A Randomized, Phase 2a, Double-blind, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics and Antiviral Activity of Multiple Doses of Orally Administered EDP-323 Against Respiratory Syncytial Virus Infection in a Virus Challenge Model in Healthy Adults
Phase: PHASE2
Conditions: RSV Infection
Sponsor: Enanta Pharmaceuticals, Inc

 
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Clinical study protocol 
 
A RANDOMIZED, PHASE 2A, DOUBLE-BLIND, PLACEBO- 
CONTROLLED STUDY TO EVALUATE THE SAFETY, 
PHARMACOKINETICS AND ANTIVIRAL ACTIVITY OF 
MULTIPLE DOSES OF ORALLY ADMINISTERED EDP-323 
AGAINST RESPIRATORY SYNCYTIAL VIRUS INFECTION 
IN THE VIRUS CHALLENGE MODEL IN HEALTHY 
ADULTS 
 
 
 
 
Brief Title: 
A controlled Phase 2a study to evaluate the efficacy of 
EDP-323 against respiratory syncytial virus infection 
in a virus challenge model 
Protocol Version and Date: 
Final version 2.0;  25-Mar-2024 
Sponsor: 
ENANTA Pharmaceuticals, Inc. 
500 Arsenal Street 
Watertown, MA 02472 
United States of America 
Protocol Number: 
EDP 323-101 
hVIVO Study Number 
ETP-CST-001 
Compound: 
EDP-323 capsules for oral administration 
IRAS ID: 
1007761 
 
 
Confidentiality and Protections Statement: 
 
This document contains confidential information of hVIVO and ENANTA Pharmaceuticals, 
Inc. This document must not be disclosed to anyone other than the study staff and members of 
the Independent Ethics Committee/Institutional Review Board or Competent Authorities. The 
information in this document cannot be used for any purpose other than the conduct or 
evaluation of the clinical investigation without the prior written consent of hVIVO and 
ENANTA Pharmaceuticals, Inc. 
 
Personal data included in the protocol is subject to the United Kingdom (UK) Data Protection 
Act considerations and protections.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
Sponsor Statement 
 
This protocol was subjected to critical review. The information it contains is consistent with 
current knowledge of the risks and benefits of the study intervention, and with the moral, 
ethical, and scientific principles governing clinical research as set out in the current Declaration 
of Helsinki and the principles of International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP). 
 
 
 
Sponsor Signatory 
 
Name, title (typed or printed):    
 
 
 
 
 
 
 
 
Signature and Date: 
 
 
 
 
 
3/27/2024

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
Investigator Agreement 
 
I have read the protocol and agree to conduct the study in accordance with the approved protocol 
and any future amendments, the Declaration of Helsinki, the principles of ICH GCP, the current 
regulatory requirements as detailed in the Medicines for Human Use (Clinical Trial) Regulations 
(Statutory Instrument 2004/1031) and all subsequent amendments, the United Kingdom (UK) 
Data Protection Act 2018, any other applicable laws, and guidance. 
 
I agree to conduct the procedures described in this protocol according to these guidelines and 
to appropriately direct and assist the study staff under my control. 
 
 
 
Principal Investigator Signatory 
 
Name (typed or printed):      
 
 
 
 
 
 
Signature and Date: 
 
3/27/2024              
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: In this protocol, the terms hVIVO and ‘investigator’ distinguish between the principal 
investigator’s (PI’s) responsibility, and actions required by the organization (hVIVO). The term 
‘investigator’ includes appropriately qualified persons to whom the PI has formally delegated 
his/her investigator roles and responsibilities.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
Study Staff Contact Information 
 
Contact 
Details 
Sponsor 
ENANTA Pharmaceuticals, Inc. 
500 Arsenal Street 
Watertown, MA 02472 
United States of America 
Sponsor’s representative 
Principal Investigator and Clinical 
Study Facilities 
 
hVIVO Services Limited 
Queen Mary BioEnterprises Innovation Centre 
42 New Road, London E1 2AX, United Kingdom 
(UK) 
hVIVO Services Limited 
The Whitechapel Clinic 
49-53 New Road, London E1 1HH, UK 
hVIVO Services Limited 
21 Plumbers Row, London E1 1EQ, UK 
hVIVO Services Limited 
36 George Street, Manchester M1 4HA, UK 
 
 
Sponsor's Medical Expert/Medical 
Monitor 
Key Protocol Contributors 
Refer to the local study contact list document 

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
TABLE OF CONTENTS 
 
Table of Contents.......................................................................................................................5 
List of Tables .............................................................................................................................9 
 
1.         SYNOPSIS ..................................................................................................................10 
1.1.        Study Schematic: On-study Participant Progression.................................................20 
1.2.        Schedule of Events (SoE)..........................................................................................22 
 
2.         INTRODUCTION......................................................................................................29 
2.1.        Background ...............................................................................................................29 
2.2.        Information about EDP-323 ......................................................................................30 
2.2.1.     Product Description ...............................................................................................30 
2.2.2.     Nonclinical Studies ................................................................................................30 
2.2.2.1.    Drug Metabolism and Pharmacokinetics ..........................................................30 
2.2.2.2.    Safety Pharmacology and Toxicology ..............................................................30 
2.2.3.     Clinical Studies ......................................................................................................31 
2.3.        Study Rationale .........................................................................................................32 
2.4.        Benefit/Risk Assessment...........................................................................................32 
2.4.1.     Risk Assessment ....................................................................................................32 
2.4.1.1.    Vulnerable Persons............................................................................................37 
2.4.1.2.    Risk Associated With Coronavirus Disease 2019 Pandemic ............................37 
2.4.2.     Benefit Assessment ................................................................................................38 
2.4.3.     Overall Benefit/Risk Conclusion ...........................................................................38 
 
3.         OBJECTIVES AND ENDPOINTS ..........................................................................39 
 
4.         STUDY DESIGN........................................................................................................43 
4.1.        Overview of Study Design ........................................................................................43 
4.2.        Scientific Rationale for Study Design.......................................................................44 
4.3.        Justification for Dose ................................................................................................44 
4.4.        End-of-Study Definition............................................................................................45 
 
5.         STUDY POPULATION ............................................................................................46 
5.1.        Inclusion Criteria.......................................................................................................46 
5.2.        Exclusion Criteria......................................................................................................48 
5.3.        Lifestyle Considerations............................................................................................51 
5.3.1.     Meals and Dietary Restrictions..............................................................................51 
5.3.2.     Caffeine, Alcohol, and Tobacco ............................................................................52 
5.3.3.     Activity ..................................................................................................................52 
5.3.4.     Other Restrictions ..................................................................................................52 
5.4.        Screen Failures ..........................................................................................................52 
 
6.         STUDY INTERVENTIONS AND CONCOMITANT THERAPY.......................53 
6.1.        Study Intervention(s) Administered ..........................................................................53 
6.2.        Preparation/Handling/Storage/Accountability ..........................................................54 
6.2.1.     Investigational Medicinal Product .........................................................................54 
6.2.2.     Challenge Agent.....................................................................................................54 
6.2.3.     All Study Interventions ..........................................................................................55 
6.3.        Randomization and Blinding.....................................................................................55 
6.3.1.     Randomization .......................................................................................................55 
6.3.2.     Blinding..................................................................................................................55 
6.4.        Study Intervention Compliance.................................................................................56

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
6.5.        Concomitant Therapy................................................................................................56 
6.6.        Dose Modification.....................................................................................................58 
6.7.        Treatment of Overdose..............................................................................................58 
 
7.         WITHDRAWAL/DISCONTINUATION OF STUDY INTERVENTION...........59 
7.1.        Participant Withdrawal..............................................................................................59 
7.2.        Participant Discontinuation .......................................................................................59 
7.2.1.     Temporary Discontinuation/Temporary Delay in Enrolment................................60 
7.3.        Lost to Follow-up ......................................................................................................60 
7.4.        Participant Replacement Strategy .............................................................................60 
7.5.        Stopping Rules ..........................................................................................................61 
7.6.        Adaptive Features......................................................................................................62 
 
8.         STUDY ASSESSMENTS AND PROCEDURES ....................................................65 
8.1.        Demographics and Baseline Characteristics .............................................................65 
8.1.1.     Demographics ........................................................................................................65 
8.1.2.     Height, Body Weight, and Body Mass Index ........................................................65 
8.1.3.     Medical and Medication History ...........................................................................65 
8.1.4.     Challenge Agent Serology Samples.......................................................................66 
8.1.5. 
Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) 
Questionnaire .........................................................................................................66 
8.2.        Respiratory Samples..................................................................................................66 
8.2.1.     Nasopharyngeal Swab............................................................................................66 
8.2.1.1.    Respiratory Pathogen Screen.............................................................................66 
8.2.1.2.    RSV Discharge Test ..........................................................................................66 
8.2.2.     Nasal Wash ............................................................................................................67 
8.2.3.     Viral Shedding for Dosing .....................................................................................67 
8.3.        Efficacy Assessments ................................................................................................67 
8.3.1.     Participant Diary Cards..........................................................................................67 
8.3.2.     Nasal Discharge Collection from Paper Tissues....................................................68 
8.3.3.     Viral Load Assessment ..........................................................................................68 
 
 
8.4.        Safety Assessments ...................................................................................................69 
8.4.1.     Complete Physical Examination ............................................................................69 
8.4.2.     Symptom-directed Physical Examination..............................................................69 
8.4.3.     Vital Signs and Tympanic Temperature ................................................................69 
8.4.4.     Electrocardiogram..................................................................................................70 
8.4.5.     Clinical Safety Laboratory Assessments ...............................................................70 
8.4.5.1.    Urinalysis...........................................................................................................70 
8.4.5.2.    Drugs of Misuse and Cotinine...........................................................................71 
8.4.5.3.    Alcohol Breath Testing .....................................................................................71 
8.4.5.4.    Safety Blood Assessments and Analysis...........................................................71 
8.4.6.     Pregnancy Tests and Follicle-stimulating Hormone..............................................71 
8.4.7.     Spirometry..............................................................................................................71 
8.5.        Adverse Events, Serious Adverse Events, and Other Safety Reporting ...................72 
8.5.1.     Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information ..................................................................................................72 
8.5.2.     Method of Detecting Adverse Events/Serious Adverse Events.............................72 
8.5.3.     Follow-up of Adverse Events/Serious Adverse Events .........................................72 
8.5.4.     Regulatory Reporting Requirements for Serious Adverse Events.........................73

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
8.5.5.     Pregnancy...............................................................................................................73 
8.6.        Pharmacokinetics ......................................................................................................73 
8.6.1.     Pharmacokinetic Blood Samples ...........................................................................73 
8.6.2.     Pharmacokinetic Parameters ..................................................................................74 
8.7.        Pharmacodynamics....................................................................................................74 
8.8.        Immunogenicity Assessments ...................................................................................74 
8.9.        Genetics.....................................................................................................................74 
8.10.      Biomarkers ................................................................................................................74 
 
9.         STATISTICAL CONSIDERATIONS .....................................................................75 
9.1.        Statistical Hypotheses ...............................................................................................75 
9.2.        Sample Size Determination.......................................................................................75 
9.3.        Analysis Sets .............................................................................................................75 
9.4.        Statistical Analysis ....................................................................................................77 
9.4.1.     Statistical Analysis Plan.........................................................................................77 
9.4.2.     General Considerations ..........................................................................................77 
9.4.2.1.    Descriptive Statistics .........................................................................................77 
9.4.2.2.    Inferential Statistics and Significance Testing ..................................................77 
9.4.3.     Planned Analysis....................................................................................................78 
9.4.3.1.    Participant Accountability .................................................................................78 
9.4.3.2.    Protocol Deviations ...........................................................................................78 
9.4.3.3.    Demographic and Baseline Characteristics .......................................................78 
9.4.3.4.    Compliance to Study Intervention.....................................................................78 
9.4.4.     Primary Efficacy Analysis .....................................................................................78 
9.4.5.     Secondary Efficacy Analysis .................................................................................78 
 
9.4.7.     Safety Analysis ......................................................................................................80 
9.4.8.     Pharmacokinetic Analysis......................................................................................80 
9.5.        Interim Analysis ........................................................................................................80 
9.6.        Data Monitoring Committee .....................................................................................81 
 
10. 
SUPPORTING            DOCUMENTATION            AND            OPERATIONAL 
CONSIDERATIONS .................................................................................................82 
10.1.      Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ...................82 
10.1.1.   Regulatory and Ethical Considerations..................................................................82 
10.1.2.   Financial Disclosure...............................................................................................82 
10.1.3.   Confidentiality .......................................................................................................82 
10.1.4.   Informed Consent Process .....................................................................................83 
10.1.5.   Data Protection.......................................................................................................83 
10.1.6.   Committee(s) Structure..........................................................................................84 
10.1.7.   Dissemination of Clinical Study Data....................................................................84 
10.1.8.   Data Quality Assurance .........................................................................................84 
10.1.9.   Source Documents .................................................................................................85 
10.1.10. Study Discontinuation............................................................................................85 
10.1.11. Publication Policy ..................................................................................................85 
10.2.      Appendix 2: Clinical Laboratory Tests .....................................................................87 
10.3. 
Appendix 3: Adverse Events – Definitions and Procedures for Recording, Evaluating, 
Follow-up and Reporting ..........................................................................................89 
10.3.1.   Adverse Event ........................................................................................................89 
10.3.2.   Adverse Drug Reaction..........................................................................................90 
10.3.3.   Unexpected Adverse (Drug) Reaction ...................................................................90

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
10.3.4.   Serious Adverse Event ...........................................................................................90 
10.3.5.   Suspected Unexpected Serious Adverse Reaction.................................................91 
10.3.6.   Recording, Assessment, and Follow-up of Adverse Events/Serious Adverse Events 
................................................................................................................................92 
10.3.6.1.  Adverse Event/Serious Adverse Event Recording ............................................92 
10.3.6.2.  Assessment ........................................................................................................93 
10.3.6.3.  Assessment of Intensity.....................................................................................94 
10.3.6.4.  Frequency ..........................................................................................................95 
10.3.6.5.  Assessment of Causality....................................................................................95 
10.3.6.6.  Action Taken .....................................................................................................96 
10.3.6.7.  Outcome ............................................................................................................97 
10.3.6.8.  Follow-up ..........................................................................................................97 
10.3.7.   Reporting of Serious Adverse Events ....................................................................98 
10.3.8.   Reporting of Suspected Unexpected Serious Adverse Reactions..........................99 
10.3.9.   Adverse Reactions to Non-investigational Medicinal Products ............................99 
10.3.10. Post-study Adverse Events and Serious Adverse Events ......................................99 
10.3.11. Pregnancy.............................................................................................................100 
10.4.      Appendix 4: Normal Ranges ...................................................................................101 
10.5.      Appendix 5: Abbreviations .....................................................................................102 
10.6.      Appendix 6: Definitions ..........................................................................................105 
10.6.1.   General.................................................................................................................105 
10.6.2.   Study Definition of Infection and Illness.............................................................106 
10.7.      Appendix 7: Protocol Amendment History.............................................................108 
 
11.       REFERENCES.........................................................................................................109

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
LIST OF TABLES 
 
Table 6-1:      Study Interventions............................................................................................53 
 
Table 6-2:      Prohibited Medication (Healthy Participants) ...................................................57 
 
Table 6-3:      Permitted Medication ........................................................................................58 
 
Table 7-1:      Study Stopping Rules ........................................................................................61 
 
Table 7-2:      Adaptive Features..............................................................................................63 
 
Table 9-1:      Analysis Sets .....................................................................................................75 
 
Table 9-2:      Methods for Analysis of Secondary Efficacy Endpoints ..................................78 
 
Table 10-1:    Protocol-required Safety Laboratory Assessments ...........................................87 
 
Table 10-2:    Classification of Adverse Event Severity..........................................................95 
 
Table 10-3:    Classification of Adverse Event Relationship...................................................96 
 
Table 10-4:    Classification of Adverse Event Outcome ........................................................97 
 
Table 10-5:    Contact Details for Reporting All Serious Adverse Events ..............................98

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
1.            SYNOPSIS 
 
Study Title: 
A Randomized, Phase 2a, Double-blind, Placebo-controlled 
Study to Evaluate the Safety, Pharmacokinetics and Antiviral 
Activity of Multiple Doses of Orally Administered EDP-323 
Against  Respiratory  Syncytial  Virus  Infection  in  a  Virus 
Challenge Model in Healthy Adults 
Short Title 
A controlled Phase 2a study to evaluate the efficacy of EDP-323 
against respiratory syncytial virus infection in a virus challenge 
model 
Protocol Number: 
EDP 323-101 
hVIVO Study Number: 
ETP-CST-001 
Sponsor 
ENANTA Pharmaceuticals, Inc 
IRAS ID 
1007761 
Study Phase: 
Phase 2a 
Clinical Study Facilities hVIVO Services Limited 
Queen Mary BioEnterprises Innovation Centre 
42 New Road, London E1 2AX, United Kingdom (UK) 
hVIVO Services Limited 
The Whitechapel Clinic 
49-53 New Road, London E1 1HH, UK 
hVIVO Services Limited 
21 Plumbers Row, London E1 1EQ, UK 
hVIVO Services Limited 
36 George Street, Manchester M1 4HA, UK 
Study Type 
Interventional 
Indication 
Respiratory syncytial virus (RSV) infection 
Design 
This is a randomized, Phase 2a, double-blind, placebo-controlled 
study to evaluate the safety, pharmacokinetics (PK), and antiviral 
activity of multiple doses of orally administered EDP-323 against 
RSV infection in healthy adults after challenge with RSV-A 
Memphis  37b.  The  study  will  test  2  doses  of  EDP-323: EDP-
323 high dose (600 mg once daily [QD] for 5 days) vs EDP- 
323 low dose (600 mg loading dose for 1 day followed by 200 mg 
QD for 4 days). 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary: 
Efficacy 
•    To    evaluate    the    antiviral 
•    Reduction in RSV area under the viral load-time 
activity of EDP-323 compared 
to placebo in healthy adult 
participants inoculated with 
RSV-A Memphis 37b 
curve  (VL-AUC)  measured  by  quantitative 
reverse transcription-polymerase chain reaction 
(qRT-PCR) in nasal samples 
Secondary: 
Efficacy 
•    To     further     evaluate     the 
•    Viral load: 
antiviral activity of EDP-323 
o
RSV viral load by qRT-PCR of nasal 
compared    to    placebo    in 
samples including: 
healthy     adult     participants 
inoculated      with      RSV-A 
•  Reduction   in   RSV   peak   viral   load 
Memphis 37b 
(VLPEAK) 
•    To evaluate the clinical disease 
•  Reduction in time to RSV VLPEAK after 
severity    in    healthy    adult 
first dosing 
participants   inoculated   with 
•  Time to RSV viral load negativity  after 
RSV-A       Memphis       37b 
first dosing 
followed by administration of 
EDP-323 compared to placebo 
•  Time to first negative slope of RSV viral 
load after first dosing 
•  Slope of the RSV viral load over  time 
(clearance   rate)   from   time   of   RSV 
VLPEAK to 1, 2, 3, and 4 days later 
o RSV viral load by cell culture (plaque assay) 
of nasal samples, including: 
•  Reduction in RSV VL-AUC 
•  Reduction in RSV VLPEAK 
•  Reduction in time to RSV VLPEAK after 
first dosing 
•  Time to RSV viral load negativity  after 
first dosing 
•  Time to first negative slope of RSV viral 
load after first dosing 
•  Slope of the RSV viral load over  time 
(clearance   rate)   from   time   of   RSV 
VLPEAK to 1, 2, 3, and 4 days later 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
•    Clinical symptoms and disease severity: 
o Effect on RSV symptoms using the symptom 
diary card [SDC]), with endpoints including: 
•  Reduction   in   area   under   the    total 
symptom score (TSS)-time curve  (TSS- 
AUC) 
•  Reduction in peak TSS 
•  Time    to    return    to    baseline    (last 
assessment before RSV inoculation) TSS 
•  Reduction in time to peak TSS 
o Total  weight  of  nasal  discharge  (mucus) 
produced 
o Total number of tissues used 
Pharmacokinetics 
• To evaluate the PK profile of 
EDP-323 (and metabolites) in 
blood samples in healthy adult 
participants inoculated with 
RSV-A Memphis 37b 
• To          characterize          the 
relationship between plasma 
PK of EDP-323 and VL-AUC 
(qRT-PCR) and TSS-AUC in 
healthy 
adult 
participants 
inoculated 
with 
RSV-A 
Memphis 37b 
• EDP-323 (and metabolites) concentrations and 
PK parameters in blood samples: maximum 
plasma concentration (Cmax), time to maximum 
plasma concentration (tmax), terminal half-life 
(t1/2), apparent systemic clearance (CL/F), 
terminal elimination rate constant (λz), volume 
of distribution (Vd/F), plasma concentration at 
12 hours    (C12h),    plasma    concentration    at 
24 hours (C24h), area under the concentration- 
time   curve   from   time   0   to   time   of   last 
quantifiable concentration (AUClast), area under 
the concentration-time curve over the dosing 
interval 
(AUC0-tau), and area under the 
concentration-time curve from time 0 to infinity 
(AUC0-∞), and other parameters as applicable 
• EDP-323  plasma  PK  (area  under  the  curve 
[AUC]) correlations with VL-AUC (e.g., qRT- 
PCR) and TSS-AUC 
Safety 
•    To evaluate the safety of EDP- 
323      in      healthy      adult 
participants   inoculated   with 
RSV-A Memphis 37b 
• Occurrence of adverse events (AEs) from initial 
administration of investigational medicinal 
product (IMP) up to discharge 
• Occurrence of AEs from initial administration 
of IMP up to Day 28 follow-up 
• Occurrence of serious adverse events (SAEs) 
from initial administration of IMP up to Day 28 
follow-up 

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Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
 
