications taken during the quarantine stage will be stored, 
prescribed and administered in line with their label-specific requirements and full 
accountability will be maintained. Any medications taken and changes in medications during 
the study up to final study contact Day 28 (±3 days) will be recorded in the source data. 
• 
All medications must be stopped prior to the planned date of dosing with IMP/viral 
challenge (whichever occurs first) unless in the opinion of the Investigator and/or 
Sponsor’s Medical Monitor, the medication will not interfere with the study procedures 
or compromise subject safety. Specifically, the following are excluded: 
 
• 
Herbal supplements within 7 days prior to the planned date of Viral Challenge. 
 
• 
Chronically used medications, vitamins or dietary supplements, including any 
medication known to be an inducer or inhibitor of CYP450 enzymes, within 21 days 
prior to the planned date of viral challenge. 
 
• 
Over-the-counter (OTC) medications (e.g., paracetamol or ibuprofen) where the dose 
taken over the preceding 7 days prior to the planned date of viral challenge has 
exceeded the maximum permissible 24-hour dose (e.g., ≥4 g paracetamol over the 
preceding week). 
 
During the quarantine, the Investigator may permit a limited amount of paracetamol (no more 
than 4 g per day i.e. maximum daily dose) or topical medication, as clinically required for the 
treatment of headache or any other pain. Other medication to treat AEs may be prescribed if 
required.  
Use of all concomitant medications will be recorded in the subject’s source notes, including all 
details/parameters that are required by the clinical database. This will include all prescription 
drugs, herbal preparations, and OTC medications.  
Any concomitant medication required for the subject’s welfare may be given by the 
Investigator. However, it is the responsibility of the Investigator to ensure that details regarding 
the medication and the reason for its use are recorded appropriately in the source notes to 
permit their transfer to the clinical database. 
 
 
 
 
 

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9 
STUDY DESIGN 
9.1 
Summary 
This is a randomised, Phase 2a, double-blind, placebo-controlled study in healthy subjects 
challenged with RSV-A Memphis 37b.  
The study is divided into 2 parts: 
• 
In Part 1:  
• 
5 consecutive days of dosing in three treatment groups, dosing BD to maintain the blind. 
Active doses administered OD (every 24 hours (±1 hour) interval) or as a single loading 
dose followed by BD (every 12 hours (±1 hour) interval) for a total 10 doses respectively 
of either: 
o Group 1: Placebo (n=38); subjects in this group will receive placebo dose BD 
(every 12 hours (±1 hour) interval) for a total of 10 doses. 
o Group 2: EDP-938 oral 
 loading dose group (n=38): subjects in this 
group will receive 500mg first dose, and at 12 hours (±1 hour) interval receive 
300mg second dose, then 300mg doses BD for a total of 10 doses. 
o Group 3: EDP-938 oral 
 600mg dose group (n=38): subjects in this 
group will receive a daily 600mg dose followed by a placebo dose at 12 hours 
(±1 hour) interval for a total of 10 doses.  
 
• 
IMP dosing to start on confirmation of positive result by qualitative integrated cycler 
polymerase chain reaction (qicPCR) on nasal wash. Nasal wash for qicPCR will be 
performed BD on Study Days 2-5 (Study Day 5 morning only), or until a positive result 
is achieved, whichever is sooner.  
 
• 
Earliest start of IMP dose will be in the evening on Study Day 2 post viral challenge (IMP 
will be initiated 12 ± 1-hour post nasal wash confirmation of a positive qicPCR result). 
 
OR 
 
• 
Dosing will start in the evening of Study Day 5 if no positive result is obtained by qicPCR.  
• 
In Part 2:  
• 
Up to a maximum of 84 subjects in total for Part 2 will be enrolled following an 
analysis of Part 1. Up to 63 subjects will complete dosing with EDP-938 and up to 
21 subjects will complete dosing with placebo.  
• 
The dose(s) of EDP-938 selected will be projected to deliver an efficacious 
exposure and will be based on emerging PK, PK/PD modelling, virology, clinical 
symptom score and safety data. 
 
 
 
• 
In Part 2, 63 subjects will be randomised equally into 1 of 3 treatment groups as 
below. Additional treatment groups may be evaluated, however, the maximum 
number of subjects enrolled in Part 2 will be 84. 
o Group 1 (n=21): Placebo dosed BD for 5 days, with dosing at 12 hours (± 1 
hour) interval   
o Group 2 (n=21): A single Loading Dose of 400mg (Dose 1), followed by 
200mg second dose at 12 hours (± 1-hour interval), then 200mg doses  BD, 
and with dosing for 5 days, 

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Follow-up phase 
 
Part 1:  
 
Follow-up Visit 
 
• 
 Study Day 28 [± 3 days] and study termination 
 
 
Part 2: 
 
Follow-up Visit 
• 
Study Day 13, where applicable (only subjects 
who started IMP dosing on the evening of Study 
Day 5 (up to Day 8 evening) will return for a PK 
sample on Study Day 13) 
• 
Study Day 14, where applicable (only subjects 
who started IMP dosing on the evening of Study 
Day 5 (up to Day 8 evening) will return for a PK 
sample on Study Day 14) 
• 
Study Day 15, where applicable (only subjects 
who started IMP dosing on the evening of Study 
Day 5 (up to Day 8 evening) will return for a PK 
sample on Study Day 15) 
• 
Study Day 28 [± 3 days] and study termination 
The overall study design is depicted in Figure 9-1. 
 
 
Part 2 Progression and Additional Evaluation Guidelines 
Part 2 will commence no earlier than after an evaluation by the Sponsor and Investigator of 
the virology, clinical symptom score, PK, and safety data from Part 1.   
 
Prior to Part 2, the Sponsor will review the emerging data to confirm dose(s) (up to 600mg 
dose) and dose frequencies (OD or BD) to be evaluated in Part 2. Higher doses may be 
evaluated in the event that there is the potential for additional antiviral responses; 
 
 
 and an acceptable safety profile is observed. Lower doses may be evaluated 
in the event that a degree of viral suppression is observed. A longer duration of dosing (up to 
7 days maximum) may be evaluated if there is evidence of incomplete viral suppression or 
viral rebound after completion of therapy, and an acceptable safety profile is observed. See 
section 18.5.1 for stopping criteria.    
 
 
 
 
The maximum duration of treatment in parts 1 & 2 will not exceed 5 days and 7 days 
respectively. 

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The timing of study procedures relative to each phase is shown in Section 9. The procedures and 
assessments which will be undertaken to evaluate safety and efficacy are described in Section 
13: Assessments and Procedures. 
Subjects will: 
• 
Attend Screening Visit from -56 to Day -3 prior to challenge  
• 
Be admitted to the Quarantine Unit on Day -2/-1 
• 
Be inoculated with Challenge Virus on Day 0 
• 
Be discharged from the Quarantine Unit on Day 12 (if necessary, subjects may reside in 
quarantine for a further night or longer before discharge) 
• 
Return to the clinic on Study Day 13, 14, 15, 16, 17 and 18, as applicable (subjects who 
start IMP dosing in the evening of study Day 5 (up to Day 8 evening) will return for a PK 
sample. 
• 
Return to the clinic for a Follow-up Visit(s) on Day 28 (± 3 days) (all subjects). 
The duration of a subject’s participation from Screening Visit to the scheduled Follow-up Visit(s) 
on Day 28 (± 3 days) will be approximately 3 months.  
The total duration of the clinical phase of the study, from the start of subject screening to the last 
subject’s last visit (LSLV) is expected to be approximately 18 months.  
9.2 
Screening Visit 
Subjects who are sero-suitable for the challenge virus (screened through the hVIVO generic 
screening process) will be invited to attend a Screening Visit within 56 days to 3 days prior to viral 
challenge.  
 
Historical generic screening data collected through the hVIVO generic screening process within 
56 days to 3 days prior to inoculation (90 days for viral serology) may be transferred to the study 
after the study specific consent form has been signed by the trial participant. Historical pre-
screening data obtained prior to this window can be re-assessed any time within 56 days to 3 
days prior to viral challenge.  
 
 
Informed consent procedure 
The Investigator will obtain a signed ICF from each subject before any study specific procedures 
are performed.  
When historical screening data collected through the hVIVO generic screening process is used 
for screening, the study specific ICF will be obtained at quarantine admission (Day -2/-1) from 
each subject before any study specific procedures are performed.  
Potential subjects will typically be sent a copy of the ICF when their Screening Visit/Quarantine 
admission visit (as applicable) is arranged and at least 24 hours prior to the visit, and will be 

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encouraged to read it prior to their appointment. Upon arrival at the Screening Visit/Quarantine 
admission visit (as applicable), the ICF is discussed by the Investigator, and they will be given the 
opportunity to ask any questions, and may take the information sheet away to consider their 
participation. 
All subjects will be required to have a good understanding of English and the Investigator will be 
responsible for ensuring that the subject understands the information contained in the ICF. Once 
the Investigator has confirmed that the subject has understood the study, including the benefits 
and risks of participation, the subject and the Investigator can sign and date the ICF.  
The ICF must be signed and dated by the subject and countersigned by the Investigator (whoever 
conducted the consent discussion). A copy of the ICF will be given to the subject, and the original 
will be held in the hVIVO TMF. 
Subjects will be assured that they can withdraw from the study at any time and for any reason 
without prejudice to their future medical care, and that they will be informed in a timely manner if 
new information becomes available that may affect their willingness to continue their participation 
in the study. This information will be included within in the ICF.  
If the ICF is amended during the study, the PI/Investigator will follow all applicable regulatory 
requirements pertaining to approval of the amendment by the research ethics committee (REC). 
The site(s) must use the amended ICF for all new subjects and if required, the consent process 
will be repeated with the amended ICF for on-going subjects. 
 
Screening Procedure 
Screening assessments will be performed as detailed in Table 9-1 and may be repeated as 
necessary on admission to the hVIVO Quarantine Unit.  
Results of tests or examinations performed under other ethically approved hVIVO protocols within 
56 days to 3 days prior to viral challenge (90 days for viral serology) may be used to determine 
eligibility. Historical pre-screening data obtained prior to this window can be re-assessed any time 
within 56 days to 3 days prior to viral challenge. Serosuitability to the Challenge Virus may be 
reconfirmed at the PI/Investigator’s discretion any time between the Screening Visit and the day 
of Viral Challenge. The subject will be excluded from the study if the results demonstrate that the 
subject is no longer serosuitable to the Challenge Virus. The specific virus neutralisation antibody 
titre used to determine subjects’ serosuitability and the associated assay will be detailed in the 
Analytical Plan (AP).  
9.3 
 Quarantine Phase 
Subjects will be monitored closely throughout their stay in the Quarantine Unit; standard 
procedures will be performed as detailed in Table 9-1.  

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Admission 
On Day -2 or Day -1, 2 or 1 days prior to the day of challenge, the subject will attend the 
Quarantine Unit; eligibility will be reviewed and a nasopharyngeal swab will be taken for 
respiratory pathogen screen (Section 13.14.1.1). Various study assessments and tests as 
detailed in Table 9-1 will be performed during this admission visit.  
When historical screening data collected through the hVIVO generic screening process is used 
for screening, the study specific ICF will be obtained at quarantine admission (Day -2/-1) from 
each subject before any study specific procedures are performed.  
If a subject is found to be ineligible based on review of the eligibility criteria, the subject will not 
proceed in that quarantine group. The Investigator/Study Physician will decide whether the 
subject should be permanently excluded from the study  or invited back  for repeat of assessments 
(i.e. repeat clinical laboratory test, if the initial screening assessments are still within the -56 to -3 
window) or rescreening for a later quarantine, as appropriate . 
Eligible subjects may be invited to attend quarantine as reserves for each group. If a subject no 
longer complies with the study eligibility criteria, the subject will be discharged and may be 
replaced with a reserve subject. 
Subjects may be admitted to the Quarantine Unit on Day -1 at the Investigator’s discretion. 
Any assessments planned for Day -2 may be performed or repeated on Day -1.  
During the Quarantine and Challenge phase, assessments and procedures will be performed as 
detailed in Table 9-1: Time and events schedule. 
Viral Challenge is described in Section 11. EDP-938 dosing is described in Section 12.5. 
 
Viral Challenge 
If the subject remains eligible for the study, he/she will be inoculated with challenge virus on Day 
0. 
 
Discharge 
On Day 12, subjects will be discharged from the Quarantine Unit if the nasopharyngeal swab 
sample, confirmed by rapid viral antigen test (RVAT), is negative for Challenge Virus. If a subject 
is still positive for RSV (using RVAT) on Day 12, he/she may be asked to remain in quarantine. A 
further test will be carried out on Day 12 evening, if negative the subject can be discharged. If the 
test is still positive on Day 12 or 13 and following review by the Investigator, the subject may be 
asked to remain in quarantine for further observation. If symptoms are present, but no virus is 

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detected (negative RVAT), discharge will be at the investigator’s discretion. If appropriate, 
subjects may reside in quarantine for extra days if required. 
Subjects may be discharged based on the subject’s clinical condition and the PI/Investigator’s 
assessment. If subjects are required to remain in quarantine longer than the scheduled day/time, 
all assessments will be at the discretion of the PI/Investigator. AEs and concomitant medications 
will be monitored.  
Various study assessments and tests will be performed during this discharge day as detailed in 
Table 9-1. 
 
