Clinical trial NCT05523089
Conditions: Influenza
Sponsor: Cidara Therapeutics Inc.
Start date: 2022-09-09; Completion date: 2023-07-17
Enrollment: 59 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the preventative antiviral activity of CD388, as compared to saline placebo, when administered as a single dose to healthy adult participants in a human viral challenge model of influenza.

Detailed description:
This is a single-center, randomized, double-blind, placebo-controlled, proof-of-concept study in healthy adult male and female participants 18 to 55 years of age, inclusive. The primary goal of this Phase 2a study is to assess the prophylactic antiviral activity against influenza, safety, tolerability, and pharmacokinetics (PK) of CD388 via a human viral challenge (HVC) model, and to explore the impact of dose levels on efficacy. Each participant will receive a single administration of CD388 or placebo; multiple dose levels of CD388 may be evaluated.

Arms: arm 1: In Cohort 1, up to 30 participants will be randomized to receive a single dose of placebo, administered by subcutaneous (SQ) injection, prior to being inoculated with the influenza challenge virus. Based on an interim analysis to be performed on data collected from the evaluation of Cohort 1 participants who have completed the inpatient phase at the time the interim analysis is performed, additional participants (of a number to be informed by the interim analysis) may be randomized into Cohort 2 in an extension of this Arm 1, to receive a single dose of placebo by SQ injection prior to viral challenge. arm 2: In Cohort 1, up to 30 participants will be randomized to receive a single dose of 150 milligrams (mg) CD388, administered by SQ injection, prior to being inoculated with the influenza challenge virus. Based on an interim analysis to be performed on data collected from the evaluation of Cohort 1 participants who have completed the inpatient phase at the time the interim analysis is performed, additional participants (of a number to be informed by the interim analysis) may be randomized into Cohort 2 in an extension of this Arm 2, to receive a single dose of 150 mg CD388 by SQ injection prior to viral challenge. arm 3: In Cohort 1, up to 30 participants will be randomized to receive a single dose of 50 mg CD388, administered by SQ injection, prior to being inoculated with the influenza challenge virus. Based on an interim analysis to be performed on data collected from the evaluation of Cohort 1 participants who have completed the inpatient phase at the time the interim analysis is performed, additional participants (of a number to be informed by the interim analysis) may be randomized into Cohort 2 in an extension of this Arm 3, to receive a single dose of 50mg CD388 by SQ injection prior to viral challenge. arm 4: Based on an interim analysis to be performed on data collected from the evaluation of Cohort 1 participants who have completed the inpatient phase at the time the interim analysis is performed, participants (of a number to be informed by the interim analysis) may be randomized into Cohort 2 in this Optional Arm 4, to receive a single dose of CD388 lower than 150 mg (TBD based on PK results obtained in the first-in-human study CD388.IM.SQ.1.01, as well as the interim analysis), administered by SQ injection, prior to being inoculated with the influenza challenge virus. arm 5: Based on an interim analysis to be performed on data collected from the evaluation of Cohort 1 participants who have completed the inpatient phase at the time the interim analysis is performed, participants (of a number to be informed by the interim analysis) may be randomized into Cohort 2 in this Optional Arm 5, to receive a single dose of CD388 lower than 150 mg (TBD based on PK results obtained in the first-in-human study CD388.IM.SQ.1.01, as well as the interim analysis), administered by SQ injection, prior to being inoculated with the influenza challenge virus. arm 6: Based on an interim analysis to be performed on data collected from the evaluation of Cohort 1 participants who have completed the inpatient phase at the time the interim analysis is performed, participants (of a number to be informed by the interim analysis) may be randomized into Cohort 2 in this Optional Arm 6, to receive a single dose of CD388 lower than 150 mg (TBD based on PK results obtained in the first-in-human study CD388.IM.SQ.1.01, as well as the interim analysis), administered by SQ injection, prior to being inoculated with the influenza challenge virus.
Interventions: intervention 1: Saline placebo intervention 2: CD388
Intervention descriptions: intervention 1: Sterile normal saline for injection intervention 2: CD388 liquid for injection

Protocol documents:
Prot_002.pdf: 
Study Protocol 
 
 
Title: 
A proof-of-concept, randomized, double-blind, placebo-controlled, Phase 
2a study to assess the prophylactic antiviral activity against influenza, 
safety, tolerability, and pharmacokinetics of CD388 via a human viral 
challenge model 
NCT Number: 
NCT05523089 
Document Date: 
06 OCT 2022 
 


 
 
 
 
CLINICAL STUDY PROTOCOL 
A PROOF-OF-CONCEPT, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2A 
STUDY TO ASSESS THE PROPHYLACTIC ANTIVIRAL ACTIVITY AGAINST INFLUENZA, 
SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF CD388 VIA A HUMAN VIRAL 
CHALLENGE MODEL 
 
Short Title: 
Phase 2a study of the prophylactic antiviral activity 
of CD388 in an influenza challenge model in healthy 
adults 
Version and Date of Protocol: 
Final Version 4.0, 06Oct2022 
Sponsor: 
Cidara Therapeutics, Inc. 
6310 Nancy Ridge Dr., Suite 101 
San Diego, California 92121, USA 
Sponsor Protocol Number: 
CD388.SQ.2.02 
hVIVO Protocol Number: 
 
Compound Number: 
CD388 
IRAS ID Number: 
1005986 
 
Confidentiality and Protections Statement: 
This document contains confidential information of hVIVO and Cidara Therapeutics. 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 Cidara Therapeutics. 
Personal data included in the protocol is subject to General Data Protection Regulation (European 
Union 2016/679) considerations and protections. 
 


 
 
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Sponsor Statement 
This protocol, CD388.SQ.2.02, 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: 
 
 
 
 
 
 
 
 
Date 
(DD MMM YYYY) 
 
 




 
 
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Study Staff Contact Information 
 
CONTACT 
DETAILS 
Sponsor 
Cidara Therapeutics, Inc. 
6310 Nancy Ridge Dr., Suite 101 
San Diego, California 92121, USA 
 
 
 
 
Sponsor’s representative 
 
Cidara Therapeutics, Inc. 
6310 Nancy Ridge Drive, Suite 101 
San Diego, California 92121, USA 
 
 
 
Principal investigator and clinical 
study unit 
 
hVIVO Services Limited 
Queen Mary BioEnterprises Innovation Centre 
42 New Road, London E1 2AX, United Kingdom (UK) 
  
Sponsor's medical expert/medical 
monitor 
 
Cidara Therapeutics, Inc. 
6310 Nancy Ridge Dr., Suite 101 
San Diego, California 92121, USA 
 
 
Key protocol contributors 
Refer to the local study contact list document 
 
 


 
 
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Table of Contents 
Table of Contents .................................................................................................................................... 5 
Table of Contents .................................................................................................................................... 5 
List of Tables ........................................................................................................................................... 8 
List of Figures .......................................................................................................................................... 9 
1. 
Protocol Synopsis .................................................................................................................... 10 
1.1. 
Study Schematic: On-study Participant Progression ............................................................. 18 
1.2. 
Schedule of Events ................................................................................................................ 19 
2. 
Introduction ............................................................................................................................... 26 
2.1. 
Influenza ................................................................................................................................ 26 
2.2. 
CD388 – A Long-acting Antiviral Fc-Conjugate ..................................................................... 27 
2.2.1. 
Nonclinical Studies ........................................................................................................... 27 
2.2.2. 
Clinical Experience ........................................................................................................... 28 
2.3. 
Study Rationale ..................................................................................................................... 30 
2.4. 
Benefit/Risk Assessment ....................................................................................................... 30 
2.4.1. 
Risk Assessment .............................................................................................................. 30 
2.4.1.1. 
Vulnerable Persons ..................................................................................................... 35 
2.4.1.2. 
Risk Associated with Coronavirus Disease 2019 Pandemic ....................................... 35 
2.4.2. 
Benefit Assessment .......................................................................................................... 36 
2.4.3. 
Overall Benefit: Risk Conclusion ...................................................................................... 36 
3. 
Objectives and Endpoints ........................................................................................................ 37 
4. 
Study Design ............................................................................................................................. 42 
4.1. 
Overall Design ....................................................................................................................... 42 
4.2. 
Scientific Rationale for Study Design .................................................................................... 44 
4.3. 
Justification for Dose ............................................................................................................. 45 
4.4. 
Population to be Studied ........................................................................................................ 45 
4.5. 
Rationale for Trial Endpoints ................................................................................................. 45 
4.6. 
End of Study Definition .......................................................................................................... 45 
5. 
Study Population ...................................................................................................................... 47 
5.1. 
Inclusion Criteria .................................................................................................................... 47 
5.2. 
Exclusion Criteria ................................................................................................................... 49 
5.3. 
Lifestyle Considerations ......................................................................................................... 53 
5.3.1. 
Meals and Dietary Restrictions ......................................................................................... 53 
5.3.2. 
Caffeine, Alcohol, and Tobacco ........................................................................................ 53 
5.3.3. 
Activity .............................................................................................................................. 53 
5.4. 
Screen Failures ...................................................................................................................... 54 
6. 
Study Intervention .................................................................................................................... 55 
6.1. 
Study Intervention(s) Administered ....................................................................................... 55 
6.2. 
Preparation/Handling/Storage/Administration/Accountability ................................................ 56 
6.2.1. 
Investigational Medicinal Product ..................................................................................... 56 
6.2.2. 
Challenge Agent ............................................................................................................... 56 
6.2.3. 
All Study Interventions ...................................................................................................... 57 
6.3. 
Randomisation and Blinding .................................................................................................. 57 
6.4. 
Study Intervention Compliance .............................................................................................. 59 
6.5. 
Concomitant Therapy ............................................................................................................ 60 
6.6. 
Dose Modification .................................................................................................................. 61 
6.7. 
Treatment of Overdose .......................................................................................................... 62 


 
 
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7. 
Discontinuation of Study Intervention/Withdrawal ............................................................... 63 
7.1. 
Participant Withdrawal ........................................................................................................... 63 
7.2. 
Participant Discontinuation .................................................................................................... 63 
7.2.1. 
Temporary Discontinuation/Temporary Delay in Enrolment ............................................ 64 
7.3. 
Lost to Follow-up ................................................................................................................... 64 
7.4. 
Participant Replacement Strategy ......................................................................................... 64 
7.5. 
Stopping Rules ...................................................................................................................... 64 
7.6. 
Adaptive Features .................................................................................................................. 66 
8. 
Study Assessments and Procedures ..................................................................................... 68 
8.1. 
Demographics and Baseline Characteristics ......................................................................... 68 
8.1.1. 
Demographics ................................................................................................................... 68 
8.1.2. 
Height, Body Weight, and Body Mass Index .................................................................... 68 
8.1.3. 
Medical and Medication History ........................................................................................ 68 
8.1.4. 
Challenge Agent Serology Samples ................................................................................. 69 
8.1.5. 
Patient Health Questionnaire and Generalised Anxiety Disorder Questionnaire ............. 69 
8.2. 
Respiratory Samples ............................................................................................................. 69 
8.2.1. 
Nasosorption ..................................................................................................................... 69 
8.2.2. 
Nasopharyngeal Swab ..................................................................................................... 69 
8.2.2.1. 
Respiratory Pathogen Screen ..................................................................................... 69 
8.2.2.2. 
Influenza Discharge Test/Rapid Viral Antigen Test ..................................................... 70 
8.2.3. 
Viral Sequencing .............................................................................................................. 70 
8.3. 
Efficacy Assessments ............................................................................................................ 70 
8.3.1. 
Viral Shedding Assessment .............................................................................................. 70 
8.3.2. 
Participant Diary Cards ..................................................................................................... 70 
8.3.3. 
Nasal Discharge Collection from Paper Tissues .............................................................. 71 
8.3.4. 
Respiratory Tract Infection Surveillance ........................................................................... 71 
8.3.4.1. 
Active Surveillance ...................................................................................................... 71 
8.3.4.2. 
Passive Surveillance ................................................................................................... 72 
8.3.4.3. 
Assessment for Potential Influenza Respiratory Tract Infection ................................. 72 
8.3.5. 
Exploratory Assessments ................................................................................................. 73 
8.4. 
Safety Assessments .............................................................................................................. 73 
8.4.1. 
Complete Physical Examination ....................................................................................... 73 
8.4.2. 
Symptom-directed Physical Examination ......................................................................... 73 
8.4.3. 
Reactogenicity Events (Diary Card) ................................................................................. 73 
8.4.3.1. 
Grading Scale .............................................................................................................. 74 
8.4.4. 
Vital Signs and Tympanic Temperature ........................................................................... 74 
8.4.5. 
Electrocardiogram ............................................................................................................ 75 
8.4.6. 
Clinical Safety Laboratory Assessments .......................................................................... 75 
8.4.6.1. 
Urinalysis ..................................................................................................................... 75 
8.4.6.2. 
Drugs of Misuse and Cotinine ..................................................................................... 76 
8.4.6.3. 
Alcohol Breath Testing ................................................................................................ 76 
8.4.6.4. 
Safety Blood Analysis and Assessments .................................................................... 76 
8.4.7. 
Pregnancy Tests and Follicle-stimulating Hormone ......................................................... 76 
8.4.8. 
Lung Function ................................................................................................................... 76 
8.5. 
Recording of Adverse Events/Serious Adverse Events ........................................................ 77 
8.5.1. 
Time Period and Frequency for Collecting Adverse Events and Serious Adverse Event 
Information ........................................................................................................................ 77 
8.5.2. 
Method of Detecting Adverse Events/Serious Adverse Events ....................................... 77 
8.5.3. 
Follow-up of Adverse Events/Serious Adverse Events .................................................... 78 
8.5.4. 
Regulatory Reporting Requirements for Serious Adverse Events ................................... 78 
8.5.5. 
Pregnancy ......................................................................................................................... 78 


 
 
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8.6. 
Pharmacokinetics .................................................................................................................. 78 
8.6.1. 
Pharmacokinetic Blood Samples ...................................................................................... 79 
8.6.2. 
Pharmacokinetic Nasopharyngeal Swab Samples........................................................... 79 
8.6.3. 
Pharmacokinetic Parameters ........................................................................................... 80 
8.6.4. 
Anti-drug Antibodies ......................................................................................................... 80 
8.7. 
Pharmacodynamics ............................................................................................................... 80 
8.8. 
Immunology Assessments ..................................................................................................... 80 
8.9. 
Genetics ................................................................................................................................. 80 
8.10. 
Biomarkers ............................................................................................................................. 80 
8.10.1. 
Immunology Biomarker Evaluations ................................................................................. 81 
9. 
Statistical Considerations ........................................................................................................ 82 
9.1. 
Statistical Hypotheses ........................................................................................................... 82 
9.2. 
Sample Size Determination ................................................................................................... 82 
9.3. 
Participant Sets for Analyses ................................................................................................. 82 
9.4. 
Statistical Analyses ................................................................................................................ 83 
9.4.1. 
Statistical Analysis Plan .................................................................................................... 83 
9.4.2. 
General Considerations .................................................................................................... 83 
9.4.2.1. 
Descriptive Statistics ................................................................................................... 83 
9.4.2.2. 
Inferential Statistics and Significance Testing ............................................................. 84 
9.4.3. 
Planned Analysis .............................................................................................................. 84 
9.4.3.1. 
Participant Accountability ............................................................................................ 84 
9.4.3.2. 
Protocol Deviations...................................................................................................... 84 
9.4.3.3. 
Demographic and Baseline Characteristics ................................................................ 84 
9.4.3.4. 
Compliance to Study Intervention ............................................................................... 84 
9.4.4. 
Primary Efficacy Analysis ................................................................................................. 85 
9.4.5. 
Secondary Efficacy Analysis ............................................................................................ 85 
9.4.6. 
Tertiary/Exploratory Analysis ............................................................................................ 86 
9.4.7. 
Safety Analyse(s) ............................................................................................................. 86 
9.4.8. 
Pharmacokinetic Analysis ................................................................................................. 87 
9.5. 
Interim Analysis ..................................................................................................................... 87 
9.6. 
Data Monitoring Committee ................................................................................................... 87 
10. 
Supporting Documentation and Operational Considerations.............................................. 88 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations ................................ 88 
10.1.1. 
Regulatory and Ethical Considerations ............................................................................ 88 
10.1.2. 
Financial Disclosure ......................................................................................................... 88 
10.1.3. 
Confidentiality ................................................................................................................... 88 
10.1.4. 
Informed Consent Process ............................................................................................... 88 
10.1.5. 
Data Protection ................................................................................................................. 89 
10.1.6. 
Committee(s) Structure .................................................................................................... 90 
10.1.7. 
Dissemination of Clinical Study Data ............................................................................... 90 
10.1.8. 
Data Quality Assurance .................................................................................................... 90 
10.1.9. 
Source Documents ........................................................................................................... 91 
10.1.10. 
Study Discontinuation ....................................................................................................... 91 
10.1.11. 
Publication Policy ............................................................................................................. 91 
10.2. 
Appendix 2: Clinical Laboratory Tests ................................................................................... 92 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting .................................................................................................................. 94 
10.3.1. 
Adverse Event .................................................................................................................. 94 
10.3.2. 
Adverse Drug Reaction .................................................................................................... 96 
10.3.3. 
Unexpected Adverse (Drug) Reaction .............................................................................. 96 
10.3.4. 
Serious Adverse Event ..................................................................................................... 96 


 
 
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10.3.5. 
Suspected Unexpected Serious Adverse Reaction .......................................................... 97 
10.3.6. 
Recording, Assessment, and Follow-up of Adverse Events/Serious Adverse Events ..... 97 
10.3.6.1. 
Adverse Event/Serious Adverse Event Recording ...................................................... 97 
10.3.6.2. 
Assessment ................................................................................................................. 98 
10.3.6.3. 
Assessment of Intensity ............................................................................................ 100 
10.3.6.4. 
Frequency .................................................................................................................. 101 
10.3.6.5. 
Assessment of Causality ........................................................................................... 101 
10.3.6.6. 
Action Taken .............................................................................................................. 102 
10.3.6.7. 
Outcome .................................................................................................................... 102 
10.3.6.8. 
Follow-up ................................................................................................................... 103 
10.3.7. 
Reporting of Serious Adverse Events ............................................................................ 103 
10.3.8. 
Reporting of Suspected Unexpected Serious Adverse Reaction ................................... 104 
10.3.9. 
Adverse Reactions to Non-investigational Medicinal Products ...................................... 104 
10.3.10. 
Pregnancy ....................................................................................................................... 104 
10.4. 
Appendix 4: Normal Ranges ................................................................................................ 106 
10.5. 
Appendix 5: Genetics ........................................................................................................... 107 
10.6. 
Appendix 6: Abbreviations ................................................................................................... 108 
10.7. 
Appendix 7: Definitions ........................................................................................................ 110 
10.7.1. 
General ........................................................................................................................... 110 
10.7.2. 
Study Definition of Infection and Illness ......................................................................... 111 
10.7.3. 
Study Definition of a Postmenopausal Woman .............................................................. 112 
10.8. 
Appendix 8: Protocol Amendment History ........................................................................... 113 
11. 
References ............................................................................................................................... 115 
 
 List of Tables 
Table 2-1: 
Duration of post-dose observations included in current blinded safety summary ........... 28 
Table 2-2: 
Blinded treatment-emergent adverse events by system organ class and preferred term in 
the safety population ........................................................................................................ 29 
Table 2-3: 
Risk Assessment ............................................................................................................. 31 
Table 6-1: 
Study Interventions .......................................................................................................... 55 
Table 6-2: 
Prohibited Medication (Healthy Participants) ................................................................... 60 
Table 6-3: 
Permitted Medication ....................................................................................................... 61 
Table 7-1: 
Study Stopping Rules ...................................................................................................... 65 
Table 7-2: 
Adaptive Features ............................................................................................................ 66 
Table 9-1: 
Study Participant Sets for Analysis .................................................................................. 82 
Table 9-2: 
Methods for Analysis of Secondary Efficacy Endpoints .................................................. 85 
Table 10-1: Protocol-required Safety Laboratory Assessments ......................................................... 92 
Table 10-2: Classification of Adverse Event Severity ....................................................................... 100 
Table 10-3: Classification of Adverse Event Relationship ................................................................ 102 
Table 10-4: Classification of Adverse Event Outcome ...................................................................... 103 


 
 
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 List of Figures 
Figure 4-1: Overview of Study Design .................................................................................................. 43 
 




 
 
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Secondary: 
Efficacy 
To evaluate the effect of CD388, in 
reducing or shortening viral shedding after 
influenza viral challenge compared to 
placebo. 
• 
Peak viral load of influenza as defined by the 
maximum viral load determined by quantifiable 
qRT-PCR measurements in nasal samples 
from Day 1 (pm) up to Day 8 (am). 
• 
Time (hours) to confirmed negative test by 
quantifiable qRT-PCR measurements in nasal 
samples from Day 1 (pm) to first confirmed 
undetectable assessment after peak measure. 
To evaluate the effect of CD388, in 
reducing 
or 
shortening 
culturable/replicating virus after influenza 
viral challenge compared to placebo. 
• 
VL-AUC of influenza challenge virus as 
determined by viral culture on nasal samples, 
from Day 1 (pm) up to Day 8 (am). 
• 
Peak viral load of influenza as defined by the 
maximum viral load determined by quantitative 
viral culture measurements in nasal samples 
from Day 1 (pm) up to Day 8 (am). 
• 
Time (hours) to confirmed negative test by 
quantifiable viral culture measurements in 
nasal samples from Day 1 (pm) to first 
confirmed undetectable assessment after peak 
measure. 
To evaluate the effect of CD388, in 
reducing clinical symptoms due to influenza 
viral challenge compared to placebo. 
• 
Area under the curve over time of total clinical 
symptoms score (TSS-AUC) as measured by 
graded symptom scoring system collected 
3 times daily from Day 1 (am) up to Day 8 (am). 
• 
Peak symptoms diary card score: peak of total 
clinical symptoms (TSS) as measured by 
graded symptom scoring system collected 
3 times daily from Day 1 (am) up to Day 8 (am). 
• 
Peak daily symptom score: individual maximum 
daily sum of symptom score from Day 1 up to 
Day 8. 
• 
Time to symptom resolution as measured by 
graded daily symptom score system from time 
of peak daily symptom score to time of 
returning to baseline score. 
To evaluate the effect of CD388, in 
reducing 
the 
incidence 
of 
influenza 
infection due to influenza viral challenge, 
compared to placebo. 
• 
RT-PCR-confirmed influenza infection, defined 
as 2 quantifiable (≥ lower limit of quantification 
[LLOQ]) qRT-PCR measurements (reported on 
2 or more independent samples over 2 days), 
from Day 1 (pm) up to Day 8 (am). 
• 
Occurrence of at least 1 positive quantitative 
(≥LLOQ) cell culture measurement in nasal 
samples, from Day 1 (pm) up to Day 8 (am). 
• 
RT-PCR-confirmed 
symptomatic 
influenza 
infection, defined as: 


 
 
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o 
RT-PCR-confirmed 
influenza 
infection 
(2 quantifiable 
[≥LLOQ] 
qRT-PCR 
measurements [reported on 2 or more 
independent samples over 2 days]), from 
Day 1 (pm) up to Day 8 (am), AND 
o 
Symptoms ≥2 at a single time point. 
• 
RT-PCR-confirmed 
moderately 
severe 
symptomatic influenza infection, defined as: 
o 
RT-PCR-confirmed 
influenza 
infection 
(2 quantifiable 
[≥LLOQ] 
qRT-PCR 
measurements [reported on 2 or more 
independent samples over 2 days]), from 
Day 1 (pm) up to Day 8 (am), AND 
o 
Any symptoms of grade ≥2 at a single time 
point. 
• 
Culture lab-confirmed symptomatic influenza 
infection, defined as: 
o 
Lab-confirmed 
culturable 
influenza 
infection 
(1 quantifiable 
[≥LLOQ] 
cell 
culture measurement), from Day 1 (pm) up 
to Day 8 (am), AND 
o 
Symptoms ≥2 at a single time point. 
Safety 
To evaluate the safety of CD388 when 
compared to placebo. 
• 
Occurrence of solicited adverse events (AEs) 
from subcutaneous dosing up to Day 0. 
• 
Occurrence 
of 
unsolicited 
AEs 
from 
subcutaneous dosing up to Day 28 (±3 days). 
• 
Occurrence 
of 
unsolicited 
AEs 
from 
subcutaneous dosing up to the final follow-up 
visit (Day 180 ±14 days). 
Tertiary / Exploratory*: 
To further evaluate the effect of CD388, in 
reducing or shortening viral shedding after 
influenza viral challenge compared to 
placebo. 
• 
Duration of quantifiable influenza qRT-PCR 
measurements in nasal samples from Day 1 
(pm) up to Day 8 (am). Duration is defined as 
the time (hours) from first detectable until first 
confirmed undetectable assessment after their 
peak measure (after which no further virus is 
detected). 
To further evaluate the effect of CD388, in 
reducing 
or 
shortening 
culturable/replicating virus after influenza 
viral challenge compared to placebo. 
• 
Duration of quantitative influenza viral culture 
measurements in nasal samples from Day 1 
(pm) up to Day 8 (am). Duration is defined as 
the time (hours) from first detectable until first 
confirmed undetectable assessment after their 
peak measure (after which no further virus is 
detected). 


 
 
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To further evaluate the effect of CD388, in 
reducing clinical symptoms due to influenza 
viral challenge compared to placebo. 
• 
Time to peak as measured by graded daily 
symptom score system (from Day 1 [am] to the 
time of peak daily symptom score). 
• 
Number (%) of participants with symptom 
scored grade 2 or higher, from Day 1 (am) up 
to Day 8 (am). 
• 
Number (%) of participants with symptom 
scored grade 2 or higher by time point, from 
Day 1 (am) up to Day 8 (am). 
To further evaluate the effect of CD388, in 
reducing 
the 
incidence 
of 
influenza 
infection due to influenza viral challenge, 
compared to placebo. 
• 
Number (%) of participants with lab-confirmed 
infection and fever (≥37.9°C). 
• 
Further sensitivity analysis may be performed 
on the above qRT-PCR-related incidence 
endpoints where detection by qRT-PCR is 
reported above the lower limit of detection 
(LLOD) instead of the LLOQ. Details will be 
provided in the statistical analysis plan (SAP). 
To evaluate the effect of CD388, in 
reducing nasal discharge compared to 
placebo. 
• 
Total weight of mucus produced from Day 1 
(am) up to Day 8 (am). 
• 
Total number of tissues used by participants 
from Day 1 (am) up to Day 8 (am). 
To evaluate the effect of CD388, in 
reducing incidence of community-acquired 
influenza infection compared to placebo. 
• 
Laboratory--confirmed symptomatic influenza 
infection (community acquired), defined as: 
o 
Self-reported 
influenza-like 
symptoms, 
AND 
o 
Community acquired (not challenge virus) 
laboratory-confirmed influenza infection 
PCR measurement and/or lateral flow 
positive, or other equivalent) reported on 
any 
occasion 
from 
discharge 
from 
quarantine up to Day 90 and/or up to 
Day 180 (±14 days). 
To monitor the safety of the challenge virus. • 
Occurrence of unsolicited AEs from virus 
challenge (Day 0) up to Day 28. 
To evaluate the plasma PK of CD388. 
• 
Pharmacokinetic (PK) parameters following 
CD388 administration will be determined as 
appropriate from the available data including: 
maximum plasma concentration (Cmax), time to 
maximum plasma concentration (Tmax), area 
under the plasma concentration-time curve 
from time 0 to time of last quantifiable sample 
(AUC0-t), 
and 
area 
under 
the 
plasma 
concentration-time 
curve 
from 
time 
0 
extrapolated to infinity (AUC0-∞). 
To explore CD388 concentrations in 
nasopharyngeal swab samples. 
• 
CD388 concentrations in nasopharyngeal 
swabs. 


 
 
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To explore PK/PD of CD388. 
• 
Plasma concentration at specific time points, or 
PK parameters across dose groups, will be 
compared to viral or symptomatic endpoints in 
an effort to characterise the exposure response 
of CD388, and will be reported separately.  
To explore cytokines and chemokines in 
nasal samples. 
• 
Cytokine/chemokine levels may be explored in 
nasal samples, related to CD388 and infection. 
To explore cytokines and chemokines in 
serum samples. 
• 
Cytokine/chemokine levels may be explored in 
serum samples, related to CD388 and 
infection. 
To explore markers associated with the 
effect of CD388 or with infection. 
• 
Gene expression (messenger RNA [mRNA]) in 
whole blood. 
To explore viral resistance markers in 
influenza viral positive nasal samples 
• 
Viral resistance markers relevant for CD388. 
*Note that tertiary objectives and endpoints are optional and might be assessed only if needed; therefore, 
not all testing might be performed and reported. 
Hypothesis 
The primary statistical hypothesis is that prophylactic treatment with CD388 at the 
dose of 150 mg will significantly reduce influenza VL-AUC as determined by qRT-
PCR on nasal samples compared to placebo 
Investigational 
medicinal 
product (IMP) 
Active: CD388 liquid for subcutaneous injection 
Placebo: sterile normal saline for injection 
Challenge 
agent 
Influenza H3N2 A/Perth/16/2009 
Challenge 
agent route 
Intranasally 
Challenge 
agent titre 
~105.5 tissue culture infective dose (50%) (TCID50) 
Study 
population 
Healthy adult male and female participants aged between 18 to 55 years, inclusive, 
with a total body weight ≥50 kg and body mass index (BMI) ≥18 kg/m2 and 
≤35kg/m2, who have been determined to be sero-suitable with regard to pre-
existing antibody levels to the influenza challenge virus. 
Summary of 
study design 
This is a single-centre, randomised, double-blind, placebo-controlled, proof-of-
concept study in healthy adult male and female participants 18 to 55 years of age, 
inclusive. The primary goal of this Phase 2a study is to assess the prophylactic 
antiviral activity against influenza, safety, tolerability, and PK of CD388 via a human 
viral challenge (HVC) model, and to explore the impact of dose levels on efficacy. 
Each participant will receive a single administration of CD388 or placebo; multiple 
dose levels of CD388 may be evaluated. 