Hypothesis 
The primary statistical hypothesis is that treatment with EDP-323 
will show an antiviral effect demonstrated by a significant 
reduction in RSV VL-AUC (measured by qRT-PRC in nasal 
samples) compared to placebo. 
Investigational 
EDP-323 capsules
 and placebo capsules for oral 
administration, to be administered once daily (QD) for a total 
dosing period of 5 days 
•    High dose: 600 mg EDP-323 QD for 5 days 
• Low dose: 600 mg EDP-323 (loading dose) for 1 day, 
followed by 200 mg EDP-323 QD for 4 days 
Medicinal Product 
(IMP) 
Challenge Agent 
RSV-A Memphis 37b 
Challenge Agent Route 
Intranasal delivery 
Challenge Agent Titer 
Total dose of approximately 4 log10 plaque-forming units (PFU) 
Study Population 
Healthy male and female participants aged between 18 to 55 years, 
who are pre-screened during the hVIVO generic screening process 
to document low antibody levels to RSV and to therefore be 
susceptible to RSV infection (“serosuitable”) and who meet the 
study-specific inclusion / exclusion criteria. 
Summary of Study 
This is a randomized, Phase 2a, double-blind, placebo-controlled 
study to evaluate the safety, PK, and antiviral activity of multiple 
doses of orally administered EDP-323 against RSV infection in 
healthy adults after challenge with RSV-A Memphis 37b. 
In this study, 2 doses of EDP-323 will be tested: EDP-323 high 
dose (600 mg QD for 5 days) vs low dose (600 mg loading dose 
for 1 day followed by 200 mg QD for 4 days). The study will have 
a placebo arm. Due to its exploratory nature, no adjustment will 
be made to the type 1 error in this proof-of-concept study. 
The study is divided into the following study phases: 
Screening: 
•    Screening prior to inoculation with challenge virus from 
Day -90 to Day -2/-1. 
Inpatient Phase: 
• Participants will be resident in the quarantine unit for 
approximately 15 days, from admission on Day -2/-1 to 
planned discharge on Day 12. Discharge from quarantine 
is foreseen at Day 12 if the participant has no clinically 
significant  symptoms.  The  detection  of  virus  by  RSV 
Design 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
discharge test  (e.g.,  qualitative rapid  viral  antigen  test 
[RVAT]) will be performed at investigator’s discretion. If 
the  participant  continues  to  have  clinically  significant 
symptoms, additional extended quarantine stay may be 
required based on the assessment of the PI/investigator. 
Procedures will include: 
•    Pre-human Viral Challenge: 
o Admission to quarantine unit on Day -2/-1. 
o Baseline   assessments   will   be   conducted   as   per 
Schedule of Events (SoE) up to Day 0, pre-challenge. 
•    Human Viral Challenge: 
o RSV-A Memphis 37b virus inoculation on Day 0. 
•    Post-human Viral Challenge: 
o Randomization to receive EDP-323 (high dose or low 
dose) or matched placebo. 
o Administration of IMP (EDP-323 or placebo). IMP 
administration   will  be  initiated  (triggered)  by   a 
positive    RSV   result    (measured    by    qualitative 
integrative  cycler  [qic]  PCR)  between  Day 2  and 
Day 5 AM (nasal sampling twice daily, morning and 
evening; on Day 5 only in the morning). 
Dosing will start approximately 12 hours after first 
detection of RSV. If no positive RSV result is obtained, 
dosing will start in the evening of Day 5. Duration of 
treatment with EDP-323 (or placebo) will be 5 days 
(QD) in the period from Days 2 to 9, with the start day 
dependent on RSV result. 
o Day 1 onwards and each day – study assessments will 
be conducted as per SoE. 
o Discharge from quarantine is planned on Day 12 post 
inoculation. 
Outpatient Phase: 
•    Follow-up visit: Day 28 (±3 days) 
Details of the activities to occur during the study are provided in 
the SoE. 
Randomization 
In this study, 132 participants will be randomized 1:1:1 into one 
of  3  treatment  groups  (n=44  each)  to  receive  EDP-323  (at 
2 different doses) or placebo. 
Participant 
Participants may be replaced in this study. 
If a participant discontinues from study intervention OR 
withdraws from the study for reasons not related to AEs, a 
replacement participant may be enrolled, if deemed appropriate by 
Replacement Policy 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
the PI/investigator and sponsor. The replacement participant will 
receive the same intervention as the participant being replaced. 
The  replacement  participant  will  be  assigned  a  new,  unique 
randomization number. The replacement participant will receive 
the same allocated, blinded treatment as the participant who is 
being replaced. 
Expected Duration of 
Participation per 
Participant 
Up to 4 months, from screening to the participant’s last scheduled 
follow-up visit. 
Overall Duration of 
Clinical Phase 
The length of the clinical phase is expected to be approximately 
8 months   from   first   participant’s   planned   first   study   visit 
(admission to the quarantine unit on Day -2/-1) to the last 
participant’s last scheduled study visit (last scheduled follow-up 
visit on Day 28 [±3 days]). 
End-of-Study 
Definition 
The end of the study is defined as the date of the last visit of the 
last participant in the study. 
Sample Size 
Determination 
The statistical powering selected for this study is estimated to be 
sufficient for the primary objective and the primary endpoint and 
important secondary endpoints. 
The sample size was calculated based on the assumptions of a 55% 
reduction in qRT-PCR VL-AUC, with a 72% coefficient of 
variation (CV) (based on similar previous studies), for a power of 
80% and a 2-sided 5% level of significance (without adjustment 
for multiple comparisons) and assuming a 70% infectivity rate 
(based on similar previous studies). On this basis, it is estimated 
that 31 evaluable RSV infected (intent-to-treat infected [ITT-I]) 
participants  per arm  and  44  inoculated participants  would  be 
sufficient for the study to demonstrate an antiviral affect as 
measured by qRT-PCR with a power of at least 80% (achieved 
power computed as 84.1%). However, with the more conservative 
assumption of a 63% infection rate, 44 recruited participants, 
resulting in 28 infected participants would allow to detect a 55% 
relative reduction in qRT-PCR VL-AUC with at least 80% 
(80.2%) power. 
The sample size of 44 participants per arm would allow to detect 
a decrease of 75% in TSS-AUC (CV of 92.9%) and 55% in TSS 
peak score (CV of 68.8%) with more than 80% power (87.8% and 
87.2% respectively) assuming an infection rate of 70% (31 
infected participants). The more conservative assumption of a 
63% infection rate (28 infected participants) would allow to detect 
a 75% relative reduction in TSS-AUC and 55% in peak-AUC with 
respectively 84.3% and 83.6% power. 
Statistics 
Primary efficacy analysis: the main estimator of the primary 
endpoint, the mean or median VL-AUC of RSV-A Memphis 37b, 
depending on whether the endpoint is normally distributed, as 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
determined by qRT-PCR on nasal samples (virology) collected 
twice daily starting 2 days post-viral challenge (Day 2) up to 
discharge from quarantine, will be analyzed on the ITT-I analysis 
set. 
The calculation  of the VL-AUC  will  be performed on  log10- 
transformed PCR data using the trapezoidal summation rule based 
on actual time intervals in hours. Results below the lower limit of 
quantification (LLOQ) will be given values as detailed in the 
statistical analysis plan (SAP). 
Descriptive statistics and the 95% confidence intervals (CI) will 
be presented by treatment group. The differences between each 
active treatment group and the placebo arm will be analyzed using 
the t-test or Wilcoxon rank sum test, depending on whether the 
endpoint is normally distributed. 
Full details of the planned analysis will be presented in the SAP. 
Any deviations from the SAP will be documented in the clinical 
study report. 
Study Analysis Sets: 
Participant 
Description 
Analysis Set 
Enrolled 
A  participant  will  be  considered  as 
‘enrolled’ into the study once he/she has 
been inoculated with the challenge virus. 
Intent-to-treat (ITT) All     participants     having     received 
analysis set 
challenge virus, randomized, and having 
received at least one dose of IMP. 
Intent-to-treat 
All     participants     having     received 
infected       (ITT-I) challenge virus, randomized, and having 
analysis set 
received at least one dose of IMP, and 
meeting the criterion for laboratory- 
confirmed RSV infection (see below for 
definition of laboratory-confirmed RSV 
infection). The ITT-I analysis set will be 
considered     the     primary     analysis 
population  for  efficacy  endpoints.  A 
participant  will  fulfil  the  criteria  for 
laboratory-confirmed RSV infection if: 
•    At least 2 positive detections by 
viral    load    qRT-PCR    assay 
specific for the challenge virus, 
reported   within   2 consecutive 
study days. 
and/or 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
• One positive detection  by  viral 
load qRT-PCR assay, specific for 
the challenge virus, in which an 
aliquot of the same sample has 
also tested positive in a cell-based 
infectivity assay appropriate for 
detecting the challenge virus. 
Intent-to-treat 
All     participants     having     received 
infected     pre-dose challenge virus, randomized, and having 
(ITT-A) analysis set received at least one dose of IMP, and 
meeting the criterion for laboratory- 
confirmed RSV infection (as per ITT-I) 
while using only assessments prior to 
taking IMP. The ITT-A analysis set will 
be   considered   a   secondary   analysis 
population for efficacy endpoints. ITT-A 
will be a subset of ITT-I. 
Intent-to-treat 
All     participants     having     received 
infected   post-dose challenge virus, randomized, and having 
(ITT-B) analysis set received at least one dose of IMP, and 
meeting the criterion for laboratory- 
confirmed RSV infection (as per ITT-I) 
while using only assessments after taking 
IMP.  The  ITT-B  analysis  set  will  be 
considered     a     secondary     analysis 
population for efficacy endpoints. ITT-B 
will be a subset of ITT-I. 
Per   protocol   (PP) 
analysis set 
All ITT-I analysis set participants who 
have no major protocol deviations, and 
who complete the quarantine period up to 
the final day of quarantine and receive all 
doses of IMP. Participant exclusions will 
be determined at a blinded data review 
meeting (BDRM), which will take place 
prior to database lock. The PP analysis set 
will   be   considered   a   secondary 
analysis     population     for     efficacy 
endpoints. 
Safety analysis set 
All     participants     having     received 
challenge  virus,  regardless  of  whether 
they received IMP or not. 
Pharmacokinetics 
All ITT analysis set participants with at 
least one post-dose PK result. The PK 
analyses will be performed on the PK 
analysis set. 
(PK) analysis set 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
The study being exploratory by nature, aiming at assessing the true 
biological effect of the IMP used in the best experimental 
conditions and not the effectiveness of the strategy to treat 
participants with the IMP in conditions closest to real life, the 
primary efficacy analysis will be on the ITT-I analysis set. The 
ITT-A, ITT-B, and PP analysis sets will be considered a secondary 
analysis population for efficacy endpoints, as defined in the SAP. 
The safety evaluation will be performed on the safety analysis set. 
Additional analysis sets may be defined in the SAP.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                                                                                                                               Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                                                                                                                          Version: Final v2.0, 25-Mar-2024 
 
 
1.1. Study Schematic: On-study Participant Progression 
 
 
 
Clinic                                                                             Quarantine                                                                                        Clinic 
 
 
 
 
 
 
Generic 
Screening 
Viral 
Challenge 
Quarantine 
Inpatient stay 
 
Quarantine 
Discharge 
 
Follow-up Visit
 
 
 
 
 
 
Day -90 to -2/-1 
Day -2/-1 
Day 0 
Days 1 to 11 
Day 12 
Day 28
 
Serology 
General practitioner 
letters 
Generic 
screening 
consent 
Medical history 
Assessments 
Check in 
Study consent 
Eligibility confirmation 
Initial assessments 
Inoculation with 
challenge virus 
Assessments 
Symptoms 
Virology 
Assessments 
Symptoms 
Randomization 
IMP administration 
triggered post 
inoculation (once 
daily [QD] for 5 days) 
Assessments 
Depart quarantine 
unit 
Final assessments 
(Day 28 (±3 days)

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                                                                                                                               Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                                                                                                                          Version: Final v2.0, 25-Mar-2024 
 
NOTES: 
 
• Screening assessments (including repeats, as required) may be performed up to Day -1 at the discretion of the Pl/investigator and in 
accordance with the design of the study. 
 
• Discharge from quarantine is foreseen at Day 12 if the participant has no clinically significant symptoms. The detection of virus by 
respiratory syncytial virus (RSV) discharge test (e.g., qualitative rapid viral antigen test [RVAT]) will be performed at PI/investigator’s 
discretion. If the participant continues to have clinically significant symptoms, additional extended quarantine stay may be required based 
on the assessment of the PI/investigator. If the participant decides to leave against medical advice, the participant will be discharged as per 
hVIVO standard operating procedures (SOPs), with consideration to include appropriate personal protective equipment, transport, and 
instructions on contact with vulnerable individuals. The participant will be advised to refer himself/herself to their general practitioner (GP) 
if they need treatment following discharge. If clinically indicated, the PI or delegated study physician will schedule follow-up calls with 
the participant every 1 or 2 days until symptoms resolved.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                                                                                                                               Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                                                                                                                          Version: Final v2.0, 25-Mar-2024 
 
1.2. Schedule of Events (SoE) 
 
Study Phase 
Screening*
Inpatient Phase 
Quarantine 
Outpatient 
Phase 
Follow-up 
Early 
Withdrawal
(p) 
Study Day (with respect to 
challenge virus inoculation) 
Day -90 to Day –2/-1 
Admission Day -2/-1 
(o) 
Day -1o 
Day 0 Pre-Challenge 
Day 0 Challenge 
Day 0 Post-Challenge 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8 
Day 9 
Day 10 
Day 11 
Day 12 
Day 28 (±3 days) 
(Final Follow-up 
Post-Challenge 
Written consent (a) 
X 
X 
Eligibility criteria (b) 
X 
X 
X 
Medical & medication history 
X 
X 
Demographics 
X 
Height & weight, body mass 
index (BMI) (c) 
X 
X 
(X) 
(X) 
(X) 
Patient Health Questionnaire 
(PHQ-9) 
(X) 
(X) 
Generalized Anxiety Disorder 
Questionnaire (GAD-7) 
(X) 
(X) 
Alcohol breath test 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
Urine drugs of misuse and cotinine 
screen 
X 
X 
X 
Urine pregnancy test (female 
participants of childbearing potential) 
X 
X 
X 
X 
Spirometry 
X 
12-lead electrocardiogram (ECG) 
X 
X 
X 
X 
X 
X 
Complete physical examination 
X 
X 
X 
X 
X 
Symptom-directed physical 
examination (including nasal) 
(X) (X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Study Phase 
Screening*
Inpatient Phase 
Quarantine 
Outpatient 
Phase 
Follow-up 
Early 
Withdrawal
(p) 
Study Day (with respect to 
challenge virus inoculation) 
Day -90 to Day –2/-1 
Admission Day -2/-1 
(o) 
Day -1o 
Day 0 Pre-Challenge 
Day 0 Challenge 
Day 0 Post-Challenge 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8 
Day 9 
Day 10 
Day 11 
Day 12 
Day 28 (±3 days) 
(Final Follow-up 
Post-Challenge 
Vital signs (heart rate [HR], 
respiratory rate [RR], systolic and 
diastolic blood pressure [BP], 
peripheral arterial oxygen saturation 
[SpO2]), temperature 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
hVIVO Symptom diary card 
(SDC) (e) 
X 
3X 
3X 
3X 3X 
3X 
3X 
3X 
3X 3X 
3X 
3X 
3X 
3X 
X 
Respiratory Infection Intensity 
and Impact Questionnaire 
[RiiQ]) (e) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
24-hour tissue count & nasal 
discharge weight (f) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
(X) 
Product Administration 
Randomization (g) 
(X) 
(X) 
(X) 
(X) 
Investigational medicinal 
product (IMP) (EDP-323 or 
placebo) dosing (m) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Challenge virus inoculation 
X 
Collection of Blood Samples 
Serum follicle-stimulating hormone 
(FSH) (postmenopausal women) 
X 
Serum beta-human chorionic 
gonadotrophin (β-HCG) pregnancy 
test (all female participants) 
X 
Human immunodeficiency (HIV), 
hepatitis B & C serology 
X 
Hematology (i) 
X 
X 
X 
X 
X 
(X) 
X 
X 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Study Phase 
Screening*
Inpatient Phase 
Quarantine 
Outpatient 
Phase 
Follow-up 
Early 
Withdrawal
(p) 
Study Day (with respect to 
challenge virus inoculation) 
Day -90 to Day –2/-1 
Admission Day -2/-1 
(o) 
Day -1o 
Day 0 Pre-Challenge 
Day 0 Challenge 
Day 0 Post-Challenge 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day 8 
Day 9 
Day 10 
Day 11 
Day 12 
Day 28 (±3 days) 
(Final Follow-up 
Post-Challenge 
Biochemistry (i) 
X 
X 
X 
X 
X 
(X) 
X 
X 
Coagulation (i) 
X 
Cardiac enzymes 
X 
X 
X 
X 
Thyroid function test 
X 
Blood serum for humoral 
immunity (j) 
X 
X 
X 
(X) 
Blood – Pharmacokinetics (PK) (d) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Blood – Proteomics (exploratory) 
X 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Collection of Respiratory Samples 
Nasopharyngeal swab - Respiratory 
pathogen screen (k) 
X 
Nasopharyngeal swab - Respiratory 
syncytial virus (RSV) discharge test 
(h) 
(X) 
(X) 
Nasal sampling – Virology 
(polymerase chain reaction [PCR] & 
culture) (e, l) 
X 
2X 
2X 
2X 
2X 
2X 
2X 
2X 
2X 
2X 
2X 
X 
qualitative integrative cycler (qic) 
PCR assay for triggered dosing** 
2X 
2X 
2X 
X 
Safety Assessments
Adverse Events (AEs) (n) 
X 
Concomitant medications (n) 
X 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
KEY NOTES FOR SCHEDULE OF EVENTS 
 
(X) 
The assessment may be optional, or at the discretion of the principal investigator (PI)/investigator. 
X 
Once daily, assessments conducted once during the 24-hour period. 
2X 
Twice daily, assessments conducted twice during the 24-hour period. 
3X 
Three times daily, assessments conducted 3 times during the 24-hour period. 
* 
Results of tests or examinations performed under hVIVO generic screening process may be used to determine eligibility without 
the need to repeat all assessment prior to inoculation with challenge agent. Hepatitis and HIV serology should be repeated on the 
first study day if outside of 56-days window. Screening assessments (including repeats, as required), may be performed up to 
Day -1 at the discretion of the PI/investigator and in accordance with the design of the study. 
** 
Assay to stop once a positive RSV result is obtained. 
a 
Study-specific consent may occur on the day of admission to the quarantine unit, providing all required eligibility information has 
been collected through the Health Research Authority approved hVIVO generic screening process. 
b 
Only the applicable inclusion/exclusion criteria will be reviewed at each time point. 
c 
Height will be measured at screening only. 
d 
Blood -Proteomics (Exploratory) 
Time points (hours) for pharmacokinetic (PK) sampling (in blood samples) are as follows: Dose 1: pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 
8, 10, 12, 15 hours post-dose; Dose 2: pre-dose; Dose 3: pre-dose; Dose 4: pre-dose; Dose 5: pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 
12, 15, 24, 30, 36, 48, 60, 72 hours post-dose 
The allowable time windows for the sampling are as follows: 
•    ± 5 minutes from the scheduled time for time points ≤ 2 hours from dosing 
•    ± 15 minutes from the scheduled time for time points > 2 hours to ≤ 24 from dosing 
•    ± 60 minutes from the scheduled time for time points > 24 hours to ≤ 48 from dosing 
•    ± 2 hours from the scheduled time for time points > 48 hours from dosing 
There is no time window requirement for the pre-dose sample. The pre-dose sample must be taken prior to dose. 
Between Day 2 and Day 12 Proteomic (exploratory) blood samples will be collected after a PK sample at the following timepoints: 
Pre each Dose: (Dose 1 through to Dose 5) and post Dose 5 at 24, 48 and 72 hrs. 
e 
After the baseline has been set, assessments will be performed at the same time each day (±1 hour from baseline) during quarantine. 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
• Symptom diary card (SDC) baseline: The assessment(s) on Day -1 are considered as the baselines for the subsequent timing 
windows (assessments on Day -1 will be performed approximately 8 hours [±1 hour] apart). 
• Respiratory Infection Intensity and Impact Questionnaire (RiiQ) baseline: The assessment on Day -1 are considered as the 
baselines for the subsequent timing windows. Assessments will be performed once daily at the same time each day (± 1 
hour from baseline) during quarantine. 
•    Nasal sample baseline: The AM and PM samples on Day 2 are considered as the baselines for the subsequent AM or PM 
timing windows (assessments on Day 2 will be performed approximately 12 hours [±1 hour] apart). 
The above baseline requirements are based on an admission on Day -2, if participants are admitted to quarantine on Day -1, 
appropriate Day 0 time points may be used for baseline timings. 
f 
Distribution of paper tissues and collection bags will start in the morning on Day -1, with the first collection on Day 0. Thereafter, 
distribution and collection of tissues will occur daily, at the same time point (±1 hour) in the morning, with tissues distributed 
24 hours ahead, until discharge from quarantine. 
g 
Randomization will take place prior to the first IMP dosing on the day of the first IMP dosing. 
h 
Viral discharge test (e.g., antigen test) is performed as required by the PI. 
i 
Blood will be drawn under non-fasted conditions. Repeat bloods may be drawn under fasted conditions if a lipid profile 
(triglyceride) or glucose is required (at the PI’s discretion). 
j 
Blood serum humoral markers assumes assays specific to the viral challenge agent (i.e., neutralization assay). Serosuitability will 
be determined from sample collected within 90 days before challenge virus inoculation. 
k 
Upper respiratory tract (URT) swab (e.g., nasopharyngeal swab) for respiratory virus screen to assess for the presence of 
respiratory pathogens; if found positive for any pathogen in the panel, the participant will not be eligible for the current quarantine. 
l 
Post inoculation nasal wash virology samples will be collected and used for quantitative reverse transcription-polymerase chain 
reaction (qRT-PCR) and viral culture assay (as appropriate). Samples collected between the morning of Day 2 and the morning of 
Day 5 will also be used for qualitative integrative cycler (qic) PCR until a positive result is received (to support triggered dosing). 
Samples may be used for related viral genomics and exploratory research. 
m 
IMP administration will be initiated (triggered) by a positive RSV result (measured by qicPCR) between Day 2 and Day 5 AM 
(nasal sampling twice daily, morning and evening; on Day 5 only in the morning). Dosing will start approximately 12 hours 
(±1 hour) after first detection of RSV. If no positive RSV result is obtained, dosing will start in the evening of Day 5. 
Duration of treatment with EDP-323 (or placebo) will be 5 days (once daily [QD], approximately 24 hours [±1 hour] apart), with 
the start day dependent on RSV result. 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
n 
Adverse events (AEs) and concomitant medications are reviewed throughout the study. 
o 
Assessments performed on Day -2 may be performed on Day -1. For example, participants may be admitted to the quarantine unit 
on Day -2 or Day -1. If admitted on Day -1, Day -2 assessments will be performed on Day -1, as appropriate. 
p 
If some of the assessments required as part of the early withdrawal visit have already been performed as per the daily SoE, the 
completed assessments will not be repeated on the same day as part of early withdrawal visit, unless clinically indicated. 
Notes: 
•    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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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
GENOMIC, TRANSCRIPTOMIC, AND PROTEOMIC SAMPLES 
Deoxyribonucleic acid (DNA) sample 
collection: 
Yes 
☐ 
No 
☒ 
Ribonucleic acid (RNA) sample collection 
Yes 
☐ 
No 
☒ 
Proteomic sample collection 
Yes 
☒ 
No 
☐ 
Consent considerations: 
Genetic consent. 
Future use samples for exploratory research: a blood sample (up to 10 mL), nasal wicks, and 
nasal swabs for further exploratory “omics” analysis relevant to the main objectives of the 
study, but yet to be defined. 
Future use of remaining samples for new ethically approved health research and laboratory 
testing protocols, according to the local laws. 

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
 
2.            INTRODUCTION 
 
EDP-323 is a novel orally administered inhibitor of the L protein of respiratory syncytial virus 
(RSV). EDP-323 is being developed as a potential treatment for RSV infection. 
 
2.1.            Background 
 
Respiratory syncytial virus is the most common cause of acute lower respiratory infection 
(ALRI) in infants and children (Bont et al, 2016; Hall et al, 2009; Nair et al, 2010). Globally, 
it was estimated in 2005 that RSV caused 33.8 million episodes of ALRI (~22% of all ALRI) 
and 3.4 million episodes of severe ALRI requiring hospitalization among children <5 years old 
worldwide (Nair et al, 2010). Mortality from RSV infection is significant, with an estimated 
66,000 to 199,000 childhood deaths in 2005 worldwide (Nair et al, 2010). The overwhelming 
majority of these deaths occur in children below the age of 2 years and in developing countries 
(Bont et al, 2016; Nair et al, 2010). The most recent estimates of global RSV disease burden 
showed that, in 2015, there were no substantial changes in the number of new episodes of RSV- 
ALRI and related hospital admissions compared to 2005, but a lower number of in-hospital 
deaths (Shi et al, 2015). Moreover, for children younger than 6 months, Shi et al reported about 
1.4 million hospital admissions and 27,300 in-hospital deaths due to RSV-ALRI in 2015 
worldwide (Shi et al, 2015). 
 
It should be noted that RSV is also increasingly being recognized as a significant cause of 
morbidity and mortality in older adults and those with underlying chronic cardiopulmonary 
disorders (Agius et al, 1990; Falsey et al, 1995). The risk of severe RSV disease is higher in the 
frail elderly and those with co-morbidities, including congestive heart failure, stroke, chronic 
kidney disease, chronic obstructive pulmonary disease, and immunosuppression. In the United 
States, RSV illness in adults >65 years old ranges from 3% to 7% annually, resulting in 
approximately 177,000 hospitalizations and 14,000 deaths. 
 