9.4 
Follow-up phase 
The follow-up phase will commence once a subject has been discharged from the Quarantine 
Unit.  
 
Further Follow-up Visits before Day 28 may be scheduled at the discretion of the PI/Investigator, 
if the subject has been symptomatic or require additional follow-up since discharge from the 
Quarantine Unit.  
 
 
 Study Day 13 to Day 18 
Subjects who started IMP dosing on the evening of Study Day 5 (up to Day 8 evening) post Viral 
Challenge for up to 7 days dosing regimen in Part 2 will return for PK sampling on Study Day 13, 
14, and 15, 16, 17 and 18 (as applicable) in order to obtain the PK sample(s) associated with the 
final dose of IMP, for the pre-dose, 0.5-hour,1-hour, 2-hour, 3-hour, 4-hour, 5-hour, 6-hour, 8-
hour, 10-hour, 12-hour, 15-hour, 24-hour, 30-hour, 36-hour, 48-hour, 60-hour, and 72-hour post 
final dose time points as applicable. 
Other assessments performed at this Follow-up Visit (s) could include ECG, AE and ConMed 
review (in addition to the PK blood draw). 
 
Day 28 (±3 days) Follow-up Visit  
Subjects will return to the hVIVO clinic for 1 scheduled Follow-up Visit; at 28 days post-Viral 
Challenge (±3 days). Assessments will be performed as detailed in Table 9-1: Time and events 
schedule. For subjects lost to follow up, refer to Section 9.6. 
 
Any AEs that are unresolved at the final Follow-up Visit may necessitate further unscheduled 
visits until the AE has resolved or the subject is deemed fit by the Investigator. Subjects may be 
discharged for GP follow-up if appropriate. 
 

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9.5 
Duration of Subject Participation 
The maximum duration of a subject’s participation from screening to the last scheduled Follow-
up Visit is expected to be approximately 3 months.  
9.6 
Lost to follow-up 
In the event that a subject does not return or cannot be contacted for the final Follow-up Visit at 
Day 28 (±3 days) post-Viral Challenge, the Investigator will make every reasonable effort to 
contact the subject to review all AEs. In the event that a subject drops out of the study at any time, 
the reason for discontinuation, if known, must be fully documented in the source data. The site 
personnel will document the AEs and any other assessments and will make every effort to 
complete all required end of study assessments. 
9.7 
End of trial  
The end of the trial is defined as the last subject’s last scheduled visit (LSLV) at Day 28 (±3 days). 
If a safety visit is required after the last scheduled visit, this will be at the PI/Investigator’s 
discretion as a duty of care, e.g., repeat spirometry or laboratory tests. These discretionary 
Follow-up Visits will not be considered part of the trial data unless they represent follow-up and 
closure on an AE or SAE identified during the trial period.  
AEs that are unresolved at the Day 28 (±3 days) post-challenge Follow-up Visit may necessitate 
further Follow-up Visits if required. 
9.8 
Clinical Trial Summary Report 
It is the Sponsor’s (or Sponsor delegate) responsibility to send the Clinical Trial Summary Report 
to the REC and Medicines and Healthcare Regulatory Agency (MHRA) (if required) within 1 year 
of the end of the trial. In addition, the Sponsor or Sponsor delegate is responsible for entering 
appropriate data into the EudraCT results database within 1 year of the end of the trial. 

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X 
Once 
BD 
Twice Daily, 12 hours between assessments (± 1 hour). 
TDS 
Three Times Daily, at the same time each day (± 1 hour). 
T 
To determine tolerance of the procedure only (sample will not be tested). 
+ 
Only the applicable Inclusion/Exclusion criteria will be reviewed at each time point. 
a 
Subjects will be assigned a randomisation number once the decision to dose is confirmed (i.e. RSV RNA positive confirmed by 
qicPCR). 
b 
 
 
   
 
  
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
c 
Height will be taken at Screening only.  

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d 
Distribution of paper issues and bags will start on Day -1, with the first collection on Day 0. Thereafter distribution 
and collection of tissues will occur at 08:00 (± 1 hour). Tissues will be handed out daily and collection will occur until discharge 
from quarantine. 
e 
Spirometry will be performed at the same time each day during quarantine (± 1 hour). 
f 
A serum follicle stimulating hormone (FSH) test will be performed in all post-menopausal women 
g 
Blood serum pregnancy test (ß-HCG) will be performed in all female subjects 
h 
Blood will be drawn under non-fasted conditions.  
Repeat bloods may be drawn under fasted conditions if a lipid profile (cholesterol and triglyceride) or glucose is required (at PI 
discretion).  
i 
Virus serology (RSV neutralisation antibody assay) will be performed within 90 days of inoculation to determine eligibility, on 
entry to Quarantine, and at Day 28 Follow-up Visit 
j 
Nasopharyngeal swab for respiratory virus screen to assess for the presence of other respiratory viruses. 
k 
Nasal wash virology/ Pharmacokinetics samples will be collected at the same time each day during quarantine (± 1 hour) and 
used for RT-qPCR, and may be used for other secondary or exploratory assessments 
 
  
Samples collected between Days 2 and 5 (Study Day 5 Morning) will also be used for qicPCR until a positive result is received 
(to support dosing decisions). 
l 
Plasma Pharmacokinetics: plasma samples for IMP assay will be collected as outlined in Appendix 7 (PK Blood Sampling 
Schedule): 
 
The allowable time windows for the sampling are as follows: 
 
▪ 
± 5 minutes from the scheduled time for time points ≤ 1 hour from dosing; 
 
▪ 
± 15 minutes from the scheduled time for time points > 1 hour from dosing, with NOTE below: 
o 
24 hours timepoint: +/- 1 hour window 
o 
30 hours timepoint: +/- 1 hour window 
o 
36 hours timepoint: +/- 1 hour window 
o 
48 hours timepoint: +/- 2 hours window 
o 
60 hours timepoint: +/- 2 hours window 
o 
72 hours timepoint: +/- 2 hours window 
 
▪ 
There is no time window requirement for the pre-dose sample. The pre-dose sample must be taken prior to dose. 

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For Part 1 subjects who start dosing on the afternoon of Day 5 post viral challenge (PM starters), the 72-hour timepoint after 
Dose 10 would occur on Day 13. Thus, for a subset of subjects, this timepoint could be after discharge. The guidance for the 72-
hour PK sample collection is as follow:  
 
▪ 
For PM starters who start dosing on Day 5 post viral challenge and meet discharge criteria on Day 12, the 72-hour 
timepoint sample can be omitted. 
▪ 
For PM starters who start dosing on Day 5 post viral challenge and do not meet discharge criteria on Day 12 and are 
therefore still in the quarantine unit for the 72-hour PK timepoint, this sample should be collected. 
▪ 
The same guidance for 72-hour PK sample collection will apply to Part 2 when the PK Blood sampling for 5 days TWICE 
a day dosing for Part 1 will be used for Part 2. 
m 
Can be performed on Study Day -2 or Study Day -1. 
n 
Historical pre-screening data collected through the hVIVO generic screening process within 56 days (90 days for viral serology) 
to 3 days prior to quarantine admission may be used for screening procedures and to determine eligibility without the need to 
repeat the assessment. Historical pre-screening data obtained prior to this window can be re-assessed any time from 56 days to 
3 days prior to viral inoculation. 
o 
 
 
 
 
 
p 
When historical pre-screening data collected through the hVIVO generic screening process within 56 days to 3 days prior to 
inoculation (90 days for viral serology) is used for screening procedures, the study specific ICF will be obtained at quarantine 
admission (Day -2/-1) from each subject before any study specific procedures are performed. 
q 
Only Subjects who started IMP dosing on the evening of Study Day 5 (up to Day 8 evening) post Viral Challenge for up to 7 days 
dosing regimen (Part 2) will return for PK sampling on Study Day 13, 14,  15, 16, 17 and 18 (as applicable) in order to obtain the 
PK sample(s) associated with the final dose of IMP, for the pre-dose, 0.5-hour, 1-hour, 2-hour, 3-hour, 4-hour, 5-hour, 6-hour, 8-
hour, 10-hour, 12-hour, 15-hour, 24-hour, 30-hour, 36-hour, 48-hour, 60-hour, and 72-hour post final dose time points as 
applicable. 
r 
ECGs will also be recorded:  
 
▪ 
First IMP dose (Dose 1): pre-dose, 4 and 8 hours after the initial dose  
▪ 
Dose 2 to Dose 6: pre-dose  

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▪ 
Last IMP dose: 24 and 48 hours post last dose  
 
All pre-dose ECGs can be obtained up to 2 hours prior to dosing.  Post dose ECGs will be obtained ± 30 minutes of the target 
time.  
Notes: 
Parenthesis indicates the assessment may be optional, or at the PI/Investigator's discretion, or as required relative to the start of 
IMP dosing. 
For all subjects TDS assessments will commence on Day 0, the first assessment will be pre-virus challenge. 
The PI/Investigator may perform additional safety assessments as required. 
Where any nasal sampling time points occur together, the order of sampling will typically be (1) Nasopharyngeal swab followed 
by (2) Nasal wash. 

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10 
RANDOMISATION AND BLINDING 
10.1 
Randomisation 
The randomisation schedule will be generated at the beginning of the study on the assumption 
that subjects will be randomised as below: 
 
▪ 
In the first part of the study, subjects will be randomised to receive one of two doses 
of EDP-938 or placebo according to 1:1:1.  
 
▪ 
Following an analysis and emerging data from Part 1, Part 2 of the study will 
commence in which up to 84 subjects will be assigned to 1 of up to 3 treatment groups 
of up to 28 subjects each randomised in a 1:1:1 ratio. Up to a maximum of 84 subjects 
in total will be enrolled in Part 2.  
 
Subjects will be assigned a randomisation number prior to administration of the IMP.  
 
In Part 1 and Part 2 of the study, dosing will be triggered once the decision to dose is 
established based on confirmation of RSV infection by qicPCR between Study Day 2 and 
Study Day 5 (Day 5 morning only). If infection is not confirmed by positive qicPCR by Study 
Day 5 morning, subjects will be randomised on Study Day 5 and will commence IMP dosing 
in the evening of Study Day 5..    
 
Randomisation numbers will be assigned sequentially in ascending order; and once assigned, 
that randomisation number shall not be reassigned. The study site will keep a log of the 
randomisation number assigned to each subject. 
The Randomisation schedule and assigned randomisation number in Part 1 of the study will 
determine whether a subject is randomised into one of three treatment groups to receive  EDP-
938 at 600mg OD or 500mg LD followed by 300 mg BD or placebo. The Randomisation 
schedule and assigned randomisation number in Part 2 of the study will determine whether a 
subject receives either EDP-938 at 400mg LD followed by 200mg BD or 600mg LD followed 
by 300mg OD, or placebo.  
For the purposes of statistical analysis, placebo subjects from Part 1 will be analysed as a 
single placebo treatment group, as will placebo subjects from Part 2 based on the assumptions 
that the placebo substance is expected to be completely inert and have no antiviral properties 
and subsequently no effect on the efficacy endpoints and their analyses. 
 
A designated unblinded statistician, separate from the conduct or analysis of the study, will be 
responsible for the computer-generated randomisation schedule. Sealed copies of the 
randomisation code will be stored in a secure location.  
Randomisation numbers will follow a 5-digit format e.g., Part 1 will start with 10001, 10002, 
etc, and Part 2 will start with 20001, 20002, etc. A copy of the randomisation code list will be 
sent to the unblinded pharmacist/ designee preparing the IMP, so that EDP-938/placebo can 
be prepared for each subject as appropriate. 
Following database lock, on receipt of authorisation from the Sponsor, a copy of the 
randomisation code list will be provided to the Study Statistician to conduct study unblinding 
prior to analysis. 

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Replacements 
Subjects that have been inoculated but not dosed will be replaced. Subjects who are 
withdrawn before they have received all doses of IMP (i.e. subject has received at least one 
IMP dose) will not be replaced (refer to Section 7.5.3).   
If any of the quarantine groups has less than the planned number of subjects, additional 
subjects may be recruited into later quarantines, or additional quarantines may be conducted 
in order to maintain the power of the study. 
10.2 
Blinding 
The PI/Investigator will be provided with a tamper evident sealed envelope containing details 
of the treatment for each subject. All opened and unopened envelopes will be collected or 
destroyed after the end of the study, as agreed with the Sponsor. 
Due to the differing treatment regimens being tested, all subjects will be treated BD in order 
to maintain the blind between treatment groups. Subjects in the active OD dosing group will 
have their regimen supplemented by the administration of a placebo matched to EDP-938 in 
order to mimic the BD dosing group, and subjects randomised to the placebo arm will receive 
placebo matched to EDP-938 twice a day. 
 
Each subject is accommodated in their own individual room within the quarantine without direct 
contact with any other subject. In this way subjects assigned to different treatment groups will 
have no awareness of differences in their treatment or treatment administered. 
With the exception of the IMP manufacturer’s unblinded  pharmacist/designee, the statistician 
preparing the randomisation code list, the unblinded Clinical Research Associate (CRA) and 
the Quality Assurance (QA) auditors where necessary, the Investigator and all other clinical 
and non-clinical staff, (including the Study Statistician, data management staff), and the 
subjects will remain blinded to the treatment allocation until after the database has been locked 
and approval for study unblinding has been given. The confidentiality of the randomisation 
code lists and study blinding will be maintained. 
10.3 
Unblinding 
An independent Statistician at 
 Biometrics 
 will prepare the randomisation 
schedule, and the IMP Manufacturer’s pharmacist/designee at Hammersmith Medicines 
Research (HMR) will prepare the subject level IMP doses in line with the randomisation 
schedule.  
Individual emergency code break envelopes will be provided to hVIVO should it be necessary 
to break the blind for a subject. The Investigator will ensure there is an appropriate procedure 
in place to allow access to the code break envelopes in case of an emergency arising during 
the quarantine period, as per hVIVO's standard operating procedures (SOPs). An emergency 
means that the relevant medical decision on the further care of a subject is dependent on the 
actual identity of the study treatment that the subject has received. 