 
 
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A total of up to 168 participants is planned to be enrolled in this study in up to 
2 cohorts. Cohort 1 will consist of up to 90 participants that will be enrolled 
simultaneously; a placebo arm (Arm 1, n=up to 30) and two CD388 dose arms 
(Arm 2 [150 mg CD388, n= up to 30] and Arm 3 [50 mg CD388, n= up to 30]). 
Cohort 2 details will be confirmed further to interim analyses as described below. 
Cohort 2 may include extension of the arms in Cohort 1 or include additional dose 
levels not exceeding 150 mg. 
A first interim analysis will be performed for participants in Cohort 1 who have 
completed the inpatient phase at the time the interim analysis is performed. 
An optional second interim analysis may be performed within Cohort 2, depending 
on the outcome of the first interim analysis. Each interim analysis will inform on: 
• 
The final participant numbers per study arm. 
• 
The CD388 dose levels to be studied. 
• 
The number of CD388 dose levels to be studied. 
Participants will receive IMP (CD388/placebo) prior to being inoculated with the 
influenza challenge virus and will undergo assessments as per Schedule of Events 
(SoE). The timing of administration of CD388 or placebo is chosen so as to 
approximate Tmax of CD388 in plasma at the time of challenge virus inoculation. In 
these cases, the timing of procedures and the admission day to quarantine would 
be altered accordingly. 
The study is divided into the following phases: 
Screening Phase: from Day -96 to Day -7/-6 quarantine admission. Historical 
generic screening data collected through the hVIVO generic screening process 
may be transferred to this study after the study-specific consent form has been 
signed by the participant. 
Inpatient Phase: Participants will be resident in the quarantine unit for 
approximately 16 days (from Day -7/-6 to Day 8). Procedures will include: 
• 
Pre-HVC: 
o 
Admission to quarantine unit on Day -7/-6. 
o 
Baseline assessments and randomisation will be conducted as per 
SoE up to Day -5, pre-dose. 
o 
Administration of CD388 or placebo on Day -5. 
• 
HVC: 
o 
Influenza virus inoculation on Day 0. 
• 
Post-HVC: 
o 
Day 1 onwards and each day – study assessments will be conducted 
as per SoE. 
o 
Participants will be discharged from the quarantine unit on Day 8 (or 
may remain longer at the principal investigator’s [PI’s] discretion). 
Outpatient Phase: 
• 
Follow-up visit(s): Day 17 (±1 day), Day 28 (±3 days), Day 60 (±7 days), and 
Day 120 (±14 days). 


 
 
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• 
Final visit: Day 180 (±14 days). 
Randomisatio
n 
In Cohort 1, the randomisation number encodes the participant’s assignment to 1 of 
3 study arms: placebo (Arm 1, n= up to 30) and two CD388 dose arms (150 mg 
CD388 [Arm 2, n= up to 30] and 50 mg CD388 [Arm 3, n= up to 30]).  The initial 
randomisation schedule used varying block sizes (12 and 3) and 2 sets of 
randomisation ratios (4:5:3 and 1:0:2) to facilitate achieving the targeted sample 
sizes for the interim analysis. This was updated as per Non-Substantial 
Amendment 03 to a 1:1 randomisation between Arm 1 and Arm 2 until the first 
interim analysis. 
Participant 
replacement 
policy 
Participants may be replaced in this study. 
 
 
 
 
 
Expected 
duration of 
participation 
per participant 
Approximately 9 months from screening to the participant’s last scheduled visit. 
Overall 
duration of 
clinical phase 
The length of the clinical phase is expected to be approximately 19 months from 
first participant’s planned first study visit (screening visit) to the last participant’s 
last scheduled study visit. 
End of study 
The end of the study is defined as the date of the last follow-up of the last participant 
in the study. 
Sample size 
determination 
A total sample size of 168 participants is estimated to be sufficient to achieve the 
objectives of this study. 
Depending on recruitment, the number enrolled at the planned first interim analysis 
is expected to be up to 30 participants in Arm 1 (placebo),Arm 2 (150 mg CD388), 
and Arm 3 (50 mg CD388). An example of sample size estimates for the interim 
analysis depending on the recruited number of subjects is shown below: 
• 
The sample size of 30 participants per arm will have 95% power to detect 
a statistically significant difference between groups, using a Wilcoxon 
rank-sum test with a one-sided type-1 error rate of 0.025, assuming that 
the probability that the VL-AUC for a participant in Arm 2 (150 mg CD388) 
is less than the VL-AUC for a participant in Arm 1 (placebo) is 0.75. 
Probability 
(AUCCD388 < AUCPlacebo) 
0.60 
0.65 
0.70 
0.75 
0.80 
Power at Interim analysis 


 
 
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Interim analysis Arm 1 n=30 vs 
Arm 2 n=30 
0.259 
0.515 
0.785 
0.951 
0.996 
 
Statistics 
Primary efficacy analysis 
The primary endpoint (VL-AUC of the influenza challenge virus as determined by 
qRT-PCR on nasal samples [virology]), will be analysed on the per protocol (PP) 
analysis set. 
The PP set will consist of all participants randomised, having received IMP 
(CD388/placebo), challenged with the study virus, who have a valid result for at 
least 80% of the planned qRT-PCR nasal samples from Day 1 (pm) up to Day 8 
(am), i.e., at least 11 out of 14, and present no major deviations likely to impact the 
evaluation of the primary efficacy endpoint. All deviations and cases with at least 
1 qRT-PCR result missing will be reviewed during the blinded data review meeting 
and adjudicated as belonging to the PP set or not. 
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. 
Descriptive statistics for the mean and median and the 2-sided 95% confidence 
interval (CI) for the mean will be presented by study arm. The significance of the 
difference between each CD388 arm and the placebo arm will be analysed using 
the Wilcoxon rank-sum test. The estimator of the difference in area under the curve 
(AUC), with 95% CI will be obtained via the Hodges-Lehman (+Moses) method. 
The one-sided p-value will be presented. No adjustment of the type-1 error rate for 
multiple comparisons will be performed and each test will use a nominal level of 
0.025 1-sided. 
The analysis will be repeated on the ITT analysis set as a sensitivity analysis. 
Interim analysis 
A first interim analysis will be performed, by an unblinded team not involved in daily 
management of the study, for participants in Cohort 1 who have completed the 
inpatient phase at the time the interim analysis is performed. An optional second 
interim analysis may be performed within Cohort 2, depending on the outcome of 
the first interim analysis. Summary results of each interim analysis will inform on: 
• 
The participant numbers per study arm. 
• 
The CD388 dose levels to be studied. 
• 
The number of CD388 dose levels to be studied. The SAP will describe 
the planned interim analyses in greater detail. 












 
 
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s that occurred over the last week. Participants will 
 
 
 
 
 
 
 
 


 
 
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l 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




 
 
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2. 
Introduction 
CD388 is a zanamivir-crystallisable fragment (Fc) conjugate. Zanamivir is a small molecule antiviral 
(neuraminidase inhibitor [NAI]). CD388 is being developed for the prevention of seasonal and pandemic 
influenza. 
2.1. 
Influenza 
Influenza viruses are associated with significant human disease and cause annual epidemics during 
autumn and winter. Although most people recover from seasonal influenza within 1 to 2 weeks without 
requiring medical attention, globally, millions are hospitalised each year and about 650,000 deaths occur 
due to influenza (Iuliano et al, 2018), particularly among the very young, elderly, and chronically ill. In the 
United States (US), an estimated 37.4 – 42.9 million symptomatic influenza-related illnesses, 
17.3 – 20.1 million influenza-related medical visits, 531,000 – 647,000 influenza-related hospitalisations, 
and 63,400 – 61,200 deaths occurred during the 2018–2019 influenza season (Xu et al, 2019). Comparable 
mortality and morbidity rates have been reported for European countries. These numbers remain high year 
after year because currently no effective medicine is available for the prevention of influenza. Currently, the 
influenza type A viruses H1N1 and H3N2 are circulating in humans, along with influenza type B viruses. 
H3N2 viruses have been predominant in most seasons and have caused a higher number of deaths and 
hospitalisations than H1N1 and influenza B viruses (Nunes et al, 2011; Thompson et al, 2004; Zucs et al, 
2005). 
Progress towards a medicinal agent that provides protection against a broad range of influenza strains with 
a longer duration of protection, otherwise known as a “universal vaccine”, has been disappointing. The 
monoclonal antibody therapeutics developed to date have suffered from limited spectrum and commercial 
limitations due to high dosing requirements and/or the need for multiple antibody cocktails to achieve a 
desired spectrum and efficacy. Thus, a significant unmet need exists for long-acting universal protective 
agents. 
The influenza human challenge model was established to not only aid understanding of influenza disease 
and transmission, but to also assess the efficacy of antivirals, immunomodulators, and vaccines (as 
reviewed by Lambkin-Williams et al, 2018; Yogaratnam et al, 2019; Bueno de Mesquita et al, 2021; Nguyen-
Van-Tam et al, 2020; Ramos-Sevillano et al, 2019). hVIVO has given different influenza strains to over 
1300 participants over the last 20 years. The influenza H3N2 A/Perth/16/2009 challenge strain used in the 
majority of studies to date has been given to over 350 healthy participants by hVIVO. The virus has been 
well tolerated with no virus-related serious adverse events (SAEs) occurring in any of the participants 
inoculated to date. Furthermore, the challenge virus has been shown to induce measurable disease profiles 
with clear distinction from non-infected participants and study participants have approximately 60% to 75% 
chance of becoming infected following the administration of the virus. Typical influenza illness is 
characterised by an abrupt onset of rhinitis, nasal stuffiness, fever, malaise, myalgia (muscle aches), and 
sore throat. In healthy adults, the illness usually resolves without any treatment, with relief of symptoms 
occurring naturally within 3 to 5 days. The disease profiles of the challenge agent are consistent with the 
mild to moderate disease profiles expected with wild-type challenge viruses in healthy adult participants 
(Fragaszy et al, 2017). In summary, the influenza H3N2 A/Perth/16/2009 challenge virus is considered safe, 


 
 
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well tolerated, and induces appropriate disease pathogenesis to be an effective viral challenge agent in the 
human viral challenge (HVC) studies. 
2.2. 
CD388 – A Long-acting Antiviral Fc-Conjugate 
Cidara Therapeutics, Inc. (Cidara) is developing a novel therapeutic and prophylactic agent that has a 
potential to provide durable single-dose “universal” coverage per flu season. Cidara has generated 
conjugates comprising multiple copies of a highly potent small molecule antiviral agent (the marketed NAI 
zanamivir) with a modified Fc domain that replace the variable domains in monoclonal antibodies. The small 
molecule targeting groups selectively engage a small, conserved pocket on the viral surface, which is not 
feasible with monoclonal antibodies. This molecule, CD388, is a first in class long-acting antiviral Fc-
conjugate combining a surface-acting antiviral agent with the Fc of a human immunoglobulin G1 (IgG1) 
antibody. 
CD388 differs from traditional antibody-drug conjugate molecules in the following aspects: 
• 
In traditional antibody-drug conjugates the drug is attached to full length human IgG (Fc + antigen-
binding fragment); in contrast, zanamivir dimers of CD388 are conjugated to an Fc fragment of 
human IgG1 (and not full length IgG1). 
• 
In traditional antibody-drug conjugates the drug is conjugated to the human IgG using a protease-
cleavable linker to allow release of the drug inside target cells; the linker between zanamivir and 
the Fc in CD388 is not a substrate for proteases, and it exerts its antiviral activity in the extracellular 
space. 
• 
Traditional antibody-drug conjugates are used to treat cancer by delivering cytotoxic payloads to 
target cells with rapid release; CD388 is designed to treat and prevent infectious disease using a 
long-acting stable conjugate of a non-cytotoxic small molecule to an Fc fragment of IgG1. 
In nonclinical in vitro and in vivo models, CD388 has demonstrated the potential for significantly higher 
antiviral activity and efficacy compared to the parent molecule, zanamivir, as well as other NAIs, including 
oseltamivir. 
2.2.1. 
Nonclinical Studies 
Several in vitro and in vivo nonclinical studies have been conducted to evaluate the safety and efficacy of 
CD388 and/or related Fc-conjugated prototype targeting molecules to support dosing in humans. In vitro 
NAI- and cell-based assays were conducted with CD388 to assess its spectrum and potency against 
wild-type as well as drug-resistant influenza strains. In vitro studies to characterise the extent of neonatal 
Fc receptor and Fc-γ receptor binding across different species were conducted. In vitro studies to 
characterise the potential for resistance development with CD388 have been undertaken. In vivo efficacy 
of CD388 was observed in treatment, and prophylaxis or preventative mouse lethal infection models. 
In vitro stability of the targeting molecules’ compound alone was quantitatively tested at 37℃ in phosphate-
buffered saline, plasma, and liver microsomes. Stability of the intact Fc-conjugated molecule, CD388, was 
qualitatively observed in liver microsomes at 37℃. In vivo, the pharmacokinetics (PK) were investigated in 
animal species that were used to characterise the pharmacological and toxicological profile of CD388 and 
related molecules; namely in mouse, rat, and monkey. More importantly, following PK studies in the mouse, 
rat, and monkey, plasma concentrations were quantified by a neuraminidase (NA)-capture or Fc-capture 
with Fc-detection enzyme-linked immunoassay (ELISA) methods, to confirm the stability of CD388 in vivo. 




 
 
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Blinded TEAEs by system organ class (SOC) and preferred term (PT) are presented in Table 2-2. 
Table 2-2: 
Blinded treatment-emergent adverse events by system organ class and preferred 
term in the safety population 
 
System Organ Class (SOC) 
    Preferred Term (PT) 
Total Subjects 
(N=22) 
n (%) 
 
 
Number of subjects with at least one treatment-emergent adverse event (TEAE) 
10 (45.5) 
 
 
Ear and labyrinth disorders 
1 ( 4.5) 
Cerumen impaction 
1 ( 4.5) 
Gastrointestinal disorders 
5 ( 22.7) 
Constipation 
3 ( 13.6) 
Diarrhoea 
3 ( 13.6) 
Faeces hard 
1 ( 4.5) 
Nausea 
1 ( 4.5) 
Saliva discolouration 
1 ( 4.5) 
Vomiting 
2 ( 9.1) 
General disorders and administration site conditions 
1 ( 4.5) 
Non-cardiac chest pain 
1 ( 4.5) 
Infections and infestations 
1 ( 4.5) 
Upper respiratory tract infection 
1 ( 4.5) 
Nervous system disorders 
7 ( 31.8) 
Dizziness 
1 ( 4.5) 
Headache 
6 ( 27.3) 
Presyncope 
1 ( 4.5) 
Somnolence 
1 ( 4.5) 
Skin and subcutaneous tissue disorders 
1 ( 4.5) 
Acne 
1 ( 4.5) 
Dermatitis contact 
1 ( 4.5) 
A TEAE is defined as an AE that occurs during or after study drug administration. 
A subject with multiple AEs within an SOC or PT is counted only once. 


 
 
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System Organ Class (SOC) 
    Preferred Term (PT) 
Total Subjects 
(N=22) 
n (%) 
Percentages are calculated using the number of subjects in the safety population. 
MedDRA Version 24.1 was used for reporting AEs. 
Based on blinded safety results from the ongoing study following single subcutaneous administration of 
50 and 150 mg CD388, these doses appear to be well tolerated. A decision was made and approved by 
the study Institutional Review Board to dose escalate to a higher subcutaneous dose of 450 mg with the 
next cohort. 
2.3. 
Study Rationale 
This is a proof-of-concept study to determine the prophylactic antiviral activity of a single subcutaneous 
administration of CD388 against experimental influenza infection and to confirm its safety, tolerability, and 
PK in a healthy adult population inoculated with the influenza H3N2 A/Perth/16/2009 challenge strain. Due 
to the current epidemiological situation with very low influenza incidence worldwide, it is challenging to 
demonstrate proof of concept of therapeutic or prophylactic efficacy of anti-influenza compounds in a 
natural infection setting. The HVC model offers a setting that is independent of the number of influenza 
cases at a given time. Also, this model has a track record of safety and has demonstrated proof-of-concept 
efficacy for numerous antiviral compounds and vaccines that were later found to be also efficacious in larger 
clinical studies in the setting of natural infection. It is important to establish proof of concept and minimally 
effective concentrations in this study in order to better design studies to establish the safety and efficacy of 
CD388. 
Influenza challenge strains have been used for over 20 years by both hVIVO and others and have helped 
assess numerous antiviral, immunomodulating, and vaccine therapies. Specifically, hVIVO have safely and 
successfully used the influenza H3N2 A/Perth/16/2009 challenge strain in over 350 healthy participants 
(18 to 64 years of age). 
2.4. 
Benefit/Risk Assessment 
2.4.1. 
Risk Assessment 
The potential risks to participants are detailed in Table 2-3. 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 minimised. Trained medical staff and appropriate facilities will 
be available to provide medical emergency care. 
More detailed information about the known and expected benefits and risks and reasonably expected AEs 
of CD388 may be found in the Investigator’s Brochure. 
 


 
 
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Table 2-3: 
Risk Assessment 
Potential Risk of 
Clinical Significance 
Description of Risk 
Mitigation Strategy 
Study Intervention 
Subcutaneous dosing 
with CD388 
There are no studies completed with CD388 in humans. 
Refer to Section 2.2.2, Clinical Experience, for a 
summary of results of an ongoing study. However, the 
study drug was tested in animals. In studies with rats and 
monkeys CD388 had no significant effect on the body 
weight, food consumption, heart activity, blood tests, 
urine tests, respiration, eye tests and other clinical tests 
conducted on the animals. 
Risks relating to procedure of administration of product: 
pain at site of administration, bruising at site, introduction 
of infection. 
Participants will be closely monitored by clinical staff for 
any AEs after dosing and throughout the study as per 
the Schedule of Events (SoE). Administration will only 
be carried out by trained professionals with thorough 
cleaning of the area beforehand with alcohol wipes and 
the use of aseptic technique throughout. 
Subcutaneous dosing 
with 
sterile 
normal 
saline (placebo) 
Given that the placebo is a pharmacologically inert 
material, there should be no risk in relation to the product 
being administered. Similar risks apply to the procedure 
of administration: pain, bruising, introduction of infection 
into the skin. 
Administration will only be carried out by trained 
professionals with thorough cleaning of the area 
beforehand with alcohol wipes and the use of aseptic 
technique throughout. 
Pregnancy and birth 
control 
Unknown. 
Female participants of childbearing potential must use 
1 form of highly effective contraception. Use of 
hormonal contraception should start at least 2 weeks 
prior to the first study visit. The contraception use must 
continue until 5 effective half-lives after the last dose of 
investigational medicinal product (IMP). 


 
 
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Potential Risk of 
Clinical Significance 
Description of Risk 
Mitigation Strategy 
Females who are pregnant or have been pregnant 
within 6 months prior to the study, and females who are 
breastfeeding, will be excluded from the study. 
Male participants must agree to the contraceptive 
requirements as described in Inclusion Criterion #7 from 
entry into quarantine and continuing until 5 effective 
half-lives after the last dose of IMP.  
In addition to the contraceptive requirements, male 
participants must agree not to donate sperm following 
discharge from quarantine until 5 effective half-lives after 
the last dose of IMP. 
Study procedures 
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. 
There is a possibility that in the process of collecting 
blood a nerve may be injured. 
Procedure to be performed by qualified personnel. 
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 (such as human 
immunodeficiency virus [HIV] or hepatitis) or an 
unexpected illness. 
The hVIVO doctor will provide the participant’s general 
practitioner (GP), or doctor with a referral letter if the 
participant agrees. 


 
 
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Potential Risk of 
Clinical Significance 
Description of Risk 
Mitigation Strategy 
Nasal sampling 
Collection of respiratory (nasal) samples may cause 
discomfort, sneezing, watery eyes, irritated nose, or 
nose bleeding. 
Sample collection will be performed by appropriately 
qualified and trained study staff. 
Influenza H3N2 A/Perth/16/2009 infection from inoculation 
Influenza 
H3N2 
A/Perth/16/2009 
infection & severe 
complications 
 
 Typical influenza illness: abrupt 
onset of rhinitis, cough, headache, chills, tiredness, nasal 
stuffiness, fever, malaise, myalgia (muscle aches), and 
sore throat. 
Severe complications are not expected as these tend to 
occur almost exclusively in infants, elderly, and persons of 
any age with chronic comorbidities and significant immune 
compromise and not in healthy adults with no comorbidities 
of coinfections. 
The safety profile of the influenza H3N2 A/Perth/16/2009 
virus is well characterised in healthy adults 
 
 
 
 
 
Influenza infection in healthy adults usually resolves 
without treatment within 3 to 5 days after symptoms onset. 
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 8 days post-HVC. 
Qualified medical and nursing staff in the quarantine unit 
will monitor for and manage any symptoms. 
Transmission 
of 
influenza 
H3N2 
A/Perth/16/2009 
to 
participants’ 
close 
contacts 
Influenza H3N2 A/Perth/16/2009 presence in nasal 
secretions can cause infection in close contacts. 
The duration of the quarantine has been designed to 
allow for resolution of infectious virus (culturable) before 
discharge. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




 
 
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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, ischaemic heart disease, known anatomic defects). 
o 
Contacts that required medical follow-up or hospitalisation 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 minimise 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 influenza H3N2 A/Perth/16/2009. 
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 CD388 
administration. 
All participants will be instructed to follow 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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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 influenza H3N2 A/Perth/16/2009 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 minimise risk to participants in this study, the potential risks identified 
in association with influenza virus infection and CD388 treatment are justified by the anticipated benefits 
linked to the evaluation of the antiviral activity of CD388 in the viral challenge model which will contribute 
to the development of a new therapy for the prevention of seasonal and pandemic influenza. 
 


 
 
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3. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary: 
Efficacy 
To evaluate the prophylactic efficacy of 
CD388 in terms of reduction of area 
under the viral load-time curve (VL-AUC) 
after influenza viral challenge when 
compared to placebo. 
• 
VL-AUC of influenza challenge virus as determined by 
quantitative reverse transcriptase-polymerase chain 
reaction (qRT-PCR) on nasal samples starting a day 
post viral challenge (Day 1, pm) up to Day 8 (am). 
Secondary: 
Efficacy 
To evaluate the effect of CD388, in 
reducing or shortening viral shedding after 
influenza viral challenge compared to 
placebo. 
• 
Peak viral load of influenza as defined by the maximum 
viral load determined by quantifiable qRT-PCR 
measurements in nasal samples from Day 1 (pm) up 
to Day 8 (am). 
• 
Time (hours) to confirmed negative test by quantifiable 
qRT-PCR measurements in nasal samples from Day 1 
(pm) to first confirmed undetectable assessment after 
peak measure. 
To evaluate the effect of CD388, in 
reducing 
or 
shortening 
culturable/replicating virus after influenza 
viral challenge compared to placebo. 
• 
VL-AUC of influenza challenge virus as determined by 
viral culture on nasal samples, from Day 1 (pm) up to 
Day 8 (am). 
• 
Peak viral load of influenza as defined by the maximum 
viral load determined by quantitative viral culture 
measurements in nasal samples from Day 1 (pm) up 
to Day 8 (am). 
• 
Time (hours) to confirmed negative test by quantifiable 
viral culture measurements in nasal samples from 
Day 1 (pm) to first confirmed undetectable assessment 
after peak measure. 


 
 
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Objectives 
Endpoints 
To evaluate the effect of CD388, in 
reducing 
clinical 
symptoms 
due 
to 
influenza viral challenge compared to 
placebo. 
• 
Area under the curve over time of total clinical 
symptoms score (TSS-AUC) as measured by graded 
symptom scoring system collected 3 times daily from 
Day 1 (am) up to Day 8 (am). 
• 
Peak symptoms diary card score: peak of total clinical 
symptoms (TSS) as measured by graded symptom 
scoring system collected 3 times daily from Day 1 (am) 
up to Day 8 (am). 
• 
Peak daily symptom score: individual maximum daily 
sum of symptom score from Day 1 up to Day 8. 
• 
Time to symptom resolution as measured by graded 
daily symptom score system from time of peak daily 
symptom score to time of returning to baseline score. 
To evaluate the effect of CD388, in 
reducing 
the 
incidence 
of 
influenza 
infection due to influenza viral challenge, 
compared to placebo. 
• 
RT-PCR-confirmed influenza infection, defined as 
2 quantifiable (≥ lower limit of quantification [LLOQ]) 
qRT-PCR measurements (reported on 2 or more 
independent samples over 2 days), from Day 1 (pm) 
up to Day 8 (am). 
• 
Occurrence of at least 1 positive quantitative (≥LLOQ) 
cell culture measurement in nasal samples, from Day 1 
(pm) up to Day 8 (am). 
• 
RT-PCR-confirmed symptomatic influenza infection, 
defined as: 
o 
RT-PCR-confirmed 
influenza 
infection 
(2 quantifiable [≥LLOQ] qRT-PCR measurements 
[reported on 2 or more independent samples over 
2 days]), from Day 1 (pm) up to Day 8 (am), AND 
o 
Symptoms ≥2 at a single time point. 
• 
RT-PCR-confirmed moderately severe symptomatic 
influenza infection, defined as: 
o 
RT-PCR-confirmed 
influenza 
infection 
(2 quantifiable [≥LLOQ] qRT-PCR measurements 
[reported on 2 or more independent samples over 
2 days]), from Day 1 (pm) up to Day 8 (am), AND 
o 
Any symptoms of grade ≥2 at a single time point. 


 
 
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Objectives 
Endpoints 
• 
Culture lab-confirmed symptomatic influenza infection, 
defined as: 
o 
Lab-confirmed 
culturable 
influenza 
infection 
(1 quantifiable 
[≥LLOQ] 
cell 
culture 
measurement), from Day 1 (pm) up to Day 8 (am), 
AND 
o 
Symptoms ≥2 at a single time point. 
Safety 
To evaluate the safety of CD388 when 
compared to placebo. 
• 
Occurrence of solicited AEs from subcutaneous 
dosing up to Day 0. 
• 
Occurrence of unsolicited AEs from subcutaneous 
dosing up to Day 28 (±3 days). 
• 
Occurrence of unsolicited AEs from subcutaneous 
dosing up to the final follow-up visit (Day 180 
±14 days). 
Tertiary / Exploratory*: 
To further evaluate the effect of CD388, in 
reducing or shortening viral shedding after 
influenza viral challenge compared to 
placebo. 
• 
Duration 
of 
quantifiable 
influenza 
qRT-PCR 
measurements in nasal samples from Day 1 (pm) up 
to Day 8 (am). Duration is defined as the time (hours) 
from first detectable until first confirmed undetectable 
assessment after their peak measure (after which no 
further virus is detected). 
To further evaluate the effect of CD388, in 
reducing 
or 
shortening 
culturable/replicating virus after influenza 
viral challenge compared to placebo. 
• 
Duration of quantitative influenza viral culture 
measurements in nasal samples from Day 1 (pm) up 
to Day 8 (am). Duration is defined as the time (hours) 
from first detectable until first confirmed undetectable 
assessment after their peak measure (after which no 
further virus is detected). 
To further evaluate the effect of CD388, in 
reducing 
clinical 
symptoms 
due 
to 
influenza viral challenge compared to 
placebo. 
• 
Time to peak as measured by graded daily symptom 
score system (from Day 1 [am] to the time of peak daily 
symptom score). 
• 
Number (%) of participants with symptom scored 
grade 2 or higher, from Day 1 (am) up to Day 8 (am). 


 
 
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Objectives 
Endpoints 
• 
Number (%) of participants with symptom scored 
grade 2 or higher by time point, from Day 1 (am) up to 
Day 8 (am). 
To further evaluate the effect of CD388, in 
reducing 
the 
incidence 
of 
influenza 
infection due to influenza viral challenge, 
compared to placebo. 
• 
Number (%) of participants with lab-confirmed 
infection and fever (≥37.9°C). 
• 
Further sensitivity analysis may be performed on the 
above qRT-PCR-related incidence endpoints where 
detection by qRT-PCR is reported above the lower limit 
of detection (LLOD) instead of the LLOQ. Details will 
be provided in the statistical analysis plan (SAP). 
To evaluate the effect of CD388, in 
reducing nasal discharge compared to 
placebo. 
• 
Total weight of mucus produced from Day 1 (am) up to 
Day 8 (am). 
• 
Total number of tissues used by participants from 
Day 1 (am) up to Day 8 (am). 
To evaluate the effect of CD388, in 
reducing incidence of community-acquired 
influenza infection compared to placebo. 
• 
Laboratory--confirmed symptomatic influenza infection 
(community acquired), defined as: 
o 
Self-reported influenza-like symptoms, AND 
o 
Community 
acquired 
(not 
challenge 
virus) 
laboratory-confirmed influenza infection PCR 
measurement and/or lateral flow positive, or other 
equivalent) reported on any occasion from 
discharge from quarantine up to Day 90 and/or up 
to Day 180 (±14 days). 
To monitor the safety of the challenge 
virus. 
• 
Occurrence of unsolicited AEs from virus challenge 
(Day 0) up to Day 28. 
To evaluate the plasma PK of CD388. 
• 
PK parameters following CD388 administration will be 
determined as appropriate from the available data 
including: maximum plasma concentration (Cmax), time 
to maximum plasma concentration (Tmax), area under 
the plasma concentration-time curve from time 0 to 
time of last quantifiable sample (AUC0-t), and area 
under the plasma concentration-time curve from time 
0 extrapolated to infinity (AUC0-∞). 
To explore CD388 concentrations in 
nasopharyngeal swab samples. 
• 
CD388 concentrations in nasopharyngeal swabs. 


 
 
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Objectives 
Endpoints 
To explore PK/PD of CD388. 
• 
Plasma concentration at specific time points, or PK 
parameters across dose groups, will be compared to 
viral or symptomatic endpoints in an effort to 
characterise the exposure response of CD388, and will 
be reported separately.  
To explore cytokines and chemokines in 
nasal samples. 
• 
Cytokine/chemokine levels may be explored in nasal 
samples, related to CD388 and infection. 
To explore cytokines and chemokines in 
serum samples. 
• 
Cytokine/chemokine levels may be explored in serum 
samples, related to CD388 and infection. 
To explore markers associated with the 
effect of CD388 or with infection. 
• 
Gene expression (messenger RNA [mRNA]) in whole 
blood. 
To explore viral resistance markers in 
influenza viral positive nasal samples 
• 
Viral resistance markers relevant for CD388. 
*Note that tertiary objectives and endpoints are optional and might be assessed only if needed; therefore, not all 
testing might be performed and reported. 
 