The RSV human challenge model was developed to not only aid understanding of RSV disease, 
but to also assess the efficacy of RSV antivirals, immunomodulators, and vaccines. The RSV- 
A Memphis 37b challenge strain has been used for over 15 years by both hVIVO and others 
and has helped assess the efficacy of numerous RSV therapies (as reviewed by DeVincenzo et 
al, 2020; DeVincenzo et al, 2022; Lambkin-Williams et al, 2018; Stevens et al, 2018) and 
vaccines (Bavarian Nordic 2021; Pfizer 2021; Sadoff et al, 2022). Specifically, hVIVO have 
safely and successfully used the RSV challenge strain in over 1,700 healthy participants (18 to 
60 years of age) including the inoculation of 24 participants between 60 and 75 years of age. 
Additionally, another clone of the same strain of live RSV (Memphis 37c) has been used as an 
inoculation agent and was shown to be safe in over 77 healthy young adults across 3 studies. 
Healthy RSV challenge study participants have approximately 65% to 85% chance of becoming 
infected with RSV following the administration of the virus (DeVincenzo et al, 
2010). Typical RSV illness is characterized by an abrupt onset of rhinitis, nasal stuffiness, 
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. 
Respiratory syncytial virus, like many viruses, can cause more substantial health issues such 
as myocarditis (inflammation or damage to the heart muscle). Adults and children present with 
RSV-related myocarditis rarely, with symptomless occurrences likely going undiagnosed in the 
community.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
2.2.            Information about EDP-323 
 
2.2.1.         Product Description 
 
EDP-323 is a potent and selective non-nucleoside inhibitor of the large protein (L protein) of 
RSV. 
 
 
 
 
 
2.2.2.         Nonclinical Studies 
 
2.2.2.1.      Drug Metabolism and Pharmacokinetics 
 
Nonclinical studies have been conducted to characterize the pharmacokinetics (PK) of EDP- 
323 in CD-1 mice, Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys following a 
single intravenous and/or oral dose. In addition, multiple-dose oral PK studies were conducted 
in mice and monkeys. The mouse and the monkey were selected as the primary toxicology 
species to evaluate the safety of EDP-323. 
 
 
 Based on the outcome of the absorption studies, EDP-323 is projected to 
have good oral absorption in humans. 
 
 
 
 
 
EDP-323 was shown to be stable in human liver microsomes, human hepatocytes, human 
intestinal S9, and human plasma
 No unique human 
metabolites have been observed to date. 
 
2.2.2.2.      Safety Pharmacology and Toxicology 
 
Safety pharmacology studies demonstrated that EDP-323 was safe for respiratory, 
cardiovascular, and nervous systems at the studied doses. 
 
 
 
 
 
 
EDP-323 was negative for mutagenicity in the in vitro Ames assay. EDP-323 was negative for 
clastogenicity in the in vivo bone marrow micronucleus assay 
. However, a positive response was observed in the long-term exposure -S9

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
condition in the GLP in vitro micronucleus assay (negative in the short-term exposures +/- S9). 
Thus, consistent with the International Council for Harmonisation (ICH) S2 (R1) (2011) weight 
of evidence approach, a second in vivo (comet) assay was conducted; EDP-323 was negative 
in CD 1 mice for DNA damage when dosed to the limit of the assay 
. 
 
Refer to the EDP-323 Investigator’s Brochure (IB) for further details of referenced nonclinical 
studies (IB, 2024). 
 
2.2.3.         Clinical Studies 
 
EDP-323 was evaluated in a Phase 1, randomized, double-blind, placebo-controlled, first-in- 
human (FIH) study in which the safety, tolerability, and PK was assessed in healthy adult 
subjects. The Phase 1 study included a single ascending dose (SAD) phase enrolling a total of 
6 dose cohorts 
 of which, one was a 2-part food effect (FE) 
cohort, and a multiple ascending dose (MAD) phase enrolling 4 dose cohorts 
 
. All SAD and MAD cohorts enrolled 8 participants who were 
randomized to receive EDP-323 or placebo in a 3:1 ratio. The 
 SAD/FE cohort enrolled 
10 subjects randomized in a 4:1 ratio. 
 
As of October 2023 unblinded safety and PK data for all SAD and MAD cohorts are available. 
Overall, no safety concerns were reported in the 
 healthy subjects dosed orally with EDP- 
323 or placebo as single or multiple doses. EDP-323 was generally well tolerated at single doses 
 with 2 subjects reporting a total of 4 treatment-emergent adverse events (TEAEs). 
Of the 4 TEAEs reported during the SAD phase, 
 
 all were deemed not related or unlikely related to the study drug. One subject in the SAD/FE 
 cohort discontinued due to an TEAE of syncope (moderate; unlikely related to study 
drug). EDP-323/placebo was also well tolerated at multiple doses 
 for 7 days. 
Ten subjects reported a total of 13 TEAEs. 
 
 Ten of the 13 TEAEs were deemed unlikely 
or  not  related  to  EDP-323/placebo.  Of  the  3  TEAEs  deemed  possibly  related  to  EDP- 
323/placebo, all were mild, with 2 headaches and 1 gastrointestinal (frequent stools) events. 
There were no discontinuations due to adverse events (AEs) in the MAD. In both the SAD and 
MAD phases, there were no serious AEs, serious adverse events (SAEs), clinically significant 
abnormal laboratory findings, vital signs, electrocardiograms (ECGs), or physical exam 
findings. 
 
Based on preliminary PK data, EDP-323 was rapidly absorbed 
 
following single and multiple dosing. 
EDP-323 exposure increased with increasing single and multiple dosing 
 with 
accumulation at Day 7 following QD multiple doses 
 
 No food effect was 
observed with a high fat meal during the 
 SAD FE cohort. 
 
 
In Summary: 
 
• 
EDP-323 was well tolerated and generally safe over a broad range of single doses 
 and multiple doses 
 QD for 7 days. 
 
• 
EDP-323  exhibited  PK  characteristics  supporting  QD  dosing  and  can  be 
administered without regard to food. 
 
These results support further clinical evaluation of EDP-323 in patients with RSV.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
For a detailed description of available clinical data, please refer to the EDP-323 IB (IB, 2024). 
 
2.3. Study Rationale 
 
The purpose of this Phase 2a study is to evaluate the safety, PK, and antiviral activity of multiple 
doses of orally administered EDP-323, compared to placebo, in a healthy adult participants 
inoculated with RSV-A Memphis 37b. 
 
The RSV-A Memphis 37b challenge strain has been used for over 15 years by both hVIVO 
and others and has helped assess numerous RSV therapies. Specifically, hVIVO have safely 
and  successfully  used  the  RSV-A  Memphis  37b  challenge  strain  in  over  1,700 healthy 
participants (18 to 60 years of age)], including the inoculation of 24 participants between 60 
and 75 years of age. 
 
2.4. Benefit/Risk Assessment 
 
Healthy participants will not benefit from this clinical study. The study is designed to provide 
information about the antiviral effect, PK, and safety/ tolerability of EDP-323. Results from 
this clinical study will be useful in developing a new antiviral therapy for RSV. 
 
Information about the known and expected benefits and risks and reasonably expected AEs of 
EDP-323 are highlighted in Section 2.2.3, Clinical Studies, and additional details may be found 
in the IB (IB, 2024). 
 
2.4.1.         Risk Assessment 
 
The known risks to participants are detailed below. However, there may also be risks that are 
unforeseen and unanticipated (e.g., unknown allergies). Every effort will be made to monitor 
the health of the participants to ensure that such risks are minimized. Trained medical staff and 
appropriate facilities will be available to provide medical emergency care.

 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
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Potential Risk of 
Description of Risk 
Mitigation Strategy 
Clinical Significance 
Study Intervention 
Oral administration of 
1. During FIH study EDP 323-001, EDP-323 was well 1.   Participant safety data will be monitored throughout 
the study, including but not limited to physical exams, 
vital signs, 12-lead ECG, and clinical laboratory 
results. 
2.   Participants will be monitored for severe RSV-related 
disease throughout the study and managed accordingly 
with supportive measures and may be withdrawn from 
the study at the investigator’s discretion at any time. 
EDP-323 capsules 
tolerated at single and multiple doses 
 
(QD). No safety concerns were identified. In both the 
SAD and MAD phases, there were no serious AEs, 
SAEs,   clinically   significant   abnormal   laboratory 
2. 
findings, vital signs, ECGs, or physical exam findings 
(see Section 2.2.3, Clinical Studies). 
EDP-323 has not previously been tested  in human 
subjects with RSV and may not confer any antiviral 
protection against RSV in humans despite encouraging 
preclinical evidence. 
Oral administration of Given  that  the  placebo  is  a  pharmacologically  inert 
material, there should be no risk. 
Not applicable. 
placebo capsules 
Study Procedures 
Intravenous catheter 
The primary risks of the placement of an  intravenous 
catheter include local discomfort, occasional bleeding or 
bruising of the skin at the site of the needle puncture, 
hematoma, and rarely, infection or fainting. 
The participant will be closely monitored and asked about 
these symptoms before being allowed to stand up. 
Blood sampling 
Pain or bruising at the site where blood is drawn. 
Blood samples will be obtained by a trained professional. 
Syncope (fainting) can occur following or even before any 
blood draw as a psychogenic response to the needle 
insertion. 
Blood samples will be obtained by a trained professional 
and procedures will be put in place to avoid injury from 
fainting. 

 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
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Potential Risk of 
Description of Risk 
Mitigation Strategy 
Clinical Significance 
There is a possibility that in the process of collecting blood 
a nerve may be injured. 
Procedure to be performed by qualified study staff. 
Blood tests performed to address the health of the 
participants at screening and during the study may indicate 
that a participant has an infection that he/she was not 
previously aware of (e.g., human immunodeficiency virus 
[HIV] or hepatitis) or an unexpected illness. 
If the infection is clinically significant and affects the 
participant psychologically or physically, this will be 
discussed with the participant and advice will be given 
accordingly.   The   hVIVO   doctor   will   provide   the 
participant’s general practitioner (GP), or doctor, with a 
referral letter if the participant agrees. 
Nasal sampling 
Collection    of    respiratory    (nasal)    samples    (e.g., Sample collection will be performed by appropriately 
qualified and trained study staff to minimize the 
discomfort 
nasopharyngeal swabs) may cause discomfort, sneezing, 
watery eyes, irritated nose, or nose bleeding. 
RSV Infection from Inoculation 
RSV     infection 
& 65% to 85% chance of becoming infected with RSV-A 
Memphis 37b. Typical RSV illness: abrupt onset of 
rhinitis, nasal stuffiness, fever, malaise, myalgia (muscle 
aches), and sore throat. 
Severe RSV infections are known to occur in both infants 
and adults. In adult populations, multiple factors but not 
older age, are independently associated with severe RSV 
complications including persons of any age with chronic 
co-morbidities and significant immune compromise. 
RSV, like many viruses, can cause more substantial health 
issues such as myocarditis (inflammation or damage to the 
heart muscle). Adults and children present with RSV- 
The safety profile of the RSV-A Memphis 37b is well 
characterized in healthy adults as this has been used for 
over   15   years   by   hVIVO.   At   hVIVO   more   than 
1,700 healthy  adults  aged  18  to  60  years  have  been 
challenged with the RSV challenge strain. 
RSV infection in healthy adults usually resolves without 
treatment within 7 to 10 days. 
Strict inclusion and exclusion criteria will apply to ensure 
only healthy adults are enrolled in this study. 
There will be a daily medical monitoring in a quarantine 
unit for at least 12 days post-human viral challenge. 
severe complications

 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
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Potential Risk of 
Description of Risk 
Mitigation Strategy 
Clinical Significance 
related myocarditis rarely, with symptomless occurrences 
likely going undiagnosed in the community. Within our 
RSV viral challenge studies, of over 1,700 participants 
who have received the challenge virus to date, the 
occurrence of myocarditis is uncommon. None of these 
participants reported any symptoms due to myocarditis 
and, where follow-up was completed, the diagnostic tests 
related to the follow-up returned to normal without 
treatment. 
Qualified medical and nursing staff in the quarantine unit 
will monitor for and manage any symptoms. 
Participants will be closely followed up while being in 
quarantine. Electrocardiograms will be performed and 
cardiac enzymes will be tested post-viral challenge. 
Transient increase in alanine aminotransferase (ALT) or ALT and AST will be monitored. 
aspartate    aminotransferase    (AST)    without    clinical 
presentation, with a good prognosis upon improvement of 
infection. 
Transmission of RSV RSV presence in nasal secretions can cause infection in 
close contacts. 
The duration of the quarantine has been designed to allow 
to  participants’  close 
for  resolution  of  infectious  virus  (culturable)  before 
contacts 
discharge. This is based on experience to date with more 
than  1,700 inoculations.  As  appropriate,  the  principal 
investigator (PI)/delegate may request additional testing of 
nasal swab samples using a qualitative virus antigen test 
or   polymerase   chain   reaction   (PCR)   to   assist   in 
determining participants’ suitability for departure. 
As an additional precaution, participants will be instructed 
to avoid close contact with vulnerable individuals as 
described  in  Section 2.4.1.1,  Vulnerable  Persons,  for 
2 weeks after they leave the quarantine unit. 

 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
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Potential Risk of 
Clinical Significance 
Description of Risk 
Mitigation Strategy 
Risk of reactivation of 
herpes infection 
If a participant ever had a herpes infection (e.g., cold sores, 
genital herpes, or shingles) there is a small possibility that 
this infection could return after viral challenge. 
Participants will be instructed to inform the study staff if 
they currently have an active herpes infection or have had 
one during the 30 days before enrolment. 
If a participant develops any cold sore, herpes, or shingles 
they may be treated symptomatically while at the 
quarantine unit. If it continues, they will be followed up 
until resolved or, if necessary and dependent on medical 
history, will be referred to their GP or any specific 
department at hospital, as required. 
Lower infection rate / 
disease than assumed 
If a lower number of participants become infected than 
expected there is a risk the study could be underpowered 
to detect a difference between placebo and EDP-323. 
A designated, blinded team may be employed to monitor 
the infection rate while the study is ongoing to assess if 
additional participants are needed to be enrolled. If 
performed, the recommendation of the infection rate 
monitoring will be reviewed by the sponsor and 
investigator to consider if additional participants are 
needed to be enrolled. 
Consult the Investigator’s Brochure (IB) for detailed information on EDP-323 (IB, 2024) 

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
 
2.4.1.1.      Vulnerable Persons 
 
For the purposes of possible contact after leaving the quarantine unit, the participant should 
avoid close contact with vulnerable individuals for 2 weeks after they leave the quarantine unit. 
A vulnerable individual is a person including but not limited to: 
 
•    Persons ≥65 years of age. 
 
•    Children ≤2 years of age. 
 
•    Residents of nursing homes. 
 
•    Women who are pregnant or who are trying to become pregnant. 
 
•    Persons of any age with significant chronic medical conditions such as: 
 
o Chronic  pulmonary  disease  (e.g.,  severe  asthma,  chronic  obstructive  pulmonary 
disease). 
 
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, haemoglobinopathies). 
 
o Immunosuppression or cancer. 
 
o Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, 
seizures). 
 
2.4.1.2.      Risk Associated With Coronavirus Disease 2019 Pandemic 
 
hVIVO  has  implemented  enhanced  infection  control  measures  during  the  pandemic  to 
minimize risks of coronavirus disease 2019 (COVID-19) infection. 
 
Risk of Increased Severity of COVID-19 Infection if Contracted After Challenge Agent 
Inoculation: 
 
It has not been established that severity of COVID-19 infection could increase if contracted 
after inoculation with RSV-A Memphis 37b. 
 
Participants will be tested for respiratory pathogens, including COVID-19, upon their arrival 
at the quarantine unit. They will be advised on protective measures and will need to follow 
infection control regimens. 
 
Risk   of   Increased   Severity   of   COVID-19   Infection   After   Study   Intervention 
Administration: 
 
There is no evidence that severity of COVID-19 infection would increase if contracted after 
EDP-323 administration. 
 
All participants will be instructed to follow United Kingdom (UK) Government COVID-19 
guidelines and will be provided with personal protective equipment while resident in the 
quarantine unit. 
 
COVID-19-related emerging data will be monitored on an ongoing basis.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
2.4.2.         Benefit Assessment 
 
Healthy participants will not receive direct benefit from treatment during their participation in 
this clinical study. 
 
Participants may develop some immunity to RSV-A Memphis 37b virus and benefit from a 
general health check at screening. Benefit may also be derived from the medical evaluations 
and assessments associated with study procedures. In addition, participants are contributing to 
the process of developing new therapies in an area of unmet medical need. 
 
2.4.3.         Overall Benefit/Risk Conclusion 
 
Considering the measures taken to minimize risk to participants in this study, the potential risks 
identified in association with EDP-323 and challenge virus administration are justified by the 
anticipated benefits linked to the evaluation of EDP-323 in a viral challenge model in healthy 
adults, which will subsequently facilitate future development of antiviral RSV therapies.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
3.            OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary: 
Efficacy 
• To    evaluate    the    antiviral 
• Reduction in RSV area under the viral load-time 
activity of EDP-323 compared 
to placebo in healthy adult 
participants inoculated with 
RSV-A Memphis 37b 
curve (VL-AUC) measured by quantitative reverse 
transcription-polymerase   chain   reaction   (qRT- 
PCR) in nasal samples 
Secondary: 
Efficacy 
• To    further    evaluate    the 
• Viral load: 
antiviral activity of EDP-323 
o
RSV viral load by qRT-PCR of nasal samples  
compared    to    placebo    in 
including: 
healthy     adult     participants 
inoculated      with      RSV-A 
•  Reduction    in    RSV    peak    viral    load 
Memphis 37b 
(VLPEAK) 
• To    evaluate    the    clinical 
•  Reduction in time to RSV VLPEAK  after 
disease   severity   in   healthy 
adult  participants  inoculated 
first dosing 
•  Time to RSV viral load negativity after first 
with   RSV-A   Memphis 37b 
dosing 
followed by administration of 
EDP-323 compared to placebo 
•  Time to first negative slope of RSV  viral 
load after first dosing 
•  Slope  of  the  RSV  viral  load  over  time 
(clearance rate) from time of RSV VLPEAK 
to 1, 2, 3, and 4 days later 
o RSV viral load by cell culture (plaque assay) of 
nasal samples, including: 
•  Reduction in RSV VL-AUC 
•  Reduction in RSV VLPEAK 
•  Reduction in time to RSV VLPEAK  after 
first dosing 
•  Time to RSV viral load negativity after first 
dosing 
•  Time to first negative slope of RSV  viral 
load after first dosing 
•  Slope  of  the  RSV  viral  load  over  time 
(clearance rate) from time of RSV VLPEAK 
to 1, 2, 3, and 4 days later 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Objectives 
Endpoints 
•    Clinical symptoms and disease severity: 
o Effect on RSV symptoms using the symptom 
diary card [SDC]), with endpoints including: 
•  Reduction in area under the total symptom 
score (TSS)-time curve (TSS-AUC) 
•  Reduction in peak TSS 
•  Time to return to baseline (last assessment 
before RSV inoculation) TSS 
•  Reduction in time to peak TSS 
o Total   weight   of   nasal   discharge   (mucus) 
produced 
o Total number of tissues used 
Pharmacokinetics 
• To evaluate the PK profile of 
EDP-323 (and metabolites) in 
blood samples in healthy adult 
participants inoculated with 
RSV-A Memphis 37b 
• To         characterize         the 
relationship between plasma 
PK of EDP-323 and VL-AUC 
(qRT-PCR) and TSS-AUC in 
healthy 
adult 
participants 
inoculated 
with 
RSV-A 
Memphis 37b 
• EDP-323 (and metabolites) concentrations and PK 
parameters in blood samples: maximum plasma 
concentration (Cmax), time to maximum plasma 
concentration (tmax), terminal half-life (t1/2), 
apparent systemic clearance (CL/F), terminal 
elimination 
rate 
constant 
(λz), 
volume 
of 
distribution   (Vd/F),   plasma   concentration   at 
12 hours (C12h), plasma concentration at 24 hours 
(C24h), area under the concentration-time curve 
from time 0 to time of last quantifiable 
concentration 
(AUClast), 
area 
under 
the 
concentration-time curve over the dosing interval 
(AUC0-tau), and area under the concentration-time 
curve from time 0 to infinity (AUC0-∞), and other 
parameters as applicable 
• EDP-323 plasma PK (area under the curve [AUC]) 
correlations with VL-AUC (e.g., qRT-PCR) and 
TSS-AUC 
Safety 
•    To evaluate the safety of EDP- 
323 
in 
healthy 
adult 
participants inoculated with 
RSV-A Memphis 37b 
• Occurrence of AEs from initial administration of 
investigational medicinal product (IMP) up to 
discharge 
•    Occurrence of AEs from initial administration of 
IMP up to Day 28 follow-up 
•    Occurrence of SAEs from initial administration of 
IMP up to Day 28 follow-up 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Objectives 
Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Objectives                                         Endpoints 
 
 
 
 

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
4.            STUDY DESIGN 
 
4.1. Overview of Study Design 
 
This is a randomized, Phase 2a, double-blind, placebo-controlled study to evaluate the safety, 
PK, and antiviral activity of multiple doses of orally administered EDP-323 against RSV 
infection in healthy adults after challenge with RSV-A Memphis 37b. 
 
In this study, 2 doses of EDP-323 will be tested: EDP-323 high dose (600 mg QD for 5 days) 
vs low dose (600 mg loading dose for 1 day followed by 200 mg QD for 4 days). The study 
will have a placebo arm. Due to its exploratory nature, no adjustment will be made to the type 1 
error in this proof-of-concept study. 
 
The expected duration of study participation for a participant is up to 4 months, from screening 
to the participant’s last scheduled follow-up visit, with the following sequence and duration of 
study phases: 
 
Screening: 
 
•    Screening prior to inoculation with challenge virus from Day -90 to Day -2/-1. 
 
Results of tests or examinations performed under hVIVO generic screening process may 
be used to determine eligibility without the need to repeat all assessment prior to 
inoculation with challenge agent. Hepatitis and HIV serology should be repeated on the 
first study day if outside of 56-days window. Screening assessments (including repeats, 
as required), may be performed up to Day -1 at the discretion of the PI/investigator and 
in accordance with the design of the study. 
 
Inpatient Phase: 
 
• Participants will be resident in the quarantine unit for approximately 15 days, from 
admission on Day -2/-1 to planned discharge on Day 12. Discharge from quarantine is 
foreseen at Day 12 if the participant has no clinically significant symptoms. The 
detection of virus by RSV discharge test (e.g., qualitative rapid viral antigen test 
[RVAT]) will be performed at investigator’s discretion. If the participant continues to 
have clinically significant symptoms, additional extended quarantine stay may be 
required based on the assessment of the PI/investigator. 
 
Procedures will include: 
 
•    Pre-human Viral Challenge: 
 
o Admission to quarantine unit on Day -2/-1. 
 
o Baseline assessments will be conducted as per SoE up to Day 0, pre-challenge. 
 
•    Human Viral Challenge: 
 
o RSV-A Memphis 37b virus inoculation on Day 0. 
 
•    Post-human Viral Challenge: 
 
o Randomization to receive EDP-323 or matched placebo. 
 
o Administration of IMP (EDP-323 or placebo). IMP administration will be initiated 
(triggered) by a positive RSV result (measured by qualitative integrative cycler [qic] 
PCR) between Day 2 and Day 5 AM (nasal sampling twice daily, morning and 
evening; on Day 5 only in the morning).

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Dosing will start approximately 12 hours after first detection of RSV. If no positive 
RSV result is obtained, dosing will start in the evening of Day 5. Duration of 
treatment with EDP-323 (or placebo) will be 5 days (QD) in the period from Days 2 
to 9, with the start day dependent on RSV result. 
 
o Day 1 onwards and each day – study assessments will be conducted as per SoE. 
 
o Discharge from quarantine is planned on Day 12 post inoculation. 
Outpatient Phase: 
 
•    Follow-up visit: Day 28 (±3 days) 
 
*Following challenge agent inoculation, participants will be closely observed for 24 hours, 
specifically for potential allergic reactions and any AEs. Post inoculation, participants will lie 
flat for 10 minutes, then sit up with nose pegs on for 20 minutes. Participants will continue to 
be monitored throughout the clinical phase of the study. 
 