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The emergency code break envelopes will contain information stating either ‘This subject was 
on active drug (and dosage)’ or ‘This subject was on placebo’. Any premature code-breaking 
will be explained and justified by the Investigator and hVIVO, and the Sponsor must be 
promptly informed. If possible, the Sponsor should be consulted before the code is broken, 
but this will only occur if the safety of the subject will not be compromised.  
When the code break envelope is opened, the Investigator must note the date, time, reason 
for unblinding and the details of the investigator and or designated site staff that broke the 
blind and record this information according to hVIVO SOPs. The Investigator must also 
immediately notify the Sponsor’s Medical Monitor (SMM) that the code has been broken. 
Even if the code is broken, blood samples for safety, efficacy, PK and other parameters 
assessments will continue to be drawn for the remainder of the planned study period following 
the last dose if doing so will not compromise subject welfare. 
The IMP must be discontinued after unblinding, but the subject will be followed up until 
resolution of any AEs. 

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11 
CHALLENGE VIRUS  
The Challenge Virus is RSV-A Memphis 37b. The Challenge Virus inoculum titre (~4 Log10 
PFU) used will be one that has supporting evidence of safety. 
11.1 
Production 
The Challenge Virus strain RSV-A Memphis 37b was isolated from an infant who developed 
respiratory symptoms without fever. A nasal aspirate taken from the infant tested positive for 
RSV by antigen detection assays. The RSV was isolated from the infant’s nasal aspirate and 
plaque purified to obtain a “single” virus entity. The selected plaque, B, was used in the 
manufacture of the Challenge Virus stock at Meridian Life Science®, Inc. USA, according to 
GMP. The Challenge Virus has undergone quality testing performed during manufacture 
(identity, appearance, sterility, infectivity, and contaminants) according to pre-determined 
specifications. The Challenge Virus is stored in a secure -80 °C freezer (normal temperature 
range -60 °C to -90 °C). 
This virus has been used in previous hVIVO Virus Challenge studies and is expected to (as it 
has in the past) produce cold-like symptoms, such as cough, nasal congestion or low-grade 
fever 6,46  
11.2 
Supply and accountability 
hVIVO is obliged to establish a system for control of Challenge Virus in accordance with hVIVO 
SOPs and as detailed in the AP or a separate Note to File (NTF). 
The Investigator will maintain accurate records of receipt and condition of all Challenge Virus 
inoculum stock used for challenge in accordance with hVIVO SOPs, including details and 
dates of the quantities dispensed and used in the study. Any departures from the protocol-
dispensing regimen will be fully documented. 
Accountability records must be maintained as per the hVIVO SOPs. All Challenge Virus 
storage and accountability records will be available for verification by auditors. 
11.3 
Preparation and administration 
Challenge Virus inoculum will be prepared according to the hVIVO AP and administered in 
accordance with hVIVO's SOPs. Each subject will be allocated a unique vial containing the 
Challenge Virus and will receive the inoculum intranasally.  
The time from the Challenge Virus inoculum thawing to inoculation should be no longer than 
2 hours. All administrations will be made by a member of the clinical team and witnessed by 
a second member of the team. The exact time of inoculation will be recorded in the 
administration log and the subject’s source notes. Accurate records will be kept of when and 
how much study inoculum is prepared and used. The oversight process will be signed off prior 
to administration of the Viral Challenge. Any non-compliance or problems with the inoculation 
will be recorded in the subject’s source notes and reported to the PI/Investigator. 
Following inoculation, subjects will be closely observed specifically for potential allergic 
reactions within 30 minutes, and for the following 24 hours. Post inoculation subjects will lie 

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flat for 10 minutes then sit up with nose pegs on for 20 minutes. Subjects will continue to be 
monitored throughout the clinical phase of the study. 
11.4 
Disposal  
Disposal of used and unused Challenge Virus inoculum vials will be in accordance with 
hVIVO’s SOPs. 
 
 
 

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12.2 
Dispensing and accountability 
hVIVO will receive individual doses of subject-specific IMP (oral 
 following 
Qualified Person (QP) certification by HMR QP. All IMP supplies will be used only for this 
protocol and for no other purpose.  
Once received at hVIVO, hVIVO will perform stock level accountability and the IMP will be 
stored as per section 12.4. IMP accountability will be controlled by hVIVO and monitored by 
the Study Monitor throughout the study and at study close-out.  
IMP will be dispensed as per hVIVO standard processes and the requirements detailed in the 
Pharmacy manual. 
The Sponsor will provide the IMP and retain responsibility for maintenance of the associated 
essential documents in the Sponsor’s TMF.  
The Investigator will ensure that all supplies are received by a responsible person, all 
deliveries and returns are documented and signed for, and the condition of the IMP is 
monitored. Accurate records will be kept of when and how much IMP is dispensed and used 
in the study. Any reasons for departure from the protocol dispensing regimen will also be 
recorded. 
Accountability records will be available for verification by the Study Monitor at each monitoring 
visit. At the completion of the study, there will be a final reconciliation of all IMP. 
12.3 
Packing and labelling 
The preparation of oral 
 and labelling of the IMP will be performed by the HMR 
Pharmacy in compliance with GMP regulations , in accordance with Annex 13 of EudraLex 
volume 4 and the current version of the ‘Rules and Guidance for Pharmaceutical 
Manufacturers and Distributors’50,52. Blinding of subject specific doses will be performed by the 
HMR Pharmacy. 
A release document signed by the HMR QP will be kept in the hVIVO TMF to document 
labelling and dispensing of the IMP to hVIVO. All documents required to perform GMP 
activities will be supplied as per the Technical Agreement between HMR and Sponsor.  
 
  
IMP will be labelled in accordance with the pre-prepared randomisation list. The statistician at 
 will prepare the randomisation schedule and HMR Pharmacy will prepare the subject 
level bottles in line with the randomisation schedule.  Package labelling will comply with the 
requirements of Annex 13 of EudraLex volume 4, and will include at least the following 
information: 

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• 
Sponsor’s name 
• 
Pharmaceutical dosage form, route of administration, quantity of dosage units  
• 
Batch and/ or code number to identify the contents and packaging operation 
• 
Trial subject randomisation number 
• 
Directions for use 
• 
‘For clinical trial use only’ 
• 
Name of the Investigator  
• 
Trial reference code allowing identification of the trial site 
• 
Storage conditions 
• 
Period of use (use-by date, expiry date or re-test date as applicable), in month/year) 
• 
‘Keep out of reach of children’. 
Labelling and packing of study medication will be in accordance with current regulatory 
standards and sample label(s) will be submitted to the MHRA according to submission 
requirements.3, 51-53 
12.4 
Storage 
 
 
  
12.5 
Administration 
• 
In Part 1:  
 
• 
5 consecutive days of dosing in three treatment groups: 
o Group 1: Placebo (n=38); subjects in this group will receive placebo dose 
BD every 12 hours (±1 hour) interval for a total of 10 doses. 
o Group 2: EDP-938 oral 
 loading dose group (n=38): subjects in 
this group will receive 500mg first dose, and at 12 hours (±1 hour) interval 
receive 300mg second dose, then 300mg doses BD for a total of 10 doses. 
o Group 3: EDP-938 oral 
 600mg dose group (n=38): subjects in 
this group will receive a daily 600mg dose followed by a placebo dose at 12 
hours (±1 hour) interval for a total of 10 doses.   
 
• 
IMP dosing to start on confirmation of positive result by qualitative integrated cycler 
polymerase chain reaction (qicPCR) on nasal wash. Nasal wash for qicPCR will 
be performed BD on Study Days 2-5 (Study Day 5 morning only), or until a positive 
result is achieved, whichever is sooner.  
IMP dosing will be initiated 12 hours (± 1hour) post nasal wash confirmation of a 
positive qicPCR result.  
• 
In Part 2:  
• 
The planned treatment groups in Part 2 are as follows: 

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o Placebo dosed BD (every 12 hours (± 1 hour) interval), and with dosing for 
5 days,   
o A single Loading dose of 400mg  (Dose 1), followed by 200mg second dose 
at 12 hours (± 1-hour interval), then 200mg doses BD. and with dosing for 5 
days 
o A single Loading Dose of 600mg (Dose 1), followed by a 300mg dose OD 
(every 24 hours (±1 hour) interval), and with dosing for 5 days. 
 
• 
In order to maintain the study blind, subjects in the active OD dosing group will 
have their regimen supplemented by the administration of  placebo matched to 
EDP-938 in order to mimic the BD dosing group. 
 
 
 
 
 
 
All subjects will be dosed orally, in the seated position, and under the direct supervision of the 
Investigator (or delegate), and in accordance with the randomisation schedule.   
 
Fasting Schedule 
Blood will be drawn under non-fasted conditions. Repeat bloods may be drawn under fasted 
conditions if a lipid profile (cholesterol and triglyceride) or glucose is required (at PI 
discretion).  
 
12.6 
Compliance 
IMP will be administered by trained clinical site staff responsible for adequate and accurate 
IMP administration, accounting and management. Dosing will take place in the quarantine unit 
and will be monitored by hVIVO quarantine staff to ensure compliance.  
The exact times of IMP dosing will be recorded in the relevant dispensing/ administration logs 
and subject’s source notes. Any non-compliance or problems with the administration of the 
IMP will be recorded in the subject’s source notes and reported to the Sponsor if appropriate. 
12.7 
Overdose 
In the event of an IMP overdose the Sponsor is responsible for notifying the MHRA and REC 
of the potential serious breach (see Section 18.4.3) within 7 days of becoming aware of it. The 
SME/Sponsor will be contacted within 24 hours or before the next scheduled dose time (see 
the Pharmacy Manual for further procedural details). General supportive measures will be 
taken to manage any AEs associated with overdose and subjects will be clinically followed up 
until the AE has resolved (see section 15).  

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12.8 
Disposal 
Unless specifically instructed by Sponsor, the Investigator will not destroy any partly used or 
unused IMP supply. 
On written authorisation from the Sponsor, the Investigator will send unused and partly used 
IMP supplies and any empty containers for destruction to the address provided at the time of 
authorisation.  
Alternatively, the destruction of unused and partly used drug supplies and any empty 
containers may be facilitated by the Investigator using a partner service, according to local 
procedures, and a destruction certificate will be provided. Destruction of any material must be 
witnessed and documented in writing.  
 

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13 
ASSESSMENTS AND PROCEDURES 
All procedures will be performed according to applicable hVIVO SOPs. 
The Investigator may perform additional safety procedures in order to evaluate or manage 
clinical illness and AEs. 
The following assessments and procedures will be performed as detailed in Table 9-1: Time 
and events schedule 
Results will be recorded in the source documents. 
Where applicable, unless otherwise stated:  
• 
Normal ranges described in Appendix 3, and local laboratory reference ranges will be 
filed in the hVIVO TMF.  
During the clinical conduct of the study, the Investigator will use Appendix 6 for clinical 
assessment of change from baseline. 
 
13.1 
Medical and medication history 
Personal medical and medication histories and family histories will be recorded, including, but 
not limited to, detailed histories on allergies (e.g. rhinitis, dermatitis, food, aspirin/non-steroidal 
anti-inflammatory drugs (NSAIDs) and asthma. 
Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder Questionnaire 
(GAD-7), may be administered at screening and/or admission at the Investigator’s discretion. 
 
13.2 
Demographics 
Demographic data will be recorded at the Screening Visit. 
13.3 
Height, weight, and body mass index 
Height and weight measurements will be recorded in compliance with hVIVO’s standard 
procedures. 
BMI will be calculated as: BMI (kg/m2) =  
Weight (kg) 
 
 
 
 
 
 
 
 
 
 
Height (m)2 
13.4 
Complete physical examination 
A complete physical examination will include but not limited to an evaluation of the following 
body systems: 
• 
General appearance 
• 
Skin 

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• 
Eyes 
• 
Ears 
• 
Nose 
• 
Throat 
• 
Heart 
• 
Lungs 
• 
Abdomen 
• 
Peripheral pulses 
• 
Lymph nodes 
• 
Neurological/ nervous system 
• 
Musculoskeletal 
• 
Head, neck, and thyroid. 
13.5 
Directed physical examination 
Directed physical examinations will be conducted as deemed appropriate by the Investigator 
and will include examination of the: 
• 
Ear 
• 
Nose 
• 
Throat 
• 
Chest (via stethoscope). 
Assessment and grading of any URT (nasal discharge, otitis, pharyngitis, sinus tenderness) 
and LRT symptoms (abnormal breath sounds externally [e.g. stridor] and on chest auscultation 
[wheezing or rhonchi, crepitations] will be performed. Physician-reported assessments of viral 
challenge related illness will be graded in accordance with their intensity and documented in 
the source data. 
Following viral challenge, URT and LRT symptoms (as described above) will be expected and 
presumed to represent virus infection consequent to viral challenge, and will not be additionally 
captured as AEs unless they meet the definition of an AE, and are deemed to be clinically 
significant (in the opinion of the Investigator) to be classed as AEs. 
Following viral challenge all unexpected (in the opinion of the Investigator) directed physical 
examination findings will be captured as AEs, along with all other occurrences that meet the 
criteria for an AE (see section 15). 
13.6 
Vital signs 
Study specific normal ranges are provided in Appendix 3. 
Vital signs assessments will be recorded as follows: 
• 
Heart rate (HR) will be recorded in beats per minute (bpm). 
• 
Respiratory rate (RR): respirations will be counted and recorded as breaths per minute. 