 
 
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4. 
Study Design 
4.1. 
Overall Design 
This is a single-centre, randomised, double-blind, placebo-controlled, proof-of-concept study in healthy 
adult male and female participants 18 to 55 years of age, inclusive, utilising: 
• 
IMP (active): a single subcutaneous dose of CD388 liquid for injection 
• 
IMP (placebo): a single subcutaneous dose of sterile normal saline for injection 
• 
Challenge agent: influenza H3N2 A/Perth/16/2009 challenge strain, ~105.5 tissue culture infective 
dose (50%) (TCID50), intranasally administered 
The primary goal of this Phase 2a study is to assess the prophylactic antiviral activity against influenza, 
safety, tolerability, and PK of CD388 via a HVC model, and to explore the impact of dose levels on efficacy. 
Each participant will receive a single administration of CD388 or placebo; multiple dose levels of CD388 
may be evaluated. 
An overview of study design is provided in Figure 4-1. 
A total of up to 168 participants is planned to be enrolled in this study in up to 2 cohorts. Cohort 1 will consist 
of up to 90 participants that will be enrolled simultaneously; a placebo arm (Arm 1, n= up to  30) and 
two CD388 dose arms (Arm 2 [150 mg CD388, n= up to 30] and Arm 3 [50 mg CD388, n= up to 30]). 
Cohort 2 details will be confirmed further to interim analysis as described below. Cohort 2 may include 
extension of the arms in Cohort 1 or include additional dose levels not exceeding 150 mg. 
A first interim analysis will be performed for participants in Cohort 1 who have completed the inpatient phase 
at the time the interim analysis is performed. An optional second interim analysis may be performed within 
Cohort 2 depending on the outcome of the first interim analysis. Each interim analysis will inform on: 
• 
The final participant numbers per study arm. 
• 
The CD388 dose levels to be studied (Section 6.6, Dose Modification). 
• 
The number of CD388 dose levels to be studied. 
Participants will receive CD388 or placebo prior to being inoculated with the influenza challenge virus and 
will undergo assessments as per SoE. The timing of administration of CD388 or placebo is chosen so as 
to approximate Tmax of CD388 in plasma at the time of challenge virus inoculation.  
 


 
 
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Figure 4-1: Overview of Study Design 


 
 
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The expected duration of study participation for a participant is approximately 9 months, with the following 
sequence and duration of study phases: 
- 
Screening Phase: from Day -96 to Day -7/-6 quarantine admission. Historical generic screening data 
collected through the hVIVO generic screening process may be transferred to this study after the study-
specific consent form has been signed by the participant. 
- 
Inpatient Phase: Participants will be resident in the quarantine unit for approximately 16 days (from 
Day -7/-6 to Day 8). Procedures will include: 
• 
Pre-HVC: 
o 
Admission to quarantine unit on Day -7/-6. 
o 
Baseline assessments and randomisation will be conducted as per SoE up to Day -5, pre-
dose. 
o 
Administration of CD388 or placebo on Day -5. 
• 
HVC: 
o 
Influenza virus inoculation on Day 0. 
• 
Post-HVC: 
o 
Day 1 onwards and each day – study assessments will be conducted as per SoE. 
o 
Participants will be discharged from the quarantine unit on Day 8 (or may remain longer at 
the principal investigator’s [PI’s] discretion). 
- 
Outpatient Phase: 
• 
Follow-up visit(s): Day 17 (±1 day), Day 28 (±3 days), Day 60 (±7 days), and Day 120 (±14 days). 
• 
Final visit: Day 180 (±14 days). 
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 influenza 
challenge studies. Numerous studies have been performed using experimental influenza infection in human 
participants. To date, in hVIVO’s studies, over 350 healthy participants have been successfully and safely 
inoculated with the influenza H3N2 A/Perth/16/2009 challenge strain. These studies demonstrated that 
healthy adults could be infected by nasal inoculation and that experimental infection was safe. This 
influenza strain has been shown to cause symptoms and virus shedding that closely match natural infection. 
Administration of IMP and challenge with influenza H3N2 A/Perth/16/2009 will take place in hVIVO’s 
specialised clinical facilities, either in a quarantine unit or an outpatient clinic. 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 Randomisation 
Placebo control in this study is sterile normal saline and 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 CD388. 


 
 
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Blinding will prevent the occurrence of conscious and unconscious bias in the conduct and interpretation of 
the study. 
Randomisation will be used to prevent bias in the assignment of participants to study arms, to increase the 
likelihood that known and unknown participant characteristics (e.g., demographic and baseline 
characteristics) are equally balanced across study arms, and to enhance the validity of statistical 
comparisons across study arms. 
4.3. 
Justification for Dose 
The dose(s) planned for this study are based on results obtained from GLP 3-month exposure toxicology 
studies in rats and primates, and the FDA’s guidance contained in “Estimating the Maximum Safe Starting 
Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers” (FDA 2005), as well as the results 
of the ongoing first-in-human study CD388.IM.SQ.1.01. From the 3-month GLP toxicology studies in rats 
and monkeys, a no-observed-adverse-effect level (NOAEL) of 500 mg/kg has been established for both 
species. CD388 safety margins generated from these pivotal 3-month exposure studies at the dose of 
150 mg proposed for this study dose are 32-fold in rats and 64.7-fold in monkeys using body surface area, 
indicating that this dose would be an acceptable highest dose from a safety perspective. 
Safety results of the ongoing clinical trial CD388.IM.SQ.1.01 have indicated no significant safety findings 
following single subcutaneous administration of 50 and 150 mg CD388, and the study is proceeding to the 
maximum planned subcutaneous dose of 450 mg (see Section 2.2.2, Clinical Experience). 
An inoculum titre of approximately 105.5 tissue culture infective dose (50%) (TCID50) of the influenza H3N2 
A/Perth/16/2009 strain has been shown to cause disease profiles that are consistent with the mild to 
moderate disease profiles expected with wild-type challenge viruses in healthy adult participants. 
4.4. 
Population to be Studied 
Healthy participants. 
4.5. 
Rationale for Trial Endpoints 
The measures for evaluation of the safety and tolerability profile of CD388 injection are standard for most 
clinical studies and follow the recommendations in the ICH guidelines. 
The measures for evaluation of the prophylactic antiviral activity of CD388 against influenza have been 
employed in previous studies conducted by hVIVO and are appropriate to characterise the efficacy of 
CD388, considering the CD388 mode of action. 
The assessments for determining CD388 plasma concentrations are appropriate to characterise the PK 
profile of CD388. 
Exploratory biomarkers, anti-drug antibodies (ADAs), and pharmacogenomic research are exploratory in 
nature and do not have predefined endpoints. 
4.6. 
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 procedure 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 


 
 
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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 follow-up (not including discretionary follow-up as 
mentioned above) of the last participant in the study. 


 
 
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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 STANDARD INCLUSION CRITERIA * 
(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 PI/investigator obtained 
before any assessment is performed. 
2. 
Adult male or female aged between 18 and 55 years old, inclusive, 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 ≤35kg/m2. 
4. 
In good health with no history, or current evidence, of clinically significant medical conditions, 
and no clinically significant test abnormalities that that will interfere with participant safety, as 
defined by medical history, physical examination, (including vital signs), electrocardiogram 
(ECG), and routine laboratory tests as determined by the PI/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: 
a. Postmenopausal females defined as amenorrhea for ≥12 months 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 <12 months of amenorrhea 2 FSH samples are 
required at least 4 to 6 weeks apart. 
b. Documented status as being surgically sterile (e.g., tubal ligation, hysterectomy, 
bilateral salpingectomy, and bilateral oophorectomy). 


 
 
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7. 
The following criteria apply to female and male participants: 
a) Female participants of childbearing potential must use 1 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 5 effective half-lives (205 
days) after the last dose of IMP. Highly effective contraception is as described below: 
a. Established use of hormonal methods of contraception described below (for a 
minimum of 30 days 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 
(oestrogen- 
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 sterilisation (with the appropriate post-vasectomy documentation of the 
absence of sperm in the ejaculate) where the vasectomised 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 study 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 5 effective half-lives (205 days) after the last dose of 
IMP. 
a. Use a condom with a spermicide to prevent pregnancy in a female partner or to 
prevent exposure of any partner (male or female) to the IMP. 


 
 
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No. 
hVIVO STANDARD INCLUSION CRITERIA * 
(Viral Challenge Volunteer Studies) 
b. Male sterilisation 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 study 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 5 effective half-lives 
(205 days) after the last dose of IMP. 
8. 
Sero-suitable for the challenge virus 
• 
A participant must be sero-suitable to take part in the study, i.e., he/she must have 
no or low pre-existing serum levels of antibodies specific to the challenge agent. 
Serology testing will be carried out by a haemagglutination inhibitory assay to 
determine serum antibody titres. As an example, a participant is considered sero-
suitable if their serology (haemagglutination inhibition [HAI]) titre result is ≤10. 
* Approved Final v11.0, 08FEB2022 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any the following criteria apply: 
No. 
hVIVO STANDARD EXCLUSION CRITERIA 
(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 respiratory tract (URT) 
or lower respiratory tract (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, haematological, hepatic, 


 
 
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No. 
hVIVO STANDARD EXCLUSION CRITERIA 
(Viral Challenge Volunteer Studies) 
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: 
a) Participants with a history of resolved depression and/or anxiety 1 or more years ago 
can be included if the Patient Health Questionnaire (PHQ-9) and the Generalised 
Anxiety Disorder Questionnaire (GAD-7) is less than or equal to 4 on admission. 
Participants with a history of stress-related illness, which is not ongoing or requiring 
current therapy, with good evidence of preceding stressors may be included at the 
PI’s discretion. As required, participants will be assessed prior to enrolment with a 
PHQ-9 and GAD-7 questionnaire. 
b) Rhinitis (including hay fever) which is clinically active or 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 not requiring 
regular treatment can be included at the discretion of the PI. 
g) Participants with a history of asthma where their last symptoms/treatment were in 
adolescence and over 6 years ago may be included at the discretion of the PI. Any 
participants with symptoms or treatment in adulthood would be excluded.  
3. 
Any participants who have smoked ≥10 pack years at any time (10 pack years is equivalent 
to 1 pack of 20 cigarettes a day for 10 years). 




 
 
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No. 
hVIVO STANDARD EXCLUSION CRITERIA 
(Viral Challenge Volunteer Studies) 
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 dosing with IMP 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 dosing 
with IMP. 
b) Receipt of 3 or more investigational drugs within the previous 12 months prior to the 
planned date of dosing with IMP. 
c) Prior inoculation with a virus from the same virus-family as the challenge virus. 
d) Prior participation in another HVC 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: 
a) Herbal supplements within 7 days prior to the planned date of dosing with IMP. 
b) Chronically used medications, vitamins, or dietary supplements within 21 days prior 
to the planned date of dosing with IMP. 
c) Over-the-counter medications (e.g., paracetamol or ibuprofen) where the dose taken 
over the preceding 7 days prior to the planned date dosing with IMP has exceeded 
the maximum permissible 24-hour dose (e.g., ≥4 grams paracetamol over the 
preceding week). 
d) Systemic antiviral administration within 4 weeks of the planned date of dosing with 
IMP. 
12. 
a) Confirmed positive test for drugs of misuse and cotinine on first study visit. 
One repeat test is 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). 
13. 
A forced expiratory volume in 1 second (FEV1) <80%. 


 
 
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No. 
hVIVO STANDARD EXCLUSION CRITERIA 
(Viral Challenge Volunteer Studies) 
14. 
Positive HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) test (HIV positive – via 3 
confirmatory tests – Vidas, Genenius, and Determine, HBV confirmed via HbsAG, anti-HBs, 
and anti-HBc [IgG/IgM], and HCV confirmed via hepatitis C viral load). 
15. 
Presence of fever, defined as participant presenting with a temperature reading of ≥37.9C 
on Day -7/-6 and/or pre-dose on Day -5. 
Other 
16. 
Those employed or immediate relatives of those employed at hVIVO or the sponsor. 
17. 
Any other finding that, in the opinion of the PI/investigator, deems the participant unsuitable 
for the study. 
* Approved Final v11.0, 08FEB2022 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
 
 
 
 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
 
 
 
 
 
 
 
 
 
5.3.3. 
Activity 
 
 
 
 


 
 
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5.4. 
Screen Failures 
 
 
 
 
 
 
 


 
 
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6. 
Study Intervention 
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. 
Study interventions administered to participants are described in Table 6-1. 
6.1. 
Study Intervention(s) Administered 
Table 6-1: 
Study Interventions 
Intervention Name 
CD388 
Placebo 
Influenza 
H3N2 A/Perth/16/2009 Virus 
Type 
Drug 
Other 
Virus 
Dose Formulation 
Liquid for injection 
Sterile normal saline 
for injection 
Capped vial, Liquid 
Unit Dose 
Strength(s) 
100 mg/mL 
- 
The challenge agent titre is 
determined in an infectivity 
assay. 
The 
dose 
is 
approximately 105.5 TCID50 
Dosage Level(s) 
Arm 2: 150 mg single 
dose 
Arm 3: 50 mg single 
dose 
Cohort 2: dose lower 
than 150 mg, TBD 
Arm 1: Single dose 
A single dose of challenge 
agent will be delivered. 
Route of 
Administration 
Subcutaneous 
injection 
Subcutaneous 
injection 
Intranasal 
Use 
Experimental 
Placebo 
Infectious challenge agent 
Sourcing 
Provided by Cidara 
Provided by Cidara or 
designee 
Provided centrally by hVIVO  
Packaging and 
Labelling 
The 
details 
of 
the 
packaging 
and 
labelling 
will 
be 
provided in the study 
specific 
pharmacy 
manual. 
The details of the 
packaging 
and 
labelling 
will 
be 
provided in the study 
specific 
pharmacy 
manual. 
Influenza challenge agent will 
be provided in vials. The 
details of the challenge agent 
provision will be provided in 
the analytical plan (AP). 


 
 
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Intervention Name 
CD388 
Placebo 
Influenza 
H3N2 A/Perth/16/2009 Virus 
Current/Former 
Name(s) or 
Alias(es) 
Not applicable 
Not applicable 
Not applicable 
 
6.2. 
Preparation/Handling/Storage/Administration/Accountability 
6.2.1. 
Investigational Medicinal Product 
hVIVO will receive supplies of IMP (CD388/placebo) 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 (CD388/placebo) supplies will be used only for this protocol and for no other 
purpose. 
IMP (CD388/placebo) will be supplied at the beginning of the study. Once received at hVIVO, hVIVO study 
staff will perform stock level accountability and the IMP (CD388/placebo) liquid for injection will be stored 
securely, according to the directions on the IMP labels. IMP (CD388/placebo) 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 (CD388/placebo) is monitored. 
Accurate records will be kept of when and how much IMP (CD388/placebo) 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 (CD388/placebo). 
A single subcutaneous dose of CD388/placebo will be given to each participant. Details on dose preparation 
and administration are provided in the study-specific pharmacy manual. An overview of the treatments per 
study arm is given below. 
• 
Arm 1: Placebo, single subcutaneous injection 
• 
Arm 2: 150 mg CD388, single subcutaneous injection 
• 
Arm 3: 50 mg CD388 , single subcutaneous injection 
• 
Arm 4 (optional): CD388 dose TBD*, single subcutaneous injection 
• 
Arm 5 (optional): CD388 dose TBD*, single subcutaneous injection 
• 
Arm 6 (optional): CD388 dose TBD*, single subcutaneous injection 
* Maximum dose will not exceed 150 mg. Doses may be adjusted based on PK results from Study 
CD388.IM.SQ.1.01. 
6.2.2. 
Challenge Agent 
The challenge agent used in this study is influenza H3N2 A/Perth/16/2009. 


 
 
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The challenge agent stock was manufactured under current GMP (cGMP). 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 -80oC freezer (normal 
temperature range -60°C to -90°C). 
Each participant will be allocated a unique vial containing the challenge agent and will receive the inoculum 
intranasally. The inoculum will be prepared and/or provided according to the hVIVO AP and administered 
in accordance with hVIVO 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. 
Following challenge agent inoculation, participants will be closely observed for 24 hours specifically for the 
occurrence of potential allergic reactions and any AEs. 
 
 
 
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 authorised 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 authorised 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 
pharmacy manual. 
6.3. 
Randomisation and Blinding 
 
 
 
 the randomisation 
number encodes the participant’s assignment to 1 of 3 study arms: placebo (Arm 1, n= 24 to 30), and 
two CD388 dose arms (150 mg CD388 [Arm 2, n=30] and 50 mg CD388, [Arm 3, n= 18 to 30]). This initial 
randomisation schedule, in use prior to Non-Substantial Amendment 03, used  2 varying block sizes (12 
and 3) and 2 sets of randomisation ratios (4:5:3 and 1:0:2) to facilitate achieving the targeted sample sizes 
for the interim analysis. 


 
 
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Block 
Cumulative 
Block 
Arm 1 
Placebo 
Arm 2 
High dose 
(150 mg CD388) 
Arm 3 
Low dose  
(50 mg CD388) 
Block size 
Arm 1 
Placebo 
Arm 2 
High dose 
(150 mg CD388) 
Arm 3 
Low dose  
(50 mg CD388) 
Randomised 
1 
4 
5 
3 
12 
4 
5 
3 
12 
2 
4 
5 
3 
12 
8 
10 
6 
24 
3 
4 
5 
3 
12 
12 
15 
9 
36 
4 
4 
5 
3 
12 
16 
20 
12 
48 
5 
4 
5 
3 
12 
20 
25 
15 
60 
6 
4 
5 
3 
12 
24 
30 
18 
72 
7 
1 
0 
2 
3 
25 
30 
20 
75 
8 
1 
0 
2 
3 
26 
30 
22 
78 
9 
1 
0 
2 
3 
27 
30 
24 
81 
10 
1 
0 
2 
3 
28 
30 
26 
84 
22 
1 
0 
2 
3 
29 
30 
28 
87 
23 
1 
0 
2 
3 
30 
30 
30 
90 
At the time of Non-Substantial Amendment 03 , this randomisation schedule was modified to ensure 
achievement of the largest possible sample-sizes in arm 1 (Placebo) and arm 2 (High dose) at the time of 
the planned first interim analysis. Participants enrolled under Non-Substantial Amendment 03 will be 
randomised 1:1 to either arm 1 (Placebo) or arm 2 (150 mg CD388) until Cohort 1 enrolment is complete. 
Afterwards, a new randomisation schedule will be prepared, taking into account the decisions taken based 
on the results of the first interim analysis. 
Randomisation numbers will be assigned sequentially in ascending order; and once assigned, that 
randomisation number shall not be reassigned. The study site will keep a log of the randomisation number 
assigned to each participant. 
A designated unblinded statistician, separate from the conduct or analysis of the study, will be responsible 
for the computer-generated randomisation schedule. Sealed copies of the randomisation code will be stored 
in a secure location. 
Randomisation numbers will follow a 4-digit format e.g., [0001]. If participants are replaced as per 
Section 7.4, Participant Replacement Strategy, the replacement participant will be assigned a new, unique 
randomisation number equalling the randomisation number of the replaced participant, plus 1000. This will 
ensure that the replacement participant receives the same allocated, blinded treatment as the participant 
who is being replaced. 
A copy of the randomisation code list will be sent to the unblinded pharmacist preparing the IMP, so that 
CD388/placebo can be prepared for each participant as appropriate. The GMP pharmacy provider ’s 
pharmacist/designee will prepare the participant level IMP doses in line with the randomisation schedule. 


 
 
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Each participant will be dispensed blinded IMP (CD388/placebo), labelled with his/her unique 
randomisation number, throughout the study. With the exception of the unblinded sponsor team, unblinded 
sponsor designated bioanalytical personnel, unblinded drug administration personnel, unblinded 
pharmacist, unblinded IMP management personnel at the clinical site, the unblinded statistician preparing 
the randomisation code list, the statisticians performing the interim analyses, and the quality assurance 
(QA) auditors where necessary, the PI/investigator and all other clinical and nonclinical staff, (including data 
management staff), and the participants will remain blinded to the treatment allocation until after the 
database has been locked and approval for study unblinding has been given. 
For the interim analysis, adequate firewalls will be setup to ensure that the clinical and nonclinical staff are 
kept blinded to treatment allocation and interim results. Details will be provided in the SAP. 
Once the interim analysis has been performed and Cohort 1 has completed the inpatient phase, new 
participants will continue to be randomized between the chosen arms for Cohort 2 using a suitable 
randomization schedule consistent with the planned number and size of the study arms. The measures 
described above to protect the blind will stay in place until the final unblinding. 
Following database lock, on receipt of authorisation from the sponsor, a copy of the randomisation code list 
will be provided to the study statistician to conduct study unblinding prior to analysis. 
Individual access to a secured Interactive Web Response System (IWRS) will be provided to the 
investigator. The website, compliant with 21CFR part 11 guidelines, will be used if unblinding is necessary. 
In case of an emergency, the 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 investigator 
decides that unblinding is warranted, the 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 investigator breaks the code, he/she will have to indicate on the web site 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 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. 
6.4. 
Study Intervention Compliance 
When participants are dosed at the site, they 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. 


 
 
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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 the final follow-up visit performed on Day 180 (±14 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. 
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 must be stopped prior to the planned date of dosing with IMP, 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. 
 
Use or anticipated use during conduct of the study 
of concomitant medications (prescription and non-
prescription), including vitamins or herbal and 
dietary supplements, unless in the opinion of the 
PI/investigator the medication will not interfere with 
the study procedures or compromise participant 
safety. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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Prohibited medication 
Washout 
Any IMP used in another study. 
 
 
 
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. 
 
 
 
 
Medications which are permitted throughout the study are shown in Table 6-3. 
Table 6-3: 
Permitted Medication 
Permitted medication 
Time period 
Paracetamol 
 
 
Ibuprofen 
 
 
 
 
Hormonal 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 programme 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 
In this study, a single dose of either CD388 or placebo is to be administered to enrolled participants. The 
CD388 dose to be administered in Arm 2 and Arm 3 have been defined (i.e., 150 mg and 50 mg, 
respectively). The CD388 doses in any additional study arms in Cohort 2 will be determined based on PK 
results obtained in the first-in-human study CD388.IM.SQ.1.01, as well as the interim analyses. However, 
the maximum dose will not exceed 150 mg. 


 
 
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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 SME/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. Document the quantity of the excess dose as well as the duration of the overdose in the eCRF. 
The sponsor and/or sponsor delegate is responsible for notifying the MHRA and Research Ethics 
Committee (REC) of the serious breach within 7 days of becoming aware of it. 


 
 
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7. 
Discontinuation of Study Intervention/Withdrawal 
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 carried out, and if clinically indicated, the 
participant should be invited back for a final follow-up visit. 
Sponsor representatives (both SME/medical monitor and clinical operations) 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. 
7.2. 
Participant Discontinuation 
Participants will be withdrawn from study intervention for any of the reasons listed below. These participants 
must not receive any additional study intervention but should continue to be followed for safety. Additional 
unscheduled visits may be performed for safety reasons. 
• 
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 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 would be in the participant’s 
best interest. 
• 
Termination of the study at the discretion of the PI/investigator or sponsor for safety, behavioural, 
or administrative reasons. 
• 
The wish of the participant. 
• 
Any intervention-related SAEs. 
• 
Anaphylactic reaction following dosing. 
• 
The participant becomes pregnant. 


 
 
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Participants who are withdrawn from the study, will be requested to attend an early withdrawal visit, with 
assessments as detailed in the SoE. 
7.2.1. 
Temporary Discontinuation/Temporary 
Delay in Enrolment 
 
 
 
 
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. 
 
 
 
 
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. 
Four 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. 


 
 
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Table 7-1: 
Study Stopping Rules 
Status 
Criterion 
Procedure 
1 
A serious adverse reaction has been 
reported (i.e. a serious adverse event 
considered at least possibly related to 
the IMP administration) in one subject. 
If such a status occurs at any point during the 
study, then further administration of the IMP in 
new participants 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 in new participants 
(approval of a substantial amendment from the 
Competent Authorities is required) or terminate 
the study. 
2 
Severe non-serious adverse reactions 
(i.e. severe non-serious adverse events 
considered as, at least, possibly related 
to the IMP administration) in two subjects 
in the same cohort, independent 
of within or not within the same system-
organ-class) 
If such a status occurs at any point during the 
study, then further administration of the IMP in 
new participants 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 in new participants 
(approval of a substantial amendment from the 
Competent Authorities is required) or terminate 
the study. 
3 
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 severity, 
but which collectively are determined to 
suggest a risk for further participant 
involvement. 
If such a status occurs at any point during the 
study, then further administration of IMP in new 
participants 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 in new participants (approval of a 
substantial amendment from the Competent 
Authorities is required) or terminate the study. 
4 
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. 


 
 
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A final follow-up visit will be performed on Day 180 (±14 days). Follow-up of any event should continue until 
resolution (return to normal or baseline values), stabilisation, or the participant is lost to follow-up. 
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). 
• 
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 utilise 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 an amendment. Generic 
adaptive features may be implemented at any time at the discretion of the PI/investigator. 
Table 7-2: 
Adaptive Features 
Adaptive Design 
Category 
Feature 
Limit 
Generic 
Cohort(s) 
1. Participants 
who 
have 
been 
withdrawn (for any reason) may be 
replaced 
(sponsor 
and/or 
PI 
discretion). 
2. Participants who are replacing a 
withdrawn 
participant 
may 
be 
randomised 
for 
inclusion, 
and 
dosed/challenged: 
a. In an ongoing cohort 
b. In a new cohort 
c. Separately 
3. The number of participants enrolled 
in each cohort may be reduced or 
increased 
(sponsor 
and/or 
PI 
discretion) to best meet the study 
objectives. 
1. The stopping rules of the study 
must be always adhered to, and 
replacement participants may not 
be enrolled to replace participants 
who have been withdrawn from the 
study due to any reason related to 
safety. 
2. The 
total 
number 
of 
study 
participants will not exceed 168. 
3. Replacement participants will be 
given replacement randomisation 
numbers 
(see 
Section 7.4, 
Participant Replacement Strategy). 
4. All 
protocol-defined 
rules 
and 
safety criteria must be met before 
any study part, 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 


 
 
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Adaptive Design 
Category 
Feature 
Limit 
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. 
case-by-case basis. As such the 
maximum number needed cannot 
be prospectively defined. 
Duration of 
inpatient stay 
1. 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 
information sheet. 
2. Participants must always be able to 
leave the study site unhindered if 
they wish to do so. 
3. The additional stay is triggered 
based 
on 
the 
minimal 
infectiousness discharge criteria 
not being met (see Section 8.2.2.2, 
Influenza 
Discharge 
Test/Rapid 
Viral 
Antigen 
Test), 
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. 
Study-specific 
Dose level and 
cohort size 
1. The CD388 dose levels in Cohort 2 
are TBD based on the PK results 
from Study CD388.IM.SQ.1.01, but 
will not exceed 150 mg. The interim 
analysis results from Cohort 1 will 
also inform the CD388 dose level 
selection and sample size in each 
study arm of Cohort 2. 
1. The dose will not exceed 150 mg. 
 
 


 
 
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8. 
Study Assessments and Procedures 
Unless otherwise stated, study assessments will be performed according to hVIVO SOPs. 
Study procedures and their timing are summarised 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. 
 
 
 
 
 
 
 
 
Where applicable, unless otherwise stated, laboratory normal ranges will be documented and saved in the 
PI/investigator 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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8.1.4. 
Challenge Agent Serology Samples 
A participant must be sero-suitable to take part in the study, i.e., he/she must have no or low pre-existing 
serum levels of antibodies specific to the challenge agent. This antibody titre cut-off for serosuitability will 
be described in the applicable hVIVO policy. 
Serum levels of pre-existing influenza-specific antibodies will be determined using a haemagglutination 
inhibitory assay, as described in the AP. 
8.1.5. 
Patient Health Questionnaire and 
Generalised Anxiety Disorder 
Questionnaire 
Patient Health Questionnaire-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 and throat (as required) sampling procedures will be performed during the 
study and are detailed in the sections below: 
• 
Nasosorption (nasal wick) 
• 
Nasopharyngeal swab 
Where any nasal sampling time points occur together the order of sampling will typically be (1) nasosorption 
(2) nasopharyngeal swab. 
8.2.1. 
Nasosorption 
A nasosorption (Class 1 Device) procedure will be used to collect samples of epithelial lining fluid for: 
• 
Inflammatory markers. 
• 
Other protein biomarkers e.g., antibodies. 
Remaining epithelial lining fluid may be stored and used for exploratory purposes. 
8.2.2. 
Nasopharyngeal Swab 
Nasopharyngeal swabs will be performed to collect samples of nasal material for: 
• 
Respiratory pathogen screen 
• 
Influenza discharge test 
• 
Viral shedding/load assessments (see Section 8.3.1) 
• 
Exploratory purposes (see Section 8.3.5). 
Remaining material from the nasopharyngeal swabs may be stored and used for exploratory purposes. 
8.2.2.1. 
Respiratory Pathogen Screen 
On entry to quarantine, a nasopharyngeal swab will be collected and tested to detect the presence of a set 
of respiratory pathogens that could potentially contraindicate a person’s participation in the study. The 
methodology to be used to conduct the respiratory pathogen screen will be documented in the AP. 


 
 
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Any additional screening tests will be conducted at the discretion of the PI/investigator. 
8.2.2.2. 
Influenza Discharge Test/Rapid Viral Antigen Test 
Where required, a rapid viral antigen test will be used to determine the presence of influenza in a 
nasopharyngeal swab sample taken prior to discharge from the quarantine unit on Day 8. A Biofire test may 
be used as an alternative test for this purpose, details of which will be documented in the AP. A rapid viral 
antigen test/Biofire test will be performed at the discretion of the PI/investigator and only if indicated for a 
clinical or other reason. 
8.2.3. 
Viral Sequencing 
 
 
 
 
8.3. 
Efficacy Assessments 
8.3.1. 
Viral Shedding Assessment 
Viral titre will be determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) 
and/or a viral culture assay to investigate the following parameters: 
• 
Viral load 
• 
Infectivity status and rate 
• 
Viral dynamics (e.g., duration, peak, time to resolution). 
8.3.2. 
Participant Diary Cards 
Symptom Diary Card 
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 symptom diary card. This 
information will be collected using a paper form. 
The following symptoms in the 13-item symptom questionnaire will be graded on a scale of 0-3 (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 


 
 
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• 
Sore throat 
• 
Earache 
• 
Malaise/tiredness 
• 
Headache 
• 
Muscle and/or joint ache 
• 
Chilliness/feverishness 
• 
Cough 
• 
Chest tightness 
• 
Shortness of breath 
• 
Wheeze 
Additional to the categorical symptom diary card, a visual analogue scale diary card using a 100 mm scale, 
with the same symptoms, will be completed by the participants. 
8.3.3. 
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 on Day -1, with the first collection on Day 0. Thereafter, distribution 
and collection of tissues will occur daily at the same time each day in the morning until discharge from 
quarantine. 
24-hour paper tissue collections will be analysed 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 
8.3.4. 
Respiratory Tract Infection Surveillance 
 
 
 
 
 
 
 
   
8.3.4.1. 
Active Surveillance 
 
 


 
 
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8.3.4.2. 
Passive Surveillance 
 
 
 
 
8.3.4.3. 
Assessment for Potential Influenza Respiratory Tract Infection 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
− 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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• 
 
 
 
 
8.3.5. 
Exploratory Assessments 
Plasma concentrations of CD388 or PK parameters across dose groups may be compared to viral and/or 
symptomatic endpoints to characterise the PK/PD relationship. In addition, CD388 concentrations in 
nasopharyngeal swabs may be explored. 
Nasal samples and/or blood cytokine and chemokine proteomic profile and/or mRNA profile may be 
assessed for associations with CD388 response, and other endpoints. 
Further details will be described in the SAP. 
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 on Days -5, 2, 3, 4, 180, and 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. 
 