The Study Schematic, showing participant progression through the study, is presented in 
Section 1.1, Study Schematic. The SoE is presented in Section 1.2, Schedule of Events. 
 
4.2. Scientific Rationale for Study Design 
 
The study will be conducted by hVIVO Services Limited, which has extensive experience with 
RSV challenge studies. Numerous studies have been performed using experimental RSV 
infection in human participants. To date, in hVIVO’s studies, over 1,700 participants have been 
successfully and safely inoculated with RSV-A Memphis 37b. These studies demonstrated that 
adults could be infected by nasal inoculation and that experimental infection was safe. This 
RSV strain has been shown to cause symptoms and virus shedding that closely match natural 
infection. 
 
Administration of IMP and challenge with RSV-A Memphis 37b will take place in hVIVO’s 
specialized clinical facilities in a quarantine 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. 
 
Blinding, Control, and Randomization 
 
The placebo control will be used to establish the frequency and magnitude of changes in 
endpoints that may occur in the absence of active treatment. It will allow a comparative 
evaluation of the efficacy of EDP-323. 
 
Randomization will be used to prevent bias in the assignment of participants to treatment groups 
(EDP-323 or placebo), to increase the likelihood that known and unknown participant 
characteristics (e.g., demographic and baseline characteristics) are equally balanced across 
treatment groups, and to enhance the validity of statistical comparisons across treatment groups. 
 
Blinding will prevent the occurrence of conscious and unconscious bias in the conduct and 
interpretation of the study. 
 
Together, the placebo-controlled, randomized, and blinded features of the study will allow a 
causal interpretation of the study results. 
 
4.3. Justification for Dose 
 
EDP-323 will be administered orally. The doses selected for the study are as follows: 
 
•    High dose: 600 mg EDP-323 QD for 5 days

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
•    Low dose: 600 mg EDP-323 (loading dose) for 1 day, followed by 200 mg EDP-323 
QD for 4 days 
 
These doses are expected to provide exposures in the anticipated therapeutic range. In the 
 EDP 323-001, EDP-323 exposure increased with increasing dose 
 
 in both the SAD and MAD phase. Single EDP-323 doses 
 
were safe and well tolerated (Section 2.2.3, Clinical Studies). Based on preliminary PK
 systemic  exposures  
 
 
 supporting QD dosing. In the MAD 
phase, where EDP-323 was administered QD for 7 days, doses 
 
were safe and well tolerated (Section 2.2.3, Clinical Studies). Available PK data from multiple- 
dose cohorts indicate that there was accumulation at Day 7 
 
 following daily dosing for 7 days, 
 
 
 
 
 
Based on in vitro testing, a protein adjusted 90% effective concentration (EC90) value for EDP- 
323 
 was determined using primary human airway epithelial cells 
grown at an air liquid interface (3D pHAEC-ALI). 
 
 
 
 
 
 based on exposures from the FIH study, these doses are expected to provide mean 
exposures approximately 33-fold over the free drug EC90  in 3D pHAEC-ALI 24 hours after 
Day 1 for both dose levels, and 44-fold and 11-fold after dosing on Day 5 at the high and low 
dose, respectively. 
 
4.4. End-of-Study Definition 
 
A participant is considered to have completed the study if he/she has completed all phases of 
the study including the last scheduled visit or the last unscheduled visit, as applicable. If a safety 
visit is required after the last scheduled visit, this will be at the discretion of the PI/investigator 
as a duty of care, e.g., repeat spirometry or laboratory tests. These discretionary follow-up visits 
will not be considered part of the study data unless they represent follow-up and closure on an 
AE or SAE identified during the study period. 
 
The end of the study is defined as the date of the last visit of the last participant in the study.

Page  46 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
5.            STUDY POPULATION 
 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also known 
as protocol waivers or exemptions, is not permitted. 
 
5.1.  Inclusion Criteria 
 
Participants are eligible to be included in the study only if all the following criteria apply: 
 
No. 
hVIVO APPROVED STANDARD INCLUSION CRITERIA 
Final v5.0_19OCT2022 (Viral Challenge Volunteer Studies) 
To be eligible for the study, participants must meet all the following inclusion criteria: 
1 
Written informed consent signed and dated by the participant and the Investigator 
obtained before any assessment is performed 
2 
Aged between 18 and 55 years on the day prior to signing the consent form. 
3 
A total body weight ≥50 kg and body mass index (BMI) ≥18 kg/m2 and ≤35 kg/m2. 
4 
In good  health with no  history, or current evidence, of clinically significant 
medical conditions, and no clinically significant test abnormalities that will 
interfere with participant safety, as defined by medical history, physical 
examination, (including vital signs), ECG, and routine laboratory tests as 
determined by the Investigator. 
5 
Participants will have a documented medical history either prior to entering the 
study or following medical history review with the study physician at screening. 
6 
The following criteria are applicable to female participants participating in the 
study: 
a)  Females of childbearing potential must have a negative pregnancy test prior 
to enrolment. 
b)  Females of non-childbearing potential: 
i. 
Postmenopausal females defined as amenorrhea for 12 months or 
greater with no alternative medical cause. A high follicle- 
stimulating 
hormone 
(FSH) 
level, 
within 
appropriate 
postmenopausal range, may be used to confirm postmenopausal 
state in the absence of combined hormonal contraception or 
hormone replacement therapy. If there is less than 12 months of 
amenorrhea 2 FSH samples are required at least 4-6 weeks apart. 
ii. 
Documented status as being permanently sterile (e.g., tubal ligation, 
hysterectomy, 
bilateral 
salpingectomy, 
and 
bilateral 
oophorectomy). 

Page  47 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
No. 
hVIVO APPROVED STANDARD INCLUSION CRITERIA 
Final v5.0_19OCT2022 (Viral Challenge Volunteer Studies) 
To be eligible for the study, participants must meet all the following inclusion criteria: 
7 
The following criteria apply to female and male participants: 
a)  Female participants of childbearing potential must use one form of highly 
effective contraception. Hormonal methods must be in place from at least 
2 weeks prior to the first study visit. The contraception use must continue 
until 90 days after the date of last dosing with IMP. Highly effective 
contraception is as described below: 
a.   Established use of hormonal methods of contraception described 
below (for a minimum of 2 weeks prior to the first study visit). 
When hormonal methods of contraception are used, male partners 
are required to use a condom with a spermicide: 
i.   combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation: 
1.   oral 
2.   intravaginal 
3.   transdermal 
ii.   progestogen-only hormonal contraception associated with 
inhibition of ovulation: 
1.   oral 
2.   injectable 
3.   implantable 
b.   Intrauterine device 
c.   Intrauterine hormone-releasing system 
d.   Bilateral tubal ligation 
e. Male 
sterilization 
(with 
the 
appropriate 
post 
vasectomy 
documentation of the absence of sperm in the ejaculate) where the 
vasectomized male is the sole partner for that woman. 
f. True abstinence – sexual abstinence is considered a highly effective 
method only if defined as refraining from heterosexual intercourse 
during the entire period of risk associated with the study treatments. 
The reliability of sexual abstinence needs to be evaluated in relation 
to the duration of the clinical trial and the preferred and usual 
lifestyle of the participant. 
b)  Male participants must agree to the contraceptive requirements below at 
entry to quarantine and continuing until 90 days after the date of last dosing 
with IMP: 
a.   Use a condom with a spermicide to prevent pregnancy in a female 
partner or to prevent exposure of any partner (male and female) to 
the IMP. 

Page  48 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
No. 
hVIVO APPROVED STANDARD INCLUSION CRITERIA 
Final v5.0_19OCT2022 (Viral Challenge Volunteer Studies) 
To be eligible for the study, participants must meet all the following inclusion criteria: 
b. Male  sterilization  with  the  appropriate  post  vasectomy 
documentation of the absence of sperm in the ejaculate (please note 
that the use of condom with spermicide will still be required to 
prevent partner exposure). This applies only to males participating 
in the study. 
c.   In  addition,  for  female  partners  of  childbearing  potential,  that 
partner must use another form of contraception such as one of the 
highly effective methods mentioned above for female participants. 
d.   True abstinence – sexual abstinence is considered a highly effective 
method only if defined as refraining from heterosexual intercourse 
during the entire period of risk associated with the study treatments. 
The reliability of sexual abstinence needs to be evaluated in relation 
to the duration of the clinical trial and the preferred and usual 
lifestyle of the participant. 
c)  In addition to the contraceptive requirements above, male participants must 
agree  not  to  donate  sperm  following  discharge  from  quarantine  until 
90 days after the date of last dosing with IMP. 
8 
Serosuitable for the challenge virus. 
• The serology result obtained from the RSV antibody assay suggests that 
the participant is sensitive to RSV infection (i.e., they are likely to be 
infected following inoculation with the challenge virus). 
 
5.2. Exclusion Criteria 
 
Participants are excluded from the study if any the following criteria apply: 
 
No. 
hVIVO APPROVED STANDARD EXCLUSION CRITERIA 
Final v5.0_19OCT2022 (Viral Challenge Volunteer Studies) 
Participants who meet any of the following exclusion criteria will not be included in the 
study: 
Medical History 
1 
History of, or currently active, symptoms or signs suggestive of upper or lower 
respiratory tract (URT or LRT) infection within 4 weeks prior to the first study 
visit. 
2 
Any history or evidence of any clinically significant or currently active 
cardiovascular, respiratory, dermatological, gastrointestinal, endocrinological, 
hematological, 
hepatic, 
immunological 
(including 
immunosuppression), 
metabolic, urological, renal, neurological, or psychiatric disease and/or other major 
disease that, in the opinion of the PI/investigator, may interfere with a participant 
completing the study and necessary investigations. The following conditions apply: 

Page  49 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
No. 
hVIVO APPROVED STANDARD EXCLUSION CRITERIA 
Final v5.0_19OCT2022 (Viral Challenge Volunteer Studies) 
Participants who meet any of the following exclusion criteria will not be included in the 
study: 
a)  Participants with a history of resolved depression and/or anxiety may be 
included at the discretion of the PI. Participants with a history of stress 
related illness, which is not ongoing or requiring current therapy, with good 
evidence of preceding stressors may also be included at the PI’s discretion. 
As required, participants will be assessed prior to enrolment with a Patient 
Health Questionnaire (PHQ-9) and/or Generalized Anxiety Disorder 
Questionnaire (GAD-7)  which  must  score less  than or equal  to  4  on 
admission. 
b)  Rhinitis (including hay fever) which is clinically active or a history of 
moderate to severe rhinitis, or history of seasonal allergic rhinitis likely to 
be active at the time of inclusion into the study and/or requiring regular 
nasal corticosteroids on an at least weekly basis, within 30 days of 
admission to quarantine will be excluded. Participants with a history of 
currently inactive rhinitis (within the last 30 days) or mild rhinitis may be 
included at the PI’s discretion. 
c) Atopic dermatitis/eczema which is clinically severe and/or requiring 
moderate to large amounts of daily dermal corticosteroids will be excluded. 
Participants with mild to moderate atopic dermatitis/eczema, taking small 
amounts of regular dermal corticosteroids may be included at the PI’s 
discretion. 
d)  Any concurrent serious illness including history of malignancy that may 
interfere with a participant completing the study. Basal cell carcinoma 
within 5 years of initial diagnosis or with evidence of recurrence is also an 
exclusion. 
e) Participants reporting physician diagnosed migraine can be included 
provided there are no associated neurological symptoms such as hemiplegia 
or visual loss. Cluster headache/migraine or prophylactic treatment for 
migraine is an exclusion. 
f)   Participants with physician diagnosed mild irritable bowel syndrome (IBS) 
not requiring regular treatment can be included at the discretion of the PI. 
3 
Any participants who have smoked ≥10 pack years at any time (10 pack years is 
equivalent to one pack of 20 cigarettes a day for 10 years). 
4 
Females who: 
a)  Are breastfeeding, or 
b)  Have been pregnant within 6 months prior to the study, or 
c)  Have a positive pregnancy test at any point during screening or prior to 
viral challenge. 

Page  50 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
No. 
Participants who meet any of the following exclusion criteria will not be included in the 
study: 
Lifetime history of anaphylaxis and/or a lifetime history of severe allergic reaction. 
5 
Significant intolerance to any food or drug in the last 12 months, as assessed by 
the PI. 
6 
Venous access deemed inadequate for the phlebotomy and cannulation demands 
of the study. 
7 
a)  Any  significant  abnormality  altering  the  anatomy  of  the  nose  in  a 
substantial way or nasopharynx that may interfere with the aims of the study 
and, in particular, any of the nasal assessments or viral challenge, (historical 
nasal polyps can be included, but large nasal polyps causing current and 
significant symptoms and/or requiring regular treatments in the last month 
will be excluded). 
b)  Any clinically significant history of epistaxis (large nosebleeds) within the 
last 3 months of the first study visit and/or history of being hospitalized due 
to epistaxis on any previous occasion. 
c)  Any nasal or sinus surgery within 3 months prior to the first study visit. 
Prior or Concomitant Medications and Assessments 
a)  Evidence of vaccinations within the 4 weeks prior to the planned date of 
viral challenge. 
b)  Intention to receive any vaccination(s) before the last day of follow-up. 
(NB. No travel restrictions will apply after the Day 28 follow-up visit). 
8 
9 
Receipt of blood or blood products, or loss (including blood donations) of 550 mL 
or more of blood during the 3 months prior to the planned date of viral challenge 
or planned during the 3 months after the final visit. 
10 
a)  Receipt of any investigational drug within 3 months prior to the planned 
date of viral challenge. 
b)  Receipt of 3 or more investigational drugs within the previous 12 months 
prior to the planned date of viral challenge. 
c)  Prior inoculation with a virus from the same virus-family as the challenge 
virus. 
d)  Prior  participation  in  another  human  viral  challenge  study  with  a 
respiratory virus in the preceding 3 months, taken from the date of viral 
challenge in the previous study to the date of expected viral challenge in 
this study. 
11 
Use or anticipated use during the conduct of the study of concomitant medications 
(prescription and/or non-prescription), including vitamins or herbal and dietary 
supplements within the specified windows, unless in the opinion of the study 
physician/PI, the medication will not interfere with the study procedures or 
compromise participant safety. Specifically, the following are excluded: 

Page  51 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
No. 
Participants who meet any of the following exclusion criteria will not be included in the 
study: 
a) Herbal supplements within 7 days prior to the planned date of viral 
challenge. 
b)  Chronically used medications, vitamins or dietary supplements, including 
any medications known to be potent inducers or inhibitors of cytochrome 
P450 enzymes or P-glycoprotein, within 21 days prior to the planned date 
of viral challenge. 
c)  Over the counter 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) 
d)  Systemic antiviral administration within 4 weeks prior to viral challenge. 
12 
13 
a)  Confirmed positive test for drugs of abuse and cotinine on first study visit. 
One repeat test allowed at PI discretion. 
b)  Recent history or presence of alcohol addiction, or excessive use of alcohol 
(weekly intake in excess of 28 units alcohol; 1 unit being a half glass of 
beer, a small glass of wine or a measure of spirits), or excessive 
consumption of xanthine-containing substances (e.g., daily intake in excess 
of 5 cups of caffeinated drinks e.g., coffee, tea, cola). 
A forced expiratory volume in 1 second (FEV1) <80%. 
14 
Positive HIV, hepatitis B, or hepatitis C test. 
15 
Presence of fever, defined as participant presenting with a temperature reading of 
≥37.9 oC on Day -2, Day -1, and/or pre-challenge on Day 0. 
16 
Those employed or immediate relatives of those employed at hVIVO or the 
sponsor. 
17 
Any other medical, psychiatric, social or occupational condition and/or 
responsibility that, in the opinion of the PI/investigator, would interfere with or 
serve as a contraindication to protocol adherence or the assessment of safety 
(including reactogenicity) will deem the participant unsuitable for the study. 
Any other reason that in the opinion of the PI/investigator raises a concern that the 
participant will not be able to cope with quarantine requirements. 
 
5.3. Lifestyle Considerations 
 
5.3.1.         Meals and Dietary Restrictions 
 
All participants will be dosed under fasted conditions. 
 
For all doses, a fasting period from 0.5 hour pre-dose to 1 hour post-dose applies. No fluid 
intake (including water) is allowed for 1 hour pre-dose to 1 hour post-dose, except for the water 
used for IMP intake.

Page  52 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Refrain from consumption of red wine, Seville oranges, grapefruit, or grapefruit juice, pomelos, 
exotic citrus fruits, grapefruit hybrids, or fruit juices from 7 days before the start of study 
intervention until after the final dose. 
 
Participants must not consume any food containing poppy seeds or any codeine-containing 
formulation starting 72 hours before any study visit and before admission to the quarantine unit 
(in order to avoid false-positive urine drug screen). 
 
5.3.2.         Caffeine, Alcohol, and Tobacco 
 
Participants must abstain from ingesting caffeine- or xanthine-containing products (e.g., coffee, 
tea, cola drinks, and chocolate) for 48 hours prior to and during quarantine and for 48 hours 
prior to all visits requiring spirometry. 
 
Participants must not consume alcohol for 72 hours prior to and during quarantine and for 
72 hours prior to any clinic visits. 
 
Participants must not smoke or use tobacco or nicotine containing products for 72 hours prior 
to and during quarantine. Participants that are current smokers may be enrolled in the study if, 
in the opinion of the PI/investigator, cessation of smoking during quarantine will not lead to 
withdrawal symptoms which could interfere with the accurate recording on the SDC. 
 
5.3.3.         Activity 
 
Participants must refrain from strenuous exercise for 48 hours prior to and during quarantine 
and for at least 48 hours prior to each clinic visit (unless it is within the usual activity of the 
participant), and participants are advised to avoid any new strenuous activities for 1 week prior 
to clinic visits such as weightlifting or running to avoid potential spurious elevation of clinical 
laboratory safety parameters. 
 
5.3.4.         Other Restrictions 
 
Participants will be instructed to avoid close contact with vulnerable people as described in 
Section 2.4.1.1, Vulnerable Persons, for 2 weeks after they leave the quarantine unit. 
 
5.4. Screen Failures 
 
Screen failures are defined as participants who sign the study-specific inform consent form 
(ICF) but are not subsequently enrolled into the study. Screen failures will not be included in 
the study database. Screen failures may be invited back for repeat assessments and screening 
and if eligible, for study enrolment. 
 
For individuals who do not meet the criteria for participation in this study (screen failure), the 
PI/investigator will decide whether the participant should be permanently excluded from the 
study or invited back for repeat assessments (i.e., repeat clinical laboratory test) if the initial 
screening assessments are still within the allowed screening windows or rescreening for a later 
quarantine, as appropriate.

Page  53 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
6.            STUDY INTERVENTIONS AND CONCOMITANT THERAPY 
 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol. 
 
6.1. Study Intervention(s) Administered 
 
Study interventions administered to participants are described in Table 6-1. 
 
Table 6-1:       Study Interventions 
 
Intervention 
EDP-323 
Placebo 
RSV-A Memphis 
Name 
37b virus 
Type 
Drug 
Other 
Challenge Virus 
Formulation 
Oral capsule 
Oral capsule 
Capped 
vial, 
liquid 
Unit Dose 
 
Not applicable 
The       challenge 
Strength(s) 
agent     titer     is 
determined  in  an 
infectivity   assay. 
The      dose      is 
approximately 
4 log10          plaque- 
forming        units 
(PFU) 
Dosage Level(s) 
•  High   dose:   600 mg Not applicable 
A  single  dose  of 
EDP-323     QD     for 
challenge     agent 
5 days 
will be delivered 
•  Low   dose:   600 mg 
EDP-323       (loading 
dose)      for      1 day, 
followed  by  200 mg 
EDP-323     QD     for 
4 days 
Route of 
Oral 
Oral 
Intranasal 
Administration 
Use 
IMP, experimental 
IMP, placebo 
Infectious 
challenge agent 
Sourcing 
Provided by sponsor 
Provided by sponsor 
Provided centrally 
by hVIVO 
Packaging and 
The    details    of    the The    details    of    the The details of the 
Labelling 
packaging and labelling packaging and labelling challenge     agent 

Page  54 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Intervention 
EDP-323 
Placebo 
RSV-A Memphis 
Name 
37b virus 
will be provided in the 
study-specific pharmacy 
manual 
will be provided in the 
study-specific 
pharmacy manual 
provision will  be 
provided in   the 
analytical 
plan 
(AP) 
Current/Former Not applicable 
Not applicable 
Not applicable 
Name(s) or 
Alias(es) 
 
6.2. Preparation/Handling/Storage/Accountability 
 
6.2.1.         Investigational Medicinal Product 
 
hVIVO will receive EDP-323 
 oral capsules and placebo to match EDP-323 
 
oral capsules to be storage at 
 after the supply has received qualified person sign off 
by the Good Manufacturing Practice (GMP) sponsor’s representative/pharmacy provider and 
has been released for shipment. All IMP supplies will be used only for this protocol and for no 
other purpose. 
 
Ready-to-dispense IMP will be supplied to hVIVO at the beginning of the study. Once received 
at hVIVO, hVIVO study staff will perform stock level accountability and the IMP will be stored 
securely. IMP accountability will be controlled by hVIVO and monitored by the study monitor 
throughout the study and at study close-out. 
 
The PI/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 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. 
 
6.2.2.         Challenge Agent 
 
The challenge agent used in this study is RSV-A Memphis 37b. 
 
The challenge agent stock was manufactured under current GMP. The challenge agent stock 
has undergone quality testing performed during manufacturing (identity, appearance, sterility, 
infectivity, and contaminants) according to pre-determined specifications, and has subsequently 
also passed an extensive panel of adventitious agent testing. The challenge agent is stored in a 
secure -80C freezer (normal temperature range -60°C to -90°C). 
 
Inoculum vials containing the challenge agent will be prepared and/or provided according to 
the hVIVO analytical plan (AP). The inoculum will be administered intranasally to each 
participant in accordance with hVIVO standard operating procedures (SOPs). 
 
All administrations will be made by a member of the study staff and witnessed by a second 
study staff member. The exact time of challenge agent inoculation will be recorded in the 
administration log. Accurate records will be kept of when and how much inoculum is prepared 
and used. The oversight process will be signed off prior to administration of the challenge agent. 
Any noncompliance or problems with the inoculation will be recorded in the participant’s 
source notes and reported to the PI/investigator.

Page  55 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
6.2.3.         All Study Interventions 
 
The PI/investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and that any discrepancies are 
reported and resolved before use of the study intervention. 
 
Only participants enrolled in the study may receive study intervention and only authorized 
investigator site staff may supply or administer study intervention. All study intervention must 
be stored in a secure, environmentally controlled area, and monitored (manual or automated) 
in accordance with the labelled storage conditions with access limited to the PI/investigator and 
authorized investigator site staff. 
 
The PI/investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records) 
 
Further guidance and information for the final disposition of unused study interventions are 
provided in the the pharmacy manual or hVIVO SOPs. 
 
6.3. Randomization and Blinding 
 
6.3.1.         Randomization 
 
hVIVO assigns a unique number to each subject in the hVIVO database. This number will be 
used to identify a subject up to the point of randomization, on source documents, on all study 
correspondence, and in the study database. A separate randomization number will be allocated 
to the participants at randomization and will be used for allocation to a study arm. 
 
A designated unblinded statistician, separate from the conduct or analysis of the study, will be 
responsible for the computer-generated randomization schedule using SAS. 
 
Randomization numbers will be assigned sequentially in ascending order; and once assigned, 
that randomization number shall not be reassigned. The study site will keep a log of the 
randomization number assigned to each participant. 
 
Randomization numbers will follow a 4 digit format, e.g., [rnnn], where r will represent a 
replacement participant (0 by default, incremented by 1 for a replacement participant) and nnn 
will be incremental (e.g., 1 to 132). 
 
In this study, 132 participants will be randomized 1:1:1 into one of 3 treatment groups (n=44 
each) to receive EDP-323 (at 2 different doses) or placebo. 
 