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• 
BP: systolic BP and diastolic BP will be measured in millimetres of mercury (mmHg); 
measurements will be made supine. Where possible, the same arm will be used for all 
measurements. 
• 
Peripheral arterial oxygen saturation (SpO2%) will be assessed using pulse oximetry. 
In the event of a subject having an unexpected abnormal or out of normal range result, the 
assessment may be repeated after at least 2 minutes to exclude a technical fault and confirm 
the original reading. The assessment may then be repeated at the PI/Investigator’s discretion 
and in accordance with hVIVO’s SOPs. 
If a result is out of the normal range and meets the criteria for an AE, the severity of the AE 
will be guided by the CTCAE (referenced in Appendix 5). 
Deterioration in a vital sign (compared to baseline) should only be reported as an AE if the 
deterioration fulfils the criteria for an AE. If deterioration in a vital sign is associated with clinical 
signs and symptoms, the sign or symptom will be reported as an AE and the associated vital 
sign will be considered as additional information. 
13.7 
Tympanic Temperature 
The study specific normal range for tympanic temperature is detailed in Appendix 3. The 
severity of out of normal range values will be assigned using the CTCAE (Appendix 5) as a 
guide. 
Temperature is related to definitions of illness (Section 4.2) and to symptomatic and specific 
therapy criteria; therefore temperatures ≥ 37.9 ºC must be confirmed by a repeat measurement 
not less than 20 minutes and not more than 60 minutes after the first reading. 
The first temperature measurement will be used if it is confirmed by the second reading; both 
readings will be recorded in the source document. 
Temperature may be more frequently monitored in quarantine if appropriate. 
Following viral challenge, pyrexia will be expected and presumed to represent virus infection 
consequent to viral challenge, and will not be additionally captured as an AE unless it meets 
the definition of an AE, and is deemed to be clinically significant (in the opinion of the 
Investigator) to be classed as an AE. 
Following viral challenge all unexpected (in the opinion of the Investigator) pyrexia will be 
captured as an AE, along with all other occurrences that meet the criteria for an AE. 
Febrile illness (FI) is defined as (see section 4.2): 
Febrile Illness 
Any occurrence of temperature ≥ 37.9 oC (confirmed by a repeat 
measurement as ≥ 37.9 oC within 20 to 60 minutes),  
 
Or 
 

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Temperature change (post inoculation) of ≥ 2 standard deviations 
(SD) greater than a baseline measure (from all scheduled 
temperatures taken by any method on Days -2, -1, and Pre-
challenge on Day 0). 
 
13.8 
ECG 
Study specific normal ranges are provided in Appendix 3. 
Twelve-lead ECGs will be obtained to evaluate the electrical activity of the heart. ECGs will 
be read on site by an appropriately qualified Investigator. Wherever possible the same 
Investigator will review subsequent ECGs from the same subject for the assessment of any 
change from baseline. 
ECGs will be obtained at Screening, at Quarantine Admission (Day -2 or -1), Day 4, Day 7, 
Day 11 and at Follow-up Visit Day 28. ECGs will also be obtained pre first IMP dose, at 4 
hours post and 8 hours post first IMP dose, then pre-dose for all subsequent doses for the 
next 2 days (ie, up to Dose 6), at 24 hours and 48 hours post last IMP dose. ECGs may be 
repeated at the discretion of the PI/Investigator.  
All pre-dose ECGs can be obtained up to 2 hours prior to dosing. Post dose ECGs will be 
obtained ± 30 minutes of the target time.  
Any changes from screening during the study will be assessed for their clinical significance. 
Clinically significant changes will be reported as AEs (Section 15). The PI/Investigator will 
assess non-clinically significant changes to determine whether they should be recorded as 
described in Section 15.2. 
13.9 
Spirometry 
Spirometry will be performed according to hVIVO’s SOPs. Height at screening will be used as 
the baseline measurement for all spirometry assessments. 
Spirometry should meet the American Thoracic Society (ATS) / European Respiratory Society 
(ERS) guidelines criteria (as per ATS/ERS guidelines for standardisation of spirometry). For 
FEV1, the highest value from 3 technically satisfactory attempts will be considered. The chosen 
value should not exceed the next one by more than 150 mL or 5%. If the difference is larger, 
up to 8 measurements will be made if appropriate. 
Predicted values will be calculated according to the formula of the European Community for 
Coal and Steel (ECCS).   
Spirometry may be repeated at any time in the event of respiratory signs or symptoms 
(repeated coughing, bradypnea, tachypnoea, râles and rhonchi) or respiratory difficulties. 

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13.10 
hVIVO Symptom Diary Cards 
Subjects will report and assess the severity of any challenge virus related signs and symptoms 
using the hVIVO Symptom Diary Card. This information will be collected using a paper source 
document.  
Following viral challenge all unexpected (in the opinion of the Investigator) post viral challenge 
symptoms will be captured as AEs, along with all other occurrences that meet the criteria for 
an AE. 
Previous studies with RSV-A Memphis 37b have used a 10-item symptom questionnaire. The 
10-item diary card total symptom score will be used for the secondary endpoint analysis
 
 
   
The following symptoms in the 10-item symptoms questionnaire will be graded on a scale of 
0-3, where Grade 0 is absence, Grade 1 is just noticeable, Grade 2 is bothersome but does 
not prevent participation in activities, and Grade 3 is bothersome and interferes with activities.  
• 
Runny nose 
• 
Stuffy nose 
• 
Sneezing 
• 
Sore throat 
• 
Earache 
• 
Malaise (Tiredness) 
• 
Cough 
• 
Shortness of breath 
• 
Headache 
• 
Muscle/ joint ache/ stiffness 
 
 
  
 
 
The Investigator will assess and review challenge virus related symptoms that are recorded 
on the Quarantine Subject Symptom Dairy Card following each scheduled completion.  
13.11 
Nasal discharge collection from paper tissues 
Each subject will be given pre-weighed packets of paper tissues. Subjects will be asked to 
place single tissues used for nose blowing or sneezing into a specified bag (for that subject 
only). 
A daily 24-hour collection will take place throughout the quarantine period. Distribution of 
paper tissues and bags will start on Day -1, with the first collection on Day 0. Thereafter 
distribution and collection of tissues will occur at 08:00h (± 1 hour). Tissues will be handed out 
daily and collection will occur until the discharge from quarantine. 

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In the event of a subject staying in quarantine beyond the planned day of discharge, the 24-
hour distribution and collection of tissues and bags will continue until the subject is finally 
discharged from quarantine. 
24-hour paper tissue collections will be analysed to determine the following over the 
quarantine period: 
• 
24-hour nasal discharge weight (mucous). 
The number of paper tissue used for nasal discharge over 24-hour period will also be 
collected. 
13.12 
Routine blood analysis 
Section 14.2 describes the routine blood tests that will be performed including, but not limited 
to, haematology, biochemistry and cardiac enzymes. Additional safety assessments (e.g. 
coagulation) will be conducted at the discretion of the PI/Investigator, as required. 
13.13 
Challenge Virus serology 
A subject must be sero-suitable to take part in the study; i.e. he/she must have no or low pre-
existing serum levels of antibodies specific to the Challenge Virus strain. This antibody titre 
cut-off for serosuitability will be described in the AP / AP NTF. 
Serum levels of pre-existing RSV-A Memphis 37b specific antibodies to the Challenge Virus 
will be determined using a RSV neutralization antibody assay.  
13.14 
Nasal samples  
The following nasal sampling procedures will be performed during the study: 
• 
Nasopharyngeal swab 
• 
Nasal wash 
Where any nasal sampling timepoints occur together the order of sampling will typically be (1) 
Nasopharyngeal swab, followed by (2) Nasal wash 
 Nasopharyngeal swab 
Nasopharyngeal swab samples will be collected for the following assessments:  
• 
Respiratory Pathogen Screen 
• 
Rapid Viral Screen  
Tolerance of the procedure will be determined at the Screening Visit. 

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13.14.1.1 
Respiratory Pathogen Screen 
On entry to quarantine, a nasopharyngeal swab will be collected and tested to detect the 
presence of a set of respiratory pathogens that could potentially contraindicate a subject’s 
participation in the study. Nasopharyngeal swabs will be tested using a direct fluorescent 
antibody assay (DFA). Any additional screening tests will be conducted at the discretion of the 
PI/Investigator. 
Tolerance of the procedure will be determined at the Screening Visit. 
13.14.1.2 
Rapid Viral Screen  
A rapid viral screen e.g. Rapid Viral Antigen Test (RVAT) will be used to determine the 
presence of RSV in a nasopharyngeal swab sample prior to discharge from the Quarantine 
Unit on Day 12. Additional screening tests may be conducted at the discretion of the 
PI/Investigator.  
 Nasal wash 
Nasal wash samples will be collected to evaluate: 
• 
Viral shedding (as described in section 14.4) 
o qicPCR 
o RT-qPCR 
o Cell based infectivity assay (e.g. plaque assay) 
o Replicative Strand PCR 
o Viral resistance monitoring 
 
• 
PK testing (as described in section 14.4) 
o Potential measurement of EDP-938 and metabolite levels 
Tolerance of the procedure will be determined at the Screening Visit. 
13.15 
Breath alcohol 
Breath alcohol samples will be obtained to determine compliance with the study alcohol 
restrictions. Alcohol and drugs of abuse testing will be conducted during the study and must 
be negative at all times. Additional samples may be taken at PI’s discretion if positive. Results 
will be recorded in the source documents.  
13.16 
Adverse events and concomitant medications 
The PI/Investigator is responsible for the detection and documentation of events meeting the 
criteria for AEs or SAEs (Section 15) from the time of completion of written informed consent 
until completion of the final Follow-up Visit. 
Throughout the study, from screening to the final Follow-up Visit, subjects will be asked to 
report any unusual, undesirable, or unwanted symptoms, worsening of existing conditions or 
changes in their health and wellbeing. Subjects will be asked to report any problems and a 

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delegated physician will periodically enquire about the occurrence of AEs and need for 
concomitant medications. 
During quarantine, subjects will be asked about AEs using open-ended questions, for 
example: 
• 
how are you feeling? 
• 
have you had any medical problems since your last visit/assessment? 
• 
have you taken any new medicines, other than those given to you in this study, since 
your last visit/assessment? 
AEs  will be assessed and recorded as described in Section 15.  
Concomitant medications (prescription and OTC drugs and supplements that a study subject 
has taken alongside the study intervention) will be recorded. 
 

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14 
LABORATORY ASSESSMENTS 
14.1 
Blood volume 
A maximum volume of 470 mL of blood may be taken from each subject from Screening Visit 
through to the final study contact. If additional samples are required in excess of this amount, 
e.g., to monitor abnormalities, these will be collected at the discretion of the Investigator. 
14.2 
Safety Blood Samples and Assessments 
During the study, safety samples will be collected as detailed below. The hVIVO designated 
laboratory will be responsible for analysing clinical blood safety samples at scheduled times 
during the study. Further details on the hVIVO designated laboratory processes for shipment, 
processing, results and reporting are documented in the Safety Blood “Scope of Work” 
document. Baseline assessments will be defined in the Statistical Analysis Pan (SAP). 
Laboratory results will be reviewed by a study physician. The Investigator may request the 
collection of additional samples if required for safety monitoring. 
Deterioration in a laboratory value (compared to baseline) should only be reported as an AE 
if the deterioration fulfils the criteria for an AE (see section 15). If deterioration in a laboratory 
result is associated with clinical signs and symptoms, the sign or symptom will be reported as 
an AE and the associated laboratory result will be considered as additional information. 
Baseline laboratory values that are out of range of normal values but within CTCAE Grade 1, 
with no accompanying relevant clinical signs and symptoms will not be deemed to be AEs. 
All clinically significant laboratory abnormalities deemed to be AEs or SAEs will be 
documented in the source documents. 
The severity of the laboratory abnormalities will be determined based on the grading scales in 
Appendix 5.  Grade 3 laboratory abnormalities must be reported to the PI, who will determine 
whether further reporting is required. 
Relationship to the challenge virus will be assessed. Challenge virus associated laboratory 
abnormalities may be recorded as AEs.  
The PI/Investigator will monitor all clinically significant abnormal laboratory results or 
assessments until they return to normal or baseline values (i.e. resolve), stabilise, or are no 
longer clinically significant. Where appropriate, (e.g., after a period of monitoring of an 
abnormal result), clinically significant abnormalities should be reassessed by the PI/ 
Investigator to determine whether an AE has changed.  
Clinically important abnormalities persisting at the end of the study will be monitored at the 
discretion of the Investigator until they are resolved or are clinically stable.  
As a minimum the following analytes will be measured, others may be included as required. 