 
 
 
 
 
 
 
 
8.4.3. 
Reactogenicity Events (Diary Card) 
Participants will be provided with the reactogenicity diary card to complete, once daily on Day -5 to Day -1. 
 
• 
 
 
 
 
 






 
 
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8.4.6.2. 
Drugs of Misuse and Cotinine 
 
 
 
 
8.4.6.3. 
Alcohol Breath Testing 
 
 
 
8.4.6.4. 
Safety Blood Analysis and Assessments 
Appendix 2, Clinical Laboratory Tests, describes the safety blood tests that will be performed including, but 
not limited to, haematology, biochemistry, coagulation, serology (HIV, hepatitis), thyroid function test, and 
cardiac enzymes. Additional safety assessments will be conducted at the discretion of the PI/investigator, 
as required. 
8.4.7. 
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. 
 
 
 
 
8.4.8. 
Lung Function 
Spirometry 
Spirometry will be performed according to hVIVO SOPs. Height at screening will be used as the baseline 
measurement for all spirometry assessments. 
 
 
 
 


 
 
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8.5. 
Recording of Adverse Events/Serious Adverse Events 
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 Events 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. 
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. 


 
 
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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), stabilisation, or the participant is lost to follow-up (as defined in Section 7.3, Lost to Follow-up). 
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 
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. 
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 (e.g., CIOMS) describing an SAE or other 
specific safety information (e.g., SAE/SUSAR) from the sponsor will review and then file it along with the 
Investigator’s Brochure 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. 
 
 
8.6. 
Pharmacokinetics 
Blood samples will be collected for measurement of CD388 concentrations as specified in the SoE. 
Instructions for the collection and handling of biological samples will be provided by the sponsor. The actual 
date and time (24-hour clock time) of each sample will be recorded. 
Samples will be used to evaluate the PK of CD388. Samples collected for analyses of CD388 blood 
concentrations may also be used to evaluate safety or efficacy aspects related to concerns arising during 


 
 
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or after the study. Genetic analyses will not be performed on these blood 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 for the evaluation of PK parameters of CD388 will be collected according to the SoE, and 
processed and sent to the sponsor’s PK vendor according to the AP. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*
 
 
 
8.6.2. 
Pharmacokinetic Nasopharyngeal Swab 
Samples 
Nasopharyngeal swabs for the evaluation of PK parameters of CD388 will be according to the SoE, and 
processed and sent to the sponsor’s PK vendor according to the AP. 


 
 
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8.6.3. 
Pharmacokinetic Parameters 
Pharmacokinetic parameters of interest may include: 
AUC0-t, AUC0-∞, Cmax, Tmax, t½ 
Pharmacokinetic parameters will be calculated using non-compartmental methods based on the actual 
elapsed time post-dose. Plasma concentrations at nominal times and PK parameters will be summarised 
descriptively. 
8.6.4. 
Anti-drug Antibodies 
Serum samples will be collected to measure the incidence of ADAs to CD388 during the study. 
8.7. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.8. 
Immunology Assessments 
 
 
 
 
 
 
 
8.9. 
Genetics 
 
 
 
 
 
 
 
8.10. Biomarkers 
Collection of samples for other biomarker research is also part of this study. The following samples for 
biomarker research are required and will be collected from all participants in this study as specified in the 
SoE: 
• 
Nasosorption 
• 
Nasopharyngeal swab 
• 
Serum 


 
 
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8.10.1. 
Immunology Biomarker Evaluations 
Nasal samples and blood may be used for exploratory immunology and genomic analysis related to viral 
infection/study intervention(s), including but not limited to: 
• 
Influenza antibodies 
• 
T cells 
• 
RNA transcriptomics 
• 
DNA 
• 
Immunoglobulin A antibodies 
Sample processing, storage, and assessments will be detailed in the AP. 


 
 
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9. 
Statistical Considerations 
9.1. 
Statistical Hypotheses 
The primary statistical hypothesis is that prophylactic treatment with CD388 at the dose of 150 mg will 
significantly reduce influenza VL-AUC as determined by qRT-PCR on nasal samples compared to placebo. 
9.2. 
Sample Size Determination 
A total sample size of 168 participants is estimated to be sufficient to achieve the objectives of this study. 
Depending on recruitment, the number enrolled at the planned first interim analysis is expected to be up to 
30 participants in Arm 1 (placebo), Arm 2 (150 mg CD388), and Arm 3 (50 mg CD388). An example of 
sample size estimates for the interim analysis depending on the recruited number of subjects is shown 
below: 
• 
The sample size of 30 participants per arm will have 95% power to detect a statistically significant 
difference between groups, using a Wilcoxon rank-sum test with a one-sided type-1 error rate of 
0.025, assuming that the probability that the VL-AUC for a participant in Arm 2 (150 mg CD388) is 
less than the VL-AUC for a participant in Arm 1 (placebo) is 0.75. 
• 
The sample size calculations used the method proposed in Shieh et al, 2009. 
Probability 
(AUCCD388 < AUCPlacebo) 
0.60 
0.65 
0.70 
0.75 
0.80 
Power at Interim analysis 
Interim analysis Arm 1 n=30 vs Arm 2 n=30 
0.259 
0.515 
0.785 
0.951 
0.996 
9.3. 
Participant Sets for Analyses 
The participant sets for analysis are defined in Table 9-1. 
Table 9-1: 
Study Participant Sets for Analysis 
Participant Analysis Set 
Description 
Enrolled 
All participants who sign the study-specific ICF. 
Intent-to-treat (ITT) analysis 
set 
All participants randomly assigned to study intervention. 
Intent-to-treat infected (ITT-I) 
analysis set 
All participants randomly assigned to study intervention and infected 
with challenge agent as per the definition of laboratory-confirmed 
infection for this protocol, i.e., qRT-PCR-confirmed influenza infection, 
defined as 2 quantifiable (≥LLOQ) qRT-PCR measurements (reported 
on 2 or more independent samples over 2 days), from Day 1 (pm) up to 
Day 8 (am). 
Per protocol (PP) analysis set All participants randomised, having received IMP (CD388/placebo), 
challenged with the study virus, who have a valid result for at least 80% 


 
 
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Participant Analysis Set 
Description 
of the planned qRT-PCR nasal samples from Day 1 (pm) up to Day 8 
(am), i.e., at least 11 out of 14, and present no major deviations likely to 
impact the evaluation of the primary efficacy endpoint. All deviations and 
all cases with at least one qRT-PCR result missing will be reviewed 
during the blinded data review meeting (BDRM) and adjudicated as 
belonging to the PP set or not. 
Safety analysis set 
All participants randomly assigned to study intervention and who 
received study intervention. Participants will be analysed according to 
the intervention they actually received. 
PK analysis set 
All participants randomly assigned to study intervention with at least 
1 post-dose PK result. 
Membership of participants in each analysis set will be determined at a planned data review meeting, prior 
to any analysis and database lock. 
The primary efficacy analysis will be on the PP analysis set. The ITT and ITT-I analysis set will be used for 
supportive analyses on all or part of the primary and secondary 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. 
9.4. 
Statistical Analyses 
This section is a summary of the planned statistical analyses of the most important endpoints including 
primary and key secondary endpoints. 
Data will be analysed and reported using SAS® version 9.4 or later. 
9.4.1. 
Statistical Analysis Plan 
The SAP will be developed and finalised prior to the first interim analysis for the study. The finalised SAP 
will be signed prior to unblinding the interim analysis data. The SAP 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 summarised 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. 


 
 
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Categorical variables will be summarised 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. If not otherwise specified in the SAP, the Wilson Score Method will be used to compute 
CIs for proportions. 
9.4.2.2. 
Inferential Statistics and Significance Testing 
Between-arm comparisons will be performed using appropriate hypothesis tests at the 2.5% 1-sided 
significance level, except if otherwise specified. No adjustment of the type-1 error rate for multiple 
comparisons will be done and each test will use a nominal level of 0.025 1-sided. 
For continuous variables (either raw data or log-transformed data) the difference in means, 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 Fisher exact test will be used to compare 
frequencies between study intervention arms. 
9.4.3. 
Planned Analysis 
9.4.3.1. 
Participant Accountability 
The number of participants receiving challenge agent, receiving IMP (CD388/placebo), withdrawing from 
(also split by reason for withdrawal), and completing the study, and the numbers in each analysis set, will 
be summarised. 
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 study intervention arm 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 (CD388/placebo) will be computed for each study intervention arm as proportion of 
participants actually receiving a full dose of IMP as prescribed. 


 
 
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9.4.4. 
Primary Efficacy Analysis 
The primary endpoint (VL-AUC of influenza challenge virus as determined by qRT-PCR on nasal samples 
starting a day post viral challenge [Day 1, pm] up to Day 8 [am], [i.e., virology]), will be analysed on the PP 
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. 
Descriptive statistics for the mean and median and the 2-sided 95% CI for the mean will be presented by 
study arm. The significance of the difference between each CD388 arm and the placebo arm will be 
analysed using the Wilcoxon rank-sum test. The estimator of the difference in area under the curve (AUC), 
with 95% CI will be obtained via the Hodges-Lehman (+Moses) method. The one-sided p-value will be 
presented. No adjustment of the type-1 error rate for multiple comparisons will be performed and each test 
will use a nominal level of 0.025 1-sided. Further details will be described in the SAP. 
The analysis will be repeated on the ITT analysis set as a sensitivity analysis. 
9.4.5. 
Secondary Efficacy Analysis 
Secondary endpoints as outlined in Section 3, Objectives and Endpoints, will be summarised by study 
intervention arm 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 
Peak viral load by qRT-PCR 
Descriptive statistics for continuous variables (see 
Section 9.4.2.1). 
Inferential analysis: Wilcoxon rank-sum test. 
Time to confirmed negative test by qRT-PCR 
Descriptive statistics for continuous variables (see 
Section 9.4.2.1). 
Kaplan-Meier curves 
No inferential analysis 
VL-AUC by viral culture 
Descriptive statistics for continuous variables (see 
Section 9.4.2.1). 
Inferential analysis: Wilcoxon rank-sum test. 
Peak viral load by viral culture 
Time to confirmed negative test by viral culture 
Descriptive statistics for continuous variables (see 
Section 9.4.2.1). 
Kaplan-Meier curves 
No inferential analysis 
TSS-AUC 
Descriptive statistics for continuous variables (see 
Section 9.4.2.1). 
Inferential analysis: Wilcoxon rank-sum test. 
Peak TSS 


 
 
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Endpoint 
Analysis 
Peak daily symptom score 
Descriptive statistics for continuous variables (see 
Section 9.4.2.1). 
Inferential analysis: Wilcoxon rank-sum test on each 
day. 
Time to symptom resolution 
Descriptive statistics for continuous variables (see 
Section 9.4.2.1). 
Kaplan-Meier curves 
Inferential analysis: Wilcoxon rank-sum test. 
Incidence of confirmed influenza infection, 
defined as 2 quantifiable (≥LLOQ) qRT-PCR 
measurements 
(reported 
on 
2 or 
more 
independent samples over 2 days) 
Descriptive statistics for categorical variables (see 
Section 9.4.2.1). 
Inferential analysis: Fisher exact test. 
Incidence of occurrence of at least 1 positive 
quantitative (≥LLOQ) cell culture 
Incidence of RT-PCR-confirmed symptomatic 
influenza infection, definition 1 (2 quantifiable 
qRT-PCR measurements [reported on 2 or 
more independent samples over 2 days]) AND 
symptoms ≥2  at a single time point 
Incidence of RT-PCR-confirmed moderately 
severe 
symptomatic 
influenza 
infection, 
definition 
2 
(2 
quantifiable 
qRT-PCR 
measurements 
[reported 
on 
2 
or 
more 
independent samples over 2 days]) AND any 
symptoms of grade ≥2 at a single time point 
Incidence of culture lab-confirmed symptomatic 
influenza infection (1 quantifiable [≥LLOQ] cell 
culture measurement AND symptoms ≥2 at a 
single time point) 
9.4.6. 
Tertiary/Exploratory Analysis 
Tertiary/exploratory endpoints as outlined in Section 3, Objectives and Endpoints, will be summarised by 
study intervention arm, as applicable. Further details are described in the SAP. 
9.4.7. 
Safety Analyse(s) 
All safety analyses will be computed on the safety analysis set. 
Unless otherwise stated, safety endpoints will be presented in terms of descriptive statistics only. 


 
 
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Adverse events will be coded using the version of the Medical Dictionary for Regulatory Activities (MedDRA) 
that is current at time of study start and summarised descriptively by SOC, PT, and study intervention arm 
for the number of AEs and treatment-emergent (relative to inoculation and separately relative to IMP 
administration) AE reported and the number and percentage of participants reporting each AE and 
treatment-emergent (relative to inoculation and separately relative to IMP administration) AE. 
 
 
 
 
 
9.4.8. 
Pharmacokinetic Analysis 
Descriptive statistics will be calculated for the plasma concentrations of CD388 at each applicable time 
point and for the derived plasma PK parameters. Statistics include sample size (n), mean, standard 
deviation, coefficient of variation, geometric mean, median, minimum, and maximum. 
For each participant, plasma concentration-time data of CD388 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. 
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 
A first interim analysis will be performed, by an unblinded team not involved in daily management of the 
study, for participants in Cohort 1 who have completed the inpatient phase at the time the interim analysis 
is performed. An optional second interim analysis may be performed by an unblinded team not involved in 
daily management of the study, within Cohort 2, depending on the outcome of the first interim analysis (see 
Figure 4-1).. Summary results of each interim analysis will inform on: 
• 
The participant numbers per study arm. 
• 
The CD388 dose levels to be studied (Section 6.6, Dose Modification). 
• 
The number of CD388 dose levels to be studied. 
The SAP will describe the planned interim analyses in greater detail. 
9.6. 
Data Monitoring Committee 
Not applicable. 


 
 
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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 Organisations of Medical Sciences International Ethical 
Guidelines. 
• 
Applicable ICH Good Clinical Practice (GCP) Guidelines. 
• 
Applicable laws and regulations. 
In addition to regulatory submission, the protocol, protocol amendments, ICF, Investigator’s Brochure, 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 is registered 
under the Data Protection Act. 
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. 


 
 
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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 or authorised designee 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 hVIVO trial master file. 
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 in 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 authorised 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. 
A separate ICF for genetic testing of samples will be required to document a participant’s agreement to 
allow any specimens to be used for related exploratory genetic research. Participants who decline to 
participate in this optional research will not provide this separate signature. 
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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The participant must be informed that his/her medical records may be examined by clinical QA auditors or 
other authorised 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 SME/medical monitor 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 Organisation list of primary registries or the International 
Committee of Medical Journal Editors list of registries, e.g., ClinicalTrials.gov or International Standardised 
Randomised Controlled Trial Number 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. 
 
hVIVO have a legal obligation to protect at all times 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. 
 
 
 
 
 
Study monitors will perform ongoing source data verification to confirm that data entered into the eCRF by 
authorised 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. 
 
 
 


 
 
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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. 
 
 
 
 
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 suggest 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. 
 
 
 
 
Termination of the clinical study may also be initiated by the MHRA or the REC. 
10.1.11. Publication Policy 
By signing the study protocol, the PI/investigator agrees that the results of this study may be used for the 
purposes of national and international registration, for publication, and as information for medical and 
pharmaceutical professionals by the sponsor. 
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 clinical study, the PI/investigator 
understands that he/she has an obligation to provide complete test results and all data developed during 
this study to the sponsor. 
If the study is to be published, the sponsor and hVIVO may jointly prepare and co-author manuscript(s) that 
could result from the clinical study. In the case the sponsor acts as fully responsible for the publication, the 
sponsor agrees to allow the PI/investigator time to review all manuscripts and abstracts prior to submission 
for publication. The sponsor reserves the right to include the report of this study in any regulatory 
documentation or submission or in any informational materials. The sponsor also reserves the right to delete 
any confidential information from any proposed manuscripts prior to submission for publication. 
Confirmation of study-specific arrangements can be found in the clinical study agreement. 
Verbal or written discussion of results prior to study completion and full reporting should only be undertaken 
with written consent from the sponsor. 
 
 




 
 
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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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
Events Meeting the AE Definition 
• 
 
 
 


 
 
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Events Meeting the AE Definition 
• 
 
 
 
 
 
 
 
Events NOT Meeting the AE Definition 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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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 authorisation, in the Summary of Product Characteristics for 
that product, 
(b) In the case of any other IMP, in the Investigator’s Brochure relating to the study in question. 
10.3.4. 
Serious Adverse Event 
SAE Definition 
An SAE is defined as any untoward medical occurrence that, at any dose: 
a. 
Results in death 
b. 
Is life threatening 
 
 
 
c. 
Requires inpatient hospitalisation or prolongation of existing hospitalisation 
• 
 
 
 
 
 
 
 
 
 
d. 
Results in persistent disability/incapacity 
• 
 
 


 
 
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• 
 
 
 
 
e. 
Is a congenital anomaly/birth defect 
f. 
Is an important medical event 
• 
 
 
 
 
 
 
 
 
 
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 Investigator’s Brochure relating to the 
study in question. 
 
 
 
 
 
 
 
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. 
 
 
 
 
 
 


 
 
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• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10.3.6.2. Assessment 
Description 
 
 
Onset and end 
The dates and times of the onset and end of the event should be recorded. 


 
 
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Assessment 
Challenge Agent-related Symptoms 
 
 
 
 
 
 
 
 
Physical Examination 
 
 
Symptom-directed Physical Examination 
 
 
 
 
 
Vital Signs 
 
 
 
 
Temperature 
 
 
 
 
 
 
 
Spirometry 
 
 
 
 


 
 
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Laboratory Values 
 
 
 
 
 
 
 
 
 
 
 
 
C-reactive Protein 
 
 
 
10.3.6.3. Assessment of Intensity 
The term ’severe’ is often used to describe the intensity (severity) of a specific event. This is not the same 
as ‘serious’ which is based on participant/event outcome or action criteria. 
The PI/investigator will use the DAIDS table 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 DAIDS table 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 
Grade 4 
Life threatening  
Extreme limitation in activity, significant assistance required; 
significant medical intervention/therapy required, hospitalisation or 
hospice care probable 


 
 
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Grade 
Classification 
Definition 
Grade 5 
Death 
Death 
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 
 
 
 
 
 
 
 
10.3.6.5. Assessment of Causality 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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Table 10-3: 
Classification of Adverse Event Relationship 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10.3.6.6. Action Taken 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10.3.6.7. Outcome 
An AE/SAE should be followed until the PI/investigator has determined and recorded the outcome. The 
outcome should be classified according to the categories shown in Table 10-4. 


 
 
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Table 10-4: 
Classification of Adverse Event Outcome 
Classification 
Definition 
Resolved 
 
Resolved with sequelae 
 
Ongoing 
 
 
Fatal 
 
 
Unknown (e.g., lost to follow-up) 
 
10.3.6.8. Follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 reporting obligations for the study.  
 
 
 
 
 
 
 
 
 


 
 
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. 
 
 
 
 
 
 
 
 
10.3.8. 
Reporting of Suspected Unexpected 
Serious Adverse Reaction 
 
. 
10.3.9. 
Adverse Reactions to Non-investigational 
Medicinal Products 
 
 
 
  
10.3.10. Pregnancy 
 
 
 
 
 
 
 
 
 
. 
 
 
 
 
 
 


 
 
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• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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10.4. Appendix 4: Normal Ranges 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 


 
 
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10.5. Appendix 5: Genetics 
Use/Analysis of Deoxyribonucleic Acid 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
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10.6. Appendix 6: Abbreviations 
Abbreviation 
Term 
ADA 
Anti-drug antibody 
AE 
Adverse event 
AP 
Analytical plan 
AUC 
Area under the curve 
AUC0-t 
Area under the plasma concentration-time curve from time 0 to time of last 
quantifiable sample 
AUC0-∞ 
Area under the plasma concentration-time curve from time 0 extrapolated to 
infinity 
β-hCG 
β-human chorionic gonadotrophin 
BMI 
Body mass index 
(c)GMP 
(current) Good Manufacturing Practice 
CI 
Confidence interval 
Cmax 
Maximum plasma concentration 
COVID-19 
Coronavirus Disease 2019 
DAIDS 
Division of AIDS 
DNA 
Deoxyribonucleic acid 
ECG 
Electrocardiogram 
(e)CRF 
Electronic case report form 
ELISA 
Enzyme-linked immunosorbent assay 
EMA 
European Medicines Agency 
ERS 
European Respiratory Society  
Fc 
Crystallisable fragment 
FDA 
Food and Drug Administration 
FEV(1) 
Forced expiratory volume (in 1 second) 
FSH 
Follicle-stimulating hormone 
FVC 
Forced vital capacity 
GAD-7 
Generalised Anxiety Disorder-7 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GP 
General practitioner 
HAI 
Haemagglutination inhibition 
HbA1c 
Haemoglobin A1c 
HIV 
Human immunodeficiency virus 
HVC 
Human viral challenge  
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IMP 
Investigational medicinal product 
ITT 
Intent-to-treat 


 
 
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ITT-I 
Intent-to-treat infected 
LRT 
Lower respiratory tract 
LLOD 
Lower limit of detection 
LLOQ 
Lower limit of quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHRA 
Medicines and Healthcare products Regulatory Agency 
mRNA 
Messenger RNA 
NA 
Neuraminidase 
NAI 
Neuraminidase inhibitor 
NOAEL 
No-observed-adverse-effect level 
PCR 
Polymerase chain reaction 
PHQ-9 
Patient Health Questionnaire-9 
PI 
Principal investigator 
PK 
Pharmacokinetic(s) 
PP 
Per protocol 
PT 
Preferred term 
PV 
Pharmacovigilance 
QA 
Quality assurance 
(q)RT-PCR 
(Quantitative) reverse transcriptase-polymerase chain reaction 
REC 
Research Ethics Committee 
RNA 
Ribonucleic acid 
RTI 
Respiratory tract infection 
SAE 
Serious adverse event 
SARS 
Severe acute respiratory syndrome 
SME 
Sponsor’s medical expert 
SOC 
System organ class 
SoE 
Schedule of events 
SOP 
Standard operating procedure 
SUSAR 
Suspected unexpected adverse reaction 
TBD 
To be determined 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to maximum plasma concentration 
TSS 
Total symptoms score 
TSS-AUC 
Area under the curve over time of total symptoms score 
UK 
United Kingdom 
URT 
Upper respiratory tract 
VL-AUC 
Area under the viral load-time curve 
 
 
 


 
 
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10.7. Appendix 7: Definitions 
10.7.1. 
General 
TERM 
hVIVO Services Limited Definition 
Completion (of a participant’s 
participation in the study) 
A participant will be considered to have completed the study after 
his/her attendance at the last planned study visit or the last 
unscheduled visit, as applicable. 
Baseline 
For safety assessments the nearest assessments completed prior to 
IMP dosing (and inoculation where appropriate) will be used as the 
baseline measure, unless stated otherwise. 
Enrolment (of a participant into 
the study) 
A participant will be considered to be ‘enrolled’ into the study once 
he/she has been randomised. 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. 
Infectious titre 
The titre of inoculum producing viral infection in a participant. The 
term ‘titre’ applies to the quantity or concentration of inoculum 
(depending on the units documented). 
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 an HVC study. 
Randomisation number 
The number allocated to a participant at randomisation, generated as 
stated in the protocol 
(NB. Not applicable will be recorded for “screen fail” participants or 
participants who are not randomised). 
Subject number 
The unique number assigned to a subject in the hVIVO subject 
database, which is used to identify the subject prior to randomisation. 
This number will be used throughout the recruitment and generic 
screening process to identify the subject. 
Challenge 
The inoculation of a participant with challenge agent inoculum. By 
definition, the day of challenge is Day 0. 
 


 
 
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10.7.2. 
Study Definition of Infection and Illness 
TERM 
CRITERIA 
(RESPIRATORY 
SYNCYTIAL 
VIRUS, 
HUMAN 
RHINOVIRUS, AND INFLUENZA STUDIES) 
The following definitions should only be applied to data collected from Day 1 onwards 
Lower respiratory tract (LRT) 
illness 
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: 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). 
Upper respiratory tract (URT) 
illness 
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: rhinorrhoea (runny nose), nasal 
congestion (stuffy nose), sore throat, sneezing. 
• 
Physician findings: nasal discharge, otitis, pharyngitis, sinus 
tenderness. 
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 
Febrile illness 
Any occurrence of temperature ≥37.9oC. 
Laboratory-confirmed influenza 
infection 
Viral shedding definition has been met. 


 
 
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10.7.3. 
Study Definition of a Postmenopausal 
Woman 
Amenorrhea for 
>12 Months with No 
Alternative Medical 
Cause 
Appropriate Agea 
Single FSH Value 
Level >40 mIU/mLb 
Meets Study 
Definition of 
Postmenopausal 
Female Participant 
Yes 
Yes 
Yes 
Yes 
No 
Yes 
Yes 
Noc 
Yes 
Yes 
No 
Yes 
No 
No 
Yes 
No 
a 45 years and above. 
b Serum FSH level must be taken in the absence of combined hormonal contraception or hormone replacement 
therapy. 
c If there is less than 12 months of amenorrhea a single raised FSH value is insufficient however, relevance of this 
for particular studies can be justified depending on nature of the IMP and at the discretion of the PI/investigator. 
Note: If consecutive FSH tests are required these should be carried out on 2 separate blood samples taken at least 
4 to 6 weeks apart. 
 
 




 
 
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4.0 
06/Oct/2022 
Non-Substantial 
Amendment 03 
Section 1, Protocol Synopsis, Summary of Study Design, 
Randomisation and Sample Size Determination and Section 9.2, 
Sample Size Determination, updated to reflect the modified 
randomisation schedule. 
Section 1, Protocol Synopsis, Summary of the Study Design and 
Section 4.1, Overall Design updated to remove the following 
paragraph “Depending on emerging PK data from the ongoing Phase 1 
study (CD388.IM.SQ.1.01), IMP administration may instead occur on a day 
between Day -7/-6 and Day -2. In these cases, the timing of procedures 
and the admission day to quarantine would be altered accordingly.” This 
statement is no longer applicable, dose confirmed as D-5 following 
Phase I data. 
Section 4.1, Overall Design and Section 6.3, Randomisation and 
Blinding updated to reflect up to of Arm 1 and Arm 2 sample size of 
up to 30. 
Figure 4-1: Overview of study design updated to reflect the 
modified randomisation schedule. 
Section 1, Protocol Synopsis, Summary of Study Design, 1.1 study 
schematic, 1.2 Schedule of Events and Section 4.1, Overall Study 
Design update to include D-7 as an additional admission day. 
Section 2, Protocol, Summary of Study Design, Statistics, Section 
4.1, Overall Design, Section 7.6, Adaptive Features, Table 7-2 and 
Section 9.5, Interim Analysis updated to highlight enrolment will not 
be halted at the time the first interim analysis is performed. 
Participants in Cohort 1 who have completed the inpatient phase at 
the time the interim analysis is performed will be included in the 
first interim analysis. This update is to supplement enrolment for 
cohort 1. 
Section 10.3, Solicited AEs, updated to reflect correct PI 
assessment for symptoms.  
Other minor administrative changes made, including correction of 
typos. 
 
 
 


 
 
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11. 
References 
Bueno de Mesquita PJ, Nguyen-Van-Tam J, Killingley B, Enstone J, Lambkin-Williams R et al. Influenza A 
(H3) illness and viral aerosol shedding from symptomatic naturally infected and experimentally infected 
cases. Influenza Other Respir Viruses. 2021;15(1):154-163. 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Paediatric Adverse Events. Corrected 
Version 2.1. July 2017. 
Fragaszy EB, Warren-Gash C, Wang L, Copas A, Dukes O, Edmunds WJ et al.; Flu Watch Group. Cohort 
Profile: The Flu Watch Study. Int J Epidemiol. 2017;46(2):e18. 
Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG et al. Standardization of spirometry 
2019 update. An official American Thoracic Society and European Society technical statement. American 
Journal and Critical Care Medicine. 2019;200(8):70-88. 
Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R et al. Estimates of global seasonal influenza-
associated respiratory mortality: a modelling study. Lancet. 2018;391(10127):1285-1300. 
Lambkin-Williams R, Noulin N, Mann A, Catchpole A, and Gilbert AS. The human viral challenge model: 
accelerating the evaluation of respiratory antivirals, vaccines, and novel diagnostics. Respir Res. 
2018;19:123. 
Nguyen-Van-Tam JS, Killingley B, Enstone J, Hewitt M, Pantelic J, Grantham ML et al. EMIT Consortium. 
Minimal transmission in an influenza A (H3N2) human challenge-transmission model within a controlled 
exposure environment. PLoS Pathog. 2020;16(7):e1008704. 
Nunes B, Viboud C, Machado A, Ringholz C, Rebelo-de-Andrade H et al. Excess mortality associated with 
influenza epidemics in Portugal, 1980 to 2004. PLoS One. 2011; 6:e20661. 
Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL et al. Multi-ethnic reference values for spirometry for 
the 3–95 year age range: the global lung function 2012 equations. Report of the Global Lung Function 
Initiative (GLI), European Respiratory Society (ERS) Task Force to establish improved lung function 
reference values. Eur Respir J. 2012;40(6):1324–1343. 
Ramos-Sevillano E, Wade WG, Mann A, Gilbert A, Lambkin-Williams R et al. The Effect of Influenza Virus 
on the Human Oropharyngeal Microbiome. Clin Infect Dis. 2019;68(12):1993-2002. 
Shieh G, Jan SL, and Randles RH (2006). On power and sample size determinations for the Wilcoxon–
Mann–Whitney test. Journal of Nonparametric Statistics. 2006;18(1):33-43. 
Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB et al. Influenza-associated hospitalizations 
in the United States. JAMA. 2004;292:1333-1340. 
Xu X, Blanton L, Elal AIA, Alabi N, Barnes J et al. Update: Influenza Activity in the United States During the 
2018-19 Season and Composition of the 2019-20 Influenza Vaccine. MMWR Morb Mortal Wkly Rep. 
2019;68(24):544-551. 
Yogaratnam J, Rito J, Kakuda TN, Fennema H, Gupta K et al. Antiviral Activity, Safety, and 
Pharmacokinetics of AL-794, a Novel Oral Influenza Endonuclease Inhibitor: Results of an Influenza Human 
Challenge Study. J Infect Dis. 2019;219(2):177-185. 


 
 
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Zucs P, Buchholz U, Haas W, and Uphoff H. Influenza associated excess mortality in Germany, 1985-2001 
Emerg Themes Epidemiol. 2005;2:6. 