If  participants  are  replaced  as  per  Section 7.4,  Participant  Replacement  Strategy,  the 
replacement participant will be assigned a new, unique randomization number. The replacement 
participant will receive the same allocated, blinded treatment as the participant who is being 
replaced. 
 
6.3.2.         Blinding 
 
Each participant will be dispensed blinded study intervention which is labelled with his/her 
unique randomization number throughout the study. 
 
Due to the differing treatment regimens being tested, all participants will receive the same 
number of capsules. Participants will have their regimen supplemented by the administration of 
a placebo matched to EDP-323 in order to mimic the same number of capsules.

Page  56 of 110 
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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Following database lock, on receipt of authorization from the sponsor, a copy of the 
randomization code list will be provided to the study statistician to conduct study unblinding 
prior to analysis. 
 
Individual access to a secured interactive web response system (IWRS) will be provided to the 
PI/investigator.  The  website,  compliant  with  21CFR  part 11  guidelines,  will  be  used  if 
unblinding is necessary. In case of an emergency, the PI/investigator has the sole responsibility 
for determining if unblinding of a participant’s intervention assignment is warranted. The blind 
should only be broken where knowledge of the IMP received is required to provide appropriate 
patient care. Participant  safety must always be the first consideration in making such a 
determination. If the PI/investigator decides that unblinding is warranted, the PI/investigator 
should make every effort to contact the sponsor prior to unblinding a participant’s intervention 
assignment unless this could delay emergency treatment of the participant. When the 
PI/investigator breaks the code, he/she will have to indicate on the website the reason for 
unblinding. The person who performed the unblinding and the date of time of code breaking 
will be automatically recorded. After confirmation, the nature of treatment will appear on the 
screen.  A notification  with  the  nature  of  treatment  will  also  be  provided  by  email.  A 
notification, without the nature of treatment, will be provided to the study team. The 
PI/investigator must notify the sponsor within 24 hours that the code has been broken. 
 
Even if the code is broken, blood samples for safety, efficacy, PK, and other assessments will 
continue to be drawn for the remainder of the planned study period following the last dose if 
doing so will not compromise participant welfare. 
 
Dosing with IMP must be discontinued after unblinding, but the participant will be followed up 
until resolution of any AEs. 
 
6.4. Study Intervention Compliance 
 
Participants will receive study intervention and challenge agent directly from the PI/investigator 
or designee, under medical supervision.  The date and  time of each dose administered at 
the study site will be recorded in the source documents and recorded in the electronic case report 
form (eCRF). The dose of study intervention and study participant identification will be 
confirmed at the time of dosing by a member of the PI/investigator site staff other than the 
person administering the study intervention. 
 
Any noncompliance or problems with the administration of the study intervention will be 
recorded in the participant’s source notes and reported to the sponsor, if appropriate. 
 
6.5. Concomitant Therapy 
 
Any medications taken and changes in medications will be recorded in the source data from the 
time of the participant signing the study-specific ICF up to final study contact Day 28 (±3 
days). Any medication (including over the counter or prescription medicines, vitamins, and/or 
herbal supplements) that the participant is receiving at the time of enrolment or receives during 
the quarantine/outpatient stage will be stored, prescribed, and administered in line with their 
label-specific requirements, and recorded according to the parameters required by the clinical 
database. 
 
Concomitant therapies and procedures related to the treatment or diagnosis of an AE will be 
recorded in the source data. 
 
Participants will be reminded to refrain from using any over the counter medication without the 
approval of the PI/investigator and must notify the study staff as soon as possible if they are 
prescribed any medication. All medications other than contraceptives must be stopped prior

Page  57 of 110 
Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
to the planned date of viral challenge unless in the opinion of the PI/investigator and/or 
sponsor’s medical expert (SME), the medication will not interfere with the study procedures or 
compromise participant safety. 
 
Medications prohibited throughout the study are shown in Table 6-2. 
 
Table 6-2:       Prohibited Medication (Healthy Participants) 
 
Prohibited Medication 
Washout 
Systemic (oral and parenteral) antiviral drugs 4 weeks prior to first study visit 
Vaccinations 
4 weeks  prior  to  planned  date  of  viral 
challenge up through the last day of follow- 
up 
Use or anticipated use during conduct of the 7 days  prior  to  the  planned  date  of  viral 
study      of      concomitant      medications challenge: 
(prescription        and        non-prescription), •
Herbal supplements 
including  vitamins  or  herbal  and  dietary 
supplements,  unless  in  the opinion  of the •    Any medication or product (prescription 
PI/investigator   the   medication   will   not 
or  over  the  counter)  for  symptoms  of 
interfere   with   the   study   procedures   or 
nasal congestion 
compromise participant safety 
•    Short and long-acting antihistamines 
Within 21 days prior to the planned date of 
viral challenge: 
• Chronically used medications, vitamins, 
or dietary supplements, including any 
medication known to be moderate/potent 
inducers or inhibitors of cytochrome 
P450 enzyme or P-glycoprotein 
Any IMP used in another study 
Within 3 months or 5 half-lives of the IMP 
used in the other study, whichever is greater, 
prior to the planned date of viral challenge 
 
Any concomitant medication required for the participant’s welfare may be given by the 
PI/investigator. However, it is the responsibility of the PI/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. 
 
The use of paracetamol and/or other allowed medications is permissible up to 7 days before the 
planned date of viral challenge. During the study, the PI/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. 
 
Medications which are permitted throughout the study are shown in Table 6-3.

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Table 6-3:       Permitted Medication 
 
Permitted Medication 
Time Period 
Paracetamol 
Maximum  4 g  daily  throughout  the  study  duration  at  the 
discretion of the PI/investigator. 
Oral contraceptives 
Allowed at any time during the study. 
Prescription and non-prescription medications, including vitamins or herbal and dietary 
supplements, not listed in prohibited medications are subject to approval by the 
PI/investigator. 
If, e.g., in an outbreak or pandemic, a newly instated national vaccination program is 
applicable to an individual participant, the PI/investigator and sponsor will discuss on an 
individual basis if concomitant vaccination may be allowed, study dosing/viral challenge 
postponed, or the participant withdrawn from the study. 
 
6.6. Dose Modification 
 
This is not applicable in this study. 
 
6.7. Treatment of Overdose 
 
For this study, any dose of any drug administered as part of the study greater than the dose 
prescribed by the protocol will be considered an overdose. 
 
In the event of an overdose, the PI/investigator should: 
 
1.   Contact the medical monitor immediately. 
 
2.   Closely monitor the participant for any AE/SAE and laboratory abnormalities possibly 
associated with overdose and the participant will be clinically followed up until any 
AE/SAE has resolved. 
 
3.   Obtain a plasma sample for PK analysis within 24 hours of the date/time of the last dose of 
study intervention. 
 
4.   Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
 
The sponsor is responsible for notifying the Medicines and Healthcare Regulatory Agency 
(MHRA) and Research Ethics Committee (REC) of the potential serious breach within 7 days 
of becoming aware of it.

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
7. 
WITHDRAWAL/DISCONTINUATION            OF            STUDY 
INTERVENTION 
 
7.1. Participant Withdrawal 
 
A participant may withdraw their consent to participate in the study at any time, for any reason, 
without prejudice to his/her future medical care. Participants may decline to give a reason for 
their withdrawal. Additionally, the PI/investigator may withdraw a participant if, in their 
clinical judgement, it is in the best interest of the participant or if the participant cannot comply 
with the protocol. Wherever possible, the tests and evaluations listed for the early withdrawal 
visit should be conducted, and if clinically indicated, the participant should be invited back for 
a final follow-up visit. 
 
The sponsor should be notified of all study withdrawals in a timely manner, and in cases where 
the withdrawal is due to a medical reason the participant would be referred to his/her GP. 
 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the PI/investigator must document this in the site study records. 
 
Participants will be counselled that an early self-discharge or their withdrawal from the human 
viral challenge phase of the study is strongly discouraged, as it may pose a risk both to the 
participant and his/her contacts. In the event of a participant insisting on an early self-discharge 
or withdrawal during the quarantine isolation period, the participant will be encouraged to stay 
and would be advised of the potential risks of carrying RSV infection into the community, and 
to vulnerable groups in particular as described in Section 2.4.1.1, Vulnerable Persons. 
 
The participant’s consent to continue or not in the study and any requirement to attend further 
scheduled follow-up visits will be discussed, confirmed, and documented. If consent is not 
being withdrawn, assessments (early withdrawal visit assessments as detailed in the SoE), may 
still be collected, as clinically required, prior to the early discharge. Scheduled follow-up visits 
may be attended as agreed or for safety reasons. Any missed assessments or follow-up visits 
i.e., a missed PK timepoint will be documented as a protocol deviation. 
 
7.2. Participant Discontinuation 
 
Participants will be discontinued from further study intervention (i.e., receipt of the challenge 
agent or IMP as applicable) or withdrawn from the study for any of the reasons listed below. 
Where IMP has been administered, these participants must not receive any additional IMP but 
should continue to be followed for safety. 
 
•    Noncompliance with the study requirements and restrictions. 
 
• Clinically  significant  abnormal  laboratory  findings,  which  in  the  opinion  of  the 
PI/investigator and/or sponsor precludes further receipt of intervention or participation in 
the study. 
 
• Development of intercurrent illness, which in the opinion of the PI/investigator would 
compromise the health of the participant or the study objectives. 
 
• The PI/investigator’s decision that withdrawal from further participation or receipt of 
intervention would be in the participant’s best interest.

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Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
• Termination of the study at the discretion of the PI/investigator or sponsor for safety, 
behavioral, or administrative reasons. 
 
•    The wish of the participant. 
 
•    Any intervention-related SAEs. 
 
•    Anaphylactic reaction following dosing. 
•    The participant becomes pregnant (if pregnancy is specified as an exclusion criterion). 
Participants who are discontinued from further receipt of intervention (IMP) may undergo 
additional assessments or visits as necessary for safety reasons.  If the participant is not 
withdrawing their consent, assessments as per the early withdrawal visit (see SoE) may still be 
collected if clinically required. Scheduled follow-up visits may also be attended as per the SoE. 
 
7.2.1.         Temporary Discontinuation/Temporary Delay in Enrolment 
 
If a participant is found to be ineligible due to transient circumstances (such as acute disease 
and/or fever) at the first study visit or quarantine admission, inoculation with challenge agent 
will be postponed until the transient circumstances have been resolved and the participant may 
be re-invited to a later quarantine group within the allowed time window. For participant 
rescreening refer to Section 5.4, Screen Failures. 
 
7.3. Lost to Follow-up 
 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
 
The following actions must be taken if a participant fails to return to the study site for a required 
study visit: 
 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether the participant wishes to and/or should continue in the study. 
 
• Before a participant is deemed lost to follow-up, the PI/investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a follow-up letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 1, 
Regulatory, Ethical, and Study Oversight Considerations. 
 
7.4. Participant Replacement Strategy 
 
Participants may be replaced in this study. 
 
If a participant discontinues from study intervention OR withdraws from the study for reasons 
not related to AEs, a replacement participant may be enrolled, if deemed appropriate by the 
PI/investigator and sponsor. The replacement participant will receive the same intervention as 
the participant being replaced. The replacement participant will be assigned a new, unique

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ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
randomization number. The replacement participant will receive the same allocated, blinded 
treatment as the participant who is being replaced. 
 
7.5. Stopping Rules 
 
The PI/investigator and the SME will perform safety reviews on available clinical and virology 
data as appropriate during the quarantine period. 
 
Three clinical scenarios relating to the incidence of SAEs/suspected unsuspected serious 
adverse reactions (SUSARs) during the study and the procedures that should be performed in 
each case are presented in Table 7-1. 
 
Table 7-1:       Study Stopping Rules 
 
Status 
Criterion 
Procedure 
1. 
A report has been received of one 
(or more) SUSAR(s) in any, one 
(or more) participant(s). 
If such a status occurs at any point during the 
study, then further administration of the IMP 
will not take place. The PI/investigator and 
the SME will review the data and decide on 
whether it is appropriate to recommence IMP 
dosing (approval of a substantial amendment 
from the Competent Authorities is required) 
or terminate the study. 
2. 
No SUSAR(s) have been reported 
but an overall pattern of clinical 
changes 
or 
symptoms 
exists, 
attributed to the IMP, which may 
appear minor or moderate in terms 
of individual  AEs  or SAEs,  but 
which collectively represent a 
concern for safety. 
3. 
Unexpected virus-related SAE(s) 
or unexpected virus-related AE(s) 
of clinical concern have been 
reported following viral challenge. 
If such a status occurs at any point during the 
study, then the PI/investigator and the SME 
will review the data and decide based on 
expectedness* of the viral event. 
If 
the 
event 
is 
unexpected, 
further 
administration of the virus will not take place. 
The PI/investigator and the SME will review 
the data and decide on whether it is 
appropriate 
to 
recommence 
inoculation 
(approval of a substantial amendment from 
the Competent Authorities is required) or 
terminate the study. 
*    Expectedness will be assessed by referring to the challenge virus dossier. 
 
A final follow-up visit will be performed on Day 28 (±3 days). Follow-up of any event should 
continue until resolution, stabilization, it is judged by the PI/investigator to be no longer 
clinically significant, the participant is lost to follow-up, or an alternative explanation has been 
provided. 
 
Further enrolment into the study may be either temporarily or permanently discontinued if: 
 
• An unacceptable number of severe or life-threatening exacerbations of AEs take place (as 
determined by the PI/investigator).

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Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
• Any clinically significant life-threatening AEs considered related to the study intervention 
as determined by the PI/investigator occur. 
 
7.6. Adaptive Features 
 
This study is designed to be able to utilize adaptive features to enhance study safety, efficiency, 
and efficacy. These design elements are predefined in their scope and limit, as detailed in Table 
7-2. 
 
The implementation of study-specific adaptive features will be documented in a non-substantial 
amendment. Generic adaptive features may be implemented at any time at the discretion of the 
PI/investigator.

 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
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Table 7-2:       Adaptive Features 
 
Adaptive   Design Feature 
Limit 
Category 
Generic 
Cohort(s) 
1. Participants who have been withdrawn (for any 
reason) may be replaced (sponsor and/or PI 
discretion). 
1. The stopping rules of the study must be always adhered to. 
Replacement participants may be enrolled to replace 
participants who have been withdrawn from the study for 
2. Participants   who   are   replacing   a   withdrawn 
reasons not related to AEs, where the study stopping rule has 
participant may be randomized for inclusion, and 
dosed/challenged: 
2. 
not been met. 
Due to considerations of the protocol specific participant 
a.   In an ongoing quarantine cohort 
b.   In a new quarantine cohort 
c.   Separately. 
replacement strategy, infection rate monitoring, and other 
rare occurrences, the number of study participants will not 
exceed 150 dosed with EDP-323/placebo. 
3  Any quarantine cohort may run at the same time 
3. Replacement   participants   will   be   given   replacement 
randomization    numbers    (see    Section 7.4,    Participant 
Replacement Strategy). 
4. All protocol-defined inclusion/exclusion criteria and safety 
criteria must be met before any study quarantine cohort, or 
participant commences the study. 
Sample/Specimen 1.   The PI/investigator may perform additional safety 
assessments, at any time, if they believe them to be 
clinically required. 
1.   The maximum blood volume will not be exceeded. 
2. Any required additional safety assessments, or specialist 
referrals, will be conducted on a case-by-case basis. As such 
the maximum number needed cannot be prospectively defined. 
2.   Where   clinically   required   (sponsor   and/or   PI 
discretion),   participants   may   be   referred   for 
consultation(s)  and/or  investigation(s)  under  the 
care of a specialist physician. 

 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
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Adaptive   Design Feature 
Limit 
Category 
Duration 
of A participant’s inpatient stay may be prolonged if 
discharge criteria of minimal infectiousness is not met 
(sponsor and/or PI discretion). 
1. Must meet the terms and criteria as detailed in the participant 
Inpatient Stay 
2. 
3. 
information sheet. 
Participants must always be able to leave the study site 
unhindered if they wish to do so. 
The additional stay is triggered based on the minimal 
infectiousness discharge criteria not being met (as detailed in 
this protocol), and the participant’s suitability for residential 
stay will be assessed on a case-by-case basis. As such, a 
maximum length of stay cannot be prospectively defined. 

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
 
8.            STUDY ASSESSMENTS AND PROCEDURES 
 
Unless otherwise stated, study assessments will be performed according to hVIVO SOPs. Study 
procedures and their timing are summarized in the SoE (Section 1.2, Schedule of 
Events). Protocol waivers or exemptions are not allowed. Adherence to the study design 
requirements, including those specified in the SoE, is essential and required for study conduct. 
Immediate safety concerns should be discussed with the sponsor upon occurrence or awareness 
to determine if the participant should continue or discontinue study intervention. 
 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The PI/investigator will maintain a screening log to record details 
of all participants screened and to document eligibility or record the reasons for screening 
failure, as applicable. 
 
For all study assessments, the pre-dose value obtained nearest to dosing will be used as the 
baseline measure for assessments, unless stated otherwise. 
 
Procedures conducted as part of the hVIVO generic screening process and obtained before 
signing of the study-specific ICF may be utilized for screening or baseline purposes provided 
the procedures met the protocol-specified criteria and were performed within the period defined 
in the SoE. 
 
The maximum volume of blood collected from each participant over the duration of the study 
(i.e.,  from  screening  through  final  follow-up  visit)  will  not  exceed  550 mL.  Repeat  or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
If additional  samples  are required  in  excess  of  this  amount,  e.g.,  to  monitor  laboratory 
abnormalities, these will be taken at the discretion of the PI/investigator. 
 
Where  applicable,  unless  otherwise  stated,  normal  ranges  will  be  identified  in  the 
PI/investigator Site File, and the Trial Master File. 
 
8.1. Demographics and Baseline Characteristics 
 
8.1.1.         Demographics 
 
Demographic data will be recorded at the screening visit. 
 
8.1.2.         Height, Body Weight, and Body Mass Index 
 
Height and body weight measurements will be recorded in compliance with hVIVO’s standard 
procedures. 
 
Body mass index will be calculated as: BMI (kg/m2) = Body Weight (kg) 
Height (m)2 
 
8.1.3.         Medical and Medication History 
 
Medical and medication histories will be recorded at screening, including, but not limited to, 
detailed histories on current contraception, and allergies (e.g., rhinitis, dermatitis, food, 
aspirin/non-steroidal anti-inflammatory drugs, and asthma).

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
8.1.4.         Challenge Agent Serology Samples 
 
A participant must be serosuitable 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 agent. This antibody titer cut- 
off for serosuitability will be described in the applicable hVIVO policy. 
 
Serum levels of pre-existing RSV-specific antibodies will be determined using RSV challenge 
virus neutralization assay as described in the AP. 
 
8.1.5.         Patient  Health  Questionnaire  (PHQ-9)  and  Generalized  Anxiety  Disorder 
(GAD-7) Questionnaire 
 
PHQ-9 and GAD-7 questionnaires will be used at the discretion of the PI/investigator to assess 
participants’ eligibility in terms of ability to tolerate isolation in the quarantine unit. 
 
8.2. Respiratory Samples 
 
The following exploratory nasal sampling procedures will be performed during the study and 
are detailed in the sections below: 
 
•    Nasopharyngeal swab 
 
•    Nasal wash 
 
Where any nasal sampling time points occur together the order of sampling will typically be 
(1) nasopharyngeal swab followed by (2) nasal wash. 
 
8.2.1.         Nasopharyngeal Swab 
 
Nasopharyngeal swabs will be performed to collect samples of nasal material for: 
 
•    Respiratory pathogen screen 
 
•    RSV discharge test 
 
Remaining material from the nasopharyngeal swabs may be stored and used for exploratory 
purposes. 
 
8.2.1.1.      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,  including  severe  acute respiratory  syndrome 
coronavirus 2 (SARS-CoV-2), that could potentially contraindicate a person’s participation in 
the study. Nasopharyngeal swabs will be tested using a multi-respiratory panel. Additional 
nasopharyngeal swabs may be collected if the results from the first test were invalid to support 
study eligibility prior to challenge agent inoculation, or if a community acquired infection is 
suspected during quarantine. 
 
Any additional screening tests will be conducted at the discretion of the PI/investigator. 
 
8.2.1.2.      RSV Discharge Test 
 
Where required, a RSV discharge test (e.g., qualitative rapid viral antigen test [RVAT]) will 
be used to determine the presence of RSV in a nasopharyngeal swab sample taken prior to 
discharge from the quarantine unit. A PCR test may be used as an alternative test for this 
purpose, details of which will be documented in the AP. The RSV discharge test will be 
performed at the discretion of the PI/investigator and only if indicated for a clinical or other 
reason. Additional tests may be performed at the discretion of the PI/investigator.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
8.2.2.         Nasal Wash 
 
Nasal wash sampling will be performed to collect samples of nasal material for: 
 
•    Viral shedding/load assessments (see Section 8.3.3, Viral Load Assessment) 
 
•    Exploratory purposes (see Section 8.3.4, Exploratory Assessments) 
 
•    Biomarkers (see Section 8.10, Biomarkers) 
 
Remaining material from the nasal wash may be stored and used for exploratory purposes in 
accordance with the AP. 
 
8.2.3.         Viral Shedding for Dosing 
 
Viral shedding for triggered dosing decisions only will be confirmed by qicPCR assay of nasal 
wash sample. 
 
8.3. Efficacy Assessments 
 
8.3.1.         Participant Diary Cards 
 
Symptom Diary Card (Ordinal) 
 
Participants will report and assess the severity of any challenge agent-related signs and 
symptoms 3 times per day during quarantine, at the same time each day (±1 hour), using the 
hVIVO SDC. This information will be administered using paper and transcribed into the eCRF. 
 
The following symptoms in the 13-item symptom questionnaire will be graded on a scale of 
0 to 3 (grade 0: no symptoms; grade 1: just noticeable; grade 2: clearly bothersome from time 
to time but does not interfere with me doing my normal daily activities;  grade 3: quite 
bothersome most or all of the time, and it stops me participating in activities); shortness of 
breath and wheeze have an additional grade, i.e., grade 4: symptoms at rest. 
 
•    Runny nose 
 
•    Stuffy nose 
 
•    Sneezing 
 
•    Sore throat 
 
•    Earache 
 
•    Malaise/tiredness 
 
•    Headache 
 
•    Muscle and/or joint ache 
 
•    Chilliness/feverishness 
 
•    Cough 
 
•    Chest tightness 
 
•    Shortness of breath 
 
•    Wheeze 
 
Additional to the categorical SDC, a visual analogue scale diary card using a 100 mm scale, 
with the same symptoms, will be completed by the participants.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
Participant Common Cold Perception Questions 
 
Two additional common cold-related questions will be answered by the participant each 
morning. The first question asks the participant’s perception of whether they have a cold or not, 
the second asks the participant’s perception of improvement/worsening of the cold. 
 
1.   Do you have a cold: Yes/No 
 
If the participant selects Yes to having a cold, then the second 7-point Likert scale “global 
change since yesterday” question is completed by the participant, as below: 
 
2.   Compared to yesterday, I feel that my cold is: 
 
o Very much better 
o Somewhat better 
o A little better 
o The same 
o A little worse 
o Somewhat worse 
o Very much worse 
Respiratory Infection Intensity and Impact Questionnaire (RiiQ) 
 
Participants will report and assess the severity of their infection once daily during quarantine, 
at the same time each day (±1 hour), using the RiiQ (Romano et al, 2023). The RiiQ is a patient- 
reported outcome tool in development for assessing the severity of naturally-acquired RSV 
infection of adults. Participants will complete the RiiQ as per provided instructions. The RiiQ 
will be administered using paper and transcribed into the eCRF. It consists of a questionnaire 
addressing approximately 7 RSV symptoms, and 2 impacts of RSV (emotional and activity 
impacts). The multiple individual questions within the RiiQ are answered on a 4-point severity 
scale. 
 
8.3.2.         Nasal Discharge Collection from Paper Tissues 
 
Each participant will be given pre-weighed packets of paper tissues. Participants will be asked 
to place single tissues used for nose blowing or sneezing into a specified collection bag (for that 
participant only). 
 