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Biochemistry 
• 
Sodium 
• 
Potassium 
• 
Glucose (random) 
• 
Albumin 
• 
Chloride 
• 
Bicarbonate 
• 
Calcium 
• 
Uric acid 
• 
Total protein 
• 
Creatinine 
• 
Total, direct, and indirect bilirubin 
• 
Inorganic phosphate 
• 
Blood urea nitrogen 
• 
C-reactive protein (CRP) 
• 
Gamma glutamyl transferase 
• 
Alkaline phosphatase (ALP) 
• 
Alanine transaminase 
• 
Lactate dehydrogenase 
• 
Aspartate transaminase (AST) 
• 
Urea. 
 
Thyroid function test 
• 
Thyroid Stimulating Hormone (TSH) 
• 
Thyroxine 
 
 
Haematology 
• 
Platelet Count. 
• 
White blood cell (WBC) count (absolute) 
• 
WBC differential: 
• 
Neutrophils 
• 
Lymphocyte 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
• 
Red blood cell (RBC) count  
• 
Reticulocyte count (% and absolute)  
• 
Haemoglobin 
• 
Haematocrit 
• 
Mean corpuscular volume (MCV) 
• 
Mean corpuscular haemoglobin (MCH) 
• 
MCH concentration (MCHC). 

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Cardiac enzymes 
• 
Creatine kinase (CK) 
• 
CK-MB 
• 
Troponin T 
 
Coagulation 
• 
Prothrombin time (PT) 
• 
Activated Partial Thromboplastin Time (APTT) 
 
Human Immunodeficiency Virus and Hepatitis A, B, and C  
Serum will be tested to detect the presence of the following: 
• 
HIV-1 and HIV-2 antibodies. 
• 
Hepatitis A antibodies (HepA IgM). 
• 
Hepatitis B surface antigen (HBsAg). 
• 
Hepatitis C antibodies (HCAb). 
 
Serum follicle stimulating hormone 
Serum samples will be tested for serum follicle stimulating hormone (FSH) in post-menopausal 
women only. 
 
Serum pregnancy test 
All female subjects will have a serum sample tested for β-human chorionic gonadotrophin (β-
hCG) on admission to quarantine. 
14.3 
Urine Samples and Assessments 
 
Urinalysis 
Clinical urine safety analysis will be undertaken using commercially available urine test strips 
that provide an instant result that will be documented in the source data. 
Urinalysis will be performed to evaluate the following parameters:  
• 
Colour 
• 
Specific gravity 
• 
Appearance 
• 
pH. 
and to detect the presence of:  
• 
Blood 
• 
Glucose 

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• 
Leukocytes 
• 
Ketones 
• 
Nitrite 
• 
Protein 
• 
Urobilinogen 
• 
Bilirubin. 
If the dipstick yields abnormal results, a urine sample may be sent for microscopy, culture and 
sensitivity (MCS), at the Investigator’s discretion. MCS will include but is not limited to RBC, 
WBC, epithelial cells, crystals, casts, and bacteria. 
Urine safety analysis values will be evaluated by the Investigator for clinical relevance. Those 
deemed to be clinically significant will be reported as AEs (Section 15.1.1 and 15.2). 
 
Drugs of abuse and cotinine 
Urinalysis will be performed for drugs of abuse and cotinine using commercially available kits 
that provide an instant result, which will be documented in the source data. 
Drugs of abuse screen will include (but is not limited to) amphetamines, barbiturates, cocaine, 
opiates, cannabinoids and benzodiazepines. 
 
Pregnancy  
Urine pregnancy tests will be performed at the times detailed in Table 9-1. 
The Investigator may request additional safety assessments and/or unscheduled pregnancy 
tests in order to evaluate or manage clinical illness. 
14.4 
Virology Assessments 
Samples will be collected as detailed in Table 9-1: Time and events schedule. Details of how 
the samples will be processed, stored and where relevant, how the analysis will be conducted 
will be documented in the AP. 
 
 
Serum RSV neutralising antibody 
A RSV neutralising antibody assay will be used to measure levels of pre-existing specific 
antibodies to the Challenge Virus strain in serum collected at Screening to determine subject 
serosuitability. The same assay will be used to measure antibody titres in serum samples 
collected on admission to quarantine and at Day 28 Follow-up Visit.  
 
 
Respiratory Pathogen Screen 
At the times outlined in Table 9-1: Time and events schedule, a respiratory pathogen screen 
will be performed on a nasopharyngeal swab sample to detect the presence of a number of 
respiratory viruses that could potentially contraindicate a subject’s participation in the study. 
Nasopharyngeal swabs will be tested using a direct fluorescent antibody assay (DFA).  

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Rapid Viral Screen 
A rapid viral screen e.g. Rapid Viral Antigen Test (RVAT) will be used to determine the 
presence of RSV in a nasopharyngeal swab sample prior to discharge from the Quarantine 
Unit.  Additional screening tests may be conducted at the discretion of the PI/Investigator.  
 
Viral load 
RSV viral load will be measured in nasal washes by RT-qPCR and Cell based infectivity assay 
(e.g. plaque assay).  
 
RT-qPCR and Cell based infectivity assay (e.g. plaque assay) will also be used to determine 
viral dynamics (e.g. duration, peak, time to peak). 
14.4.4.1 Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR) 
A Quantitative Reverse transcription polymerase chain reaction (RT-qPCR) assay will be used 
to quantify RSV-A Memphis 37b in nasal wash samples.  
14.4.4.2 Cell Based Infectivity Assay 
A cell based infectivity assay (e.g. Plaque assay) will be used to quantify infectious RSV-A 
Memphis 37b in nasal wash samples.  
 
 
Viral shedding for dosing 
Viral shedding will be confirmed by positive qualitative qicPCR assay of nasal wash.  
 
14.4.5.1 Qualitative Integrated Cycler Polymerase Chain Reaction (qicPCR)  
A qualitative integrative cycler PCR (qicPCR) assay will be used to demonstrate virus 
shedding in nasal wash samples to indicate Challenge Virus infection. The qicPCR assay will 
be used to support dosing decisions.  
 
 
Replicative Strand PCR 
A replicative strand PCR may be used to evaluate viral replication in cells isolated from nasal 
wash samples.  
 
 
Viral resistance 
Nasal wash samples may be analysed 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 resistance mutations.  

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14.5 
PK Assessments 
 
Blood Plasma Samples 
Blood (plasma) samples for the evaluation of PK parameters of EDP-938 will be collected as 
outlined in Appendix 7 (PK Blood Sampling Schedule). 
Blood samples will be transported, processed and stored in accordance with the AP, and 
analysed using a bioanalytical assay. 
 
Nasal Wash samples 
Nasal wash for the evaluation of PK parameters of EDP-938 will be collected in accordance 
with Table 9-1 and processed and sent to the Sponsor’ PK vendor according to the AP.  
  

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15 
ADVERSE EVENTS AND TOXICITY MANAGEMENT 
The PI/Investigator is responsible for ensuring that all AEs, SAEs and pregnancies are 
identified, evaluated, recorded and reported in a timely manner as per Regulatory 
requirements and hVIVO’s SOPs, and also for ensuring that the medical management 
(including 
follow 
up) 
of 
AEs, 
SAEs 
and, 
where 
appropriate, 
pregnancy 
symptoms/complications is provided by competent Investigator Site staff. 
15.1 
Definitions  
 
Adverse Event 
An AE is defined as any untoward medical occurrence in subjects. An AE can therefore be 
any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of an investigational medicinal product, whether 
or not considered related to the investigational medicinal product, or for the purposes of 
Human Viral Challenge studies, the Challenge Virus. 
An AE includes: 
• 
Exacerbation of a pre-existing illness. 
• 
Increase in frequency or severity of a pre-existing episodic condition. 
• 
A condition detected or diagnosed after IMP or inoculum administration even though it 
may have been present prior to the start of the study. 
• 
A complication that occurs during a hospitalisation. 
• 
A clinically significant change in laboratory parameter. 
An AE does not include: 
• 
Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, 
transfusion); the condition that leads to the procedure is an AE. 
• 
Pre-existing disease or conditions present or detected prior to start of IMP or Challenge 
Virus inoculation administration that does not worsen (including screening findings 
such as abnormal laboratory results). 
• 
Hospitalisation for elective surgery, social and/or convenience admissions provided 
they are arranged before the start of IMP administration. 
• 
Over-administration of either the challenge virus, IMP or concomitant medication 
without any signs or symptoms. 
• 
An uncomplicated pregnancy or an induced elective abortion to terminate a pregnancy 
without medical reason. 
• 
Typical/normal viral symptoms on symptom diary cards (see Section 15.3.6). 
 
Adverse Drug Reaction 
An adverse drug reaction (ADR) is any untoward and unintended response in a subject to an 
IMP which is related to any dose administered to that subject. 

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‘Response’ in this context means that a causal relationship between a medicinal product and 
an AEis at least a reasonable possibility32. 
All AEs judged by either the reporting investigator or the Sponsor as having a reasonable 
causal relationship to a medicinal product qualify as ADRs. The expression ‘reasonable causal 
relationship’ means to convey in general that there is evidence or argument to suggest a 
causal relationship. 
 
Unexpected Adverse (Drug) Reaction 
An “Unexpected Adverse (Drug) Reaction” means an adverse reaction, the nature and severity 
of which is not consistent with the information about the medicinal product in question set out: 
(a) In the case of a product with a marketing authorisation, in the Summary of Product 
Characteristics for that product, 
(b) In the case of any other investigational medicinal product, in the Investigator’s Brochure 
relating to the trial in question’4. 
 
Serious Adverse Event 
A SAE is any adverse event that - 
(a) results in death, 
(b) is life-threatening, 
(c) requires hospitalisation or prolongation of existing hospitalisation, 
(d) results in persistent or significant disability or incapacity, or 
(e) consists of a congenital anomaly or birth defect;4  
(f) is an important medical event. 
The above characteristics/consequences have to be considered at the time of the event, for 
example: 
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the subject 
was at risk of death at the time of event; it does not refer to an event which, hypothetically, 
might have caused death if it were more severe2. 
‘Important medical events’ - some medical events may jeopardise the subject or may require 
an intervention to prevent one of the above characteristics/consequences. Such events should 
also be considered as ‘serious’ in accordance with the above definition.  
Medical judgement should be exercised in deciding whether an adverse event/reaction is 
serious. Important adverse events/reactions that are not immediately life threatening or do not 
result in death or hospitalisation, but may jeopardise the subject or may require intervention 
to prevent one of the other outcomes listed in the definition above occurring, should also be 
considered serious. Details of the SAE must be provided. 

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 Suspected Unexpected Serious Adverse Reaction  
A suspected unexpected serious adverse reaction (SUSAR) is ‘a serious adverse reaction, 
the nature and severity* of which is not consistent with the information about the medicinal 
product in question, as defined in the Investigator’s Brochure relating to the trial in question. 
Medical events will be assessed for expectedness by the PI/Investigator against the Summary 
of Data and Guidance for the Investigator section of the IB, and any available IB addendum. 
Any changes to the referenced safety information will be deemed as a change to the 
risk/benefit profile and will require a substantial amendment to be submitted to the MHRA. 
This amendment must be approved before the changes are implemented in the study. 
*The term ‘severity’ is used here to describe the intensity of a specific event. This is not the 
same as ‘serious’ which is based on subject/event outcome or action criteria. 
15.2 
Recording and reporting 
All AEs and SAEs will be collected from the time of written informed consent until study 
completion/final study contact or until the resolution of the AE. AEs will be fully recorded in the 
source documents as they are reported, whether spontaneously volunteered by a subject or 
in response to questioning about wellbeing at each face to face study visit and during 
telephone calls. Enquiries about AEs should cover the period between the previous and 
current visit. 
The following are examples of open ended, non-leading questions that may be used to obtain 
this information:  
• 
How are you feeling? 
• 
Have you had any medical problems since your last visit/assessment?  
• 
Have you taken any new medicines, other than those given to you in this study, 
since your last visit/assessment? 
Following the reporting of AEs and concomitant medication, the Investigator should assess 
the subject’s eligibility to continue in the study.  
The Investigator will record all relevant information regarding an AE/SAE in the source 
documents and evaluate AEs using the following guidelines:  
• 
Description of events (if the event consists of a cluster of signs and symptoms, a 
diagnosis should be recorded) 
• 
Seriousness 
• 
Severity (or grade) 
• 
Onset date and time 
• 
Frequency 
• 
Date and time of resolution (or ‘continuing’ if unresolved) 
• 
Action taken  
• 
Concomitant medication 

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• 
Clinical outcome 
• 
Relationship or causality (IMP/Challenge Virus/ study procedures/ concomitant 
medication/other). 
Any clinically significant abnormal laboratory result, vital sign or other measure will be followed 
until it returns to normal or baseline values, stabilises, or is judged by the Investigator to be 
no longer clinically significant.  
If an AE is not resolved at the end of the study, the AE should be followed until it has resolved 
or (in the case of pregnancy) the pregnancy has been terminated (including spontaneous 
abortion), resulted in a birth, or a decision has been made by the Sponsor that no further 
follow-up is required. 
Even if the AE or SAE is assessed by the Investigator as not reasonably attributable to the 
challenge virus, its occurrence must be fully documented in the source notes.  
15.3 
Assessment  
 
Description 
If the event consists of a cluster of signs and symptoms, where possible, a diagnosis should 
be recorded (e.g. gastroenteritis) rather than each sign and symptom.  
 
Onset and end 
The dates and times of the onset and end of the event should be recorded.  
 