SAP_001.pdf: 
Statistical Analysis Plan 
 
 
Title: 
A proof-of-concept, randomized, double-blind, placebo-controlled, Phase 
2a study to assess the prophylactic antiviral activity against influenza, 
safety, tolerability, and pharmacokinetics of CD388 via a human viral 
challenge model 
NCT Number: 
NCT05523089 
Document Date: 
25 JUL 2023 
 


 
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Cidara Therapeutics, Inc. 
CDT-CSP-001 / CD388.SQ.2.02 
 
 A proof-of-concept, Randomised, Double-blind, Placebo-controlled, Phase 2a 
Study to assess the prophylactic antiviral activity against influenza, safety, 
tolerability and pharmacokinetics of CD388 via a human viral challenge model 
 
Statistical Analysis Plan 
 
 
Version: v2 
Date: 25Jul2023 
 
 
 
 
Antoinette Anger 
Venn Life Sciences Biometry Services 
24-26 rue de la Pépinière | 75008 Paris | France 
Tel Office: +33 (0)1 40 21 04 10 
antoinette.anger@vennlife.com 
http://www.vennlifesciences.com 
 
 
 
This document is to be considered CONFIDENTIAL and is for the sole use and review by Cidara Therapeutics, Inc. to whom the 
document is addressed. This document may not be shared with third parties, including but not limited to contract research 
organisations and other pharmaceutical service providers, without the express written permission of Venn Life Sciences. 


 
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Signatures and version history 
 
 
 
Signature 
Venn Life Sciences 
 
Name 
Function 
Date and Signature 
Written by 
Antoinette 
Anger 
Associate Head of 
Statistics 
 
Reviewed 
by 
Elodie 
Blondiaux 
Methodology & 
Biometrics 
Consultant 
 
 
Cidara 
 
Name 
Function 
Date and Signature 
Approved by 
Ozlem Equils 
Medical Monitor  
 
Document version history 
 
Version 
Date 
Author 
Modifications since previous version 
V1 
16DEC2022 
Antoinette Anger 
NA (initial release) 
V2 
25JUL2023 
Antoinette Anger 
Update to section 12.3 
 
 


 
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Table of Contents 
ABBREVIATIONS AND DEFINITIONS ................................................................................................................ 6 
1 
INTRODUCTION ..................................................................................................................................... 8 
2 
HIGHLIGHTS FROM STUDY PROTOCOL ................................................................................................... 8 
2.1 
BACKGROUND/RATIONALE ............................................................................................................................ 8 
2.2 
STUDY OBJECTIVES AND ENDPOINTS ................................................................................................................ 8 
2.2.1 
Primary objective and endpoint ......................................................................................................... 8 
2.2.2 
Secondary objectives and endpoints .................................................................................................. 8 
2.2.3 
Tertiary/exploratory objectives* ...................................................................................................... 10 
2.3 
INVESTIGATIONAL PLAN ............................................................................................................................... 12 
2.3.1 
Study design and study assessments ................................................................................................ 12 
2.3.2 
Randomization ................................................................................................................................. 14 
2.3.3 
Determination of sample size ........................................................................................................... 16 
3 
ANALYSIS DATASETS ............................................................................................................................ 16 
3.1 
PROTOCOL DEVIATIONS ............................................................................................................................... 16 
3.1.1 
Major protocol deviations ................................................................................................................ 16 
3.1.2 
Minor protocol deviations ................................................................................................................ 17 
3.2 
STUDY TREATMENT DISCONTINUATIONS - STUDY DISCONTINUATIONS ................................................................... 17 
3.2.1 
Participant Withdrawal .................................................................................................................... 17 
3.2.2 
Participant Discontinuation .............................................................................................................. 17 
3.2.3 
Lost to Follow up .............................................................................................................................. 17 
3.2.4 
Participant Replacement Policy ........................................................................................................ 17 
3.3 
ANALYSIS SET DEFINITIONS ........................................................................................................................... 17 
3.3.1 
Enrolled analysis set ......................................................................................................................... 17 
3.3.2 
Intent-to-treat (ITT) analysis set ....................................................................................................... 17 
3.3.3 
Intent-to-treat Infected (ITT-I) analysis set ....................................................................................... 17 
3.3.4 
Per-protocol (PP) analysis set ........................................................................................................... 18 
3.3.5 
Safety (SAF) analysis set ................................................................................................................... 18 
3.3.6 
Pharmacokinetic (PK) analysis set .................................................................................................... 18 
4 
ENDPOINTS FOR ANALYSIS .................................................................................................................. 18 
4.1 
EFFICACY ENDPOINTS .................................................................................................................................. 18 
4.1.1 
Primary efficacy endpoint ................................................................................................................. 18 
4.1.2 
Secondary efficacy endpoints ........................................................................................................... 18 
4.1.3 
Tertiary/Exploratory efficacy endpoints ........................................................................................... 21 
4.2 
SAFETY ENDPOINTS .................................................................................................................................... 23 
4.2.1 
Adverse events.................................................................................................................................. 23 
4.2.2 
Laboratory endpoints ....................................................................................................................... 24 
4.2.3 
Other safety endpoints ..................................................................................................................... 24 
4.2.4 
Concomitant medications ................................................................................................................. 26 
5 
STATISTICAL AND ANALYTICAL METHODS ............................................................................................ 27 
5.1 
GENERAL CONSIDERATIONS .......................................................................................................................... 27 


 
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5.1.1 
Presentation of results ...................................................................................................................... 27 
5.1.2 
Significance testing and estimation.................................................................................................. 27 
5.2 
SEQUENCE OF ANALYSES .............................................................................................................................. 28 
5.3 
PLANNED ANALYSIS .................................................................................................................................... 28 
5.3.1 
Participant disposition and study discontinuations .......................................................................... 28 
5.3.2 
Protocol deviations ........................................................................................................................... 28 
5.3.3 
Demographics and baseline characteristics ..................................................................................... 29 
5.3.4 
Medical history – Prior medications ................................................................................................. 29 
5.3.5 
Concomitant medications ................................................................................................................. 29 
5.3.6 
Spirometry ........................................................................................................................................ 30 
5.3.7 
Efficacy analyses ............................................................................................................................... 30 
5.3.8 
Safety analyses ................................................................................................................................. 36 
6 
DATA HANDLING CONVENTIONS ......................................................................................................... 42 
6.1 
DEFINITIONS ............................................................................................................................................. 42 
6.1.1 
Baseline definition ............................................................................................................................ 42 
6.1.2 
Quarantine discharge ....................................................................................................................... 42 
6.2 
RETEST, OUTLIERS ..................................................................................................................................... 43 
6.2.1 
Retests .............................................................................................................................................. 43 
6.2.2 
Outliers ............................................................................................................................................. 43 
6.3 
VISIT WINDOWS, UNSCHEDULED VISITS ........................................................................................................... 43 
6.3.1 
Windows for time points .................................................................................................................. 43 
6.3.2 
Unscheduled visits ............................................................................................................................ 43 
6.4 
MISSING DATA AND ANALYSIS RULES .............................................................................................................. 43 
6.4.1 
Missing data ..................................................................................................................................... 43 
6.4.2 
Analysis rules .................................................................................................................................... 44 
7 
DERIVED DATA .................................................................................................................................... 45 
8 
INTERIM ANALYSIS .............................................................................................................................. 46 
9 
STATISTICAL/ANALYTICAL ISSUES ........................................................................................................ 47 
9.1 
ADJUSTMENTS FOR COVARIATES ................................................................................................................... 47 
9.2 
HANDLING OF DROPOUTS OR MISSING DATA ................................................................................................... 47 
9.3 
INTERIM ANALYSES AND DATA MONITORING .................................................................................................. 47 
9.4 
MULTICENTRE STUDIES ............................................................................................................................... 47 
9.5 
MULTIPLE COMPARISON/MULTIPLICITY ......................................................................................................... 47 
9.6 
USE OF AN “EFFICACY SUBSET” OF PARTICIPANTS ............................................................................................ 48 
9.7 
ACTIVE-CONTROL STUDIES INTENDED TO SHOW EQUIVALENCE ........................................................................... 48 
9.8 
EXAMINATION OF SUBGROUPS ..................................................................................................................... 48 
10 
MODIFICATIONS FROM THE STATISTICAL SECTION OF THE PROTOCOL ................................................. 48 
11 
SOFTWARE DOCUMENTATION ............................................................................................................. 48 
12 
TABLES, FIGURES AND LISTINGS ........................................................................................................... 49 
12.1 
LIST OF TABLES .......................................................................................................................................... 49 
12.2 
LIST OF FIGURES ......................................................................................................................................... 49 


 
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12.3 
LIST OF LISTINGS ........................................................................................................................................ 49 
13 
REFERENCES ........................................................................................................................................ 50 
14 
SCHEDULE OF EVENTS .......................................................................................................................... 51 
 
 
 


 
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Abbreviations and definitions 
ADA 
Anti-drug antibody 
AE 
Adverse Event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
aPTT 
Activated Partial Thromboplastin Time 
ATC 
Anatomical Therapeutic Chemical 
AUC 
Area Under the Curve 
BDRM 
Blind Data Review Meeting 
BHCG 
Beta-Human chorionic gonadotropin 
BMI 
Body Mass Index 
BP 
Blood Pressure 
Bpm 
Beats per minute 
CI 
Confidence interval 
CM 
Concomitant Medication 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAIDS 
Division of AIDS 
ECG 
Electrocardiogram 
EOS 
End of Study 
FEV1 
Forced expiratory volume (in 1 second) 
FSH 
Follicle-stimulating hormone 
FVC 
Forced vital capacity 
GGT 
Gamma-Glutamyl Transferase 
HIV 
Human immunodeficiency virus 
HR 
Heart Rate 
HVC 
Human Viral Challenge 
ICH 
International Council of Harmonization 
IMP 
Investigational Medical Product 
IP 
Investigational Product 
ITT 
Intention-to-Treat 
ITT-I 
Intention-to-Treat infected 
LDH 
Lactate Dehydrogenase 
LLN 
Lower Limit Normal 
LLOD 
Lower limit of detection 
LLOQ 
Lower limit of quantification 
LRT 
Lower Respiratory Tract 
MedDRA 
Medical Dictionary for Regulatory Activities 
MH 
Medical History 
Ms 
Millisecond 
NCS 
Non-Clinically Significant 
PI 
Principal Investigator 
PK 
Pharmacokinetic(s) 
PP 
Per-Protocol 


 
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PT 
Prothrombine Time 
PT 
Preferred Term 
Q1 
First quartile – 25th percentile 
Q3 
Third quartile – 75th percentile 
RR 
Respiratory Rate 
qRT PCR 
quantitative Reverse Transcriptase-Polymerase Chain Reaction 
SAE 
Serious Adverse Event 
SAF 
Safety dataset 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
SOP 
Standard operating procedure 
SoE 
Schedule of events 
TBD 
To be defined 
TEAE 
Treatment-Emergent Adverse Event 
TESAE 
Treatment-Emergent Serious Adverse Event 
TFL 
Tables Figures Listings 
TSS 
Total Symptom Score 
ULN 
Upper Limit Normal 
URT 
Upper Respiratory Tract 
VL 
Viral load 
WHO 
Word Health Organization 


 
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1 Introduction 
This document is the statistical analysis plan (SAP) for the CDT-CSP-001 study. The purpose of 
this SAP, developed following the International Council of Harmonization (ICH) E9 guideline, is 
to provide a comprehensive and detailed description of the statistical analyses that will be 
carried out to assess the clinical efficacy and safety of the study treatment, as outlined in the 
study protocol version 1.0, dated June 7, 2022. The SAP pre-specifies the statistical approaches 
to be used and is validated prior to the first interim analysis and the unblinding of the 
randomisation schedule, to ensure the credibility of the study findings. 
2 Highlights from study protocol 
2.1 Background/Rationale 
Full details on the background and rationale for the study are provided in Sections 2.1 to 2.3 
of the protocol. 
The purpose of this Phase 2a study is to evaluate the safety, tolerability, and prophylactic 
antiviral efficacy of CD388 compared to placebo in healthy adult participants who have not 
received an influenza vaccine and who are naïve to the influenza H3N2 A/Perth/16/2009 
challenge virus as defined by HA titres ≤1:10. 
 
2.2 Study Objectives and Endpoints 
2.2.1 
Primary objective and endpoint 
To evaluate the prophylactic antiviral effect of CD388 compared to placebo when treatment 
is initiated prior to administration with the influenza H3N2 A/Perth/16/2009 challenge virus 
by assessing the reduction of area under the viral load-time curve (VLAUC) measured by 
quantitative reverse transcriptase-polymerase chain reaction (qRT PCR) on nasal samples 
starting a day post viral challenge (Day 1, pm) up to Day 8 (am) in treated participants vs. 
placebo participants. 
2.2.2 
Secondary objectives and endpoints 
2.2.2.1 Efficacy 
To evaluate the antiviral effect of CD388 in:  
• reducing or shortening viral shedding after influenza viral challenge compared to 
placebo by assessing the following endpoints 
o Peak viral load of influenza as defined by the maximum viral load determined 
by quantifiable qRT-PCR measurements in nasal samples from Day 1 (pm) up to 
Day 8 (am). 
o Time (hours) to confirmed negative test by quantifiable qRT-PCR 
measurements in nasal samples from Day 1 (pm) to first confirmed 
undetectable assessment after peak measure. 
 


 
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• reducing or shortening culturable/replicating virus after influenza viral challenge 
compared to placebo by assessing the following endpoints: 
o VL-AUC of influenza challenge virus as determined by viral culture on nasal 
samples, from Day 1 (pm) up to Day 8 (am). 
o Peak viral load of influenza as defined by the maximum viral load determined 
by quantitative viral culture measurements in nasal samples from Day 1 (pm) 
up to Day 8 (am). 
o Time (hours) to confirmed negative test by quantifiable viral culture 
measurements in nasal samples from Day 1 (pm) to first confirmed 
undetectable assessment after peak measure. 
 
• reducing clinical symptoms due to influenza viral challenge compared to placebo by 
assessing the following endpoints: 
o Area under the curve over time of total clinical symptoms score (TSS-AUC) as 
measured by graded symptom scoring system collected 3 times daily from 
Day 1 (am) up to Day 8 (am). 
o Peak symptoms diary card score: peak of total clinical symptoms (TSS) as 
measured by graded symptom scoring system collected 3 times daily from 
Day 1 (am) up to Day 8 (am). 
o Peak daily symptom score: individual maximum daily sum of symptom score 
from Day 1 up to Day 8. 
o Time to symptom resolution as measured by graded daily symptom score 
system from time of peak daily symptom score to time of returning to baseline 
score. 
• reducing the incidence of influenza infection due to influenza viral challenge, 
compared to placebo by assessing the following endpoints: 
o RT-PCR-confirmed influenza infection, defined as 2 quantifiable (≥ lower limit 
of quantification [LLOQ]) qRT-PCR measurements (reported on 2 or more 
independent samples over 2 days), from Day 1 (pm) up to Day 8 (am). 
o Occurrence of at least 1 positive quantitative (≥LLOQ) cell culture measurement 
in nasal samples, from Day 1 (pm) up to Day 8 (am). 
o RT-PCR-confirmed symptomatic influenza infection, defined as: 
 RT-PCR-confirmed influenza infection (2 quantifiable [≥LLOQ] qRT-PCR 
measurements [reported on 2 or more independent samples over 
2 days]), from Day 1 (pm) up to Day 8 (am), AND 
 Symptoms ≥2 at a single time point (from Day 1 to Day 8) 
o RT-PCR-confirmed moderately severe symptomatic influenza infection, defined 
as: 
 RT-PCR-confirmed influenza infection (2 quantifiable [≥LLOQ] qRT-PCR 
measurements [reported on 2 or more independent samples over 
2 days]), from Day 1 (pm) up to Day 8 (am), AND 


 
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 Any symptoms of grade ≥2 at a single time point (from Day 1 to Day 8). 
o Culture lab-confirmed symptomatic influenza infection, defined as: 
 Lab-confirmed culturable influenza infection (1 quantifiable [≥LLOQ] 
cell culture measurement), from Day 1 (pm) up to Day 8 (am), AND 
 Symptoms ≥2 at a single time point (from Day 1 to Day 8). 
2.2.2.2 Safety 
To evaluate the safety of CD388 when compared to placebo on the basis of the following 
endpoints: 
• Occurrence of solicited Adverse Events (AEs) from subcutaneous dosing up to Day 0. 
• Occurrence of unsolicited AEs from subcutaneous dosing up to Day 28 (±3 days). 
• Occurrence of unsolicited AEs from subcutaneous dosing up to the final follow-up visit 
(Day 180 ±14 days). 
 
2.2.3 
Tertiary/exploratory objectives* 
To further evaluate the antiviral effect of CD388 in:  
• reducing or shortening viral shedding after influenza viral challenge compared to 
placebo by assessing the following endpoint: 
o Duration of quantifiable influenza qRT-PCR measurements in nasal samples 
from Day 1 (pm) up to Day 8 (am). Duration is defined as the time (hours) from 
first detectable until first confirmed undetectable assessment after their peak 
measure (after which no further virus is detected). 
• reducing or shortening culturable/replicating virus after influenza viral challenge 
compared to placebo by assessing the following endpoint: 
o Duration of quantitative influenza viral culture measurements in nasal samples 
from Day 1 (pm) up to Day 8 (am). Duration is defined as the time (hours) from 
first detectable until first confirmed undetectable assessment after their peak 
measure (after which no further virus is detected). 
• reducing clinical symptoms due to influenza viral challenge compared to placebo by 
assessing by assessing the following endpoints: 
o Time to peak as measured by graded daily symptom score system (from Day 1 
[am] to the time of peak daily symptom score). 
o Number (%) of participants with symptom scored grade 2 or higher, from Day 1 
(am) up to Day 8 (am). 
o Number (%) of participants with symptom scored grade 2 or higher by time 
point, from Day 1 (am) up to Day 8 (am). 
• reducing the incidence of influenza infection due to influenza viral challenge, 
compared to placebo by assessing by assessing the following endpoints: 
o Number (%) of participants with lab-confirmed infection and fever (≥37.9°C). 


 
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o Further sensitivity analysis may be performed on the above qRT-PCR-related 
incidence endpoints where detection by qRT-PCR is reported above the lower 
limit of detection (LLOD) instead of the LLOQ. 
• reducing nasal discharge compared to placebo by assessing the following endpoints: 
o Total weight of mucus produced from Day 1 (am) up to Day 8 (am). 
o Total number of facial tissues used by participants from Day 1 (am) up to Day 8 
(am). 
 
• reducing incidence of community-acquired influenza infection compared to placebo by 
assessing the following endpoint: 
o Laboratory--confirmed symptomatic influenza infection (community acquired), 
defined as: 
 Self-reported influenza-like symptoms, AND 
 Community acquired (not challenge virus) laboratory-confirmed 
influenza infection PCR measurement and/or lateral flow positive, or 
other equivalent) reported on any occasion from discharge from 
quarantine up to Day 90 and/or up to Day 180 (±14 days). 
 
• To monitor the safety of the challenge virus in the basis of the the following endpoint: 
o Occurrence of unsolicited AEs from virus challenge (Day 0) up to Day 28. 
 
• To evaluate the plasma PK of CD388 based on the following endpoints: 
o Pharmacokinetic (PK) parameters following CD388 administration will be 
determined as appropriate from the available data including: maximum plasma 
concentration (Cmax), time to maximum plasma concentration (Tmax), area 
under the plasma concentration-time curve from time 0 to time of last 
quantifiable sample (AUC0-t), and area under the plasma concentration-time 
curve from time 0 extrapolated to infinity (AUC0-∞). 
 
• To explore CD388 concentrations in nasopharyngeal swab samples 
 
 
• To explore PK/PD of CD388: 
o Plasma concentration at specific time points, or PK parameters across dose 
arms, will be compared to viral or symptomatic endpoints in an effort to 
characterise the exposure response of CD388, and will be reported separately 
 
• To explore cytokines and chemokines in nasal samples: 
o Cytokine/chemokine levels may be explored in nasal samples, related to CD388 
and infection. 
 


 
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• To explore cytokines and chemokines in serum samples: 
o Cytokine/chemokine levels may be explored in serum samples, related to 
CD388 and infection 
 
• To explore markers associated with the effect of CD388 or with infection: 
o Gene expression (messenger RNA [mRNA]) in whole blood 
 
• To explore viral resistance markers in influenza viral positive nasal samples: 
o Viral resistance markers relevant for CD388. 
 
*Note that tertiary objectives and endpoints are optional and might be assessed only if 
needed; therefore, not all testing might be performed and reported. 
2.3 Investigational plan 
2.3.1 
Study design and study assessments 
This is a single-centre, randomised, double-blind, placebo-controlled, proof-of-concept study 
in healthy adult male and female participants 18 to 55 years of age, inclusive, utilising: 
• IMP (active): a single subcutaneous dose of CD388 liquid for injection 
• IMP (placebo): a single subcutaneous dose of sterile normal saline for injection 
• Challenge agent: influenza H3N2 A/Perth/16/2009 challenge strain, ~105.5 tissue 
culture infective dose (50%) (TCID50), intranasally administered 
The primary goal of this Phase 2a study is to assess the prophylactic antiviral activity against 
influenza, safety, tolerability, and PK of CD388 via a HVC model, and to explore the impact of 
dose levels on efficacy. Each participant will receive a single administration of CD388 or 
placebo; multiple dose levels of CD388 may be evaluated. 
 
Participants will be recruited based upon the following criteria: Healthy adult male and female 
participants aged between 18 to 55 years, inclusive, with a total body weight ≥50 kg and body 
mass index (BMI) ≥18 kg/m2 and ≤35kg/m2, who have been determined to be sero-suitable 
with regard to pre-existing antibody levels to the influenza H3N2 A/Perth/16/2009 challenge 
virus. 
 A total of up to 168 participants is planned to be enrolled in this study in up to 2 cohorts. 
Cohort 1 will consist of up to 90 participants that will be enrolled simultaneously; a placebo 
arm (Arm 1, n= up to 30) and two CD388 dose arms (Arm 2 [150 mg CD388, n= up to 30] and 
Arm 3 [50 mg CD388, n= up to 30]). Cohort 2 details will be confirmed further to interim 
analysis as described below. Cohort 2 may include extension of the arms in Cohort 1 or include 
additional dose levels not exceeding 150 mg. 
Participants will receive CD388 or placebo prior to being inoculated with the influenza 
challenge virus and will undergo assessments as per Scheduled of Event (SoE). The timing of 


 
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administration of CD388 or placebo is chosen so as to approximate Tmax of CD388 in plasma 
at the time of challenge virus inoculation.  
 
 
Figure 1: Overview of Study Design 
The expected duration of study participation for a participant is approximately 9 months, with 
the following sequence and duration of study phases: 
- 
Screening Phase: from Day -96 to Day -7/-6 quarantine admission. Historical generic 
screening data collected through the hVIVO generic screening process may be transferred 
to this study after the study-specific consent form has been signed by the participant. 
- 
Inpatient Phase: Participants will be resident in the quarantine unit for approximately 
16 days (from Day -7/-6 to Day 8). Procedures will include: 
• Pre-HVC: 
o Admission to quarantine unit on Day -7/-6. 
o Baseline assessments and randomisation will be conducted as per SoE up to Day 
-5, pre-dose. 
o Administration of CD388 or placebo on Day -5. 
• HVC: 
o Influenza virus inoculation on Day 0. 
• Post-HVC: 
o Day 1 onwards and each day – study assessments will be conducted as per SoE. 


 
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o Participants will be discharged from the quarantine unit on Day 8 (or may remain 
longer at the principal investigator’s [PI’s] discretion). 
- 
Outpatient Phase: 
• Follow-up visit(s): Day 17 (±1 day), Day 28 (±3 days), Day 60 (±7 days), and Day 120 
(±14 days). 
• Final visit: Day 180 (±14 days). 
 
2.3.1.1 Study Schematic: On-study Participant Progression 
SCREENING 
PHASE 
 
INPATIENT PHASE: QUARANTINE/ISOLATION, DOSING, AND HUMAN 
VIRAL CHALLENGE 
 
OUTPATIENT 
PHASE 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day -96 to 
Day  
-7/-6 
 
Screening* 
 
Day -7/6 to 
Day -5, 
pre-dose 
Admission 
to 
quarantine 
unit, 
baseline 
assessment
s & 
randomisati
on 
 
Day -5 
 
Subcutaneou
s dosing with 
CD388 or 
placebo 
 
Day 0 
 
Influenza 
virus 
inoculation 
 
Days 1 to 7 
 
Assessments 
as per 
Schedule of 
Events 
 
Day 8 
 
Discharge 
from 
quarantine 
unit** 
 
Follow-up visits: 
Day 17 (±1 day), 
Day 28 (±3 days), 
Day 60 (±7 days), 
and 
Day 120 (±14 day
s) 
Final visit: 
Day 180 (±14 day
s) 
 
 
 
 
 
 
 
 
 
 
 
 
NOTES: 
*Screening assessments (including repeats, as required), may be performed up to Day -7/-6, (quarantine admission) at the 
discretion of the PI/investigator and in accordance with the design of the study. 
**Release from quarantine is foreseen at Day 8 (8 days post inoculation) provided that, where appropriate, no virus is detected by 
qualitative virus antigen test (negative virus antigen test) and the participant has no clinically significant symptoms. If the participant 
continues to have clinically significant symptoms and/or detectable virus on Day 8, additional extended quarantine stay may be 
required at the discretion of the PI/investigator. 
 
 
 
2.3.2 
Randomization 
 
In Cohort 1, the randomisation number encodes the participant’s assignment to 1 of 3 study 
arms: placebo (Arm 1, n= 24 to 30), and two CD388 dose arms (150 mg CD388 [Arm 2, n=30] 


 
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and 50 mg CD388, [Arm 3, n= 18 to 30]). This initial randomisation schedule, in use prior to 
Non-Substantial Amendment 03, used 2 varying block sizes (12 and 3) and 2 sets of 
randomisation ratios (4:5:3 and 1:0:2) to facilitate achieving the targeted sample sizes for the 
interim analysis. 
Block 
Cumulative 
Block 
Arm 1 
Placebo 
Arm 2 
High dose 
(150 mg CD388) 
Arm 3 
Low dose  
(50 mg CD388) 
Block size 
Arm 1 
Placebo 
Arm 2 
High dose 
(150 mg CD388) 
Arm 3 
Low dose  
(50 mg CD388) 
Randomised 
1 
4 
5 
3 
12 
4 
5 
3 
12 
2 
4 
5 
3 
12 
8 
10 
6 
24 
3 
4 
5 
3 
12 
12 
15 
9 
36 
4 
4 
5 
3 
12 
16 
20 
12 
48 
5 
4 
5 
3 
12 
20 
25 
15 
60 
6 
4 
5 
3 
12 
24 
30 
18 
72 
7 
1 
0 
2 
3 
25 
30 
20 
75 
8 
1 
0 
2 
3 
26 
30 
22 
78 
9 
1 
0 
2 
3 
27 
30 
24 
81 
10 
1 
0 
2 
3 
28 
30 
26 
84 
22 
1 
0 
2 
3 
29 
30 
28 
87 
23 
1 
0 
2 
3 
30 
30 
30 
90 
 
At the time of Non-Substantial Amendment 03 , this randomisation schedule was modified to 
ensure achievement of the largest possible sample-sizes in arm 1 (Placebo) and arm 2 (High 
dose) at the time of the planned first interim analysis. Participants enrolled under Non-
Substantial Amendment 03 will be randomised 1:1 to either arm 1 (Placebo) or arm 2 (150 mg 
CD388) until Cohort 1 enrolment is complete. Afterwards, a new randomisation schedule will 
be prepared, taking into account the decisions taken based on the results of the first interim 
analysis. 
Randomisation numbers will be assigned sequentially in ascending order; and once assigned, 
that randomisation number shall not be reassigned. The study site will keep a log of the 
randomisation number assigned to each participant. 
A designated unblinded statistician, separate from the conduct or analysis of the study, will be 
responsible for the computer-generated randomisation schedule. Sealed copies of the 
randomisation code will be stored in a secure location. 
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 and sponsor.  
If participants are replaced, the replacement participant will be assigned a new, unique 
randomisation number equalling the randomisation number of the replaced participant, plus 


 
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1000. This will ensure that the replacement participant receives the same allocated, blinded 
treatment as the participant who is being replaced. 
 
2.3.3 
Determination of sample size  
 
A total sample size of 168 participants is estimated to be sufficient to achieve the objectives 
of this study. 
Depending on recruitment, the number enrolled at the planned first interim analysis is 
expected to be up to 30 participants in Arm 1 (placebo), Arm 2 (150 mg CD388), and Arm 3 (50 
mg CD388). An example of sample size estimates for the interim analysis  is shown below: 
• The sample size of 30 participants per arm will have 95% power to detect a statistically 
significant difference between groups, using a Wilcoxon rank-sum test with a one-
sided type-1 error rate of 0.025, assuming that the probability that the VL-AUC for a 
participant in Arm 2 (150 mg CD388) is less than the VL-AUC for a participant in Arm 1 
(placebo) is 0.75. 
• The sample size calculations used the method proposed in Shieh et al, 2009. 
Probability 
(AUCCD388 < AUCPlacebo) 
0.60 
0.65 
0.70 
0.75 
0.80 
Power at Interim analysis 
Interim analysis Arm 1 n=30 vs Arm 2 n=30 
0.259 
0.515 
0.785 
0.951 
0.996 
AUC: area under the curve 
 
3 Analysis datasets 
3.1 Protocol deviations 
All deviations will be determined to be major or minor according to the Project Management 
Plan.   The impact of the deviation on the primary endpoint will be reviewed, during a blinded 
data review meeting before database lock and code break. Reasons for exclusion of 
participants from analysis sets due to major protocol deviations will be documented in the 
meeting minutes. A blinded data review meeting will be performed before each (interim) 
analysis. 
3.1.1 
Major protocol deviations 
Major protocol deviations are defined as deviations liable to either impact the rights, safety 
or well-being of the participant or prevent or bias the interpretation of the efficacy results of 
the study. The following deviations may be considered as major (this list is not exhaustive)): 
• 
Non-compliance with the inclusion or non-inclusion criteria 
• 
Non-compliance with the randomisation procedure 
• 
Non-compliance with study treatment 
• 
Non-compliance with protocol-specified challenge virus inoculation procedures 


 
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• 
Missing data for the primary efficacy endpoint (or data collected for the primary 
efficacy endpoint in a manner diverging from protocol specifications) 
• 
Intake of forbidden medication 
3.1.2 
Minor protocol deviations 
All deviations not identified as 'major' will be considered to be minor. 
3.2 Study treatment discontinuations - Study discontinuations 
3.2.1 
Participant Withdrawal 
See section 7.1 in the study Protocol. 
3.2.2 
Participant Discontinuation 
See section 7.2 in the study Protocol. 
3.2.3 
Lost to Follow up 
See section 7.3 in the study Protocol. 
3.2.4 
Participant Replacement Policy 
See section 7.4 in the study Protocol. 
3.3 Analysis set definitions 
Membership of participants in the per-protocol analysis set will be determined at planned 
blinded data review meetings, prior to any analysis. All other analysis sets will be determined 
programmatically based on data in the eCRF. 
The primary efficacy analysis will be on the PP analysis set. The ITT analysis set will be used for 
supportive analyses on part of the primary and secondary efficacy endpoints. The safety 
evaluation will be performed on the safety analysis set.  
3.3.1 
Enrolled analysis set 
All participants who sign the study-specific ICF. 
3.3.2 
Intent-to-treat (ITT) analysis set 
All participants randomly assigned and given study intervention. They will be analysed 
according to the treatment actually received 
 
3.3.3 
Intent-to-treat Infected (ITT-I) analysis set 
All participants randomly assigned and given the study intervention and infected with 
challenge agent as per the definition of laboratory-confirmed infection for this protocol, i.e., 
qRT-PCR-confirmed influenza infection, defined as 2 quantifiable (≥LLOQ) qRT-PCR 
measurements (2 quantifiable results reported within 4 consecutive scheduled assessments 
and from 2 independent samples), from Day 1 (pm) up to Day 8 (am). 