A daily 24-hour paper tissue collection will take place throughout the quarantine period. 
Distribution of paper tissues and collection bags will start in the morning on Day -1, with the 
first collection on Day 0. Thereafter, distribution and collection of tissues will occur daily, at 
the same time point (±1 hour) in the morning, with tissues distributed 24 hours ahead, until 
discharge from quarantine. 
 
24-hour paper tissue collections will be analyzed to determine the following over the quarantine 
period: 
 
•    24-hour nasal discharge weight 
 
•    The number of paper tissues used for nose blowing or sneezing over each 24-hour period 
 
8.3.3.         Viral Load Assessment 
 
Viral load will be determined by qRT-PCR and a viral culture assay to investigate the following 
parameters:

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
•    Viral load 
 
•    Infectivity status and rate 
 
•    Viral dynamics (e.g., duration, peak, time to peak) 
 
 
 
 
 
 
 
 
 
8.4. Safety Assessments 
 
8.4.1.         Complete Physical Examination 
 
A complete physical examination to include a full systemic assessment. 
 
8.4.2.         Symptom-directed Physical Examination 
 
Symptom-directed physical examinations will be conducted as deemed appropriate by the 
PI/investigator and may include (as applicable) examination of the eyes, ears, nose, throat, and 
respiratory system/chest (via stethoscope). Based upon the presence or absence of clinical signs 
and symptoms, PI/investigator discretion will be used to determine the requirement to perform 
certain ongoing assessments. 
 
Assessment and grading of any upper respiratory tract (URT) (nasal discharge, otitis, 
pharyngitis, sinus tenderness) and lower respiratory tract (LRT) symptoms (abnormal breath 
sounds externally [e.g., stridor, wheezing] and on chest auscultation [rhonchi, crepitations, or 
other]) will be performed, as applicable. Physician-reported assessments of challenge agent- 
related illness will be graded in accordance with its intensity and documented in the source 
data. 
 
Following challenge agent inoculation, additional symptoms that are not available in the list of 
symptoms of the SDC and are deemed to be clinically significant (in the opinion of the 
PI/investigator) will be captured as AEs (for more details see Section 10.3.6.2, Assessment). 
 
Following challenge agent inoculation all unexpected (in the opinion of the PI/investigator) 
symptom-directed physical examination findings will be captured as AEs, along with all other 
occurrences that meet the criteria for an AE. 
 
8.4.3.         Vital Signs and Tympanic Temperature 
 
Vital signs assessments will be recorded in supine position, after being supine for at least 
5 minutes. 
 
Vital signs assessments will be recorded as follows: 
 
•    Heart rate (HR) will be recorded in beats per minute. 
 
•    Respiratory rate (RR): respirations will be counted and recorded as breaths per minute.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
• Blood pressure (BP): systolic BP and diastolic BP will be measured in millimeters of 
mercury (mmHg). Where possible, the same arm will be used for all measurements. 
 
•    Peripheral arterial oxygen saturation (SpO2%) will be assessed using pulse oximetry. 
 
•    Tympanic temperature will be measured. 
 
If a participant has 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 result. 
The assessment may then be repeated at the discretion of the PI/investigator and in accordance 
with hVIVO SOPs. 
 
Study-specific normal ranges for vital signs are provided in Appendix 4, Normal Ranges. 
 
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 sponsor requirements using the Common Terminology Criteria for Adverse 
Events (CTCAE) grading table November 2017. 
 
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 may be monitored more frequently during quarantine, if appropriate. 
 
Following challenge agent inoculation, pyrexia (temperature ≥37.9C) will be expected and 
presumed to represent 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 PI/investigator) to be classed as an AE. 
 
Following challenge agent inoculation, all unexpected (in the opinion of the PI/investigator) 
pyrexia will be captured as an AE, along with all other occurrences that meet the criteria for an 
AE. 
 
8.4.4.         Electrocardiogram 
 
Study-specific normal ranges are provided in Appendix 4, Normal Ranges. 
Twelve-lead ECGs will be recorded in supine position, after being supine for at least 5 minutes. 
Twelve-lead  ECGs  will  be  obtained  to  evaluate  the  electrical  activity  of  the  heart. 
Electrocardiograms will be read on-site by an appropriately qualified physician or a member 
or the investigator site staff. Wherever possible the same qualified physician or a member or 
the investigator site staff will review subsequent ECGs from the same participant for the 
assessment of any change from baseline. 
 
Any changes from baseline during the study will be assessed for their clinical significance. 
Clinically significant changes will be reported as AEs. The PI/investigator or delegate will 
assess nonclinical significant changes to determine whether they should be recorded. 
 
8.4.5.         Clinical Safety Laboratory Assessments 
 
8.4.5.1.      Urinalysis 
 
Clinical urine safety analysis will be undertaken using commercially available urine test strips 
(i.e., dipsticks) that provide an instant result, which will be documented in the source data. 
 
Urinalysis will be performed to evaluate the parameters described in Appendix 2, Clinical 
Laboratory Tests.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
If the dipstick yields clinically significant abnormal results, a urine sample may be sent for 
microscopy, culture, and sensitivity examination, at the discretion of the PI/investigator. 
Microscopy, culture, and sensitivity examination will include but is not limited to red blood 
cells, white blood cells, epithelial cells, crystals, casts, and bacteria. 
 
Urine safety analysis values will be evaluated by the PI/investigator for clinical relevance. 
Those values that meet the criteria for an AE and are deemed to be clinically significant, will 
be reported as AEs. 
 
8.4.5.2.      Drugs of Misuse and Cotinine 
 
Urinalysis will be performed for drugs of misuse and cotinine using commercially available 
kits that provide an instant result, which will be documented in the source data. 
 
Drugs of misuse screen will include (but is not limited to) amphetamines, barbiturates, cocaine, 
opiates, cannabinoids, and benzodiazepines. 
 
8.4.5.3.      Alcohol Breath Testing 
 
Alcohol breath testing will be conducted to determine compliance with the study alcohol 
restrictions. Additional tests may be conducted for assessing eligibility at the discretion of the 
PI/investigator. Results will be recorded in the source documents. 
 
8.4.5.4.      Safety Blood Assessments and Analysis 
 
Appendix 2, Clinical Laboratory Tests, describes the safety blood tests that will be performed 
including, but not limited to, hematology, coagulation, biochemistry, serology (HIV, hepatitis), 
thyroid function test, and cardiac enzymes. Additional safety assessments will be conducted at 
the discretion of the PI/investigator, as required. 
 
8.4.6.         Pregnancy Tests and Follicle-stimulating Hormone 
 
Female participants of childbearing potential are to have a urine pregnancy test at screening. 
Participants will only be enrolled if the pregnancy test is negative. 
 
Note: Pregnancy test must be performed even if the participant is menstruating at the time of 
the study visit. 
 
All  female  participants  will  have  a  serum  sample  tested  for  beta-human  chorionic 
gonadotrophin (β-hCG) on admission to quarantine. 
 
Blood samples will be tested for serum FSH in all postmenopausal female participants. 
 
8.4.7.         Spirometry 
 
Spirometry will be performed according to hVIVO SOPs. Height at screening will be used as 
the baseline measurement for all spirometry assessments. 
 
Spirometry should meet the American Thoracic Society/European Respiratory Society 
(ATS/ERS) guidelines criteria (Graham et al, 2019). For FEV1 and forced vital capacity (FVC), 
the highest value from a minimum of 3 technically satisfactory attempts will be considered. 
For FEV1  and FVC the highest and the second-highest value should not exceed more than 
150 mL or 5% (whichever is greater). If the difference is larger, up to 8 technically acceptable 
measurements will be made with repeatability assessed after each additional attempt. If after 
8 technically acceptable attempts the difference remains greater than 150 mL or 5% (whichever 
is greater) the highest values will be reported, and an operator comment will be made to the

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
source data. Values for FEV1  and FVC will be assessed and reported as the highest values 
regardless of curve. 
 
Predicted values will be calculated according to the formula of the Report of the Global Lung 
Function Initiative, ERS Task Force Lung Function Reference Values (Quanjer et al, 2012). 
 
Spirometry may be repeated at any time in the event of respiratory signs or symptoms (repeated 
coughing, bradypnea, tachypnoea, rales, and rhonchi) or respiratory difficulties. 
 
8.5. Adverse Events, Serious Adverse Events, and Other Safety Reporting 
 
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, 
hVIVO SOPs, and the study-specific protocol. The PI/investigator is also responsible 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. 
 
The sponsor of the study will also perform an evaluation of seriousness, causality, and 
expectedness of all SAEs. 
 
The definitions of an AE/SAE, as well as the method of recording, evaluating, and assessing 
causality of AE and SAE and the procedures for completing and transmitting AE/SAE, and 
other reportable safety event reports can be found in Appendix 3, Adverse Events: Definitions 
and Procedures for Recording, Evaluating, Follow-up, and Reporting. 
 
8.5.1.         Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information 
 
All AEs/SAEs will be collected from signing of the study-specific ICF until the last scheduled 
follow-up visit at the time points specified in the SoE. For subjects who are not enrolled into 
the study, AEs will only be recorded in the source documents and SAEs should be reported to 
sponsor. 
 
Investigators are not obligated to actively seek AEs/SAEs after conclusion of study 
participation. However, if the PI/investigator learns of any SAE, including a death, at any time 
after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the PI/investigator must 
promptly notify the sponsor. 
 
8.5.2.         Method of Detecting Adverse Events/Serious Adverse Events 
 
The method of recording, evaluating, and assessing causality of AEs/SAEs and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3, Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting. 
 
Care will be taken not to introduce bias when detecting AEs/SAEs. Open-ended and non- 
leading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences. 
 
8.5.3.         Follow-up of Adverse Events/Serious Adverse Events 
 
After the initial AE/SAE report, the PI/investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs/SAEs will be followed until resolution (return 
to normal or baseline values), stabilization, it is judged by the PI/investigator to be no longer 
clinically significant, the participant is lost to follow-up (as defined in Section 7.3, Lost to

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
Follow-up), or an alternative explanation has been provided. Further information on follow-up 
procedures  is  provided  in  Appendix 3,  Adverse  Events:  Definitions  and  Procedures  for 
Recording, Evaluating, Follow-up, and Reporting. 
 
8.5.4.         Regulatory Reporting Requirements for Serious Adverse Events 
 
Any SAE will be reported immediately by the PI/investigator to the sponsor (in practice 
reporting within 24 hours of the PI/investigator’s knowledge of the event. This is essential so 
that the sponsor can meet its regulatory and REC reporting obligations for the study. Immediate 
reports may be verbal (a written record of this verbal notification will be retained) or in writing. 
Immediate reports must be followed up promptly by detailed, written reports. 
 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting 
to the regulatory authority, REC, and investigators. 
 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators, as necessary. 
 
A PI/investigator who receives an investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then 
file it along with the IB and will notify the REC, if appropriate according to local requirements. 
 
Further information on regulatory reporting requirements is provided in Appendix 3, Adverse 
Events: Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting. 
 
8.5.5.         Pregnancy 
 
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected from signing of the study-specific ICF onwards until the last study 
assessment as outlined in the SoE. If a pregnancy is reported, the PI/investigator should inform 
the sponsor within 24 hours of learning of the pregnancy and should follow the procedures 
outlined  in  Appendix 3,  Adverse  Events:  Definitions  and  Procedures  for  Recording, 
Evaluating, Follow-up, and Reporting. 
 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal distress, fetal death, stillbirth, 
congenital anomaly/birth defect, ectopic pregnancy) are considered SAEs. 
 
8.6. Pharmacokinetics 
 
Instructions for the collection and handling of biological samples will be provided by the 
sponsor. The actual calendar date and time (24-hour clock time) of each sample will be 
recorded. 
 
Genetic analyses will not be performed on these plasma samples. Participant confidentiality 
will be maintained. 
 
Drug concentration information that may unblind the study will not be reported to investigative 
sites or blinded study staff until the study has been unblinded. 
 
8.6.1.         Pharmacokinetic Blood Samples 
 
Blood samples will be collected for measurement of plasma concentrations of EDP-323 (and 
metabolites) as specified in the SoE.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
Blood  plasma  samples  for  measurement  of  plasma  concentrations  of  EDP-323  (and 
metabolites) will be processed and sent to the sponsor’s PK vendor according to the AP. 
 
At the PI’s discretion, blood samples may be collected at additional time points during the study 
if warranted and agreed upon between the PI/investigator and the sponsor. The timing of 
sampling may be altered during the study based on newly available data (e.g., to obtain data 
closer to the time of peak plasma concentrations) to ensure appropriate monitoring. 
 
Samples will be used to evaluate the PK of EDP-323 (and metabolites). Samples collected for 
analyses of EDP-323 (and metabolites) plasma concentration may also be used to evaluate 
safety or efficacy aspects related to concerns arising during or after the study. 
 
8.6.2.         Pharmacokinetic Parameters 
 
Pharmacokinetic parameters of interest may include but are not limited to: 
 
•    Cmax, tmax, t1/2, CL/F, λz, Vd/F, C12h, C24h, AUClast, AUC0-tau, AUC0-∞ 
 
Pharmacokinetic parameters will be calculated using non-compartmental methods. Parameters 
will be summarized descriptively. 
 
8.7. Pharmacodynamics 
 
Pharmacodynamic parameters may be evaluated in this study. 
 
8.8. Immunogenicity Assessments 
 
Aliquot(s) of blood (serum) will be collected for immunological analysis. 
 
Humoral immune responses, e.g., RSV-neutralizing antibodies, will be evaluated from serum 
samples collected from all participants at the end of the study to evaluate the generation of 
natural immunity to the challenge virus with and without EDP-323 treatment, in accordance 
with the AP. 
 
8.9. Genetics 
 
Participant human genetics are not evaluated in this study. 
 
8.10.    Biomarkers 
 
In addition to the planned blood plasma sample taken specifically for protein biomarker 
analysis, other serum and respiratory secretion samples may have their residual volumes 
aliquoted and stored for analysis as described in the AP. These aliquots may be used for protein 
biomarker analyses evaluating protein signatures and their correlations with disease severity, 
viral load, viral dynamics, and effects of EDP-323. Where aliquots are to be used for protein 
biomarker analyses, these samples will be sent to a sponsor-designated laboratory (or hVIVO 
where applicable) for such analysis in accordance with the AP.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
9.            STATISTICAL CONSIDERATIONS 
 
9.1. Statistical Hypotheses 
 
The primary statistical hypothesis is that treatment with EDP-323 will show an antiviral effect 
demonstrated by a significant reduction in RSV VL-AUC (measured by qRT-PRC in nasal 
samples) compared to placebo. 
 
9.2. Sample Size Determination 
 
The statistical powering selected for this study is estimated to be sufficient for the primary 
objective and the primary endpoint and important secondary endpoints. 
 
The sample size was calculated based on the assumptions of a 55% reduction in qRT-PCR VL- 
AUC, with a 72% coefficient of variation (CV) (based on similar previous studies), for a power 
of 80% and a 2-sided 5% level of significance (without adjustment for multiple comparisons) 
and assuming a 70% infectivity rate (based on similar previous studies). On this basis, it is 
estimated that 31 evaluable RSV infected (intent-to-treat infected [ITT-I]) participants per arm 
and 44 inoculated participants would be sufficient for the study to demonstrate an antiviral 
affect as measured by qRT-PCR with a power of at least 80% (achieved power computed as 
84.1%). However, with the more conservative assumption of a 63% infection rate, 44 recruited 
participants, resulting in 24 infected participants would allow to detect a 55% relative reduction 
in qRT-PCR VL-AUC with at least 80% (81.0%) power. 
 
The sample size of 44 participants per arm would allow to detect a decrease of 75% in TSS- 
AUC (CV of 92.9%) and 55% in TSS peak score (CV of 68.8%) with more than 80% power 
(87.8% and 87.2% respectively) assuming an infection rate of 70% (31 infected participants). 
The more conservative assumption of a 63% infection rate (28 infected participants) would 
allow to detect a 75% relative reduction in TSS-AUC and 55% in peak-AUC with respectively 
84.3% and 83.6% power. 
 
9.3. Analysis Sets 
 
For the purposes of analysis, the following analysis sets are defined (Table 9-1). 
 
Table 9-1:       Analysis Sets 
 
Participant   Analysis Description 
Set 
Enrolled 
A participant will be considered as enrolled into the study once 
he/she has been inoculated with the challenge virus. 
Intent-to-treat 
(ITT) All participants having received challenge virus, randomized, and 
having received at least one dose of IMP. 
analysis set 
Intent-to-treat infected All participants having received challenge virus, randomized, and 
having received at least one dose of IMP, and meeting the criterion 
for laboratory-confirmed RSV infection (see below for definition 
of laboratory-confirmed RSV infection). The ITT-I analysis set will 
be considered the primary analysis population for efficacy 
endpoints. A participant will fulfil the criteria for laboratory- 
confirmed RSV infection if: 
(ITT-I) analysis set 

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
Participant   Analysis Description 
Set 
• At least 2 positive detections by viral load qRT-PCR assay 
specific    for    the    challenge    virus,    reported    within 
• 
2 consecutive study days. 
and/or 
One positive detection by viral load qRT-PCR assay, 
specific for the challenge virus, in which an aliquot of the 
same sample has also tested positive in a cell-based 
infectivity assay appropriate for detecting the challenge 
virus. 
Intent-to-treat infected All participants having received challenge virus, randomized, and 
having received at least one dose of IMP, and meeting the criterion 
for laboratory-confirmed RSV infection (as per ITT-I) while using 
only assessments prior to taking IMP. The ITT-A analysis set will 
be considered a secondary analysis population for efficacy 
endpoints. ITT-A will be a subset of ITT-I. 
pre-dose         (ITT-A) 
analysis set 
Intent-to-treat infected All participants having received challenge virus, randomized, and 
having received at least one dose of IMP, and meeting the criterion 
for laboratory-confirmed RSV infection (as per ITT-I) while using 
only assessments after taking IMP. The ITT-B analysis set will be 
considered a secondary analysis population for efficacy endpoints. 
ITT-B will be a subset of ITT-I. 
post-dose        (ITT-B) 
analysis set 
Per     protocol 
(PP) All ITT-I analysis set participants who have no major protocol 
deviations, and who complete the quarantine period up to the final 
day of quarantine and receive all doses of IMP. Participant 
exclusions will be determined at a blinded data review meeting 
(BDRM), which will take place prior to database lock. The PP 
analysis set will be considered a secondary analysis population for 
efficacy endpoints. 
analysis set 
Safety analysis set 
All  participants  having  received  challenge  virus,  regardless  of 
whether they received IMP or not. 
Pharmacokinetics 
All ITT analysis set participants with at least one post-dose PK 
result. The PK analyses will be performed on the PK analysis set. 
(PK) analysis set 
 
 
Membership of participants in each analysis set will be determined at a planned BDRM, prior 
to any analysis and database lock. 
 
The study being exploratory by nature, aiming at assessing the true biological effect of the IMP 
used in the best experimental conditions and not the effectiveness of the strategy to treat 
participants with the IMP in conditions closest to real life, the primary efficacy analysis will 
be on the ITT-I analysis set. The ITT-A, ITT-B, and PP analysis sets will be considered a 
secondary analysis population for efficacy endpoints, as defined in the statistical analysis plan

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
(SAP). The safety evaluation will be performed on the safety analysis set. Additional analysis 
sets may be defined in the SAP. 
 
9.4. Statistical Analysis 
 
This section is a summary of the planned statistical analyses of the most important endpoints 
including primary and key secondary endpoints. 
 
Data will be analyzed and reported using SAS® version 9.4 or later. 
 
9.4.1.         Statistical Analysis Plan 
 
Full details of the planned statistical analysis will be presented in the SAP that will provide a 
more technical, detailed, and comprehensive description of the statistical analyses that will be 
computed, expanding on the protocol-specified analysis. 
 
Any deviation(s) from the original statistical plan outlined in the protocol will be described and 
justified in an amendment to the protocol and/or SAP, as appropriate, and referenced in the 
final clinical study report. 
 
Further post-hoc evaluations of any exploratory endpoints may be conducted and reported 
separately. 
 
9.4.2.         General Considerations 
 
9.4.2.1.      Descriptive Statistics 
 
Continuous variables will be summarized using number of available data, number of missing 
data, mean (and/or geometric mean, where applicable), standard deviation, median, lower 
quartile, upper quartile, minimum, and maximum values. When relevant, confidence intervals 
(CIs) will be computed for the mean and/or the median. 
 
Categorical variables will be summarized using number of available data, number of missing 
values, frequency counts for each category and corresponding percentage. Percentages will be 
calculated using the number of available data as the denominator (i.e., not including missing 
values). When relevant, CIs will be computed. 
 
9.4.2.2.      Inferential Statistics and Significance Testing 
 
Between-group comparisons will be performed using appropriate hypothesis tests at the 5% 
2-sided significance level, except if otherwise specified. No adjustment for multiple testing will 
be performed (see Section 9.1, Statistical Hypothesis). 
 
For continuous variables (either raw data or log-transformed data) the difference in means or 
medians,  the standard error and  the 95% 2-sided  CI will  be presented.  In  case of log- 
transformed variables, in addition to the previous statistics on the log-transformed data, the 
geometric means and geometric mean ratio and its 95% 2-sided CI for the original variable will 
be presented. The Wilcoxon rank sum test, t-test, or analysis of covariance will be used, 
depending on whether the endpoints are normally distributed. Details on the method used for 
each endpoint will be provided in the SAP. Methods for checking statistical model assumptions 
and alternative methods of analysis if the assumptions are not fulfilled will be described in the 
SAP. 
 
For categorical  variables,  differences  in  absolute frequency  and/or  relative risks  will  be 
presented, with their 95% 2-sided CIs. Except otherwise specified in the SAP, the Chi-square 
test (or Fisher exact test) will be used to compare frequencies between treatment groups.

 
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ENANTA Pharmaceuticals, Inc /hVIVO                                            Study number: EDP 323-101/ETP-CST-001 
Clinical Study Protocol                                                                                       Version: Final v2.0, 25-Mar-2024 
 
9.4.3.         Planned Analysis 
 
9.4.3.1.      Participant Accountability 
 
The number of participants receiving challenge agent, receiving EDP-323, withdrawing from 
(also split by reason for withdrawal) and completing the study, and the numbers in each analysis 
set, will be summarized. 
 
9.4.3.2.      Protocol Deviations 
 
Participant’s 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, participants will be reviewed for their inclusion/exclusion from the analysis sets. 
 
9.4.3.3.      Demographic and Baseline Characteristics 
 
Descriptive statistics of demographics (age, sex, height, body weight, BMI, and ethnicity) will 
be presented by treatment group and across all participants. Medical history information will 
be listed. Other baseline characteristics will be defined in the SAP. 
 
9.4.3.4.      Compliance to Study Intervention 
 
Compliance with IMP will be computed for each treatment group as proportion of participants 
actually receiving IMP as prescribed. 
 
9.4.4.         Primary Efficacy Analysis 
 
The primary efficacy analysis will be conducted on the ITT-I analysis set. 
 
The main estimator of the primary endpoint, the mean or median VL-AUC of RSV-A Memphis 
37b, depending on whether the endpoint is normally distributed, as determined by qRT-PCR 
on nasal samples (virology) collected twice daily starting 2 days post-viral challenge (Day 2) up 
to discharge from quarantine, will be analyzed on the ITT-I analysis set. 
 
The calculation of the VL-AUC will be performed on log10-transformed PCR data using the 
trapezoidal summation rule based on actual time intervals in hours. Results below the lower 
limit of quantification (LLOQ) will be given values as detailed in the SAP. 
 
Descriptive statistics and the 95% CI will be presented by treatment group. The differences 
between each active treatment group and the placebo arm will be analyzed using the t-test or 
Wilcoxon rank sum test, depending on whether the endpoint is normally distributed. 
 
Further details will be described in the SAP. 
 