Seriousness 
The PI/Investigator must record whether the AE meets the definition of serious. If the event is 
serious (Section 15.5), the PI/Investigator must complete an SAE report form.  
 
Intensity and severity  
Severity is a measure of intensity (whereas seriousness is defined by the criteria provided in 
Section 15.4.). 
CTCAE (Appendix 5) will be used as a reference to standardise the severity and grading of 
AEs and anatomical/ pathophysiological terms, and when collecting, reporting and clarifying 
database queries of AEs and SAEs.  
The severity of an AE that does not appear in Appendix 5 should be determined according to 
the definitions in Tables 15.1. 
 
Adverse Events critical to the safety evaluation 
For AEs deemed critical to the safety evaluation, and therefore to be reported to the 
Sponsor, refer to Section 15.1.5. 

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Challenge Virus symptoms  
The Investigator will assess and review Challenge Virus related symptoms recorded in 
subjects’ hVIVO Symptom Diary Cards. Symptoms greater than Grade 0 will be expected and 
presumed to represent virus infection consequent to Viral Challenge, and will not be 
additionally captured as AEs unless they meet the definition of an AE, and are deemed to be 
clinically significant (in the opinion of the Investigator) to be classed as AEs.  
Following Viral Challenge all unexpected (in the opinion of the Investigator) symptoms post 
inoculation will be captured as AEs, along with all other occurrences that meet the criteria for 
an AE. 
 
Physical Examination 
Any clinically significant change in complete physical examination findings during the study 
will be documented as an AE. 
 
Directed Physical Examination 
Following Viral Challenge, upper and lower respiratory symptoms (nasal discharge, otitis, 
pharyngitis, sinus tenderness, wheeze and crepitation) may be seen and presumed to 
represent virus infection consequent to Viral Challenge, and will not be additionally captured 
as AEs unless they meet the definition of an AE, and are deemed to be clinically significant 
(in the opinion of the Investigator) to be classed as AEs. 
 
Vital signs 
Deterioration in a vital sign (compared to baseline) should only be reported as an AE if the 
deterioration fulfils the criteria for an AE. If deterioration in a vital sign is associated with clinical 
signs and symptoms, the sign or symptom will be reported as an AE and the associated vital 
sign will be considered as additional information. 
 Temperature 
Following Viral Challenge, pyrexia will be expected and presumed to represent virus infection 
consequent to Viral Challenge, and will not be additionally captured as an AE unless it meets 
the definition of an AE, and is deemed to be clinically significant (in the opinion of the 
Investigator) to be classed as an AE.  
Following Viral Challenge all unexpected (in the opinion of the Investigator) pyrexia post 
inoculation will be captured as an AE, along with all other occurrences that meet the criteria 
for an AE. 
 Spirometry 
A 15% drop in a spirometry value (compared to baseline), confirmed by a repeat on the same 
day, will be a Grade 1 (mild) AE. The PI/Investigator will use his/her clinical judgement to 

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assign severity grades above Grade 1, based on evaluation of clinical signs and symptoms. If 
the repeated value has returned to normal an AE will not be raised. 
 Laboratory values 
Deterioration in a laboratory value (compared to baseline) should only be reported as an AE 
if the deterioration fulfils the criteria for an AE. If deterioration in a laboratory result is 
associated with clinical signs and symptoms, the sign or symptom will be reported as an AE 
and the associated laboratory result will be considered as additional information. 
The Investigator and/or SME will judge whether abnormal laboratory values are clinically 
significant or not clinically significant, and record this in the source document. This entry 
should be signed and dated by the relevant Investigator. Laboratory abnormalities detected at 
screening will be considered as part of the medical history and will not be reported as AEs. 
Challenge Virus associated laboratory abnormalities (e.g.: elevated ALT, AST or GGT; 
decreased neutrophils) may be recorded as AEs (at the discretion of the PI/Investigator).   
15.3.12.1 
C-reactive protein 
Any value above 5 mg/L but less than 60 mg/L will be a Grade 1 (mild) AE (unless deemed 
non-clinically significant by the PI/Investigator). The PI/Investigator will use his/her clinical 
judgement to assign severity grades above Grade 1, based on evaluation of clinical signs and 
symptoms.  
15.4 
Classification of Adverse Events 
 
Severity  
The term ’severe’ is often used to describe the intensity (severity) of a specific event. This is 
not the same as ‘serious’ which is based on subject/event outcome or action criteria. 
The CTCAE (see Appendix 5) will be used to standardise the severity and grading of AEs and 
anatomical/ pathophysiological terms. 
The Investigator will use the CTCAE as a reference when collecting, reporting and clarifying 
database queries of AEs, SAEs and ADRs.  
The severity of an AE that does not appear in the CTCAE should be determined according to 
the definitions in Table 15-1. 

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Reporting of SUSARs  
The Sponsor is responsible for assessing SUSARs, unblinding potential SUSARs, and 
reporting SUSARs to the MHRA and REC.  
The Sponsor shall ensure that all relevant information about a SUSAR that occurs during the 
course of a clinical trial in the UK and is fatal or life threatening, is reported as soon as possible 
to the MHRA and the REC. This needs to be done within 7 calendar days after the Sponsor 
became aware of the event. Any additional relevant information should be sent within 8 
calendar days of the first report being sent. 
The Sponsor shall ensure that a SUSAR which is not fatal or life-threatening is reported as 
soon as possible and in any event within 15 calendar days after the Sponsor became aware 
of the event. 
In accordance with ICH GCP guidelines, the Sponsor will also inform the Investigator of 
findings that could affect adversely the safety of subjects and/or impact the conduct of the 
trial. 
 
Annual safety reporting to the national Competent Authority (MHRA) and the Ethics 
Committee will be in agreement with ICH guideline E2F “Note for guidance on Development 
Safety Update Reports (DSUR)”. 
 
In addition, any other safety issue which may alter the current benefit–risk assessment of the 
IMP will be reported by the Sponsor (or delegate) on an expedited basis to Competent 
Authorities, Ethics Committees and the Investigator. 
 
The detailed procedure of the SAE/SUSAR reporting will be described in a 
Pharmacovigilance Management Plan that will be finalised before the start of the study to 
exactly define the different tasks of the Investigator, Enanta (the Sponsor) and 
 
 (acting on behalf of Enanta). 
 
Adverse Drug Reactions to non-IMPs 
Any AEs and SAEs which are related to/caused by a concomitant medication or Challenge 
Agent, should not be classed as ADRs, SARs, or SUSARs (ADRs, SARs, SUSARs relate only 
to IMP by definition). However, an SAE caused by a non-IMP would need to be reported to 
the MHRA/REC for the appropriate action to be taken. 
 
Post-study AEs and SAEs  
All SAEs that occur during and up to the Follow-up Visit after the last dose of IMP must be 
reported by the Investigator to the Sponsor’s Pharmacovigilance provider, 
 
 Sciences as soon as possible, in accordance with Regulatory requirements and 
hVIVO’s SOPs, and at the latest within 24 hours of becoming aware of the event.  
SAEs occurring after the subject has completed the clinical trial, and for which a reasonable 
possibility of a causal relationship to IMP is assessed by the Investigator, should be reported 
by the Investigator to the Sponsor regardless of the time that has elapsed (post-trial events). 
 

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Pregnancy 
If a female subject or partner of a male subject becomes pregnant within 90 days after the last 
dose of IMP, this must be reported by the Investigator to the Sponsor’s Pharmacovigilance 
provider, 
 and Study Monitor/SME by telephone as soon as 
possible, in accordance with hVIVO’s SOPs, and at the latest within 24 hours of becoming 
aware of the event.  
Following the telephone notification, the Investigator must fully and accurately complete the 
appropriate pregnancy reporting form, which must be e-mailed to the SME and the Study 
Monitor at the latest within 24 hours of becoming aware of the pregnancy.  
Subjects will be advised to contact their GP, as appropriate.  
Consent for follow-up of the pregnancy and pregnancy outcome will be sought from the 
pregnant study subject or the pregnant partner of the male study subject as applicable. 
Consent for follow-up will be documented in accordance with hVIVO SOPs.   
Provided that the appropriate consent is in place, information related to the pregnancy will be 
collected as per hVIVO’s SOPs and the Sponsor’s requirements. The completed Pregnancy 
Reporting Form(s) will be sent to the Sponsor’s Pharmacovigilance provider, 
 
 for review and assessment, and subsequent reporting as required. 
• 
A complete evaluation will be documented in the source data to permit transfer to the 
clinical database.  
• 
The emergency code break envelopes will be requested (Section 10.3) to break the 
blind for the appropriate study subject to ensure that further care can be based on the 
actual identity of the study treatment that the subject received. 
• 
hVIVO will maintain contact with the subject for a protracted period of time, but certainly 
until after the birth, in order to assess for outcomes that may be reportable as related 
AEs, and for reporting to the Sponsor as appropriate.  
• 
hVIVO in consultation with the subject will keep the subject’s GP informed.  
• 
All cases of foetal drug exposure via the parent as a study subject will be reported to 
the Sponsor and the REC.  
• 
Pregnant females will be referred to their GP or to a specialist, as appropriate 
Pregnancy of a study subject or subject’s partner during or within 3 months of the date of 
Challenge is not a SAE, but must still be reported to the Sponsor. However, complications of 
pregnancy and abnormal outcomes of pregnancy are AEs, and may meet the criteria for an 
SAE, therefore pregnancies occurring during the study must be followed up until the outcome 
of the pregnancy is known (spontaneous miscarriage, elective termination, normal birth or 
congenital abnormality). Please refer to Section 15.5 for details on the SAE reporting 
procedure. The Investigator will recommend that male subjects whose partners become 
pregnant from Quarantine discharge through to the Day 28 Follow-up Visit should contact their 
GP or a specialist as appropriate. Consent for follow-up will be requested from both partners 
and a complete evaluation will be documented in the source 
data.  
Subjects who are lost to follow-up will be managed as described in Section 9.6. 

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16 
STATISTICAL METHODS AND PLANNED ANALYSES 
 will perform the statistical analysis for the study. Full details of the planned statistical 
analysis (including the Part 1 analysis) will be presented in the Statistical Analysis Plan (SAP). 
Any deviations from the SAP will be documented in the Clinical Study Report (CSR). 
Part 1 data analysis will be reported after completion of Part 1, and based on these results, 
Part 2 of the study will commence. Data Presentations will be the same in both parts of the 
study, unless otherwise stated. Part 2 placebo subjects will be pooled across the Part 2 
treatment cohorts unless there is a clear difference seen in the data of these subjects, in which 
they will be analysed only against the active treatment group in their treatment cohort. 
16.1 
Study analysis sets 
The following analysis sets are defined for this study: 
• 
The Intent to Treat (ITT) Analysis Set is defined as all randomised subjects receiving 
Challenge Virus and at least one dose of IMP. The ITT analysis set will be considered 
a secondary analysis population for efficacy endpoints. 
• 
The Intent to Treat Infected (ITT-I) Analysis Set is defined as all randomised subjects 
receiving Challenge Virus and at least one dose of IMP, and meeting the criterion for 
laboratory confirmed RSV infection as per the definition of laboratory confirmed 
infection for this protocol (see Section 4.2). The ITT-I set will be considered the primary 
analysis population for efficacy endpoints.   
• 
The Intent to Treat Infected (ITT-A) Analysis Population is defined as all randomised 
subjects receiving Challenge Virus and at least one dose of IMP, and meeting the 
criterion for laboratory confirmed RSV infection (as per the definition of laboratory 
confirmed infection for this protocol (see Section 4.2) using only assessments prior to 
taking IMP.  
• 
The Intent to Treat Infected (ITT-B) Analysis Population is defined as all randomised 
subjects not already in the ITT-A Analysis Population, receiving Challenge Virus and 
at least one dose of IMP, and meeting the criterion for laboratory confirmed RSV 
infection (as per the definition of laboratory confirmed infection for this protocol (see 
Section 4.2) using only assessments after IMP.  
• 
The Per Protocol (PP) Analysis Set is defined as all ITT-I Analysis Set subjects who 
have no major protocol deviations, and who complete the quarantine period up to the 
final day of quarantine (Study Day 12), and receive all doses of IMP. The PP Analysis 
Set will be considered a secondary analysis population for efficacy endpoints.  
• 
The Safety Analysis Set is defined as all subjects receiving challenge virus, regardless 
of whether they have received IMP or not. 
• 
The PK Analysis set is defined as all ITT subjects with at least one post-dose PK result. 
The primary analysis will be on the ITT-I Analysis Set. Analysis of the ITT-A, ITT-B and PP 
Analysis Sets will be secondary. The safety evaluation will be performed on the Safety 
Analysis Set. 
Membership of subjects in each analysis set will be determined at a planned blinded data 
review meeting (BDRM), prior to the any analysis and database lock. 