 
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3.3.4 
Per-protocol (PP) analysis set 
All participants randomised, having received IMP (CD388/placebo), challenged with the study 
virus, who have a valid result for at least 80% of the planned qRT-PCR nasal samples from Day 
1 (pm) up to Day 8 (am), i.e., at least 11 out of 14, and present no major deviations likely to 
impact the evaluation of the primary efficacy endpoint. All deviations and all cases who do not 
have at least 80% valid qRT-PCR result will be reviewed during blinded data review meetings 
(BDRM) and adjudicated as belonging to the PP set or not. 
3.3.5 
Safety (SAF) analysis set 
All participants who received study intervention. Participants will be analysed according to the 
intervention they actually received. 
3.3.6 
Pharmacokinetic (PK) analysis set 
All participants randomly assigned to study intervention with at least 1 post-dose PK result. 
4 Endpoints for analysis 
The derivations of each endpoint for analysis are described in the following sections. In case 
of missing data, analysis rules are presented in Section 6.4. 
4.1 Efficacy endpoints 
4.1.1 
Primary efficacy endpoint 
The primary efficacy endpoint for the study is the total viral load AUC measured by qRT-PCR  
after viral challenge on Day 0: from (Day 1 pm) up to Day 8 (am). 
The VL-AUC will be computed on the qRT PCR results from nasal samples collected twice daily 
starting with the first day post-viral challenge (Day 1 pm) up to discharge from quarantine (Day 
8). The viral load data will be supplied as log10 copies/mL and the AUC will be calculated using 
the trapezium rule (method described in Section 7). The VL-AUC results will be expressed in 
log10 copies/mL * day. 
 
4.1.2 
Secondary efficacy endpoints 
The secondary efficacy endpoints for the study are: 
4.1.2.1 Influenza infection 
• Peak viral load of influenza as defined by the maximum viral load determined by 
quantifiable qRT-PCR measurements in nasal samples from Day 1 (pm) up to Day 8 
(am) will be calculated per participant and will be supplied as log10 copies/mL.  
• Time (hours) to confirmed negative test by quantifiable qRT-PCR measurements 
in nasal samples from Day 1 (pm) to first confirmed undetectable assessment 
(Result equal to Not detected, <LLOD) after peak measure (after which no further 
virus is detected). Participants who did not have a confirmed undetectable qRT-
PCR assessment after their peak will be censored at their last detectable 
assessment. Participants who do not have a detectable qRT-PCR value during 


 
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quarantine will be excluded from the analysis.  In case of missing assessments, the 
LOCF type imputation will be used. 
• VL-AUC of influenza challenge virus as determined by viral culture on nasal 
samples, from Day 1 (pm) up to Day 8 (am). The viral load data will be supplied as 
log10 PFU/mL and the AUC will be calculated using the trapezium rule (described 
in Section 7). The VL-AUC results will be expressed in log10 PFU/mL * day. 
• Peak viral load of influenza as defined by the maximum viral load determined by 
quantitative viral culture measurements in nasal samples from Day 1 (pm) up to 
Day 8 (am) will be calculated per participant and will be supplied as log10 PFU/mL.  
• Time (hours) to confirmed negative test by quantifiable viral culture 
measurements in nasal samples from Day 1 (pm) to first confirmed undetectable 
assessment (Result equal to Not detected (<LLOD)) after peak measure. 
Participants who did not have a confirmed undetectable viral culture 
measurement after their peak will be censored at their last detectable assessment. 
Participants who do not have a detectable viral culture measure during quarantine 
will be excluded from the analysis. The number of these excluded participants will 
be displayed. In case of missing assessments, the LOCF type imputation will be 
used. 
• qRT-PCR-confirmed influenza infection, defined as 2 quantifiable (≥ lower limit of 
quantification [LLOQ]) qRT-PCR measurements (2 quantifiable results reported 
within 4 consecutive scheduled assessments and from 2 independent samples), 
from Day 1 (pm) up to Day 8 (am).  
To define the condition 2 quantifiable results reported within 4 consecutive 
scheduled assessments and from 2 independent samples, we will use the following 
rule: 
 
Assessment 1 
Assessment 2 
Assessment 3 
Assessment 4 
Condition met? 
Quantifiable 
Quantifiable 
Quantifiable 
Quantifiable 
Yes 
Quantifiable 
Not quantifiable 
Quantifiable 
Quantifiable 
Yes 
Quantifiable 
Quantifiable 
Not quantifiable 
Quantifiable 
Yes 
Quantifiable 
Quantifiable 
Quantifiable 
Not quantifiable 
Yes 
Quantifiable 
Not quantifiable 
Not quantifiable 
Quantifiable 
Yes 
Quantifiable 
Quantifiable 
Not quantifiable 
Not quantifiable 
Yes 
Quantifiable 
Not quantifiable 
Quantifiable 
Not quantifiable 
Yes 
Quantifiable 
Not quantifiable 
Not quantifiable 
Not quantifiable 
No 
Not quantifiable 
Quantifiable 
Quantifiable 
Quantifiable 
Yes 
Not quantifiable 
Not quantifiable 
Quantifiable 
Quantifiable 
Yes 
Not quantifiable 
Quantifiable 
Not quantifiable 
Quantifiable 
Yes 
Not quantifiable 
Quantifiable 
Quantifiable 
Not quantifiable 
Yes 
Not quantifiable 
Not quantifiable 
Not quantifiable 
Quantifiable 
No 
Not quantifiable 
Quantifiable 
Not quantifiable 
Not quantifiable 
No 


 
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Not quantifiable 
Not quantifiable 
Quantifiable 
Not quantifiable 
No 
Not quantifiable 
Not quantifiable 
Not quantifiable 
Not quantifiable 
No 
In case of missing data, no imputation will be done. 
 
• Occurrence of at least 1 positive quantitative (≥LLOQ) viral culture measurement 
in nasal samples, from Day 1 (pm) up to Day 8 (am). 
• qRT-PCR-confirmed symptomatic influenza infection, defined as: 
o RT-PCR-confirmed influenza infection (2 quantifiable [≥LLOQ] qRT-PCR 
measurements [2 quantifiable results reported within 4 consecutive 
scheduled assessments and from 2 independent samples]), from Day 1 
(pm) up to Day 8 (am) derived following the method above, AND 
o At least one TSS ≥2 at a single time point from Day 1 (pm) up to Day 8 (am) 
• qRT-PCR-confirmed moderately severe symptomatic influenza infection, defined 
as: 
o RT-PCR-confirmed influenza infection (2 quantifiable [≥LLOQ] qRT-PCR 
measurements [2 quantifiable results reported within 4 consecutive 
scheduled assessments and from 2 independent samples]), from Day 1 
(pm) up to Day 8 (am), AND 
o At least one single symptom of grade ≥2 at a single time point from Day 1 
(pm) up to Day 8 (am) 
• Culture lab-confirmed symptomatic influenza infection, defined as: 
o Lab-confirmed culturable influenza infection (1 quantifiable [≥LLOQ] cell 
culture measurement), from Day 1 (pm) up to Day 8 (am), AND 
o At least one total clinical symptom score (TSS) ≥2 at a single time point 
from Day 1 (pm) up to Day 8 (am) 
4.1.2.2 Clinical Symptoms 
• AUC over time of total clinical symptoms score (TSS-AUC) as measured by graded 
symptom scoring system collected 3 times daily from Day 1 (am) up to Day 8 (am). 
The method to derive the TSS is described in Section 7. The TSS-AUC will be 
calculated using the trapezium rule (method described also in Section 7) 
• Peak symptoms diary card score: peak of TSS as measured by graded symptom 
scoring system collected 3 times daily from Day 1 (am) up to Day 8 (am). The TSS 
is calculated at each day and at each 3 timepoints. Per participant, the highest TSS 
will be determined between all calculated TSS from Day 1 (am) up to Day 8 (am). 
• Peak daily symptom score: individual maximum daily sum of symptom score from 
Day 1 up to Day 8. The TSS is calculated at each day and at each 3 timepoints. Per 
participant and per day, the highest TSS will be selected between the 3 times daily. 
• Time to symptom resolution as measured by graded daily symptom score system 
from time of peak daily symptom score to time of returning to baseline score is 
measured as the time (hours) from peak daily symptom score (as defined in the 


 
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previous endpoint) until first time with TSS equal to the TSS at baseline after which 
no further increase above the baseline TSS is observed.  
Participants who do not have a TSS equal to baseline TSS after their peak TSS will 
be censored at their last TSS. Participants who have the baseline TSS during the 
whole quarantine will be excluded from this analysis.  
In case of missing TSS, we can consider several cases: If the missing values are not 
the last assessments, these missing values will be imputed by the previous not 
missing assessment. If the missing TSS values are the last measurements, the LOCF 
imputation method will be used. If the baseline score is missing, the baseline TSS 
will be imputed to 0. 
4.1.3 
Tertiary/Exploratory efficacy endpoints 
• Duration of quantifiable influenza qRT-PCR measurements in nasal samples from 
Day 1 (pm) up to Day 8 (am). Duration is defined as the time (hours) from first 
quantifiable until first confirmed unquantifiable assessment after their peak 
measure (after which no further virus is detected).  
In case of some unquantifiable assessment in-between series of one or more 
quantifiable assessments, the last quantifiable assessment of the last series is to 
be used as the end of the duration period. Participants who do not have a 
confirmed unquantifiable (i.e., <LLOQ, detected or not detected) assessment after 
their peak, will be censored at their last quantifiable assessment. Participants who 
stay unquantifiable during quarantine will be excluded from this analysis. The 
number of the excluded participants will be displayed. 
In the case of one or more missing qRT PCR result in between two quantifiable PCR 
results, the duration will still be computed.  
In the case of one or more missing qRT PCR measurements at the end of the 
period, not followed by any quantifiable result (i.e. without any available result 
or with only non-quantifiable ones), the exact timing of the end of the viral 
shedding is unknown and the exact duration cannot be computed.  
• Duration of quantifiable influenza viral culture measurements in nasal samples 
from Day 1 (pm) up to Day 8 (am). Duration is defined as the time (hours) from 
first quantifiable until first confirmed unquantifiable assessment after their peak 
measure (after which no further virus is detected). Similar approach as for the 
duration of quantifiable qRT-PCR will be used. 
• Time to peak as measured by graded daily symptom score system (from Day 1 [am] 
to the time of peak daily symptom score). The TSS is calculated at each day and at 
each 3 timepoints. Per participant, the first time with the highest daily TSS will be 
selected between all calculated TSS.  
• Number (%) of participants with at least one single symptom scored grade 2 or 
higher at any time, from Day 1 (am) up to Day 8 (am). 
• Number (%) of participants with at least one single symptom scored grade 2 or 
higher by time point, from Day 1 (am) up to Day 8 (am). 


 
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• Number (%) of participants with lab-confirmed infection and fever (≥37.9°C). the 
derivation of the lab-confirmed infection is described the section 14.1.2.1 (RT-PCR-
confirmed influenza infection). 
• Total weight of mucus produced from Day 1 (am) up to Day 8 (am). The sum of 
mucus weight will be calculated by participant over the period. 
• Total number of tissues used by participants from Day 1 (am) up to Day 8 (am). 
The sum of number of tissues will be calculated by participant over the period. 
• Number (%) of participants with Laboratory-confirmed symptomatic influenza 
infection (community acquired), defined as: 
o Self-reported influenza-like symptoms, AND 
o Community acquired (not challenge virus) laboratory-confirmed influenza 
infection PCR measurement and/or lateral flow positive, or other 
equivalent) reported on any occasion from discharge from quarantine up 
to Day 90 and/or up to Day 180 (±14 days). 
• Pharmacokinetic (PK) parameters following CD388 administration will be 
determined as appropriate from the available data including: maximum plasma 
concentration (Cmax), time to maximum plasma concentration (Tmax), area under 
the plasma concentration-time curve from time 0 to time of last quantifiable 
sample (AUC0-t), and area under the plasma concentration-time curve from time 0 
extrapolated to infinity (AUC0-∞).  
• CD388 concentrations in nasopharyngeal swabs: All collected parameters will be 
described by day/timepoint. 
• Plasma concentration at specific time points, or PK parameters across dose arms, 
will be compared to viral or symptomatic endpoints in an effort to characterize the 
exposure response of CD388, and will be reported separately. 
• Cytokine/chemokine levels may be explored in nasal samples, related to CD388 
and infection: . All collected parameters will be described by day/timepoint.  
Description will be presented by sub-groups (infected vs uninfected (definition in 
section 4.1.2.1 (RT-PCR-confirmed influenza infection) and symptomatic infected 
vs asymptomatic infected subjects (definition in section 4.1.2.1 (RT-PCR-confirmed 
symptomatic influenza infection)) for comparison. 
• Cytokine/chemokine levels may be explored in serum samples, related to CD388 
and infection: All collected parameters will be described by day/timepoint.  
Description will be presented by sub-groups (infected vs uninfected (definition in 
section 4.1.2.1 (RT-PCR-confirmed influenza infection) and symptomatic infected 
vs asymptomatic infected subjects (definition in section 4.1.2.1 (RT-PCR-confirmed 
symptomatic influenza infection)) for comparison. 
 
• Viral resistance markers relevant for CD388. All collected parameters 
corresponding to viral resistance markers will be described by day/timepoint. 


 
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4.2 Safety endpoints 
The safety and tolerability will be evaluated by the monitoring of the occurrence of AEs and 
SAEs, reactogenicity events (diary card), physical examinations, vital signs, 12-lead ECG, clinical 
laboratory results (haematology, biochemistry, coagulation, serology, cardiac enzymes, 
urinalysis, urine pregnancy test, thyroid function test), spirometry and concomitant 
medications. 
Safety and tolerability will be assessed over the whole study period, up to EOS (planned on 
Day 180 ± 14 days). 
4.2.1 
Adverse events 
Adverse events (solicited and unsolicited) will be coded using the latest available version of 
the Medical Dictionary for Regulatory Activities (MedDRA) and will be classified by MedDRA 
Preferred Term (PT) and System Organ Class (SOC). 
A Treatment Emergent Adverse Event (TEAE) will be defined as any AE that started from the 
time of first study treatment dose administered to the participant until last study visit (Day 
180). 
Two categories of AE will be defined: 
• 
Solicited AE: predefined events for which participants are specifically questioned 
and which are noted by participants in a participant diary (Erythema, 
swelling/induration, pain/tenderness) 
• 
Unsolicited AE: any AEs observed by the participant or PI/investigator which are 
not pre-listed/on a symptom diary card.  
 
For this study, 4 periods will be defined for solicited/unsolicited TEAE reporting:  
• Period 1 between the intake of the first dose of the IMP on Day -5 until just before the 
challenge virus inoculation on Day 0 (Period 1),  
• Period 2 from challenge virus inoculation until Day 8/Discharge from the quarantine 
unit 
• Period 3 from Day 8/ discharge from the quarantine unit to Day 28 (±3 days)  
• Period 4 from Day 28 (±3 days) until EOS (Day 180 ± 14 days). 
 
Handling of missing or incomplete dates in the definition of treatment emergence and 
attribution between the 4 periods is provided in Section 6.4.1.1. 
The relatedness of AE will be defined as follow: 
• Unrelated = Not related and Unlikely related 
• Related = possibly, probably and definitely related 
 
The grading of the severity of the AEs will use the Division of AIDS (DAIDS) Table for Grading 
the Severity of Adult and Paediatric Adverse Events, Corrected Version 2.1 (July 2017).   


 
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4.2.2 
Laboratory endpoints 
The following clinical laboratory tests are to be performed on collected blood samples at 
screening, admission (Day -6), Day -1, Day 7, Day 17, Day 28, Day 60, Day 120 and Day 180: 
• 
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 
(GGT), alkaline phosphatase, alanine transaminase (ALT), lactate dehydrogenase 
(LDH), aspartate transaminase (AST) and urea. 
• 
Haematology: platelet count, white blood cell count (absolute), white blood cell 
differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), red blood 
cell count, reticulocyte count (% and absolute), haemoglobin, haematocrit, mean 
corpuscular volume, mean corpuscular haemoglobin, and mean corpuscular 
haemoglobin concentration. 
• 
Coagulation: prothrombin time (PT), activated partial thromboplastin time (APTT) 
• 
Urinalysis: colour, specific gravity, appearance, pH, presence of blood, glucose, 
leukocytes, ketones, nitrites, proteins, urobilinogen, bilirubin by dipstick. Microscopy, 
culture, and sensitivity examination will be performed if the dipstick yields abnormal 
results. 
The laboratory values will be graded using Division of AIDS (DAIDS) will be used for grading.  
4.2.3 
Other safety endpoints 
4.2.3.1 Physical examinations 
Complete physical examinations will be conducted to include a full systemic assessment and 
will be performed according to the SoE. 
Directed physical examinations will be conducted as deemed appropriate by the investigator 
and may include examination of the eyes, ears, nose, throat, and chest (via stethoscope). 
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. Physician-reported assessments of viral challenge-related illness 
will be graded in accordance with its intensity and documented in the source data. 
Following viral challenge, additional symptoms that are not available in the list of symptoms 
of the symptom diary card and are deemed to be clinically significant in the opinion of the 
investigator will be captured as an AE. 
Following viral challenge all unexpected (in the opinion of the investigator) directed physical 
examination findings will be captured as AEs, along with all other occurrences that meet the 
criterion for an AE. 
4.2.3.2 Vital signs and temperature 
Vital signs assessments will be recorded as follows: 


 
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• 
Tympanic temperature will be recorded in degrees Celsius.). 
• 
Heart rate (HR) will be recorded in beats per minute. 
• 
Respiratory rate (RR): respirations will be counted and recorded as breaths per minute. 
• 
Blood pressure (BP): systolic BP and diastolic BP will be measured in millimeters of 
mercury (mmHg); measurements will be made whilst the participant is in a supine 
position. Where possible, the same arm will be used for all measurements. 
• 
Peripheral arterial oxygen saturation (SpO2%) will be assessed using pulse oximetry. 
Study specific normal ranges are provided in Table 1. If a result is out of the normal range and 
meets the criteria for an AE, the severity of the AE will be determined based on the DAIDS 
Table (July 2017). 
Table 1: Vital signs normal range 
Vital Signs 
Lower 
Limit 
Higher 
Limit 
Units 
Tympanic temperature  
 
(above 37.8 classed as pyrexia) 
35.5 
37.8 
oC 
Oxygen saturation 
Normal is ≥95 
% 
Respiratory rate 
10 
20 
breaths per minute 
Heart rate 
40 
100 
beats per minute 
Systolic BP 
90 
140 
mmHg 
Diastolic BP 
50 
90 
mmHg 
Source: Protocol Appendix 4: Normal Ranges 
4.2.3.3 12-lead electrocardiogram (ECG): 
The following 12-lead ECG parameters will be performed at screening, admission (Day -6), Day 
-1, Day 7 and Day 180: 
• 
Heart rate in beats per minute 
• 
QRS, PR interval, QT, QTc in milliseconds 
Study specific normal ranges are provided in Table 2 
Table 2: ECG normal range 
ECG Parameters 
Lower Limit 
Higher Limit 
Units 
Heart rate 
40 
100 
bpm 
QRS 
60 
120 
ms 
PR interval 
120 
220 
ms 
QT 
320 
450 
ms 
QTc (Fridericia/Bazett) 
320 
<450 (females) 
ms 
<430 (males) 
 


 
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4.2.3.4 Reactogenicity events (diary card) 
Participants will be provided with the reactogenicity diary card to complete, once daily from 
Day -5 to Day -1. Participants will be asked to provide severity grade for the following items in 
the diary card:  
• 
Redness (recorded in cm)  
• 
Swelling (recorded in cm)  
• 
Pain/tenderness (at the injection site)  
The grading scale used to assess the local reactions of injectable products as reported in the 
reactogenicity diary has been adopted from the FDA Center for Biologics Evaluation and 
Research (CBER) guidelines on toxicity grading scales for healthy adult volunteers enrolled in 
preventative vaccine clinical trials. In the event a local reaction is reported as an (S)AE, the 
grading scale will be documented in the associated AE/SAE form by the investigator. 
Local Reaction Grading Scale: 
 
 
4.2.4 
Concomitant medications 
Concomitant medication data will be coded according to the latest available version of the 
WHO-Drug dictionary. 
Concomitant medications are defined as any medication which was taken at any time on or 
after the start of study treatment, i.e:  
• Started before or on first IMP intake and still ongoing at first IMP intake 
• Started after first IMP intake 
Local Reaction to 
Injectable Product 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe (Grade 
3) 
Potentially Life 
Threatening 
(Grade 4) 
Pain 
Does not interfere 
with activity 
Repeated use of 
non-narcotic pain 
reliever >24 hours 
or interferes with 
activity 
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity 
Emergency room 
(ER) visit or 
hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
ER visit or 
hospitalization 
Erythema/Rednessa 
2.5 – 5 cm 
5.1 cm – 10 cm 
>10 cm 
Necrosis or 
exfoliative 
dermatitis 
Induration/Swellingb 
2.5 – 5 cm and does 
not interfere with 
activity 
5.1 – 10 cm or 
interferes with 
activity 
>10 cm or 
prevents daily 
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Necrosis 


 
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All other medications started and stopped before first IMP intake will be considered prior 
medications. 
In case of missing start date, the medication should be assumed prior and concomitant unless 
the end data indicates was stopped prior to first IMP intake. 
Handling of missing or incomplete dates is described in Section 6.4.1.1. 
5 Statistical and Analytical Methods 
5.1 General considerations 
The statistical analyses are performed in accordance with the ICH E9 guideline and other 
relevant guidance. 
The statistical analyses will be performed by an external Contract Research Organisation 
(CRO), under the responsibility of the Sponsor. 
5.1.1 
Presentation of results 
The following descriptive statistics will be presented: 
• For quantitative variables: number of available participants with the data point, 
number of missing data, mean, standard deviation (SD), median, Q1 (first quartile), Q3 
(third quartile), minimum, and maximum values. When relevant, confidence intervals 
(CIs) will be computed for the mean (Student CI) and/or the median (Hahn & Meeker 
1991). 
• For qualitative variables: number of available participants with the data point, number 
of missing values, frequency counts for each category and corresponding percentage. 
Except if otherwise specified, 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. If not otherwise specified, the Clopper-Pearson method will be 
used to compute CIs for proportions. 
5.1.2 
Significance testing and estimation 
5.1.2.1 Between group comparisons: 
For continuous variables (either raw data or log-transformed data) the difference in means, 
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 will be used.  
 
For categorical variables, differences in absolute frequency and/or relative risks will be 
presented, with their 95% 2-sided CIs. Except otherwise specified the Fisher exact test will be 
used to compare frequencies between study intervention arms 
5.1.2.2 Control of overall type-I error: 
Between-arm comparisons will be performed using appropriate hypothesis tests at the 2.5% 
1-sided significance level, except if otherwise specified. No adjustment of the type-1 error rate 
for multiple comparisons will be done and each test will use a nominal level of 0.025 1-sided. 


 
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5.2 Sequence of analyses 
 A first interim analysis will be performed, by an unblinded team not involved in daily 
management of the study, for participants in Cohort 1 who have completed the inpatient 
phase at the time the interim analysis is performed. An optional second interim analysis may 
be performed by an unblinded team not involved in daily management of the study, within 
Cohort 2, depending on the outcome of the first interim analysis (See Figure 1 in section 
2.3.1)  
A final analysis (Day 180) is planned after all participants have completed the EOS (or early 
withdrawal) visit, after data management is complete and after the blind data review and 
database lock. 
All statisticians/programmers except those involved in the interim analysis will remain blinded 
until the final DB lock. If SAP updates are necessary, they will be handled by this blinded team. 
5.3 Planned analysis 
The lists of statistical Tables, Figures and Listings (TFL) are provided in Section 12. 
5.3.1 
Participant disposition and study discontinuations 
Participant disposition will be described in a table (Statistical Table 14.1.1). The following 
variables will be tabulated: 
• Number of randomized participants by randomised arm and overall 
• Number of participants receiving IMP doses of CD388/placebo, by randomised arm and 
overall 
• Number of participants receiving challenge virus, by randomised arm and overall 
Analysis sets will be tabulated, overall and by randomised arm along with reasons for exclusion 
from the Enrolled, ITT, ITT-I, PP and SAF sets (Statistical Table 14.1.2). Individual data on the 
inclusion to/exclusion from each of the defined analysis sets will be provided in Listing 16.2.3. 
Study duration and premature study discontinuation will be summarized using the following 
variables on the Enrolled Set, overall and by randomized arm: 
• 
Number of participants who completed/discontinued the study, total and per 
treatment arm 
• 
Reason for study discontinuation, total and per randomised arm 
• 
Study duration defined as the difference between end of study date and date of 
enrolment +1, total and per randomised arm 
The results will be included in Statistical Table 14.1.1. 
Individual data on end of study information and reasons for discontinuation will be provided 
in Listing 16.2.1. 
Visit dates (including date of consent) will be presented in Listing 16.2.4.10. 
5.3.2 
Protocol deviations 
All protocol deviations 3.1.13.1.2 will be summarized (number and percentage of subjects with 
at least one protocol deviation, with at least one minor deviation and at least one major 


 
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deviation, and the number of major protocol deviations by deviation category) by randomised 
arm for the ITT set (Statistical Table 14.1.3). Individual data on protocol deviations will also be 
provided in Listing 16.2.2. 
5.3.3 
Demographics and baseline characteristics  
The following demographics variables will be summarised by randomised arm on the ITT, ITT-
I, PP and SAF analysis sets (Statistical Table 14.1.4.1 to .4) and individual data provided in 
Listing 16.2.4.1:  
• 
Sex  
• 
Age  
• 
Ethnicity 
• 
Race 
• 
Weight 
• 
Height 
• 
BMI 
The following baseline characteristics will be listed by treatment arm on the ITT set:  
• 
Weight, height and BMI (Listing 16.2.4.2)  
• 
Alcohol breath test and drugs of abuse and cotinine use (Listings 16.2.4.3 and 16.2.4.4)  
• 
Urine pregnancy test, serum follicle-stimulating hormone (FSH) levels and serum beta-
human chorionic gonadotrophin (β-HCG) pregnancy test (Listing 16.2.4.5)  
• 
HIV, hepatitis B and C and thyroid function data will be presented in Listing 16.2.4.6  
Eligibility criteria and randomisation information will be presented respectively in Listings 
16.2.4.7 and 16.2.4.8.  
Nasal swab respiratory pathogen screen data will be presented in Listing 16.2.4.11.  
5.3.4 
Medical history – Prior medications 
Medical history will be tabulated by SOC and PT by randomisation arm on the ITT set 
(Statistical Table 14.1.5). Note that the participant with the same System Organ Class 
/Preferred Term will be counted once. 
Medical history for each participant will be reported in Listing 16.2.4.9. 
Prior medications will be tabulated by ATC Level 2 code and Preferred Name by randomisation 
arm on ITT and PP set (Statistical Tables 14.1.6. and 14.1.6.2)  
Prior medications for each participant will be reported in Listing 16.2.4.12 (together with 
concomitant medications). 
5.3.5 
Concomitant medications  
Concomitant medications will be tabulated on the ITT and PP by ATC Level 2 code and 
Preferred Name by randomised arm (Statistical Tables 14.1.7.1 and 14.1.7.2). Note that the 
participant with the same ATC Level 2/Preferred Name will be counted once. 
Concomitant medications for each participant will be reported in Listing 16.2.4.12 (together 
with prior medications). 