9.4.5.         Secondary Efficacy Analysis 
 
Secondary endpoints as outlined in Section 3, Objectives and Endpoints, will be summarized 
by treatment group as described in Table 9-2. Further details will be provided in the SAP. 
 
Table 9-2:       Methods for Analysis of Secondary Efficacy Endpoints 
 
Endpoint 
Analysis 
RSV VLPEAK (RSV viral load by qRT- 
PCR in nasal samples) 
Descriptive statistics for continuous variables 
(see Section 9.4.2 , General Considerations). 
Inferential analysis: t-test or Wilcoxon rank 
sum test. 

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Version: Final v2.0, 25-Mar-2024 
 
 
 
 
Endpoint 
Analysis 
Time to RSV VLPEAK after first dosing 
(RSV viral load by qRT-PCR in nasal 
samples) 
Descriptive statistics for continuous variables 
(see Section 9.4.2, General Considerations). 
Kaplan Meier estimated will be computed. 
No inferential analysis. 
Time to RSV viral load negativity after first 
dosing (RSV viral load by qRT-PCR in nasal 
samples) 
Time to first negative slope of RSV viral 
load after first dosing (RSV viral load by 
qRT-PCR in nasal samples) 
Slope of the RSV viral load over time 
(clearance rate) from time of RSV VLPEAK 
to 1, 2, 3, and 4 days later (RSV viral load 
by qRT-PCR in nasal samples) 
Descriptive statistics for continuous variables 
(see Section 9.4.2, General Considerations). 
No inferential analysis. 
RSV  VL-AUC  (RSV  viral  load  by  cell 
culture [plaque assay] of nasal samples) 
Descriptive statistics for continuous variables 
(see Section 9.4.2, General Considerations). 
Inferential analysis: t-test or Wilcoxon rank 
sum test. 
RSV  VLPEAK  (RSV  viral  load  by  cell 
culture [plaque assay] of nasal samples) 
Time to RSV VLPEAK after first dosing 
(RSV viral load by cell culture [plaque 
assay] of nasal samples) 
Descriptive statistics for continuous variables 
(see Section 9.4.2, General Considerations). 
Kaplan Meier estimates will be computed. 
No inferential analysis. 
Time to RSV viral load negativity after first 
dosing (RSV viral load by cell culture 
[plaque assay] of nasal samples) 
Time to first negative slope of RSV viral 
load after first dosing (RSV viral load by cell 
culture [plaque assay] of nasal samples) 
Slope of the RSV viral load over time 
(clearance rate) from time of RSV VLPEAK 
to 1d, 2d, 3d, and 4d later (RSV viral load by 
cell culture [plaque assay] of nasal samples) 
Descriptive statistics for continuous variables 
(see Section 9.4.2, General Considerations). 
No inferential analysis. 
TSS-AUC 
Descriptive statistics for continuous variables 
(see Section 9.4.2, General Considerations). 
Inferential analysis: t-test or Wilcoxon rank 
sum test. 
Peak TSS 
Time to return to baseline (last assessment 
before RSV inoculation) TSS 
Descriptive statistics for continuous variables 
(see Section 9.4.2, General Considerations). 
Kaplan Meier estimates will be computed. 
No inferential analysis. 
Time to peak TSS 
Total  weight  of  nasal  discharge  (mucus) 
produced 
Descriptive statistics for continuous variables 
(see Section 9.4.2, General Considerations). 

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Endpoint 
Analysis 
Total number of tissues used by participants No inferential analysis 
AUC=area  under  the  curve;  qRT-PCR=quantitative  reverse  transcriptase-polymerase  chain  reaction; 
RSV=respiratory syncytial virus; TSS=total symptom score; TSS-AUC=area under the total symptom score- 
time curve; VL-AUC= area under the viral load-time curve; VLPEAK=peak viral load 
 
 
 
 
 
 
9.4.7.         Safety Analysis 
 
All safety analyses will be computed on the safety analysis set. 
 
Unless otherwise stated in the SAP, safety endpoints will be presented in terms of descriptive 
statistics only. 
 
Adverse events will be coded using the most current version of the Medical Dictionary for 
Regulatory Activities (MedDRA) and summarized descriptively by system organ class, 
preferred term, and treatment group for the number of AEs and the number of TEAEs reported 
and the number and percentage of participants reporting each AE and TEAE. A TEAE will be 
defined as any AE that occurs from the time of first study treatment dose administered to the 
participant until last study visit, i.e. an AE that was not present prior to receiving the first dose 
of IMP. 
 
A by-participant AE data listing including onset and resolution dates, verbatim term, preferred 
term, blinded treatment, severity, relationship to treatment, action taken, and outcome will be 
provided. 
 
Other safety endpoints that will be presented by treatment group include laboratory evaluations 
(biochemistry, hematology, coagulation, cardiac enzymes, and urinalysis), vital signs 
assessments, physical examinations, 12-lead ECG, and spirometry. Additionally, physical 
examinations will be listed. 
 
9.4.8.         Pharmacokinetic Analysis 
 
Descriptive statistics will be calculated for the plasma concentrations of EDP-323 (and 
metabolites) at each applicable time point and for the derived plasma PK parameters. Statistics 
include sample size (n), mean, standard deviation (SD), CV, geometric mean, median, 
minimum, and maximum. 
 
For each participant, plasma concentration-time data of EDP-323 (and metabolites) will be 
graphically presented. Similarly, graphs of the mean plasma concentration-time profiles and 
overlay graphs with combined individual plasma concentration-time profiles will be produced. 
 
Plasma PK (AUC) correlations with VL-AUC (e.g., qRT-PCR) and TSS-AUC or other efficacy 
endpoints may be conducted if supported by the data. 
 
Additional PK analyses may be performed as deemed necessary. 
 
The details of the PK analyses will be provided in a separate PK analysis plan. 
 
9.5. Interim Analysis 
 
No interim analysis is planned for this study.

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Version: Final v2.0, 25-Mar-2024 
 
 
 
 
9.6. Data Monitoring Committee 
 
Not applicable.

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Version: Final v2.0, 25-Mar-2024 
 
 
 
 
10. 
SUPPORTING   DOCUMENTATION   AND   OPERATIONAL 
CONSIDERATIONS 
 
10.1.    Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
 
10.1.1.       Regulatory and Ethical Considerations 
 
This study will be conducted in accordance with the protocol and with the following: 
 
• Consensus   ethical   principles   derived   from   international   guidelines   including   the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
International Ethical Guidelines. 
 
• Applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines. 
 
•    Applicable laws and regulations. 
 
In addition to regulatory submission, the protocol, protocol amendments, ICF, IB, and other 
relevant documents (e.g., advertisements) must be submitted to an REC by the PI/investigator 
and reviewed and approved by the REC before the study is initiated. 
 
Substantial amendments to the protocol will require regulatory authority and REC approval 
before implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
 
The PI/investigator will be responsible for the following: 
 
• Providing written summaries of the status of the study to the REC annually, or more 
frequently, in accordance with the requirements, policies, and procedures established by the 
REC. 
 
•    Notifying the REC of SAEs or other significant safety findings as required by  REC 
procedures. 
 
• Providing oversight of the conduct of the study at the site and adherence to requirements 
of ICH guidelines, the REC, the REC, UK SI 2004/1031 The Medicines for Human Use 
(Clinical Trials) Regulations, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations. 
 
10.1.2.       Financial Disclosure 
 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the study and for 1 year after 
completion of the study. 
 
10.1.3.       Confidentiality 
 
The PI/investigator will preserve the confidentiality of participants taking part in the study and 
confirms that the PI/investigator is registered under the Data Protection Act.

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10.1.4.       Informed Consent Process 
 
The trained and delegated study staff competent to perform the informed consent procedure 
will obtain a signed study-specific ICF from each participant before any study-specific 
procedures are performed. 
 
Historical screening data may be collected through the hVIVO generic screening process, which 
is a comprehensive assessment of health status including previous medical history. For 
assessments taken under the hVIVO generic screening, a separate informed consent is 
obtained. 
 
When historical screening data collected through the hVIVO generic screening process is used 
for screening, the study-specific ICF will be obtained at the first study-specific visit from each 
participant before any study-specific procedures are performed. 
 
Potential participants will typically be sent a copy of the REC approved study-specific ICF at 
the time of invite to the first study-specific visit and at least a day prior to the visit and will be 
encouraged to read it prior to their appointment. Upon arrival at the screening visit/quarantine 
admission visit (as applicable), the study-specific ICF is discussed by the trained and delegated 
study staff competent to perform the informed consent procedure, and the participants will be 
given the opportunity to ask any questions and may take the information sheet away to consider 
their participation. 
 
All participants will be required to have a good understanding of English and the PI/investigator 
will be responsible for ensuring that the participant understands the information contained in the 
ICF. Once the PI/investigator has confirmed that the participant has capacity and has understood 
the study, including the benefits and risks of participation, the participant and the PI/investigator 
can sign and date the study-specific ICF. 
 
The study-specific ICF must be signed and dated by the participant and countersigned by the 
trained and  delegated  study  staff competent  to  perform  the  informed  consent  procedure 
(whoever conducted the consent discussion). A copy of the study-specific ICF will be given to 
the participant, and the original will be held in the in the ISF. 
 
Participants 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 the study-specific ICF. 
 
The study-specific ICF will contain a separate section that addresses the use of samples for 
future research. The PI/investigator or authorized designee will explain to each participant the 
objectives of the exploratory research. Participants will be told that they are free to refuse to 
participate (with no requirements to disclose the reason for withdrawal) and may withdraw their 
consent at any time and for any reason. 
 
10.1.5.       Data Protection 
 
Participants will be assigned a unique identifier by hVIVO. Any participant records or datasets 
that are transferred to the sponsor will contain the identifier only; participant names or any 
information which would make the participant identifiable will not be transferred. 
 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant in ICF.

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Version: Final v2.0, 25-Mar-2024 
 
 
 
 
The participant must be informed that his/her medical records may be examined by clinical 
quality assurance auditors or other authorized study staff appointed by the sponsor, by 
appropriate REC members, and by inspectors from regulatory authorities. 
 
10.1.6.       Committee(s) Structure 
 
This study will not include an early safety data review. However, participant safety will be 
continuously monitored by the study and sponsor medical monitors which includes safety signal 
detection at any time during the study. 
 
10.1.7.       Dissemination of Clinical Study Data 
 
The key design elements of this protocol will be posted on publicly accessible registry. 
A ‘public registry’ is defined as any register on the World Health Organization (WHO) list of 
primary registries or the International Committee of Medical Journal Editors (ICMJE) list of 
registries, e.g., ClinicalTrials.gov or International Standardized Randomized Controlled Trial 
Number (ISRCTN) registry. 
 
It is the sponsor’s (or sponsor delegate) responsibility to send the Clinical Trial Summary 
Report to the REC and MHRA (if required) within 1 year of the end of the study, and where 
applicable, to publish the summary results within 1 year of the end of the study in the public 
register(s) where the clinical study was registered. 
 
The PI/investigator shall provide assurance to participants that their confidentiality will be 
maintained hVIVO have a legal obligation to always protect the confidentiality of participant 
personal data from the point of capture, through processing, dissemination in line with consent 
from the participant and to its final disposition. 
 
10.1.8.       Data Quality Assurance 
 
Participant data will be collected at site using paper source casebooks which will then be data 
entered into the eCRF database unless transmitted to the sponsor or designee electronically 
(e.g., laboratory data). The PI/investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the eCRF. 
 
The PI/investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. This can be paper source and/or eSource. 
 
The PI/investigator must permit study-related monitoring, audits, REC review, and regulatory 
agency inspections and provide direct access to source data documents. Monitoring details 
describing strategy (e.g., risk-based initiatives in operations and quality such as Risk 
Management  and Mitigation Strategies  and Analytical Risk-based  Monitoring), methods, 
responsibilities, and requirements, including handling of noncompliance issues and monitoring 
techniques (remote or on-site monitoring) are provided in the Monitoring Plan. 
 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized investigator site staff are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the PI/investigator during the retention period as agreed with the sponsor and as 
required by local regulations or institutional policies.

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10.1.9.       Source Documents 
 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
 
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
PI/investigator may need to request previous medical records or transfer of records, depending 
on the study. Also, current medical records must be available. 
 
Definition of what constitutes source data for the study can be found in the Source Data 
Agreement. 
 
10.1.10.     Study Discontinuation 
 
The sponsor reserves the right to temporarily suspend or terminate the study for any reason at 
any time. In addition, the study may be temporarily suspended or terminated at any time if, in 
the opinion of the PI/investigator, the safety data suggests that the medical safety of participants 
is being compromised. 
 
If the study is suspended or terminated for safety reason(s), the sponsor will promptly inform 
the PI/investigator, and will also inform the regulatory authorities of the suspension or 
termination of the study and the reason(s) for the action. 
 
The PI/investigator is responsible for promptly informing the REC and providing the reason(s) 
for the suspension or termination of the study. 
 
If the study is prematurely terminated, all study data must be returned to the sponsor. In 
addition, the site must conduct final disposition of all unused IMPs in accordance with the 
sponsor’s procedures for the study. 
 
Termination of the clinical study may also be initiated by the MHRA or the REC. 
 
10.1.11.     Publication Policy 
 
By signing the protocol, the PI/investigator agrees that the results of this study may be used by 
sponsor in any manner sponsor deems appropriate, including but not limited to regulatory 
submissions, publications, annual reports and other scientific or business affairs of the 
company. 
 
If necessary, the authorities will be notified of the PI/investigator’s name, address, 
qualifications, and extent of involvement. To allow the use of the information derived from this 
study, the PI/investigator understands that he/she has an obligation to provide to sponsor 
complete and accurate results and all data developed during this study. 
 
hVIVO agrees that the first publication of Sponsor Data (as defined in the Master Services 
Agreement (MSA) shall be made by the sponsor. The sponsor agrees to allow the 
PI/investigator time to review all manuscripts and abstracts prior to submission for publication, 
and, that all reasonable comments made by hVIVO in relation to the publication will be 
considered by sponsor. 
 
If sponsor does not have a publication planned, submitted or under review within twenty-four 
(24) months after the study has been completed, hVIVO may publish Sponsor Data with 
sponsor’s prior written consent. Subject to terms of the MSA, hVIVO shall be permitted to 
present at symposia, national or regional professional meetings, and to publish in journals, 
theses or dissertations, or otherwise of their own choosing, methods and results of the study. 
 
.

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Prior to submitting or presenting a manuscript or other materials relating to the study to a 
publisher, reviewer, or other outside person/entity, hVIVO shall provide to sponsor a copy of 
all such manuscripts and materials, and sponsor shall have at least 60 days from receipt of such 
manuscripts and material to review and comment. hVIVO agrees that all reasonable comments 
made by the sponsor in relation to the publication will be considered by hVIVO. 
 
At sponsor’s request, hVIVO shall remove any sponsor confidential information, including 
Sponsor Data, prior to submitting or presenting the materials. Sponsor shall be entitled to 
require hVIVO to delay any publication for a period of up to 6 months from the date of first 
submission to the sponsor in order to enable the sponsor to take steps to protect property owned 
by sponsor and any associated intellectual property rights. hVIVO shall not unreasonably 
withhold or delay its consent to a request from the sponsor for an exceptional additional delay 
if, in the reasonable opinion of the sponsor, the property owned by sponsor and any associated 
intellectual property rights might otherwise be compromised or lost. 
 
For the avoidance of doubt, hVIVO shall not require sponsor’s consent nor shall the above 
requirements apply to any publication of property owned by hVIVO in so far as such publication 
does not include property owned by sponsor or any other confidential information of the 
sponsor.

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10.2.    Appendix 2: Clinical Laboratory Tests 
 
The tests detailed in Table 10-1 will be performed by the local laboratory. 
 
Study-specific requirements for inclusion or exclusion of participants are detailed in Section 5, 
Study Population. 
 
Additional tests may be performed at any time during the study as determined necessary by the 
PI/investigator or required by local regulations. 
 
Table 10-1:    Protocol-required Safety Laboratory Assessments 
 
Laboratory Assessments 
Parameters 
Hematology 
Platelet count 
White blood cell count (absolute) 
White blood cell count differential: 
•    Neutrophils 
•    Lymphocyte 
•    Monocytes 
•    Eosinophils 
•    Basophils 
Red blood cell count 
Reticulocyte count (% and absolute) 
Hemoglobin 
Hematocrit 
Mean corpuscular volume 
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin concentration 
Biochemistry 
Sodium 
Potassium 
Glucose 
Albumin 
Chloride 
Bicarbonate 
Calcium 
Uric acid 
Total protein 
Creatinine 
Total, direct, and indirect bilirubin 
Inorganic phosphate 
Blood urea nitrogen 
C-reactive protein 
Gamma glutamyl transferase 
Alkaline phosphatase 
Alanine aminotransferase (ALT) 
Lactate dehydrogenase 
Aspartate aminotransferase (AST) 
Urea 

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Laboratory Assessments 
Parameters 
Coagulation 
Prothrombin time 
Activated partial thromboplastin time 
Thyroid function 
Thyroid stimulating hormone 
Thyroxine 
Cardiac enzymes 
Creatine kinase 
Troponin 
Routine urinalysis 
Color 
Specific gravity 
Appearance 
pH 
Presence  of  blood,  glucose,  leukocytes,  ketones,  nitrites, 
proteins, urobilinogen, and bilirubin by dipstick. 
If the dipstick yields clinically significant abnormal results: 
microscopy, culture, and sensitivity examination. 
Other screening/eligibility FSH* 
tests 
β-hCG* 
Urine pregnancy test* 
Urine drugs of misuse and cotinine 
Alcohol breath test 
Total cholesterol** 
Antibodies against HIV type 1/2 (HIV-1)/(HIV-2) 
Hepatitis A immunoglobulin M** 
Hepatitis B surface antigen 
Hepatitis C antibodies 
Glycated hemoglobin** 
Immunoglobulin A antibodies** 
*     FSH only for postmenopausal female participants, β-hCG for all female participants, and urine 
pregnancy test only for female participants of childbearing potential. 
**   Optional at the discretion of the PI/investigator. 
 
Investigators must document their review of each laboratory safety report. 
 
Laboratory results that could unblind the study will not be reported to investigative sites or 
other blinded study staff until the study has been unblinded.

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10.3. Appendix  3:  Adverse  Events  –  Definitions  and  Procedures  for  Recording, 
Evaluating, Follow-up and Reporting 
 
10.3.1.       Adverse Event 
 
Adverse Event Definition 
 
An AE is defined as any untoward medical occurrence in clinical study participants 
administered a pharmaceutical (investigational or non-investigation) product. An AE does 
not necessarily have a causal relationship with the study intervention. An AE can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal (investigational or 
non-investigational) product (definition as per ICH). 
 
This will also cover any AEs occurring after study intervention(s) including administration 
with the challenge agent in viral challenge studies. 
 
 
 
Events Meeting the Adverse Event Definition 
 
•    Exacerbation of a pre-existing illness. 
 
•    Increase in frequency or severity of a pre-existing episodic condition. 
 
• A condition detected or diagnosed after study intervention administration even though it 
may have been present prior to the start of the study. 
 
•    A complication that occurs during a hospitalization. 
 
•    A clinically significant change in laboratory parameter. 
 
 
 
Events NOT Meeting the Adverse Event Definition 
 
•    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 condition present or detected prior to start of study intervention 
administration that does not worsen (including screening findings such as abnormal 
laboratory results). 
 
• Hospitalization for elective surgery, social and/or convenience admissions provided they 
are arranged before the start of study intervention administration and the reason does not 
worsen. 
 
• Over-administration of either the study intervention 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/solicited viral infection symptoms on SDCs. 
 
• Procedure-related events may be noted during the study while conducting nasal sampling 
(collection of nasal wash samples, nasopharyngeal swabs, or other nasal samples), 
specifically:

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Events NOT Meeting the Adverse Event Definition 
 
o Nasal discomfort/irritation 
o Nasal abrasions 
o Nasal epistaxis 
o Sneezing 
o Watery eyes 
When mild in nature and as expected in the opinion of the PI/investigator or delegated 
physician, these events will not be reported as AEs. 
 
•    Asymptomatic bruising following venipuncture, or removal of an intravenous cannula. 
 
• Dry lips and skin if solely due to the air conditioning in the quarantine unit, with or 
without the use of emollients to maintain skin integrity. 
 
 
10.3.2.       Adverse Drug Reaction 
 
An adverse drug reaction is any untoward and unintended response in a participant to an IMP 
which is related to any dose administered to that participant. 
 
‘Response’ in this context means that a causal relationship between a medicinal product and 
an AE is at least a reasonable possibility. 
 
All AEs assessed by either the reporting PI/investigator or the sponsor as having a reasonable 
causal relationship to an IMP qualify as adverse drug reactions. The expression ‘reasonable 
causal relationship’ means to convey in general that there is evidence or argument to suggest a 
causal relationship. 
 
10.3.3.       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 authorization, in the Summary of Product 
Characteristics for that product, 
 
b)  In the case of any other IMP, in the Investigator’s Brochure (IB) relating to the study 
in question. 
 
10.3.4.       Serious Adverse Event 
 
Serious Adverse Event Definition 
 
An SAE is defined as any untoward medical occurrence that, at any dose: 
 
a)  Results in death 
b)  Is life threatening 
The term ‘life threatening’ in the definition of ‘serious’ refers to an event in which 
the participant was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe. 
 
c)  Requires inpatient hospitalization or prolongation of existing hospitalization

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Serious Adverse Event Definition 
 
• In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfils any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
 
d)  Results in persistent disability/incapacity 
 
•    The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle) which may interfere with 
or prevent everyday life functions but do not constitute a substantial disruption. 
 
e)  Is a congenital anomaly/birth defect 
f)   Is an important medical event 
• Important medical events’ – some medical events may jeopardize the participant 
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 hospitalization but may 
jeopardize the participant 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. 
 
 
10.3.5.       Suspected Unexpected Serious Adverse Reaction 
 
A 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 IB relating to the 
study in question. 
 
Medical events will be assessed for expectedness against the reference safety information 
section of the IB or equivalent, and any available IB addendum. Any changes to the reference 
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 different 
from ‘serious’ which is based on participant/event outcome or action criteria.

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Version: Final v2.0, 25-Mar-2024 
 
 
 
 
10.3.6.       Recording, Assessment, and Follow-up of Adverse Events/Serious Adverse 
Events 
 
10.3.6.1.    Adverse Event/Serious Adverse Event Recording 
 
All AEs/SAEs will be collected from the time of written study-specific informed consent until 
study completion/final study contact or until the resolution of the AE. Adverse events will be 
fully recorded in the source documents as they are reported whether spontaneously reported by 
a participant 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 PI/investigator should assess 
the participant’s eligibility to continue in the study. 
 
The PI/investigator will record all relevant information regarding an AE/SAE in the source 
documents and evaluate AEs/SAEs using the following guidelines: 
 
• Description of event (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 
 
•    Clinical outcome 
 
• Relationship    or    causality     (IMP/challenge     agent/study     procedures/concomitant 
medication/other). 
 
Any clinically significant abnormal laboratory result, vital sign or other measure will be 
followed until resolution (return to normal or baseline values), stabilization, it is judged by the 
PI/investigator to be no longer clinically significant, the participant is lost to follow-up, or an 
alternative explanation has been provided. 
 
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.

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Even if the AE/SAE is assessed by the PI/investigator as not reasonably attributable to the 
challenge agent, its occurrence must be fully documented in the source notes. 
 
10.3.6.2.    Assessment 
 
Description 
 
If the event consists of a cluster of signs and symptoms, 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. 
 
Assessment 
Challenge Agent-related Symptoms 
The PI/investigator will assess, and review challenge agent-related symptoms recorded in 
participants’ hVIVO symptom diary cards (SDCs). Symptoms greater than grade 0 will be 
expected and presumed to represent infection consequent to challenge agent inoculation 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 PI/investigator). 
Following challenge agent inoculation all unexpected (in the opinion of the PI/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. 
Symptom-directed Physical Examination 
Following challenge agent inoculation, URT symptoms (nasal discharge, otitis, pharyngitis, 
sinus tenderness) and LRT symptoms (abnormal breath sounds externally [e.g., stridor, 
wheezing] and on chest auscultation [rhonchi, crepitations or other]) will be expected and 
presumed to represent infection consequent to challenge agent 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 PI/investigator). 
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. 