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Subgroup analysis 
A ‘Laboratory confirmed infected’ subgroup will be identified and certain pre-specified 
analyses (to be documented in the SAP) will also be performed by using the ITT-I, ITT-A, and 
ITT-B analysis sets. 
16.2 
Sample size 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
The results of Part 1 may be used to inform a sample size reassessment for Part 2 prior to the 
start of Part 2 enrolment.  
16.3 
Interim Analysis 
No formal interim analysis will be performed. However, an analysis of Part 1 data will be 
performed prior to starting Part 2 of the study.  
16.4 
Statistical Analysis Plan 
Data will be analysed and reported using SAS® version 9.4 or later.  
Primary and secondary efficacy endpoints will be analysed descriptively. Continuous variables 
will be summarised using number of observations, mean (and/or geometric mean, where 
applicable), standard deviation, standard error, median, lower quartile, upper quartile, 
minimum and maximum values. Categorical variables will be summarised using proportions 
(counts and percentages). Statistical analyses will be performed using appropriate two-sided 
hypothesis tests at the 5% significance level. Normally distributed continuous variables will be 
presented as mean, difference in means and a 95% confidence interval (CI).  The t-test will 
be used to compare means between groups (and/or an appropriate alternative test, if the t-
test assumptions are not satisfied). Methods for checking statistical model assumptions will 
be described in the SAP.  
 

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For endpoints that are not normally distributed (such as total symptom scores), the Wilcoxon 
Rank-Sum test will be used. No adjustment for multiple comparisons are planned, as this is 
an early stage study.  
 
The detailed SAP will be developed by 
 and approved by the Sponsor prior to any 
lock of the study database. The SAP will give a more detailed description of the report 
presentations to be produced for Parts 1 and 2 of the study, respectively, expanding on the 
protocol specified analysis. Any deviation(s) from the original statistical plan should be 
described and justified in an amendment to the protocol and/or SAP as appropriate and 
referenced also in the final clinical study report (CSR). The SAP will describe and account for 
the occurrence of and extent of missing data, and its possible impact on the study analysis. 
All baseline assessments will be described in the SAP.  
 
  
 
Clinical Study Report 
The CSR for the study will be written as set out in the roles and responsibilities.  
 
Subject accountability 
The number of subjects receiving Challenge Virus, receiving EDP-938 or Placebo, 
withdrawing from (also split by reason for withdrawal), and completing the study, and the 
numbers in each analysis set, will be summarised. 
 
Protocol deviations 
Subject data will be reviewed for major protocol deviations prior to database lock at a planned 
BDRM, and decisions will be documented within the meeting minutes. At this meeting, 
subjects will be reviewed for their inclusion/exclusion from the analysis sets. 
 
Demographic and baseline characteristics 
Descriptive statistics of demographics (age, sex, height, weight, BMI, and ethnicity) will be 
presented by treatment group and across all subjects. Medical history information will be listed. 
Other baseline characteristics will be defined in the SAP.  
16.5 
Primary efficacy analysis 
The AUC for RSV-A Memphis 37b viral load measured in nasal washes by RT-qPCR will be 
summarised and each active treatment group compared to placebo via a t-test or Wilcoxon 
Rank-Sum test as appropriate. The primary efficacy analysis will be supported by sensitivity 
analyses and these will be specified in the SAP.  
16.6 
Secondary efficacy analysis  
The following secondary endpoints will be presented by treatment group: 
Clinical Symptoms: 

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o Effect of EDP-938 compared to placebo on RSV symptoms (using the 10- item diary 
card), with endpoints including: 
o AUC of total symptom score 
o Peak total symptom score over the duration of quarantine 
o Total symptom score  
o Time to peak symptom score after IMP dosing.  
o Time to resolution from peak symptom. 
o Total weight of nasal mucus produced (via weighed paper tissues).  
Viral Load: 
o Additional viral load endpoints calculated separately using data from RT-qPCR of nasal 
wash comparing placebo and EDP-938 treated including: 
▪ 
Peak viral load 
▪ 
Time to peak viral load 
▪ 
Time to resolution from peak 
▪ 
Time to cessation of virus quantifiable post first dosing 
 
Safety analysis 
The following safety endpoints will be presented by treatment group: 
• 
AEs 
• 
Physical Examinations 
• 
Vital signs 
• 
12-lead ECGs 
• 
Spirometry 
• 
Clinical laboratory results (including biochemistry, haematology, coagulation (if 
required), cardiac enzymes and urine analysis) 
 
Pharmacokinetic analysis 
The following pharmacokinetic endpoints will be presented by treatment group: 
• 
Plasma PK parameters of EDP938 (and metabolites) following repeat dose 
administration in healthy adult subjects inoculated with RSV-A Memphis 37b: Cmax, 
Tmax, t1/2, CL/F, λz, Vd/F, C12, C24, AUClast, AUC0-tau, or AUC0-inf 
Plasma PK (AUC) correlations with viral load AUC (e.g. RT-PCR) and TSS AUC  
PK parameters will be calculated using non-compartmental methods. Parameters will be 
summarised descriptively. 

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16.7 
Exploratory analysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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The assigned study monitor will review the study data for accuracy and completeness during 
on-site monitoring visits. Any discrepancies will be resolved with the PI or designee as 
appropriate. After upload of the data into the study database, data will be verified for accuracy 
and consistency with the data sources. 
17.5 
Data coding 
AEs and medical histories will be coded using the most current version of Medical Dictionary 
for Regulatory Activities (MedDRA). 
 
Concomitant medications will be coded using the most current version of the World Health 
Organization (WHO) Drug Dictionary Enhanced version.  
At the time of coding, the latest version will be used for coding and the version number will be 
documented in the DMP.  
17.6 
Database lock 
The 
 database will undergo validation prior to database lock.  
Following 
 locking of the database the final database will be transferred to the Study 
Statistician for statistical analysis and reporting. 
17.7 
Data protection 
The study site will comply with the General Data Protection Regulation (EU) 2016/67953 and 
the UK Data Protection Act 2018. hVIVO has in place Data Processing Agreements (which 
comply with the above laws) with all vendors and partners where personal data will be 
transferred outside the EU, to bridge the differences in the privacy approaches for data 
protection law in other countries (e.g. the US).

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STUDY MANAGEMENT AND ETHICAL RESPONSIBILITIES 
The study will be sponsored by ENANTA Pharmaceuticals Inc. and managed by hVIVO 
Services Limited. 
18.1 
Regulatory and Ethics Opinions and Good Clinical Practice 
This study will be conducted in accordance with the Ethical Principles for Medical Research 
Involving Human Subjects outlined in the Declaration of Helsinki 19961, the principles of ICH 
GCP2, current regulatory requirements as detailed in the Medicines for Human Use (Clinical 
Trials) Regulations (SI 2004/1031)4 and all subsequent amendments, the UK Data Protection 
Act 20185, any other applicable laws and guidance, and any Sponsor requirements.  
 All ethical and legal requirements will be met before the first subject is enrolled in the study.  
18.2 
Quality Assurance 
A quality assurance (QA) programme is in place to provide assurance that the trial/study is 
performed and data are generated, documented and reported in compliance with applicable 
regulatory requirements. The QA audit programme includes audits of systems, processes, 
facilities and documents. 
18.3 
Quality Control 
QC activities are performed throughout hVIVO to verify compliance and accuracy of all 
trial/study related activities. These are described in hVIVO SOPs and documented in the 
records. 
18.4 
Deviations from the Protocol 
 
Protocol Waivers 
Protocol waivers are never acceptable as per all EU competent authorities’ guidance 
(including the MHRA). It is not acceptable to include any subject by protocol waiver – i.e., 
included despite not meeting all inclusion criteria or fulfilling at least one exclusion criteria.  
 
Protocol Deviations  
A protocol deviation log will be used to document any unplanned or unintended departures 
from the study protocol. Protocol deviations should be recorded as soon as possible after they 
occur, and if major, reported to the Sponsor immediately by the PI/Investigator. 
The PI or delegate will maintain a log of protocol deviations on the study.  
 
Serious breach of the protocol or GCP 
Regulation 29A of the Medicines for Human Use (Clinical Trials) Regulations 2004 (SI 
2004/1031)4, as amended by SI 2006/192838, contains a requirement for the notification of 
‘serious breaches’ of GCP or the trial protocol: 

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‘29A.  
(1) The sponsor of a clinical trial shall notify the licensing authority in writing of any serious 
breach of: 
(a) the conditions and principles of GCP in connection with that trial; or 
(b) the protocol relating to that trial, as amended from time to time in accordance with 
regulations 22 to 25,  
within 7 days of becoming aware of that breach. 
 
(2) For the purposes of this regulation, a ‘serious breach’ is a breach which is likely to 
effect to a significant degree: 
(a) the safety or physical or mental integrity of the subjects of the trial; or 
(b) the scientific value of the trial’. 
Any serious breach of the conditions and principles of GCP or the study protocol in connection 
with the study will be reported to the Sponsor and the REC.   
The Sponsor will be responsible for notifying the MHRA within 7 days of becoming aware of 
any potential serious breach. 
Any potential serious breach of the conditions and principles of GCP in connection with the 
study will be escalated within hVIVO as soon as an individual becomes aware of the potential 
breach. Rapid escalation will permit the urgent notification to the Sponsor and allow sufficient 
time for hVIVO to fulfil the reporting timelines for the potential breach, as specified in UK 
Regulation 29A4, should reporting be necessary.  
 
Protocol amendments 
Neither the PI nor the Sponsor will alter the study protocol without obtaining the written 
agreement of the other. For all amendments, an evaluation will be made by the PI and the 
Sponsor as to whether the amendment is ‘substantial’ or ‘non-substantial’.  
Non-substantial amendments include for example, minor administrative or typographical 
changes to the protocol. 
Amendments are ‘substantial’ where they are likely to have a significant impact on subject risk 
or the clinical trial objectives, specifically the: 
• 
Safety or physical or mental integrity of the subjects 
• 
Scientific value of the trial 
• 
Conduct or management of the trial 
• 
Quality or safety of the IMP used in the trial. 
Substantial amendments must be reviewed and approved by the MHRA and/or REC prior to 
their implementation unless subject safety would be otherwise compromised (i.e., Urgent 
Safety Measures [USMs]). It is the responsibility of the Sponsor to decide whether an 
amendment is substantial or not, and therefore whether a substantial amendment requires 
MHRA authorisation, or an ethical opinion, or both. 

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When a protocol amendment substantially alters the clinical trial design or the potential risks 
or burden to subjects, the VIS/ICF will also be amended and approved by the REC, and all 
active subjects will be asked to reconfirm their continued willingness to participate in the trial. 
A log of all protocol amendments, together with their designation as substantial or non-
substantial, will be maintained to support clinical study reporting.  
 
Urgent Safety Measures 
The Sponsor and the Investigator may take appropriate ‘urgent safety measures’ to protect 
clinical trial subjects from any immediate hazard to their health and safety.  
USM should be taken immediately. There is no need to wait for MHRA approval before 
implementing USM. 
The Sponsor should telephone the Clinical Trial Unit at the MHRA and discuss the issue with 
a safety scientist immediately. Should further clarification be required the Sponsor will be 
contacted by a medical assessor. 
The Sponsor must notify the MHRA and the REC in writing, of the measures taken and the 
reason for the measures within 3 days. This notification should include a covering letter 
detailing the measures taken, the reason for them, an Annex II substantial amendment form 
and any supporting documentation. 
If the PI (and not the Sponsor) has instigated the USM, the Sponsor should be notified 
immediately so that they can assess and report the USM within the timelines required.  
18.4.5.1 Pandemic 
For any period during which a disease is pandemic and a serious risk to human health or 
potentially a serious risk to human health, notice of USMs taken in order to protect the subjects 
of a clinical trial against any immediate hazard to their health or safety and the circumstances 
giving rise to those measures, may be given ‘as soon as possible’ to the MHRA and the REC.  
Written notification to the MHRA and the REC should be provided within 3 days in the form of 
a substantial amendment and should describe the event, the measures taken and justification 
for the measures taken. 
18.5 
Discontinuation of the study 
The Sponsor reserves the right to temporarily suspend or discontinue the study for any reason 
at any time. In addition, the study may be stopped at any time if, in the opinion of the PI or 
SME, the safety data suggest that the medical safety of subjects is being compromised. 
If the study is suspended or terminated for safety reason(s), the Sponsor will promptly inform 
the PI, and will also inform the regulatory authorities of the suspension or termination of the 
study and the reason(s) for the action.  

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Archiving 
Paper and electronic records generated by hVIVO during the study will be archived as agreed 
in the CTA and in accordance with the applicable regulations and Sponsor requirements.  
18.7 
Sponsor responsibilities 
 
General 
The Sponsor agrees to adhere to the study protocol, and to comply with the principles of ICH 
GCP2, the Declaration of Helsinki 20131, the current regulatory requirements, as detailed in 
the Medicines for Human Use (Clinical Trials) Regulations (SI 2004/1031)4, and all subsequent 
amendments, the UK Data Protection Act 20185 and any other applicable regional and local 
regulations.  
The Sponsor has a legal responsibility to obtain MHRA approval to perform the study and to 
report the results of the study in full to the MHRA. A copy of the MHRA approval will be 
provided to the PI/Investigator before the start of the study. 
 
No-fault compensation and indemnity 
The Sponsor will comply with the Association of the British Pharmaceutical Industry (ABPI)39 
Clinical Trial Compensation Guidelines. The Sponsor will compensate subjects injured as a 
result of participation in the study, in accordance with the ABPI guidelines, for any harm or ill 
health incurred. The Sponsor has insurance to cover study-related injuries. 
The Sponsor will indemnify the PI (as detailed in a separate document). The indemnity will 
only apply where all study procedures have been carried out according to this protocol.  
hVIVO confirms that it holds a corporate medical professional liability insurance policy which 
insures hVIVO against any liability incurred as a result of the malpractice or negligence of any 
of its medical staff (including the PI), while acting within the scope of their role; and that this 
insurance policy satisfies any local insurance requirements. 
 