 
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5.3.6 
Spirometry 
Spirometry will be performed according to hVIVO SOPs. Height at screening will be used as the 
baseline measurement for all spirometry assessments. 
The following parameters will be performed at eligibility only (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): 
• 
FEV1 (observed and percent predicted) 
• 
FVC (observed and percent predicted) 
• 
FEV1/FVC (observed and percent predicted) 
 
Study specific normal ranges are provided on Table 3 
Table 3: Spirometry normal range 
Spirometry Parameters 
Lower Limit 
Higher Limit 
FEV1  
Normal if ≥80% of the predicted value 
FEV1/FVC 
Normal if ≥70% (≥0.7) of the predicted value  
 
5.3.7 
Efficacy analyses 
5.3.7.1 Primary efficacy analysis 
5.3.7.1.1 Statistical hypotheses for primary efficacy analysis 
The primary statistical hypothesis is that prophylactic treatment with CD388 at the dose of 
150 mg will statistically significantly reduce influenza VL-AUC as determined by qRT-PCR on 
nasal samples compared to placebo. The second dose arm (50 mg) will also be compared to 
placebo, using a similar hypothesis. 
Note that, as stated in Section 5.1.2, these two hypotheses will both be tested and compared 
to a one-sided type-1 error rate of 0.025, without adjustment. 
The following statistical hypotheses will be tested: 
1: H01: AUC VL (150 mg) ≥ AUC VL (Placebo) vs HA1: AUC VL (150 mg) < AUC VL (Placebo) 
2: H02: AUC VL (50 mg) ≥ AUC VL (Placebo) vs HA2: AUC VL (50 mg) < AUC VL (Placebo) 
 
5.3.7.1.2 Statistical methods for primary efficacy analysis 
The primary efficacy endpoint is the total AUC of Influenza H3N2 A/Perth/16/2009 viral load 
measured by qRT-PCR on nasal samples. 
Provided this is a phase IIa, proof of concept study, the primary scientific question is that of 
the prophylactic effect when treatment and viral challenge are administered as per protocol 
(efficacy) rather than that of the prophylactic effect in real life condition (effectiveness). 
Consequently, the primary efficacy analysis will be conducted on the PP analysis population. 
Descriptive statistics for the mean and median and the 2-sided 95% CI for the mean will be 
presented by study arm. The significance of the difference between each CD388 arm and the 


 
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placebo arm will be analysed using the Wilcoxon rank-sum test. The estimator of the location 
shift in area under the curve (AUC), with 95% CI will be obtained via the Hodges-Lehman 
(+Moses) method. The one-sided p-value will be presented (Statistical Table 14.2.1.1). 
Boxplots of the VL-AUC per randomized arm (Figure 14.2.1.1.1) and a plot of VL mean values 
over time per randomised arm (Figure 14.2.1.1.2) will be prepared. 
Individual qRT-PCR data and VL-AUC for each participant will be reported respectively in the 
listings 16.2.6.1 and 16.2.6.4. 
5.3.7.1.3 Supplementary efficacy analyses for primary efficacy endpoint 
These supplementary analyses aim at documenting the influence of the choice of the analysis 
set on the results. 
The same analyses methods as described in Section 5.3.7.1.2 for the PP analysis set and the 
same figures will be produced for the ITT (Statistical Table 14.2.1.2.1, Figures 14.2.1.2.1.1 and 
14.2.1.2.1.2) and the ITT-I (Statistical Table 14.2.1.2.2, Figures 14.2.1.2.2.1 and 14.2.1.2.2.2) 
analysis sets. 
5.3.7.2 Secondary efficacy analyses 
Secondary efficacy analyses will be based on the PP analysis set only except if otherwise 
specified. 
5.3.7.2.1 Virologic endpoints 
Individual viral load data and derived efficacy response data for each participant by 
day/timepoint will be reported respectively in the listings 16.2.6.1 and 16.2.6.4. 
Viral load from qRT-PCR and from viral culture will be described by day and by timepoint 
(respectively Statistical Tables 14.2.4.1 (PP), 14.2.4.2 (ITT), 14.2.4.3 (ITT-I) and Statistical 
Tables 14.2.8.1 (PP), 14.2.8.2 (ITT), 14.2.8.3 (ITT-I)) 
5.3.7.2.1.1 Peak viral load by qRT-PCR 
The peak viral load of influenza from Day 1 (pm) up to Day 8 (am) will be presented by 
randomized arm using descriptive statistics for quantitative variables with 95% CI for the 
mean. The between mean difference and its 95% CI will be presented.  The significance of the 
differences between each CD388 arm and the placebo arm will be analyzed using the Wilcoxon 
rank sum test. The one-sided p-values will be presented (Statistical Table 14.2.2.1). Boxplot of 
the Peak viral load for each randomized arm will be prepared (Figure 14.2.2.1).  
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.2.2 and Figure 
14.2.2.2). 
 
5.3.7.2.1.2 Time to confirmed negative test by qRT-PCR  
The Time (in hours) to confirmed negative test by qRT-PCR will be analysed using the Kaplan-
Meier method. A Kaplan-Meier plot by randomized arm will be displayed showing the Time to 
confirmed negative test by qRT-PCR (with the time axis in hours since Day 1 (pm)). A table will 
accompany the plot and will display by randomised arm, the number of participants with 
event, the number of participants censored, the median, 25th percentile and 75th percentile 
of the time to confirmed negative test by qRT-PCR and their 95% confidence intervals. It will 


 
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also display the Kaplan-Meier estimates of the cumulative proportion of subjects with an event 
(ie, with a negative qRT-PCR test) at specific time points in hours. The actual time of each 
assessment will be used in the calculation of Kaplan-Meier estimates. The significance of the 
difference between each CD388 arm and placebo will be analyzed using the Gehan-Wilcoxon 
test (one side p-value).The number of participants who do not have a detectable qRT-PCR 
value during quarantine excluded from the analysis will be also displayed. (Statistical Table 
14.2.3.1 and Figure 14.2.3.1). 
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.3.2 and Figure 
14.2.3.2). 
 
5.3.7.2.1.3 VL-AUC by viral culture 
The VL-AUC will be computed on the viral culture results from nasal samples collected twice 
daily starting with the first day post-viral challenge (Day 1 pm) up to discharge from quarantine 
(Day 8).  
The same analyses methods as described in Section 5.3.7.1.2 will be performed for the PP and 
the ITT-I analysis sets (Statistical Tables 14.2.5.1 and 14.2.5.2). 
Boxplots of the VL-AUC per randomized arm (Figure 14.2.4.1.1 (PP) and 14.2.4.2.1 (ITT-I)) and 
a plot of VL mean values over time per randomized arm (Figure 14.2.4.1.2 (PP) and 14.2.4.2.2 
(ITT-I)) will be prepared. 
 
5.3.7.2.1.4 Peak viral load by viral culture 
The peak viral load of influenza will be presented by randomized arm using descriptive 
statistics for quantitative variables with 95% CI for the mean. The between mean difference 
and its 95% CI will be presented.  The significance of the difference between CD388 arm and 
placebo will be analysed using the Wilcoxon rank sum test. The one-sided p-value will be 
presented. (Statistical Table 14.2.6.1) 
Boxplot of the Peak viral load by viral culture per randomized arm will be prepared (Figure 
14.2.5.1).  
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.6.2 and Figure 
14.2.5.2). 
 
5.3.7.2.1.5 Time to confirmed negative test by viral culture  
The Time (in hours) to confirmed negative test by quantifiable viral culture will be analysed 
using Kaplan-Meier method. A Kaplan-Meier plot by randomized arm will be displayed 
showing the Time to confirmed negative test by quantifiable viral culture (with the time axis 
in hours since Day 1 (pm)). A table will accompany the plot and will display by randomized 
arm, the number of participants with event, the number of participants censored, the median, 
25th percentile and 75th percentile of the time to confirmed negative test by viral culture and 
their 95% confidence intervals. It will also display the Kaplan-Meier estimates of the 
cumulative proportion of subjects’ event free with an event (ie, with a negative viral culture 
test) at specific time points by randomized arm in hours. The actual time of each assessment 


 
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will be used in the calculation of Kaplan-Meier estimates. The significance of the difference 
between each CD388 arm and placebo will be analyzed using the Gehan-Wilcoxon test (one 
sided p-value). The number of participants who do not have a detectable viral culture value 
during quarantine excluded from the analysis will be also displayed.  (Statistical Table 14.2.7.1 
and Figure 14.2.6.1). 
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.7.2 and Figure 
14.2.6.2). 
 
5.3.7.2.1.6 Incidence of qRT-PCR-confirmed influenza infection  
The incidence of qRT-PCR-confirmed influenza infection will be presented by randomized arm 
using descriptive statistics for qualitative variables with the 95% CI for the incidence. The 
significance of the difference between each CD388 arm and the placebo arm will be analysed 
using the Fisher’s exact test with a one-sided alpha level of 0.025 (Statistical Table 14.2.14.1). 
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.14.2). 
 
5.3.7.2.1.7 Incidence of occurrence of at least 1 positive quantitative (≥LLOQ) cell culture  
The occurrence of at least 1 positive quantitative (≥LLOQ) cell culture measurement in nasal 
samples, from Day 1 (pm) up to Day 8 (am) will be presented by randomized arm using 
descriptive statistics for qualitative variables with the 95% CI for the incidence. The 
significance of the difference between each CD388 arm and the placebo arm will be analysed 
using the Fisher’s exact test with a one-sided alpha level of 0.025 (Statistical Table 14.2.15.1). 
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.15.2). 
5.3.7.2.1.8 Incidence of qRT-PCR-confirmed symptomatic influenza infection 
The incidence will be presented by randomized arm using descriptive statistics for qualitative 
variables with the 95% CI for the rate. The significance of the difference between each CD388 
arm and the placebo arm will be analysed using the Fisher’s exact test with a one-sided alpha 
level of 0.025 (Statistical Table 14.2.16.1). 
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.16.2). 
 
5.3.7.2.1.9 Incidence of qRT-PCR-confirmed moderately severe symptomatic influenza 
infection 
The incidence will be presented by randomized arm using descriptive statistics for qualitative 
variables with the 95% CI for the rate. The significance of the difference between each CD388 
arm and the placebo arm will be analysed using the Fisher’s exact test with a one-sided alpha 
level of 0.025 (Statistical Table 14.2.17.1). 
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.17.2). 
 
5.3.7.2.1.10 Culture lab-confirmed symptomatic influenza infection 
The incidence will be presented by randomized arm using descriptive statistics for qualitative 
variables with the 95% CI for the rate. The significance of the difference between each CD388 


 
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arm and the placebo arm will be analysed using the Fisher’s exact test with a one-sided alpha 
level of 0.025 (Statistical Table 14.2.18.1). 
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.18.2). 
 
5.3.7.2.2 Clinical symptoms 
 
Individual and total clinical symptoms score and derived efficacy response data for each 
participant by day/timepoint will be reported respectively in the listings 16.2.6.2 and 16.2.6.4. 
The TSS will be described by day and by timepoint (Statistical Tables 14.2.13.1 (PP), 14.2.13.2 
(ITT) and 14.2.13.3 (ITT-I). 
5.3.7.2.2.1 Area under the curve over time of total clinical symptoms score (TSS-AUC) 
The TSS-AUC collected from Day 1 (am) up to Day 8 (am) will be presented by randomized arm 
using descriptive statistics for quantitative variables with 95% CI for the mean. The between 
mean difference and its 95% CI will be presented.  The significance of the difference between 
each CD388 arm and the placebo arm will be analysed using the Wilcoxon rank sum test. The 
one-sided p-value will be presented (Statistical Table 14.2.9.1). 
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.9.2). 
Boxplots of the TSS-AUC per randomized arm (Figure 14.2.7.1.1 (PP) and 14.2.7.2.1 (ITT-I)) and 
a plot of TSS mean values over time per randomised arm (Figure 14.2.7.1.2 (PP) and 14.2.7.2.2 
(ITT-I)) will be prepared. 
 
5.3.7.2.2.2 Peak of total clinical symptoms score 
The peak of TSS will be presented by randomized arm using descriptive statistics for 
quantitative variables with 95% CI for the mean. The between mean difference and its 95% CI 
will be presented.  The significance of the difference between CD388 arm and placebo will be 
analysed using the Wilcoxon rank sum test. The one-sided p-value will be presented. 
(Statistical Table 14.2.10.1) 
Boxplot of Peak total clinical symptoms score per randomised arm will be prepared (Figure 
14.2.8.1).  
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.10.2 and Figure 
14.2.8.2). 
 
5.3.7.2.2.3 Individual peak daily total clinical symptoms score 
The individual peak daily TSS from Day 1 up to Day 8 will be presented by randomized arm 
using descriptive statistics by day for quantitative variables with 95% CI for the mean. The 
between mean difference and its 95% CI will be presented.  The significance of the difference 
between CD388 arm and placebo will be analysed using the Wilcoxon rank sum test. The one-
sided p-value will be presented. (Statistical Table 14.2.11.1) 
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.11.2). 


 
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A plot of peak daily TSS mean values over time per randomised arm (Figure 14.2.9.1 (PP) and 
14.2.9.2 (ITT-I)) will be prepared. 
 
5.3.7.2.2.4 Time to symptom resolution 
The Time to symptom resolution will be analysed using the Kaplan-Meier method. A Kaplan-
Meier plot by randomised arm will be displayed showing the Time to symptom resolution (with 
the time axis as hours since peak daily symptom score). A table will accompany the plot and 
will display by randomized arm, the number of participants with event, the number of 
participants censored, the median, 25th percentile and 75th percentile of the time to 
symptom resolution and their 95% confidence intervals. It will also display the Kaplan-Meier 
estimates of the cumulative proportion of subjects’ event free with an event (ie, with symptom 
resolution) at specific time points by randomized arm in hours. The actual time of each 
assessment will be used in the calculation of Kaplan-Meier estimates. The significance of the 
difference between each CD388 arm and placebo will be analyzed using the Gehan-Wilcoxon 
test (one sided p-value) (Statistical Table 14.2.12.1 and Figure 14.2.10.1). 
This analysis will be repeated on the ITT-I analysis set (Statistical Table 14.2.12.2 and Figure 
14.2.10.2). 
 
5.3.7.3 Tertiary/exploratory efficacy analyses 
No inferential statistics will be computed for tertiary/exploratory efficacy endpoints. Their 
analyses will be only descriptive on PP analysis set.  
Other tertiary/exploratory efficacy analyses may be conducted and will be described in a SAP 
amendment. 
5.3.7.3.1 Quantitative tertiary/exploratory endpoints 
Descriptive statistics for quantitative variables, including the 95% CI for the mean, will be 
tabulated for: 
• Duration of quantifiable influenza qRT-PCR measurements in nasal samples from 
Day 1 (pm) up to Day 8 (am). (Statistical Table 14.2.19). 
• Duration of quantitative influenza viral culture measurements in nasal samples 
from Day 1 (pm) up to Day 8 (am). (Statistical Table 14.2.20). 
• Time to peak as measured by graded daily symptom score system (from Day 1 (am) 
to the time of peak daily symptom score). (Statistical Table 14.2.21). 
• Total weight of mucus produced from Day 1 (am) up to Day 8 (am) (Statistical 
Table 14.2.22). 
• Total number of tissues used by participants from Day 1 (am) up to Day 8 (am) 
(Statistical Table 14.2.23). 
• Cytokine/chemokine levels may be explored in nasal samples, related to CD388 
and infection. (Statistical Table 14.2.28.1 overall, by sub-groups 16.2.28.2 and 
16.2.28.3 and listing 16.2.6.5) 


 
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• Cytokine/chemokine levels may be explored in serum samples, related to CD388 
and infection. (Statistical Table 14.2.29.1 overall, by sub-groups 16.2.29.2 and 
16.2.29.3 and listing 16.2.6.5) 
 
5.3.7.3.2 Qualitative tertiary/exploratory endpoints 
Descriptive statistics for qualitative variables, including the 95% CI for the rates, will be 
tabulated for: 
• Number (%) of participants with symptom scored grade 2 or higher, from Day 1 
(am) up to Day 8 (am) (Statistical Table 14.2.24). 
• Number (%) of participants with symptom scored grade 2 or higher by time point, 
from Day 1 (am) up to Day 8 (am) (Statistical Table 14.2.25). 
• Number (%) of participants with lab-confirmed infection and fever (≥37.9°C) 
(Statistical Table 14.2.26). 
• Number (%) of participants with Laboratory-confirmed symptomatic influenza 
infection (community acquired) (Statistical Table 14.2.27), defined as: 
o Self-reported influenza-like symptoms, AND 
o Community acquired (not challenge virus) laboratory-confirmed influenza 
infection PCR measurement and/or lateral flow positive, or other 
equivalent) reported on any occasion from discharge from quarantine up 
to Day 90 and/or up to Day 180 (±14 days). 
• Viral resistance markers relevant for CD388. (Statistical Table 14.2.30 and listing 
16.2.6.6) 
 
5.3.7.4 Other efficacy variables  
The following data will be presented in listings on the ITT analysis set: 
• Nasopharyngeal swab for rapid viral antigen test at discharge from quarantine (Listing 
16.2.6.7) 
• 24-hour tissue count and nasal discharge weight (Listing 16.2.6.3) 
• Blood - Serum anti-drug antibodies (ADA) will be presented by randomized arm by day 
in term of presence/absence of ADA (Statistical table 14.2.31.1) and in term of titer 
levels (Statistical table 14.2.31.2) and Listing 16.2.6.8. 
 
5.3.8 
Safety analyses 
Safety variables will be tabulated and presented for all participants included in the Safety 
analysis set (SAF). 
5.3.8.1 Extent of exposure and compliance 
Compliance with IMP (CD388/placebo) will be computed on the ITT and SAF set by randomized 
arm (Statistical Tables 14.1.8.1 and 14.1.8.2) by assessing the proportion of participants 
actually receiving a full dose of IMP as prescribed. 


 
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IMP/ Placebo dosing and Challenge virus inoculation information for each participant will be 
reported respectively in Listings 16.2.5.1 and 16.2.5.2. 
5.3.8.2 Adverse events 
5.3.8.2.1 Adverse event tabulations: 
Tabulation of solicited or unsolicited AEs will be done according to four periods based on their 
date and time of start, as presented in Table 4: 
Table 4: periods for AE tabulation 
Period 
Description 
from 
to 
Period 1 
Treatment Emergent/ Pre-viral  
Challenge Emergent Adverse Events 
First intake of 
IMP on Day -5 
Just before challenge virus 
inoculation on Day 0 
Period 2 
Treatment 
and 
Viral 
Challenge 
Emergent Adverse Events 
Challenge 
virus 
inoculation 
on 
Day 0 
 
Actual discharge from the 
quarantine 
unit 
(as 
scheduled on Day 8 or later 
on PI’s decision)  
Period 3 
Post quarantine Adverse Events  
Actual discharge 
from the quaran-
tine unit  
Day 28 (±3 days) 
Period 4 
Post Day 28 Adverse Events 
Day 28 
Day 180 (±14 days) (EOS 
visit) 
Tabulation of adverse events will present the following information: number of participants 
with at least one occurrence of the event, corresponding percentage and number of events (if 
relevant).  
The following tables will be produced by treatment arm (as treated): 
5.3.8.2.1.1 Summary table of adverse events (Statistical Table 14.3.1): 
• Any AE 
• Any TEAE (solicited + unsolicited TEAE) 
• Any solicited AE during Period 1 
• Any unsolicited TEAE across all periods (i.e. period 1, 2, 3 or 4) 
• Any unsolicited TEAE during Period 1 
• Any unsolicited TEAE during Period 1 and Period 2 
• Any unsolicited TEAE during Period 2 
• Any unsolicited TEAE during Period 2 and Period 3 
• Any unsolicited TEAE during Period 3 
• Any unsolicited TEAE during Period 3 and Period 4 
• Any unsolicited TEAE during Period 4 
• Any unsolicited TEAE during Period 1 leading to study treatment discontinuation (only 
relevant for Period 1) 


 
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• Any unsolicited TEAE across all periods (i.e. period 1, 2, 3 or 4) leading to study 
discontinuation 
• Any unsolicited TEAE during Period 1 leading to study discontinuation 
• Any unsolicited TEAE during Period 1 and Period 2 leading to study discontinuation 
• Any unsolicited TEAE during Period 2 leading to study discontinuation 
• Any unsolicited TEAE during Period 2 and Period 3 leading to study discontinuation 
• Any unsolicited TEAE during Period 3 leading to study discontinuation 
• Any unsolicited TEAE during Period 3 and Period 4 leading to study discontinuation 
• Any unsolicited TEAE during Period 4 leading to study discontinuation 
• Any unsolicited TEAE across all periods (i.e. period 1, 2, 3 or 4) considered related to 
the study treatment (at least possibly related) 
• Any unsolicited TEAE during Period 1 considered related to the study treatment (at 
least possibly related) 
• Any unsolicited TEAE during Period 1 and Period 2 considered related to the study 
treatment (at least possibly related) 
• Any unsolicited TEAE during Period 2 considered related to the study treatment (at 
least possibly related) 
• Any unsolicited TEAE during Period 2 and Period 3 considered related to the study 
treatment (at least possibly related) 
• Any unsolicited TEAE during Period 3 considered related to the study treatment (at 
least possibly related) 
• Any unsolicited TEAE during Period 3 and Period 4 considered related to the study 
treatment (at least possibly related) 
• Any unsolicited TEAE during Period 4 considered related to the study treatment (at 
least possibly related) 
• Any serious adverse events (SAE) across all periods (i.e. period 1, 2, 3 or 4) 
• Any SAE during Period 1 
• Any SAE during Period 1 and Period 2 
• Any SAE during Period 2 
• Any SAE during Period 2 and Period 3 
• Any SAE during Period 3 
• Any SAE during Period 3 and Period 4 
• Any SAE during Period 4 
• Any TESAE leading to study treatment discontinuation, across all periods (i.e. period 1, 
2, 3 or 4).  
• Any TESAE leading to study discontinuation, across all periods (i.e. period 1, 2, 3 or 4) 
• Any SAE considered related to the study treatment, across all periods (i.e. period 1, 2, 
3 or 4) 
• Death (if any) 


 
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5.3.8.2.1.2 Detailed Tables:  
• Any solicited AE by PT during Period 1 (Statistical Table 14.3.2.1) 
• Any unsolicited TEAE by SOC and PT  
o across all periods (i.e. period 1, 2, 3 or 4) (Statistical Table 14.3.2.2) 
o Period 1 (Statistical Table 14.3.2.3) 
o Period 1 and Period 2 (Statistical Table 14.3.2.4) 
o Period 2 (Statistical Table 14.3.2.5) 
o Period 2 and Period 3 (Statistical Table 14.3.2.6) 
o Period 3 (Statistical Table 14.3.2.7) 
o Period 3 and Period 4 (Statistical Table 14.3.2.8) 
 
 
• Any unsolicited TEAE by SOC, PT and relatedness 
o Across all periods (i.e. period 1, 2, 3 or 4) (Statistical Table 14.3.3.1) 
o Period 1 (Statistical Table 14.3.3.2) 
o Period 1 and Period 2 (Statistical Table 14.3.3.3) 
o Period 2 (Statistical Table 14.3.3.4) 
o Period 2 and Period 3 (Statistical Table 14.3.3.5) 
o Period 3 (Statistical Table 14.3.3.6) 
o Period 3 and Period 4 (Statistical Table 14.3.3.7) 
 
 
• Any solicited AE by PT and maximum severity during Period 1 (Statistical Table 14.3.4.1) 
• Any unsolicited TEAE by SOC/PT and maximum severity  
o Across all periods (i.e. period 1, 2, 3 or 4) (Statistical Table 14.3.4.2) 
o Period 1 (Statistical Table 14.3.4.3) 
o Period 1 and Period 2 (Statistical Table 14.3.4.4) 
o Period 2 (Statistical Table 14.3.4.5) 
o Period 2 and Period 3 (Statistical Table 14.3.4.6) 
o Period 3 (Statistical Table 14.3.4.7) 
o Period 3 and Period 4 (Statistical Table 14.3.4.8) 
 
 
• All unsolicited TEAE leading to study treatment discontinuation, by SOC and PT during 
Period 1 (only relevant for Period 1) (Statistical Table 14.3.5) 


 
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• Any unsolicited TEAE leading to study discontinuation, across all periods (i.e. period 1, 
2, 3 or 4), by SOC and PT (Statistical Table 14.3.6) 
• All unsolicited TESAEs by SOC and PT across all periods (i.e. period 1, 2, 3 or 4) 
(Statistical Table 14.3.7.1) 
• Any SAE by SOC and PT  
o Period 1 (Statistical Table 14.3.7.2) 
o Period 1 and Period 2 (Statistical Table 14.3.7.3) 
o Period 2 (Statistical Table 14.3.7.4) 
o Period 2 and Period 3 (Statistical Table 14.3.7.5) 
o Period 3 (Statistical Table 14.3.7.6) 
o Period 3 and Period 4 (Statistical Table 14.3.7.7) 
• Any SAE by SOC, PT and relatedness across all periods (i.e. period 1, 2, 3 or 4) (Statistical 
Table 14.3.8) 
5.3.8.2.2 Adverse event listings: 
A by-participant AE data listing including participant identifier, onset and resolution dates, 
relative study days based on date of first dose IMP/Placebo (for start and end date of AE, 
duration of AE), period, verbatim term, system organ class, preferred term, treatment, 
severity, relationship to treatment, action taken, and outcome will be provided: 
• For solicited Adverse events in listing 16.2.7.1.1 
• For unsolicited Adverse Events in Listing 16.2.7.1.2 
• For unsolicited Serious Adverse Events in Listing 16.2.7.1.3 
• For unsolicited treatment related TEAES in Listing 16.2.7.1.4 
• For unsolicited AE leading to study discontinuation in Listing 16.2.7.1.5 
• For Deaths (if any) Listing 16.2.7.1.6 
5.3.8.3 Laboratory safety variables 
The laboratory data will be directly transferred from the central laboratory to the data 
management department. Any clinically significant change occurring during the trial must be 
recorded as an Adverse Event in the CRF. 
Laboratory evaluations will be summarised by visit and by treatment arm on the SAF analysis 
set. 
For each biochemistry, haematology and coagulation variable: 
• Quantitative descriptive statistics will be tabulated at each time point over the course 
of the study (e.g., at each visit) on raw values and change from baseline (Statistical 
Table 14.3.9.1.1 and 14.3.9.1.2) 
 Shift tables will be presented to show the number of subjects with each toxicity grade (1,2,3, 
or 4/5) at baseline versus each post-baseline visit and the worst post-baseline grade (including 
any unscheduled visits). For those laboratory parameters for which high toxicity grades are 
specified for both low and high values (e.g., sodium, potassium), shifts in toxicity will be 
presented for high and low toxicities separately. The percentages will be based on the number 


 
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of subjects with both a baseline and post-baseline (at the specified visit) assessment of the 
specific laboratory parameter. For parameters which can not be graded with DAIDS, shift 
tables will be presented using investigator’s interpretation (normal, abnormal NCS and 
abnormal CS (Statistical Table 14.3.9.2)The number and percentage of subjects with at least a 
2-grade increase from baseline at any post-baseline study visit, including unscheduled visits, 
will be summarized by laboratory parameter and treatment group. Percentages for each lab 
test will be based on the number of subjects with both a baseline and a post-baseline 
evaluation of the particular laboratory test(Statistical Table 14.3.9.3)Plots of mean raw values 
of each biochemistry, haematology and coagulation parameters over time per randomized 
arm will be produced (Statistical Figures 14.3.1). 
 
All urinalysis parameters will also be tabulated as qualitative and/or quantitative variables 
(Statistical table 14.3.9.4) 
All laboratory results will be presented in Listings 16.2.8.1 to .4. 
The following listings will be presented: 
• Biochemistry 
• Biochemistry – all results for subjects who have at least one 2-grade increase in a 
biochemistry parameter 
• Haematology 
• Haematology  - all results for subjects who have at least one 2-grade increase in a 
hematology parameter  
• Urinalysis 
• Coagulation 
5.3.8.4 Physical examinations 
All individual data for complete and direct physical examination will be provided respectively 
in Listing 16.2.9. 
5.3.8.5 Vital signs and tympanic temperature 
• Quantitative descriptive statistics (Raw values and change from baseline) will be 
tabulated by treatment arm for each vital sign recorded (tympanic temperature, heart 
rate, respiratory rate, systolic and diastolic blood pressure and peripheral arterial 
oxygen saturation) at each time point over the course of the study (Statistical Table 
14.3.10.1 for Raw values and 14.3.10.2 for Change from baseline). 
• Qualitative descriptive statistics (normal/abnormal (outside of normal range)) will be 
presented for each vital sign at each time point over the course of the study by 
randomised arm (Statistical Table 14.3.10.3). 
• All individual measurements will be provided in Listing 16.2.10 
 
5.3.8.6 12-Lead Electrocardiogram 
• 
Quantitative descriptive statistics (Raw values and change from baseline) will be 
tabulated by treatment arm for each 12-Lead ECG parameters recorded (Heart rate, 


 
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QRS, PR interval, QT, QTc) at each time point over the course of the study (Statistical 
Tables 14.3.11.1.1 and 14.3.11.1.2). 
• Qualitative descriptive statistics (normal/abnormal (outside of normal range)) will be 
presented for each 12-ead ECG parameters at each time point over the course of the 
study by treatment arm (Statistical Table 14.3.11.2). 
• All individual measurements will be provided in Listing 16.2.11 
 
5.3.8.7 Spirometry 
All individual data for spirometry will be provided in Listing 16.2.12. 
 
5.3.8.8 Reactogenicity events (diary card) 
All individual data for reactogenicity events will be provided in Listing 16.2.13. 
 
5.3.8.9 Concomitant medications 
Concomitant medications will be presented by ATC class level 2 and Preferred Name by 
treatment arm (Statistical Table 14.1.7).  
Individual data on previous and concomitant medications for each participant will be reported 
in Listing 16.2.4.12.  
 
6 Data handling conventions 
6.1 Definitions 
6.1.1 
Baseline definition 
For this study, the definition of a baseline value is only needed for the computation of changes 
for baseline for safety endpoints. 
The baseline is defined as the last non-missing observation prior to the administration of the 
dose of study IMP will be used as the baseline value. This will usually correspond to the 
measurement performed at the admission visit on Day -6 or a re-test performed thereafter 
but before IMP administration on Day -5. In case of missing value at Day -5, the last available 
value recorded during the screening period will be used as the baseline value. 
 
If all pre-dose/pre-challenge measurements are missing then baseline will be considered as 
missing, and no change from baseline and no percentage change from baseline will be 
computed. 
 
6.1.2 
Quarantine discharge 
Unless otherwise specified, Quarantine Discharge refers to the actual quarantine discharge 
day regardless of whether discharge from quarantine occurred as scheduled on Day 8, or later 
following the PI’s decision to extend the quarantine period for a given participant. 


 
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6.2 Retest, Outliers 
6.2.1 
Retests 
The retests will be managed as follow: 
• Any retest before first IMP administration: the last available value before first IMP 
administration will be used as the baseline (see Section 6.1.1) 
• Any other retest: Retest values will not be used in statistical analyses except if 
otherwise specified during the data review meeting. All available values (including 
retest values) will be presented in the data listings. 
6.2.2 
Outliers 
All available data points will be included in the analyses, unless a clear reason is available to 
exclude a given data point. Consequently, all potential outlier data will be reviewed during the 
Blinded Data Review Meeting (BDRM) and decisions regarding their use in the statistical 
analyses will be made.  
6.3 Visit windows, unscheduled visits 
6.3.1 
Windows for time points 
All visits will be analysed as entered in the database except if otherwise specified during the 
data-review meeting. 
6.3.2 
Unscheduled visits 
Unscheduled visit measurements may be used to provide a measurement for a baseline or 
endpoint value if appropriate according to their definition. Other unscheduled visits data will 
not be analysed, but corresponding data will be presented in the individual data listings and 
any relevant safety data will be described in the CSR. 
6.4 Missing data and analysis rules 
In the presence of missing data, analysis rules are described in the following sections. In case 
of specific cases, data will be reviewed during the BDRM and decisions to derive the 
considered endpoint and how to derive it, will be documented in the BDRM minutes. If 
necessary, the SAP will be updated accordingly. 
6.4.1 
Missing data 
6.4.1.1 Missing or incomplete dates:  
For calculation / sorting / assignation based on dates (e.g. treatment emergent AEs, 
assignation of AEs between periods, concomitant medications, etc.), the following rules will 
apply: 
• In case of AE with missing start date, it could be included in different analysis periods 
at the same time. If the AE could have started in multiple periods based on all the 
available information, it will be analysed in all the possible periods (i.e; for an AE with 
complete missing start date and end date after Day 28, the AE will belong to the 4 
periods, for an AE with only the information that the AE started the month of 
treatment start and inoculation but before the Day 28, the AE will belong to period 1, 


 
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2 and period 3). In case of partial date without ambiguity on the period, the date will 
be imputed by the first day of the month. In case of partial date without ambiguity on 
the period,  the date will be imputed by the first month of the year. 
 