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Assessment 
Temperature 
Following challenge agent inoculation, pyrexia (temperature ≥37.9C) will be expected and 
presumed to represent infection consequent to challenge agent 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 PI/investigator) to be classed as an AE. 
Following challenge agent inoculation all unexpected (in the opinion of the PI/investigator) 
pyrexia 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 and confirmed by a repeat on the 
same day) may be judged a grade 1 (mild) AE. However, due to variability in participants’ 
ability to perform these tests with adequate technique, the PI/investigator and/or SME will 
use his/her clinical judgement to assess whether abnormal spirometry readings are consistent 
with a true drop and whether an AE should be raised. The PI/investigator will use his/her 
clinical judgement to assign severity grades above grade 1, based on evaluation of clinical 
signs and symptoms. If a spirometry reading on repeat assessment 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 meets the criteria for an AE and is deemed to be clinically significant (in 
the opinion of the PI/investigator). 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 PI/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 PI/investigator. Laboratory abnormalities detected 
at screening will be considered as part of the medical history and will not be reported as AEs. 
Challenge agent associated laboratory abnormalities (e.g., elevated alanine aminotransferase 
(ALT), aspartate aminotransferase (AST), or gamma glutamyl transferase; decreased 
neutrophils) may be recorded as AEs (at the discretion of the PI/investigator). 
C-reactive Protein 
Any value above 5 mg/L but less than 60 mg/L will be a grade 1 (mild) AE (unless deemed 
nonclinically 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. 
 
10.3.6.3.    Assessment of Intensity 
 
The term ’severe’ is often used to describe the intensity (severity) of a specific event. This is 
different from ‘serious’ which is based on participant/event outcome or action criteria.

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Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
The PI/investigator will use the CTCAE grading scale as a reference when collecting, reporting, 
and clarifying database queries of AEs, SAEs, and adverse reactions. 
 
The severity of an AE that does not appear in the CTCAE grading scale should be determined 
according to the definitions in Table 10-2. 
 
Table 10-2:     Classification of Adverse Event Severity 
 
Grade 
Classification 
Definition 
Grade 1 
Mild 
Mild level of discomfort and does not interfere with regular 
activities. 
Grade 2 
Moderate 
Moderate level of discomfort and significantly interferes with 
regular activities. 
Grade 3 
Severe 
Significant level of discomfort and prevents regular activities. 
 
An event is defined as ‘serious’ when it meets at least one of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
 
10.3.6.4.    Frequency 
 
The frequency of the AE should be categorized as one of the following: 
 
•    Single 
 
•    Intermittent 
 
•    Continuous 
 
10.3.6.5.    Assessment of Causality 
 
• The PI/investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
 
•    A ‘reasonable possibility’ of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
 
•    The PI/investigator will use clinical judgement to determine the relationship. 
 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention administration 
will be considered and investigated. 
 
•    The PI/investigator will also consult the IB or Product Information (for marketed products) 
in his/her assessment. 
 
• For each AE/SAE, the PI/investigator  must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
 
• There may be situations in which an SAE has occurred, and the PI/investigator has minimal 
information to include in the initial report to sponsor’s medical expert (SME) or the 
pharmacovigilance representative. However, it is very important that the PI/investigator 
always assesses causality for every event before the initial transmission of the SAE data to 
the SME or pharmacovigilance representative.

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• The  PI/investigator  may  change  his/her  opinion  of  causality  considering  follow-up 
information and send an SAE follow-up report with the updated causality assessment. 
 
• The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
The relationship of an AE to the IMP will be categorized as shown in Table 10-3. 
 
Table 10-3:     Classification of Adverse Event Relationship 
 
Classification 
Definition 
Not related 
The AE is related to an etiology other than the IMP (the alternative 
etiology must be documented in the participant’s medical record). 
Unlikely to be related 
The AE is unlikely to be related to the IMP and likely to be related 
to factors other than IMP. 
Possibly related 
There is an association between the AE and the administration of 
the IMP, and there is a plausible mechanism for the AE to be related 
to the IMP, but there may also be alternative etiology, such as 
characteristics of the participant’s clinical status or underlying 
disease. 
Probably related 
A reasonable temporal sequence of the AE and the IMP 
administration exists and based upon the known pharmacological 
action of the drug, known or previously reported adverse reactions 
to the drug or class of drugs, or judgement based on the 
PI/investigator’s clinical experience, the association of the AE with 
the IMP seems likely. 
Definitely related 
A definite causal relationship exists between the AE and the 
administration of the IMP, and other conditions do not appear to 
explain the AE. 
 
Unless an AE is ‘definitely related’ to the IMP, a causal relationship to one of the following 
should be considered, and full details provided on the AE reporting form as appropriate. 
 
•    Challenge agent 
 
•    Study procedures 
 
•    Concomitant medication 
 
•    Other 
 
10.3.6.6.    Action Taken 
 
The PI/investigator should ensure that adequate medical care is provided to participants for any 
AEs/SAEs, including clinically significant laboratory values related to the study intervention. 
In addition, the PI/investigator will describe whether any treatment was given for the AE. 
 
The PI/investigator will classify the action taken regarding the AE/SAE. The action taken 
should be classified according to the following categories and full details provided as 
appropriate:

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•    None 
 
•    Nondrug therapy given 
 
•    Concomitant medication taken 
 
•    IMP dose not changed 
 
•    IMP dose reduced 
 
•    IMP dose increased 
 
•    IMP administration interrupted 
 
•    IMP administration withdrawn 
 
•    Participant withdrawn 
 
•    Participant hospitalized 
 
•    Other 
 
10.3.6.7.    Outcome 
 
An AE/SAE should be followed until the PI/investigator has determined and recorded the 
outcome or an alternative explanation. The outcome should be classified according to the 
categories shown in Table 10-4. 
 
Table 10-4:     Classification of Adverse Event Outcome 
 
Classification 
Definition 
Resolved 
Resolution of the AE with no residual signs or symptoms. 
Resolved with sequelae 
Resolution of the AE with residual signs or symptoms. 
Not resolved 
Either incomplete improvement or no improvement of the AE, 
such that it remains ongoing. 
Fatal 
Outcome of the AE was death. ‘Fatal’ should be used when death 
was at least possibly related to the AE. 
Unknown  (e.g.,  lost  to 
follow-up) 
Outcome of the AE is not known (e.g., the participant is lost to 
follow-up). 
 
10.3.6.8.    Follow-up 
 
All AEs/SAEs must be followed up by the PI/investigator for follow-up until they are: 
 
•    Resolved (return to normal or baseline values), or 
 
•    Stabilized, or 
 
•    Judged by the PI/investigator to be no longer clinically significant, or 
 
•    The participant is lost to follow-up, or 
 
•    An alternative explanation has been provided.

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Where appropriate, the participant may be referred to the participant’s GP or other healthcare 
professional. 
 
Additional measurements and/or evaluations may be necessary to investigate the nature and/or 
causality of an AE/SAE. This may include additional laboratory tests, diagnostic procedures, 
histopathological examinations, or consultation with other healthcare professionals. If the 
participant dies, any post-mortem findings (including histopathology) will be provided to the 
sponsor if possible. 
 
10.3.7.       Reporting of Serious Adverse Events 
 
Serious AEs must be documented and reported as per hVIVO SOPs. 
 
Prompt notification of SAEs by the PI/investigator to the sponsor is essential so that the sponsor 
can meet its regulatory and REC reporting obligations for the study. If the PI/investigator does 
not have all of the details regarding the SAE, he/she will not wait until this information becomes 
available before making the initial report to sponsor. Contact details are detailed in Table 10-5. 
 
Notification should be made: 
 
• By telephone as soon as possible and within 24 hours of the PI/investigator being made 
aware of the event. 
 
• In a detailed written report within 24 hours of the PI/investigator becoming aware of the 
event. 
 
All reports should be directed to the SME and pharmacovigilance representative. The 
PI/investigator at the site is responsible for ensuring that a member of the sponsor study team 
is made aware of any SAE reports that have been transmitted. 
 
Table 10-5:     Contact Details for Reporting All Serious Adverse Events 
 
Contact 
Details 
Name of sponsor’s medical expert (SME) 
or pharmacovigilance representative: 
 
SME SAE telephone number: 
Mobile Phone: 
 
Pharmacovigilance reporting email: 
Email: 
 
Pharmacovigilance telephone reporting: 
 Safety Helpline 
EAPA: 
 
SAE email address: 
 Drug Safety Center Email Address 
EAPA: 
 
 
In addition, any AE resulting in permanent study discontinuation for a participant, even if not 
serious and regardless of expectedness or causality, must be reported by telephone, email, or 
fax to the sponsor within 7 calendar days of the PI/investigator or any other investigator site 
staff’s knowledge of the event. 
 
The SAE form, AE record and relevant concomitant medication record should be emailed to 
the   sponsor’s   SME   and   pharmacovigilance   representative   within   24 hours   of   the

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PI/investigator or any investigator site staff’s knowledge of an SAE. An updated SAE report 
form should be forwarded to the sponsor within 24 hours of receipt of the new/updated 
information as relevant. 
 
Information relating to the participant’s subsequent medical progress must be submitted to the 
sponsor or pharmacovigilance representative as available, until the SAE has subsided or, in the 
case of permanent impairment, until it stabilizes, and the overall clinical outcome has been 
ascertained. 
 
The PI/investigator will also provide additional information, including a copy of the following 
documents (where applicable): 
 
•    Copies of test results, as available. 
 
•    Hospital discharge summary (as soon as it is available to the PI). 
 
•    Autopsy report (as soon as it is available to the PI). 
 
The PI/investigator  must  report  SAEs/SUSARs to  the relevant  REC in  accordance with 
applicable regulatory requirements and within the relevant timelines. 
 
The REC will be sent annual safety updates in order to facilitate their continuing review of the 
study. 
 
10.3.8.       Reporting of Suspected Unexpected Serious Adverse Reactions 
 
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 a 
clinical study 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 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. 
 
10.3.9.       Adverse Reactions to Non-investigational Medicinal Products 
 
Any AEs/SAEs which are related to/caused by a concomitant medication or challenge agent, 
should not be classed as adverse reactions, serious adverse reactions, or SUSARs (adverse 
reactions, serious adverse reactions, SUSARs relate only to IMP by definition). However, an 
SAE caused by a non-IMP would need to be reported to the MHRA/REC and participants must 
be followed up until the event is considered resolved, judged by the PI/investigator to be no 
longer clinically significant, the participant is lost to follow-up, an alternative reason has been 
provided, or until the PI in conjunction with the sponsor deem the event stable and a decision 
for no further follow-up has been taken (see Section 10.3.6.7, Outcome, and Section 10.3.6.8, 
Follow-up). 
 
10.3.10.     Post-study Adverse Events and Serious Adverse Events 
 
All SAEs that occur during the study from ICF signature must be reported by the PI/investigator 
to the SME as soon as possible, in accordance with hVIVO SOPs, and at the latest within 
24 hours of becoming aware of the event.

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All AEs/SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the participant’s participation in the study, must be followed up until the 
event is considered resolved, judged by the PI/investigator to be no longer clinically significant, 
the participant is lost to follow-up, an alternative reason has been provided, or until the PI in 
conjunction with the sponsor deem the event stable and a decision for no further follow-up has 
been taken (see Section 10.3.6.8, Follow-up). 
 
10.3.11.     Pregnancy 
 
If a female participant or female partner of a male participant becomes pregnant during of the 
study, this must be reported by the PI/investigator to the SME and study monitor by telephone 
as soon as possible, in accordance with hVIVO SOPs, and at the latest within 24 hours of 
becoming aware of the event. 
 
Following the telephone notification, the PI/investigator must fully and accurately complete the 
appropriate pregnancy reporting form, which must be emailed to the SME and the study monitor 
at the latest within 24 hours of becoming aware of the pregnancy. 
 
Participants will be advised to contact their GP or a specialist, as appropriate. 
 
Consent for follow-up of the pregnancy and pregnancy outcome will be sought from the 
pregnant study participant or the pregnant partner of the male study participant as applicable. 
Consent for follow-up will be documented on an hVIVO Pregnancy follow-up ICF. 
 
Provided that the appropriate consent is in place, information related to the pregnancy will be 
collected as per hVIVO SOPs and the sponsor’s requirements. The completed reporting form(s) 
will be sent to the sponsor 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 IWRS will be used (Section 6.3, Randomization and Blinding) to break the blind for 
the appropriate study participant to ensure that further care can be based on the actual 
identity of the study intervention that the participant received. 
 
• hVIVO will maintain contact with the participant for a protracted period, 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 participant, will keep the participant’s GP informed. 
 
• All cases of fetal drug exposure via the parent as a study participant will be reported to the 
sponsor and the REC. 
 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal distress, fetal death, 
stillbirth, congenital anomaly/birth defect, ectopic pregnancy) are considered SAEs.

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Version: Final v2.0, 25-Mar-2024 
 
 
 
 
10.4.    Appendix 4: Normal Ranges 
 
hVIVO Normal Ranges for Healthy Participants 
 
Vital signs normal ranges 
 
Vital Signs 
Lower Limit 
Higher Limit 
Units 
Tympanic 
temperature 
(above 37.8 classed as 
pyrexia) 
35.5 
37.8 
C 
Oxygen saturation 
Normal is ≥95 
Respiratory rate 
10 
20 
Breaths per minute 
Heart rate 
40 
100 
Beats per minute 
Systolic blood pressure 
90 
140 
mmHg 
Diastolic blood pressure 
50 
90 
mmHg 
 
Electrocardiogram 
 
ECG Parameters 
Lower Limit 
Higher Limit 
Units 
HR 
40 
100 
Beats per minute 
QRS 
60 
120 
ms 
PR interval 
120 
220 
ms 
QT 
320 
450 
ms 
QTc (Fridericia/Bazett) 
320 
<450 (females) 
ms 
<430 (males) 
 
Spirometry 
 
Spirometry Parameters 
Lower Limit 
Higher Limit 
Units 
FEV1 
Normal if ≥80% of the predicted value 
Liters 
FEV1/FVC 
Normal if ≥70% (≥0.7) of the predicted value Liters 
 
No single value should be used in isolation, all spirometry reference ranges require physician 
interpretation of the participant’s overall status to determine their relevance.

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10.5.    Appendix 5: Abbreviations 
 
Abbreviation 
Term 
AE 
Adverse event 
ALRI 
Acute lower respiratory infection 
ALT 
Alanine aminotransferase 
AM 
Alveolar macrophages 
AP 
Analytical plan 
AST 
Aspartate aminotransferase 
ATS/ERS 
American Thoracic Society/European Respiratory Society 
AUC 
Area under the curve 
AUC0-24 
Area under the concentration-time curve from time 0 to 24 hours in the 
dosing period 
AUC0-∞ 
Area under the concentration-time curve from time 0 to infinity 
AUClast 
Area under the concentration-time curve from time 0 to time of last 
quantifiable concentration 
AUC0-tau 
Area under the concentration-time curve over the dosing interval 
β-hCG 
Beta-human chorionic gonadotrophin 
BDRM 
Blinded data review meeting 
BMI 
Body mass index 
BP 
Blood pressure 
C12h 
Plasma concentration at 12 hours 
C24h 
Plasma concentration at 24 hours 
CI 
Confidence interval 
CL/F 
Apparent systemic clearance ( 
Cmax 
Maximum plasma concentration 
COVID-19 
Coronavirus disease 2019 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of variation 
DNA 
Deoxyribonucleic acid 
EC90 
90% Effective concentration 
ECG 
Electrocardiogram 
(e)CRF 
(Electronic) case report form 
FE 
Food effect 
FEV(1) 
Forced expiratory volume (in 1 second) 
FIH 
First-in-human 
FSH 
Follicle-stimulating hormone 
FVC 
Forced vital capacity 
GAD 
Generalized Anxiety Disorder 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
GP 
General practitioner 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
IB 
Investigator’s Brochure 
IBS 
Irritable bowel syndrome 
ICF 
Inform consent form 

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Abbreviation 
Term 
ICH 
International Council for Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IMP 
Investigational medicinal product 
ISRCTN 
International Standardized Randomized Controlled Trial Number 
ITT 
Intent-to-treat 
ITT-I 
Intent-to-treat infected 
ITT-A 
Intent-to-treat infected pre-dose 
ITT-B 
Intent-to-treat infected post-dose 
IWRS 
Interactive web response system 
λz 
Terminal elimination rate constant 
LLOQ 
Lower limit of quantification 
LRT 
Lower respiratory tract 
MAD 
Multiple ascending dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHRA 
Medicines and Healthcare products Regulatory Agency 
MSA 
Master Services Agreement 
NGS 
Next Generation Sequencing 
NOAEL 
No observed adverse effect level 
PCR 
Polymerase chain reaction 
PFU 
Plaque-forming unit 
PHQ 
Patient Health Questionnaire 
PI 
Principal investigator 
PK 
Pharmacokinetic(s) 
PP 
Per protocol 
QD 
Once daily 
qicPCR 
Qualitative integrative cycler polymerase chain reaction 
qRT-PCR 
Quantitative reverse transcriptase-polymerase chain reaction 
REC 
Research Ethics Committee 
RiiQ 
Respiratory Infection Intensity and Impact Questionnaire 
RiiQ-AUC 
Area under the total RiiQ-time curve 
RNA 
Ribonucleic acid 
RR 
Respiratory rate 
RSV 
Respiratory syncytial virus 
RVAT 
Rapid viral antigen test 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SD 
Standard deviation 
SDC 
Symptom diary card 
SME 
Sponsor’s medical expert 
SoE 
Schedule of events 
SOP 
Standard operating procedure 
SpO2 
Peripheral arterial oxygen saturation 
SUSAR 
Suspected unexpected adverse reaction 
t1/2 
Terminal half-life 
TEAE 
Treatment-emergent adverse event 

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Abbreviation 
Term 
tmax 
Time to maximum plasma concentration 
TSS 
Total symptom score 
TSS-AUC 
Area under the total symptom score-time curve 
UK 
United Kingdom 
URT 
Upper respiratory tract 
Vd/F 
Volume of distribution 
VL-AUC 
Area under the viral load-time curve 
VLPEAK 
Peak viral load 
WHO 
World Health Organization 

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10.6.    Appendix 6: Definitions 
 
10.6.1.       General 
 
Term 
hVIVO Services Limited Definition 
Baseline 
For safety assessments the nearest assessments completed 
prior to inoculation will be used as the baseline measure, 
unless stated otherwise. 
Challenge 
The  inoculation  of  a  participant  with  challenge  agent 
inoculum. By definition, the day of challenge is Day 0. 
Completion (of a participant’s 
participation in the study) 
A participant is considered to have completed the study if 
he/she has completed all phases of the study including the 
last scheduled visit shown in the SoE or the last 
unscheduled visit as applicable. If a safety visit is required 
after the last scheduled visit, this will be at the discretion 
of the PI/investigator as a duty of care, e.g., repeat 
spirometry or laboratory tests. These discretionary follow- 
up visits will not be considered part of the study data unless 
they represent follow-up and closure on an AE or SAE 
identified during the study period. 
End-of-study 
The end of the study is defined as the date of the last visit 
of the last participant in the study. 
Enrolment (of a participant into 
the study) 
A participant will be considered as enrolled into the study 
once he/she has been inoculated with the challenge virus. 
Potential participants who are screened for the purpose of 
determining suitability for the study, but do not participate 
in the study, are not considered enrolled, unless otherwise 
specified by the protocol. 
First study visit 
The visit in which the study-specific consent is signed, 
therefore this may be admission to quarantine. 
Infectious titer 
The titer of inoculum producing viral infection in a 
participant. The term ‘titer’ applies to the quantity or 
concentration of inoculum (depending on the units 
documented). 
Last study visit 
The last visit of the last participant in the study. 
Quarantine group 
A group of participants who are admitted to and are 
resident in the quarantine unit for a particular quarantine 
period (i.e., participants whose Day 0 and scheduled 
discharge date are the same). 
Quarantine period 
The period when clinical study participants are isolated in 
the quarantine unit during a human viral challenge study. 

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Randomization number 
The number allocated to a participant at randomization, 
generated as stated in the protocol (NB. Not applicable will 
be recorded for “screen fail” participants or participants 
who are not randomized). 
Screen failures 
Screen failures are defined as participants who sign the 
study-specific ICF but are not subsequently enrolled into 
the study. Screen failures will not be included in the study 
database. Screen failures may be invited back for repeat 
assessments and screening and if eligible, for study 
enrolment. 
Subject number 
The unique number assigned to a subject in the hVIVO 
database, which is used to identify a subject prior to 
randomization. This number will be used throughout the 
recruitment and generic screening process to identify the 
subject. 
 
10.6.2.       Study Definition of Infection and Illness 
 
Term 
CRITERIA 
Seroconversion 
A  ≥4-fold  increase  in  RSV-specific  antibodies  from 
baseline to follow-up post-quarantine 
The following definitions should only be applied to data collected from Day 1 onwards 
Febrile illness 
Any occurrence of temperature ≥37.9C 
Laboratory-confirmed 
RSV 
• At least 2 positive detections by viral load qRT- 
infection 
• 
PCR assay specific for the challenge virus, reported 
within 2 consecutive study days 
and/or 
One positive detection by viral load qRT-PCR 
assay, specific for the challenge virus, in which an 
aliquot of the same sample has also tested positive 
in a cell-based infectivity assay appropriate for 
detecting the challenge virus 
Upper respiratory tract (URT) Any  one  of  the  following  signs  and/or  symptoms  on 
2 consecutive scheduled assessments, at least one of which 
must feature grade 2 severity, or if any of the following 
attain grade 3 severity once: 
• Self-reported  symptoms:  rhinorrhea  (runny  nose), 
nasal congestion (stuffy nose), sore throat, sneezing 
• Physician findings: nasal discharge, otitis, pharyngitis, 
sinus tenderness 
Illness 

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Term 
CRITERIA 
Lower respiratory tract (LRT) Any  one  of  the  following  signs  and/or  symptoms  on 
Illness 
2 consecutive scheduled assessments, at least one of which 
must feature grade 2 severity, or if any of the following 
attain grade 3 severity once: 
• Self-reported symptoms: cough, shortness of breath, 
chest tightness and wheeze 
•    Physician    findings:    Abnormal    breath     sounds 
externally  (e.g.,  stridor,  wheezing)  and  on  chest 
auscultation (rhonchi, crepitations or other) 
Systemic illness 
Fulfils  the  criteria  for  febrile  illness,  or  fulfils  the 
definition of URT illness and/or LRT illness, 
and 
any  one  of the  following  symptoms  on  2  consecutive 
scheduled assessments, at least one of which must feature 
grade 2 severity, or if any of the following attain grade 3 
severity once: 
•    malaise 
•    headache 
•    muscles and/or joint ache 
•    chilliness 
•    feverishness 
Viral shedding (for dosing) 
One positive detection by qualitative integrative cycler 
polymerase chain reaction (qicPCR) 

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11.          REFERENCES 
 
Agius G, Dindinaud G, Biggar RJ, Peyre R, Vaillant V, Ranger S, et al. An epidemic of 
respiratory syncytial virus in elderly people: clinical and serological findings. J Med Virol. 
1990;30:117-127. 
 
Bavarian Nordic. MVA-BN RSV Human Challenge Trial Results (Accessed September 16, 
2021, 
at 
https://www.bavarian-nordic.com/media/309881/210901-mva-bn-hct-results- 
en.pdf.). 
 
Bont L, Checchia PA, Fauroux B, Figueras-Aloy J, Manzoni P, Paes B, et al. Defining the 
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Confidential 
 
ENANTA Pharmaceuticals, Inc /hVIVO 
Clinical Study Protocol 
Study number: EDP 323-101/ETP-CST-001 
Version: Final v2.0, 25-Mar-2024 
 
 
 
 
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