Monitoring  
The Study Monitor will contact the site prior to the start of the study to discuss the protocol 
and data collection procedures with site personnel. In accordance with applicable regulations, 
ICH GCP, and the procedures of the Sponsor, the Study Monitor will also periodically contact 
the site and conduct on-site visits. The Study Monitor will ensure that all monitoring visits are 
conducted according to protocol and regulatory requirements. 
During contacts with the study site, the Study Monitor’s activities will include: 
• 
Checking and assessing the progress of the study 
• 
Reviewing study data collected to date for completeness and accuracy 
• 
Checking the supply, storage, accountability, disposition and records pertaining to IMP 
• 
Conducting source data verification 

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• 
Identifying any issues and addressing resolutions. 
These activities will be done in order to verify that the: 
• 
Data are authentic, accurate, and complete 
• 
Study documentation is maintained properly 
• 
AEs are reported accurately 
• 
Safety and rights of the subjects are being protected 
• 
Study is conducted in accordance with the currently approved protocol (and any 
amendments), GCP, and all applicable regulatory requirements. 
The PI/Investigator will allow the Study Monitor direct access to all relevant documents and 
records, and allocate his/her time and the time of his/her staff to the Study Monitor to discuss 
findings and any relevant issues. 
At study closure, the Study Monitors will conduct all activities as indicated in Section 18.9.  
 
Audits and inspections 
At its discretion, the Sponsor may conduct a QA audit of this study. The Sponsor’s auditing 
procedures will be followed in order to comply with GCP guidelines and ensure acceptability 
of the study data for registration purposes. If such an audit occurs, the PI/Investigator will give 
the auditor direct access to all relevant documents, and will allocate his/her time and the time 
of his/her staff to the auditor as may be required to discuss findings and any relevant issues.  
In addition, regulatory agencies (e.g., MHRA) may conduct an inspection of the study. If such 
an inspection occurs, the PI/Investigator will allow the inspector direct access to all source 
documents and other study documentation for source data check and/or on-site audit 
inspection. The PI must allocate his/her time and the time of his/her staff to the inspector(s) to 
discuss findings of any relevant issues. 
 
Reports to the REC and MHRA 
The Sponsor will submit an Annual Safety Report (ASR) and an Annual Progress Report to 
the REC once a year throughout the clinical trial or on request. The Sponsor will submit a 
Development Safety Update Report (DSUR) to the MHRA, the DSUR will take into account all 
new available safety information received during the reporting period. 
18.8 
Investigator responsibilities 
 
Ethical considerations 
In accordance with hVIVO SOPs, hVIVO will submit study related documents to the REC for 
review and approval including but not limited to the protocol, VIS/ICF, IB and any 
advertisements. Written approval of these documents must be received from the REC before 
the first subject is enrolled into the study.   

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The PI/Investigator will notify the REC of any protocol amendments as described in Section 
18.4.4. Written approval must be obtained from the REC for all substantial amendments to the 
protocol, prior to their implementation, except when necessary to eliminate apparent 
immediate hazard to the subject (Section 18.4.5).  
The PI/Investigator should also obtain a written statement of the composition of the REC. 
Appropriate reports on the progress of the study will be made to the REC and the Sponsor by 
the PI/Investigator in accordance with local regulatory practices and in agreement with the 
Sponsor. 
IMP can only be supplied to the PI/Investigator after documentation of all ethical and legal 
requirements for starting the study has been received by the Sponsor. 
The REC and MHRA will be informed about the end of the trial within the required timelines: 
▪ 
In the event of early termination this is 15 days from trial completion and the reason 
for termination is required. 
▪ 
In the case of routine termination, this is 90 days from the protocol-defined end of trial. 
 
Laboratory certification and normal values 
The PI/Investigator will provide the Sponsor with the name and location of the clinical 
laboratory(ies) used for laboratory tests, plus a copy of the certification for all laboratory tests 
included in the protocol, certification number(s), date(s) of certification, and a list(s) of the 
normal values for all laboratory tests required by the protocol. These documents must be 
available prior to any subject being treated in the study. Updated versions of these documents 
must be provided to Sponsor as appropriate. 
 
Delegation of Investigator responsibilities 
The PI should ensure that all persons assisting with the study are adequately informed and 
trained about the protocol, any amendments to the protocol, their study-related duties and 
functions, and the study medication. The PI should maintain a list of Investigators and other 
appropriately qualified persons to whom he/she has delegated significant study-related duties. 
 
Informed Consent Process 
A properly executed, written, ICF, in compliance with the Declaration of Helsinki, ICH GCP, 
and other applicable regulations will be obtained from participants who are willing to 
participate. 
Potential subjects will be sent copies of the VIS and ICF at least 24 hours prior to their 
Screening Visit/Quarantine admission visit (as applicable) and will be encouraged to read 
them prior to their appointment. Upon arrival at the Screening Visit/Quarantine admission visit 
(as applicable), the VIS and ICF are explained and discussed in detail by an investigator and 
the subjects are given the opportunity to ask any questions, and can also take the information 
sheet away to consider their participation. 

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All subjects are required to have a good understanding of English and it is the PI’s (or 
designated individual/delegate) responsibility to ensure that the subject understands the 
information contained in the VIS and ICF. Once the PI (or designated individual/delegate) has 
confirmed that the subject has understood the study, including the benefits and risks of 
participation, the subject and the PI (or designated individual/delegate) must sign and date the 
ICF. 
The ICF must be signed and dated by the subject and countersigned by the PI or designated 
individual (whoever conducted the consent discussion). All subjects will receive a copy of the 
signed consent form, and VIS. The VIS and ICF will be copied and filed within the subject 
notes; the original will be held in the hVIVO TMF. 
The subjects will be assured that they can withdraw from the study at any time and for any 
reason without prejudice to their future medical care, and that they will be informed in a timely 
manner if new information becomes available that may affect their willingness to continue 
participation in the study. The communication of this information must be documented. 
If the ICF is amended during the study, the PI/Investigator must follow all applicable regulatory 
requirements pertaining to approval of the amended ICF by the REC. The site must use the 
amended ICF for all new subjects and repeat the consent process with the amended ICF for 
any on-going subjects, if required. 
 
Information for General Practitioners 
Subjects will be required to consent to their GPs being contacted by the hVIVO team. 
Confirmation of the subject's medical history will be requested from the subject’s GP in order 
for the PI/Investigator to judge the subject’s suitability for the study.  
 
Compensation and Expenses 
The Sponsor will reimburse subjects for their inconvenience and out-of-pocket expenses, 
including travelling costs. All proposed payments to subjects will be approved by the REC prior 
to the start of the study and the amount of payment will be specified in the VIS. 
 
Liability and insurance 
Liability and insurance provisions for this study are specified in the CTA. 
 
Investigator’s Protocol Agreement 
The Investigator's Protocol Agreement at the front of this document must be signed by the PI. 
The original or a copy must be kept on file by the Sponsor and the PI/Investigator must retain 
the original or a copy. The completed Protocol Agreement signifies review and acceptance of 
the protocol by the PI prior to initiation of the study. 

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Quality assurance 
hVIVO must implement and maintain QA and QC systems which may involve auditing the 
study.  
Any contracted individual or group working on the study must implement QC and/or QA 
systems in their work on the study. 
18.9 
Study termination 
Upon completion of the study, the following activities, when applicable, must be conducted by 
the Study Monitor in conjunction with the PI/Investigator, as appropriate: 
• 
Review of site study records for completeness and accuracy 
• 
Return of all study data to the Sponsor (excluding source data) 
• 
Data clarifications and/or resolutions 
• 
Accounting, reconciliation, and final disposition of used and unused study medication 
(EDP-938 or placebo).  
In addition, the Sponsor reserves the right to temporarily suspend or prematurely terminate 
this study for any reason (see Section 18.518.5). 
18.10 
GCP Compliance 
The Investigator must undertake to perform the study in accordance with ICH GCP Guidelines, 
EU Directive 2001/20/EC, and the applicable regulatory requirements. 
 
It is the Investigator’s responsibility to ensure that adequate time and appropriate resources 
are available at the study site prior to commitment to participate in this study. The Investigator 
should also be able to estimate or demonstrate a potential for recruiting the required number 
of suitable subjects within the agreed recruitment period. 
 
Agreement with the final CSR will be documented by the dated signature of the PI, in 
compliance with Directive 75/318/EC, Directive 2001/83/EC, and ICH E3. 

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19 
DISCLOSURE OF DATA 
19.1 
Subject confidentiality 
In line with EU Directive 95/46/EEC37, as transposed into the UK Data Protection Act 20185, 
the PI and hVIVO have a legal obligation to protect at all times the confidentiality of subject 
personal data from the point of capture, through processing, dissemination in line with consent 
from the subject and to its final disposition. 
The PI/Investigator shall provide assurance to subjects that their confidentiality will be 
maintained during all audits and inspections of the study site and in any documentation by 
third parties.  
hVIVO investigators, study nurses and other hVIVO personnel will record information about 
the subjects in a computerised database and in an hVIVO medical record. If the subject 
consents to participate in this study, any of their medical records may be reviewed by hVIVO 
staff and auditors for the purposes of checking that the study is being carried out correctly.  
Subjects’ medical records may also be reviewed by representatives from the REC, 
government agencies and the MHRA; all have the same legal obligation in respect of 
confidentiality. Subjects will be assigned a unique number prior to enrolment into the study 
(Section 7.7). Subjects’ names will not be supplied to the Sponsor. 
Any samples taken for analysis during the study will be labelled using the subject number. 
Some laboratories in the UK may require up to two or three identifiers for the accurate tracking 
and processing of samples, such as subject number, and date of birth. Under no 
circumstances will a laboratory involved in the analysis of samples in this study be given 
information regarding the identity of subjects, such as their full name. 
19.2 
Sponsor confidentiality 
As detailed in the CTA, information concerning the IMP and any information such as clinical 
indications for the IMP, its formula, methods of manufacture and other scientific data relating 
to it, that have been provided by the Sponsor and are unpublished, are confidential and must 
remain the sole property of the Sponsor. The PI/Investigator will agree to use the information 
only for the purposes of carrying out this study and for no other purpose, unless prior written 
permission from the Sponsor is obtained.  
19.3 
Publication 
 
 
 
 
 
 
 

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20 
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15. 
Sigurs N, Gustafsson PM, Bjarnason R, Lundberg F, Schmidt S, Sigurbergsson F, et 
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53.      Directive 2016/679 of the European Parliament and of the Council of 14 April 2016 on 
the protection of natural persons with regard to the processing of personal data and on 
the free movement of such data, and repealing Directive 95/46/EC (General Data 
Protection Regulation)  
 
 

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21 
APPENDICES 
Appendix 1: Patient Health Questionnaire (PHQ-9)40 ................................................................. 133 
Appendix 2: Generalised Anxiety Disorder Questionnaire (GAD-7)41 ........................................ 134 
Appendix 3: Normal ranges ........................................................................................................ 135 
Appendix 4: hVIVO Symptom Diary Card ................................................................................... 136 
Appendix 5: AE and Toxicity Grading Scales ............................................................................. 137 
Appendix 6: Assessment of Baseline by Investigator for Clinical Conduct ................................ 138 
Appendix 7: PK Blood Sampling Schedule ................................................................................. 140 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV  
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
Version: Amendment 4.0 (v5.0)_07NOV2019 
 
 
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Appendix 1: Patient Health Questionnaire (PHQ-9)40 

Safety, Pharmacokinetics and Antiviral Activity of Orally Administered EDP-938 Against RSV 
ENANTA Protocol No: EDP 938-101 
 
 
hVIVO Protocol No: ENA-CS-001 
 
 
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Appendix 2: Generalised Anxiety Disorder Questionnaire (GAD-7)41 

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Appendix 5: AE and Toxicity Grading Scales 
Common Terminology Criteria for Adverse Events (CTCAE); Version 5.0. Published: 
November 27, 2017 (v50: November 27, 2017). U.S. Department of Health and Human 
Services, National Institutes of Health National Cancer Institute. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Patient Health Questionnaire (PHQ-9) 
Nearest to Inoculation 
Generalised Anxiety Disorder Questionnaire (GAD-7) 
Nearest to Inoculation 
Note: Nearest to inoculation is defined as the nearest assessment pre-inoculation. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix 7: PK Blood Sampling Schedule 
Blood (plasma) samples for the evaluation of PK parameters of EDP-938 will be collected at the following time points based on the schedule of 
dosing.  
Based on the dose selection for Part 2 (i.e. a combination of different dosing schedule i.e. OD and BD dosing for 5 days), the PK Blood sampling 
for 5 days TWICE a day dosing for Part 1 will be used for Part 2.  
The allowable time windows for the sampling are as follows: 
 
▪ 
± 5 minutes from the scheduled time for time points ≤ 1 hour from dosing; 
 
▪ 
± 15 minutes from the scheduled time for time points > 1 hour from dosing, with NOTE below: 
o 24 hours timepoints: +/- 1 hour window 
o 30 hours timepoint: +/- 1 hour window 
o 36 hours timepoint: +/- 1 hour window 
o 48 hours timepoint: +/- 2 hours window 
o 60 hours timepoint: +/- 2 hours window 
o 72 hours timepoint: +/- 2 hours window 
 
▪ 
There is no time window requirement for the pre-dose sample. The pre-dose sample must be taken prior to dose.