• Medication with missing start date will be assumed prior and concomitant medication 
unless the end date indicates was stopped prior to first IMP intake. 
• Medical history or disease diagnosis with missing/incomplete date will be assumed to 
have occurred before any study treatment except when the partial onset date or other 
available data indicates differently. 
 
6.4.1.2 Missing Viral Load and Total Symptom Score data 
Missing Viral Load and Total Symptom Score data may impact the derivation of some of the 
study endpoints (AUC, sum of TSS, peak). General rules on how to derive these endpoints in 
the presence of missing data are provided in Section 7.  
 
6.4.1.3 Other missing data 
No other missing data will be imputed except if otherwise specified in the SAP. Any other 
mechanisms to handle missing data will be outlined within the relevant endpoints section. 
 
6.4.2 
Analysis rules 
Except if otherwise specified, any data recorded as Detected, Not detected, Invalid, N/A or 
NDA will be presented as such in listings but will be replaced with the Assigned value described 
in the following table: 
Table 5: Rules for handling qRT-PCR viral load, Viral culture results and HAI serology levels 
Analysis 
Assay 
Assay Reporting 
Reported result 
Assigned value 
Influenza titre 
 
Influenza Viral Culture assay 
(TCID50/mL assay) 
Value 
Use reported value 
DETECTED 
1.0 TCID50/mL 
NOT DETECTED 
0.5 TCID50/mL 
INVALID 
Missing data point 
N/A 
Missing data point 
PANFLU Viral Load 
qRT-PCR 
(Log10 copies/mL) 
Value 
Use reported value 
DETECTED 
1.94 Log10 Copies/mL  
NOT DETECTED 
 0.97 Log10 Copies/mL  
INVALID 
Missing data point 
N/A 
Missing data point 
Influenza antibody 
titre 
 
Influenza Neutralisation Assay  
(virus focus reduction 
neutralisation 
assay) 
Value 
Use reported value 
NDA 
5 
INVALID 
Missing data point 
N/A 
Missing data point 
N/A, not applicable; NDA, no detectable antibody 


 
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Samples with titres above the assay ULOQ may be pre-diluted to obtain a quantifiable result 
and corrected for the dilution used, where possible. 
 
7 Derived data 
Derived variable 
Derivation algorithm 
Change from baseline to visit V 
(continuous) 
Change from baseline of variable X: 
𝑋𝑋 (𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉 𝑉𝑉) −𝑋𝑋(𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏) 
o 
Negative values indicate a decrease in X 
o 
Positive values indicate an increase in X 
Event Duration (in days) 
(𝐸𝐸𝐸𝐸𝐸𝐸 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) −(𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆𝑆 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑) + 1 
Total symptom score  
 
The TSS computation is based on the diary cards that participants 
complete 3 times per day from Day -1 to Day 7 and once on Day 8.  
At each assessment, the participants provide scores from 0 to 3 for a list 
of 13 symptoms (Runny nose, Stuffy nose, Sneezing, Sore throat, Earache, 
Malaise/tiredness, 
Headache, 
Muscle 
and/or 
joint 
ache, 
Chilliness/Feverishness, Cough, chest tightness, shortness of breath and 
wheeze), resulting in possible values from 0 to 39 for the TSS. 
An individual TSS is derived at each assessment of the diary card as the 
sum of the scores given to the 13 symptoms on that symptom score card. 
Handling of missing data for TSS calculations: 
If scores are missing for two or less symptoms within an otherwise 
completed diary card it will be assumed that the symptom(s) was(were) 
not present and as such a score of 0 will be given for that(/these) 
symptom(s) and the TSS endpoint derived as the sum of the available item 
scores.  
If more than two symptoms have not been completed for a specific 
assessment this will be treated as missing and no score will be derived for 
the TSS at that timepoint. 
Area Under the Curve (AUC) of 
Viral Load and Total Symptom 
Score 
(in log10 copies/mL * day for 
VL AUC) 
(in points * day for TSS AUC) 
Calculated using the trapezium rule [3]:  
With n+1 measurements yi at times ti, (I = 0,.n), the AUC is calculated as: 
𝐴𝐴𝐴𝐴𝐴𝐴= 1
2 ෍(𝑡𝑡𝑖𝑖+1 − 𝑡𝑡𝑖𝑖) (𝑦𝑦𝑖𝑖+ 𝑦𝑦𝑖𝑖+1)
𝑛𝑛−1
𝑖𝑖=0
 
The actual time of each assessment will be used in the calculation. 
For VL AUC, 14 measurements are used for the computation (1 on Day 1, 
2 on each day from Day 2 to Day 7 and 1 on Day 8). For TSS AUC, 22 
measurements are used (3 on each day from Day 1 to Day 7 and 1 on Day 
8).  
Handling of missing data for AUC calculations: 
The AUC calculation will be based on the available non-missing 
assessment values between the start and end of the defined AUC time 
period (Day 1 pm to Day 8 am for viral load, Day 1 am to Day 8 am for TSS) 
with the following exceptions: 
• 
If the first measurement or the last measurement of the AUC 
time period is missing, the following rules will be applied: In case 


 
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Derived variable 
Derivation algorithm 
of the missing last measurement, the method of LOCF will be 
used. In case of the missing first measurement, the non missing 
first measurement will be reported at all missing measurement 
before.   
• 
Even if the formula above can still be calculated, too many 
missing measurements other than the first or last will impact  the 
precision of the AUC for the given participant. As a general rule, 
the participant must have at least 1 non-missing data recording 
on each day between the start and end of the defined AUC time 
period to compute the AUC. 
• 
Each specific case will be reviewed during the BDRM and 
decisions with their rationale documented in the BDRM minutes. 
Peak Viral Load   
(or Peak Total Symptom score) 
Computed as the maximum observed value for VL or TSS over the defined 
time period (D1 to D8) 
Handling of missing data for peak value calculation: 
In the presence of missing data, the maximum of the available data can 
still be identified, but it may not correspond to the true peak for the 
participant, when the peak would have corresponded to one of the 
missing assessments. 
Each specific case will be reviewed during the BDRM and decisions to 
derive a peak value and which value to use, with their rationale 
documented in the BDRM minutes. 
 
8 Interim analysis 
A first interim analysis will be performed, by an unblinded team not involved in daily 
management of the study, for participants in Cohort 1 who have completed the inpatient 
phase at the time the interim analysis is performed. An optional second interim analysis may 
be performed by an unblinded team not involved in daily management of the study, within 
Cohort 2, depending on the outcome of the first interim analysis  
 
The following tables/figures will be produced at each interim analysis on PP population: 
• Participant disposition (Statistical Table 14.1.1) 
• Demographics and baseline characteristics – PP analysis set (Statistical Table 14.1.4.3) 
• Demographics and baseline characteristics – SAF analysis set (Statistical Table 14.1.4.4) 
• Primary efficacy analysis – Area under the viral load-time curve (VL-AUC) from qRT-PCR 
(Statistical Table 14.2.1.1 and Figures 14.2.1.1.1 and 14.2.1.1.2) 
• Peak viral load from qRT-PCR (Statistical Table 14.2.2.1 and Figure 14.2.2.1) 
• Time to confirmed negative test by qRT-PCR (statistical Table 14.2.3.1 and Figure 
14.2.3.1) 
• Area under the curve over time of total clinical symptoms score (TSS-AUC) (Statistical 
Table 14.2.9.1 and Figures 14.2.7.1.1, 14.2.7.1.2) 
• Peak of total clinical symptoms score (TSS) (Statistical Table 14.2.10.1 and figure 
14.2.8.1) 


 
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• Time to symptom resolution (statistical Table 14.2.12.1 and Figure 14.2.10.1) 
• Incidence of confirmed influenza infection by qRT-PCR (Statistical Table 14.2.14.1) 
• Incidence of qRT-PCR-confirmed symptomatic influenza infection (Statistical Table 
14.2.16.1) 
• Incidence of qRT-PCR-confirmed moderately severe symptomatic influenza infection 
(Statistical Table 14.2.17.1) 
 
  The following tables/listings will be produced at each interim analysis on SAF population: 
• Summary of adverse events (Statistical Table 14.3.1) 
• Any unsolicited TEAE across all periods by SOC, PT and relatedness (Statistical Table 
14.3.3.1)* 
• Any solicited AE by SOC/PT and maximum severity during Period 1 (Statistical Table 
14.3.4.1)* 
* Tables will be produced in case if at least 20 reported adverse events in the database. 
• Solicited adverse events (Listing 16.2.7.1.1) 
• Unsolicited adverse events (Listing 16.2.7.1.2) 
• Reactogenicity events (Listing 16.2.13) 
In the listings the participant numbers should be scrambled. 
9 Statistical/Analytical issues 
This section systematically reviews the topics listed in Section 11.4.2 of the ICH E3 guidance 
the ICH E3 as important features of the analysis, to ensure none of these topics has been 
overlooked in the current SAP and to facilitate the writing of the corresponding section in the 
CSR. 
9.1 Adjustments for Covariates 
No adjustment for demographic or baseline measurements, or any other covariate are 
planned. 
9.2 Handling of Dropouts or missing data 
Methods for handling missing data are described in Section 6.4.1. 
9.3 Interim Analyses and Data Monitoring 
The interim analysis is described in Section 8. 
9.4 Multicentre studies 
Not applicable: single centre study. 
9.5 Multiple Comparison/Multiplicity 
See Section 5.1.2.2: as the study is of exploratory purpose, no adjustment for multiple 
comparisons / multiplicity of endpoints will be performed.  


 
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9.6 Use of an “Efficacy Subset” of Participants 
Two subsets of the ITT efficacy set have been defined: the Intent-to-treat Infected (ITT-I) set 
and the Per Protocol (PP) set (see Section 3.3 for details). 
9.7 Active-Control Studies Intended to Show Equivalence 
Not applicable. 
9.8 Examination of Subgroups 
No specific subgroup analysis will be performed. 
10 Modifications from the statistical section of the protocol 
Not applicable 
11 Software documentation 
All summaries and statistical analyses will be generated using SAS version 9.4 or higher. 
 
 


 
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12 Tables, Figures and Listings 
12.1 
List of tables 
The list of tables is described in a separate document with mocks tables. 
12.2 
List of figures 
The list of figures is described in a separate document with mocks figures. 
12.3 
List of listings 
n° 
 
16.2.1 
End of study information / Discontinuation 
16.2.2 
Protocol deviations 
16.2.3 
Analysis sets membership and reasons for exclusion 
16.2.4 
Demographics and Baseline characteristics data 
16.2.4.1 
Demographic characteristics 
16.2.4.2 
Weight, Height and BMI 
16.2.4.3 
Alcohol breath test 
16.2.4.4 
Drugs of abuse and Cotinine use 
16.2.4.5 
Urine pregnancy test, serum FSH and β-HCG pregnancy test 
16.2.4.6 
HIV, Hepatitis B & C and Thyroid function 
16.2.4.7 
Eligibility criteria 
16.2.4.8 
Randomisation 
16.2.4.9 
Medical History 
16.2.4.10 
Visit dates 
16.2.4.11 
Nasal Swab for respiratory Pathogen Screen data 
16.2.4.12 
Prior and Concomitant Medication 
16.2.5 
Compliance and/or Drug Concentration Data 
16.2.5.1 
IMP/ Placebo dosing 
16.2.5.2 
Challenge virus Inoculation 
16.2.6 
Individual Efficacy Response Data 
16.2.6.1 
Viral Load Data – qRT-PCR/Culture 
16.2.6.2 
Symptom Diary Cards including Total clinical symptoms score 
16.2.6.3 
24-hour tissue count & nasal discharge weight 
16.2.6.4 
Derived efficacy response data 
16.2.6.5 
Cytokine/chemokine levels 
16.2.6.6 
Viral resistance markers 
16.2.6.7 
Nasopharyngeal swab for rapid viral antigen test at discharge from quarantine 
16.2.6.8 
Blood - Serum ant-drug antibodies (ADA) 
16.2.6.9 
Community acquired virus results  
16.2.6.10 
HAI data 


 
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Safety Data 
16.2.7 
Adverse Events 
16.2.7.1.1 
Solicited adverse events 
16.2.7.1.2 
Unsolicited Adverse Events 
16.2.7.1.3 
Unsolicited Serious Adverse Events 
16.2.7.1.4 
Unsolicited Treatment related 
16.2.7.1.5 
Unsolicited AE leading to study discontinuation 
16.2.7.1.6 
Deaths (if any) 
16.2.8 
Laboratory Safety Data 
16.2.8.1.1 
Biochemistry 
16.2.8.1.2 
Biochemistry – abnormal results 
16.2.8.2.1 
Haematology 
16.2.8.2.2 
Haematology – abnormal results 
16.2.8.3 
Urinalysis 
16.2.8.4 
Coagulation 
 
Other Safety Data 
16.2.9 
Complete and direct physical examination 
16.2.10 
Vital signs and tympanic temperature 
16.2.11 
12-Lead Electrocardiogram 
16.2.12 
Spirometry 
16.2.13 
Reactogenicity events 
 
 
13 References 
1. Shieh G, Jan SL, and Randles RH (2006). On power and sample size determinations for the 
Wilcoxon–Mann–Whitney test. Journal of Nonparametric Statistics. 2006;18(1):33-43. 
2. Hahn, G. J., & Meeker, W. Q. (2011). Statistical intervals: a guide for practitioners (Vol. 
328). John Wiley & Sons. 
3. Wilson, E. B. (1927). Probable inference, the law of succession, and statistical inference. 
Journal 
of 
the 
American 
Statistical 
Association. 
22 
(158): 
209–212. 
doi:10.1080/01621459.1927.10502953 
 
 


 
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14 Schedule of events 
Study Phase  
Screening Phase* 
Inpatient Phase (Quarantine Isolation and Human Viral Challenge [HVC]) 
Outpatient Phase 
Early Withdrawal 
Visit 
Admission 
to 
quarantine  
Dosing with CD388 
HVC 
Post-HVC 
Discharge 
Follow-up Clinic Visits 
Study Day #  
Day-96 to Day    -
7/-6 
D-7 
D-6 
D -5 (dosing) 
D-4 
D-3 
D-2 
D-1 
D0 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D 8 
D17 (±1 day) 
D28 (±3 days) 
D60 (±7 days) 
D120 (±14 days) 
D180 (±14 days) 
Quarantine post 
challenge 
Procedure  
Pre-HVC 
HVC 
Post-HVC 
Eligibility criteria (+) 
X 
X 
X(a) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Written consent (b) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical & medication history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height & weight, body mass index 
(BMI) (c) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
 
 
 
 
(X) 
(X) 
Patient 
Health 
Questionnaire-9 
(PHQ-9) 
(X) 
(X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generalised 
Anxiety 
Disorder 
Questionnaire-7 (GAD-7) 
(X) 
(X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alcohol breath test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysis (d) 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
(X) 
Urine drugs of misuse and nicotine 
screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
(X) 
Complete physical examination 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
(X) 
Symptom-directed 
physical 
examination 
 
 
X(a) 
(X) 
(X) 
(X) 
(X) 
(X) 
 
(X) 
(X) 
X 
X 
X 
(X) 
(X) 
(X) 
 
 
 
 
 
X 
 


 
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Study Phase  
Screening Phase* 
Inpatient Phase (Quarantine Isolation and Human Viral Challenge [HVC]) 
Outpatient Phase 
Early Withdrawal 
Visit 
Admission 
to 
quarantine  
Dosing with CD388 
HVC 
Post-HVC 
Discharge 
Follow-up Clinic Visits 
Study Day #  
Day-96 to Day    -
7/-6 
D-7 
D-6 
D -5 (dosing) 
D-4 
D-3 
D-2 
D-1 
D0 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D 8 
D17 (±1 day) 
D28 (±3 days) 
D60 (±7 days) 
D120 (±14 days) 
D180 (±14 days) 
Quarantine post 
challenge 
Procedure  
Pre-HVC 
HVC 
Post-HVC 
Vital signs (heart rate, respiratory 
rate, systolic and diastolic blood 
pressure, 
peripheral 
oxygen 
saturation [SpO2]) (e) 
X 
X 
X(f) 
X(f) 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
Tympanic temperature (e) 
X 
X 
X(f) 
X(f) 
X 
X 
3X 
3X 
3X 
3X 
3X 
3X 
3X 
3X 
3X 
X 
 
X 
 
 
 
X 
Symptom diary card (e) 
 
 
 
 
 
 
3X 
3X 
3X 
3X 
3X 
3X 
3X 
3X 
3X 
X 
 
 
 
 
 
 
24-hour 
tissue 
count 
& 
nasal 
discharge weight (g) 
 
 
 
 
 
 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
(X) 
Spirometry (h) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead electrocardiogram (ECG) 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
(X) 
 
Respiratory Tract Infection Surveillance 
Weekly 7-day recall diary card (i) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Nasal/throat swab self-collection (j) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
 
 
Product Administration 
Randomisation 
 
 
X(a) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigational medicinal product 
(IMP; CD388/placebo) dosing 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reactogenicity diary card (k) 
 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Challenge virus inoculation 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collection Of Blood Samples 


 
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Study Phase  
Screening Phase* 
Inpatient Phase (Quarantine Isolation and Human Viral Challenge [HVC]) 
Outpatient Phase 
Early Withdrawal 
Visit 
Admission 
to 
quarantine  
Dosing with CD388 
HVC 
Post-HVC 
Discharge 
Follow-up Clinic Visits 
Study Day #  
Day-96 to Day    -
7/-6 
D-7 
D-6 
D -5 (dosing) 
D-4 
D-3 
D-2 
D-1 
D0 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D 8 
D17 (±1 day) 
D28 (±3 days) 
D60 (±7 days) 
D120 (±14 days) 
D180 (±14 days) 
Quarantine post 
challenge 
Procedure  
Pre-HVC 
HVC 
Post-HVC 
Serum follicle-stimulating hormone 
(FSH) (postmenopausal women) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum 
β-human 
chorionic 
gonadotrophin (β-HCG) pregnancy 
test (all females) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Human immunodeficiency virus (HIV) 
& hepatitis serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Haematology (l) 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
(X) 
Biochemistry (l) 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
(X) 
Coagulation 
X 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
X 
X 
(X) 
Thyroid function test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiac enzymes 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood – serum markers humoral 
immunity (m) 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
(X) 
Blood 
– 
serum 
proteomics 
(cytokine/chemokine) (n) 
 
 
X(a) 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Blood PAXgene for transcriptomics 
 
 
X(a) 
 
 
 
 
X 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Blood – plasma pharmacokinetics 
(PK) (n) 
 
 
X 
X 
 
X 
 
X 
 
 
X 
X 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
 
Blood – serum anti-drug antibodies 
(ADA) 
 
 
X(a) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
(X) 


 
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Study Phase  
Screening Phase* 
Inpatient Phase (Quarantine Isolation and Human Viral Challenge [HVC]) 
Outpatient Phase 
Early Withdrawal 
Visit 
Admission 
to 
quarantine  
Dosing with CD388 
HVC 
Post-HVC 
Discharge 
Follow-up Clinic Visits 
Study Day #  
Day-96 to Day    -
7/-6 
D-7 
D-6 
D -5 (dosing) 
D-4 
D-3 
D-2 
D-1 
D0 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D 8 
D17 (±1 day) 
D28 (±3 days) 
D60 (±7 days) 
D120 (±14 days) 
D180 (±14 days) 
Quarantine post 
challenge 
Procedure  
Pre-HVC 
HVC 
Post-HVC 
Blood 
– 
PAXgene 
DNA 
for 
pharmacogenomics 
 
 
X(a) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collection Of Respiratory Samples 
Nasopharyngeal swab – Respiratory 
pathogen 
screen 
including 
SARS-Cov-2 (e.g., Biofire) (o) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nasopharyngeal 
swab 
– 
viral 
discharge test 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
(X) 
 
 
 
 
 
 
Nasopharyngeal swab for virology 
and 
exploratory 
purposes 
(qRT-PCR & culture, CD388) (p) 
 
 
X 
X 
 
X 
 
X 
 
 
2X 
2X 
2X 
2X 
2X 
2X 
2X 
X 
X 
X 
X 
X 
X 
(X) 
Nasosorption 
for 
cytokine/chemokine (q) 
 
 
X(a) 
 
 
 
 
X 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Safety Assessments 
Adverse event recording (r) 
 
Continuous 
Concomitant medications (r) 
 
Continuous 
 
 


 
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KEY NOTES FOR TIME AND EVENTS SCHEDULE 
* 
Results of tests or examinations performed under hVIVO generic screening process may be used to determine eligibility without the need to repeat the assessment if 
it is within 28 days prior to dosing with IMP. 
# 
With respect to challenge virus inoculation. 
(+) 
Only the applicable inclusion/exclusion criteria will be reviewed at each time point. 
(X) 
The assessment may be optional, or at the PI’s discretion. The PI may perform additional safety assessments as required. 
X 
Once, at approximately the same time each day, where applicable. 
2X 
Twice daily, at approximately the same time each day, where applicable. 
3X 
Three times daily, at approximately the same time each day, where applicable. 
a 
Assessments performed prior to administration of IMP. 
b 
Study-specific consent may occur on the day of admission, providing all required eligibility information has been collected through the Health Research Authority-
approved hVIVO Generic Screening process. 
c 
Height will be measured at screening only. 
d 
If participant is ADA positive, additional urinalysis sample will be collected to detect haematuria and proteinuria. Additional assessments relating to ADA positive 
participants will be managed on a case by case basis. Participants with symptoms and signs at the respective visit may require an additional blood sample including full 
haematology, biochemistry, CH50 complement levels and rheumatoid factor if not already scheduled as part of the SoE. During the RTI bi-weekly call reminder, any 
new symptoms reported by the participant will be recorded. If a Grade 2 or higher AE is recorded, sponsor medical monitor should be notified immediately.  
e 
Apart from assessment timepoints with an (f) footnote, symptoms, temperature, and samples will be collected at approximately the same time each day (±1 hour). 
f 
On the dosing day (Day -5), vital signs and temperature will be taken 5 times: pre-dose and at 2, 6, 10 (+15 min), and 16 hours (+30 min) post-dose, and subsequently 
on Day -4 (24 hours [± 30min] post-dose). 
g 
Distribution of paper tissues and 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. 


 
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h 
Eligibility only. 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. 
i 
Symptom diary cards will be completed every 7 days to capture the worst grade of symptoms that occurred over the last week. Participants will complete these from 
quarantine discharge until the final follow-up visit (Day 180 ±14 days), or until the resolution of a lab-confirmed influenza respiratory tract infection (RTI), whichever is 
first. 
Study site staff will contact the participants every 2 weeks to ask if an RTI has occurred and confirm that the diary cards have been completed. 
j 
Participants will be provided kits for taking nasal/throat swabs when an RTI occurs between discharge from quarantine until the final follow-up visit (Day 180 ±14 
days), or until the confirmation of a lab-confirmed influenza RTI, whichever occurs first. 
k 
Collected post-dose, once daily at approximately the same time after 5 pm. 
l 
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 
principal investigator’s [PI] discretion). 
m 
Virus serology (influenza haemagglutination inhibition [HAI] assay) will be performed to determine eligibility and seroconversion. Samples may be used for related 
exploratory research. 
n 
Plasma PK: blood samples will be collected as outlined in Section 8.6.1. The allowable time windows for the sampling are as follows: 
• 
During quarantine: 
o 
Day -5 (dosing): there is no time window requirement for the pre-dose sample 
o 
Day -5 (dosing), 2-hour time point: ±15-minute window 
o 
Day -5 (dosing), 4-hour time point: ±15-minute window 
o 
Day -4 (post-dose, pre-challenge sample 1; ~24-hour time point): ±2-hour window 
o 
Day -2 (post-dose, pre-challenge sample 2; ~72-hour time point): ±2-hour window 
o 
Day 0 (~120-hour time point): at approximately the same time as the viral challenge that day 
o 
Day 1 (~144-hour time point): at approximately the same time as the first nasopharyngeal swab that day 
o 
Day 2 (~168-hour time point): at approximately the same time as the first nasopharyngeal swab that day 
o 
Day 3 (~192-hour time point): at approximately the same time as the first nasopharyngeal swab that day 
• 
After discharge from quarantine, blood PK samples will be taken at timepoints with acceptable windows as below, or until a confirmed community-acquired 
infection (whichever is first): 


 
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o 
Day 17 time point: ±1-day window 
o 
Day 28 time point: ±3-day window 
o 
Day 60 time point: ±7-day window 
o 
Day 120 time point: ±14-day window 
o 
Day 180 time point: ±14-day window. 
The timepoints and number of serum proteomics sampling and PK sampling may be adjusted according to available PK data and timing of IMP relative to challenge 
virus inoculation. 
o 
Upper respiratory tract (URT) swab (e.g., nasopharyngeal swab, mid-turbinate swab, oropharyngeal swab) for respiratory virus screen to assess for the presence of 
other respiratory viruses; if found positive for any pathogen in the panel, the participant will not be eligible for the current quarantine. 
p 
Nasopharyngeal swabs will be taken for multiple purposes: influenza virology (PCR, and culture on those that are ≥ lower limit of quantification [LLOQ] on quantitative 
reverse transcriptase-polymerase chain reaction [qRT-PCR]) on Days 1 to 8 inclusive; CD388 assays on all days as per SoE. Post inoculation nasal virology samples will 
be collected at the same time each day during quarantine (± 1 hour). Samples may be used for related exploratory research. 
q 
Nasosorption devices will be taken for biomarkers (such as cytokines/chemokines) on all days in the morning. 
r 
Adverse events and concomitant mediations are reviewed throughout the study including pre- and post-dosing with IMP and pre- and post-influenza virus inoculation. 
Notes: 
Where any nasal sampling time points occur together, the order of sampling will typically be (1) nasosorption followed by (2) nasopharyngeal swab, with appropriate 
amount of time between sampling. 
 
GENOMIC, TRANSCRIPTOMIC, AND PROTEOMIC SAMPLES 
Deoxyribonucleic acid (DNA)/ ribonucleic acid 
(RNA)/ proteomic sample collection: 
Yes 
 
No 
 
Nasal samples and/or blood cytokine and chemokine proteomic profile and/or mRNA profile may be assessed for 
associations with CD388 response, and other endpoints. 
Viral RNA sequencing may be performed on laboratory-confirmed positive nasal samples. 
Consent considerations: 
DNA pharmacogenomics may be explored in appropriate samples. 


 
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Genetic consent. 
Future use of remaining samples for new ethically approved health research and laboratory testing protocols according to 
the local laws. 
 
 


 
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Cidara Therapeutics, Inc. 
CDT-CSP-001 / CD388.SQ.2.02 
 
A proof-of-concept, Randomised, Double-blind, Placebo-controlled, Phase 2a Study to assess the prophylactic 
antiviral activity against influenza, safety, tolerability and pharmacokinetics of CD388 via a human viral challenge 
model 
 
 
Version: v1 
Date: 16DEC2022 
 
 
Antoinette Anger 
Venn Life Sciences Biometry Services 
24-26 rue de la Pépinière | 75008 Paris | France 
Phone: +33 1 40 21 04 10 
http://www.vennlifesciences.com 
Antoinette.anger@vennlife.com 
 


 
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List of Tables ........................................................................................................................................................................................................................................................... 3 
List of Figures ....................................................................................................................................................................................................................................................... 42 
 
 


 
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List of Tables  
 
n° 
 
Enrolled 
ITT 
ITT-I 
PP 
SAF 
IA 
 
Demographics and Baseline characteristics 
 
 
 
 
 
 
14.1.1 
Participant disposition 
X 
 
 
 
 
X 
14.1.2 
Study populations and reasons for exclusion 
X 
 
 
 
 
 
14.1.3 
Protocol deviations 
 
X 
 
 
 
 
14.1.4.1,.2,.3, 
.4 
Demographic data and baseline characteristics 
 
X 
X 
X 
X 
X (PP 
+ 
SAF) 
14.1.5 
Medical History 
 
X 
 
 
 
 
14.1.6.1,.2 
Prior Medication 
 
X 
 
X 
 
 
14.1.7.1,.2 
Concomitant Medication 
 
X 
 
X 
 
 
14.1.8.1,.2 
Compliance to Study intervention 
 
X 
 
 
X 
 
 
Efficacy 
 
 
 
 
 
 
14.2.1.1 
Primary efficacy analysis – Area under the viral load-time 
curve (VL-AUC) from RT-qPCR 
 
 
 
X 
 
X 
14.2.1.2.1, .2 
Primary efficacy, supplementary analysis – Area under the 
viral load-time curve (VL-AUC) from qRT-PCR 
 
X 
X 
 
 
 
14.2.2.1, .2 
Peak viral load from qRT-PCR 
 
 
X 
X 
 
X 
14.2.3.1, .2 
Time to confirmed negative test by qRT-PCR 
 
 
X 
X 
 
X 
14.2.4.1, .2 
Viral load from qRT-PCR by day and by timepoint 
 
X 
X 
X 
 
 
14.2.5.1, .2 
VL-AUC from viral culture 
 
 
X 
X 
 
 
14.2.6.1, .2 
Peak viral load from viral culture 
 
 
X 
X 
 
 
14.2.7.1, .2 
Time to confirmed negative test by viral culture 
 
 
X 
X 
 
 
14.2.8.1, .2 
Viral load from viral culture by day and by timepoint 
 
X 
X 
X 
 
 


 
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n° 
 
Enrolled 
ITT 
ITT-I 
PP 
SAF 
IA 
14.2.9.1, .2 
Area under the curve over time of total clinical symptoms 
score (TSS-AUC) 
 
 
X 
X 
 
X 
14.2.10.1, .2 
Peak of total clinical symptoms score (TSS) 
 
 
X 
X 
 
X 
14.2.11.1, .2 
Individual peak daily total clinical symptoms score (TSS) 
 
 
X 
X 
 
 
14.2.12.1, .2 
Time to symptom resolution 
 
 
X 
X 
 
X 
14.2.13.1,.2 
Total clinical symptoms score by day and by timepoint 
 
X 
X 
X 
 
 
14.2.14.1, .2 
Incidence of confirmed influenza infection by qRT-PCR  
 
 
X 
X 
 
X 
14.2.15.1, .2 
Incidence of occurrence of at least 1 positive quantitative 
(≥LLOQ) cell culture 
 
 
X 
X 
 
 
14.2.16.1, .2 
Incidence of qRT-PCR-confirmed symptomatic influenza 
infection  
 
 
X 
X 
 
X 
14.2.17.1, .2 
Incidence of qRT-PCR-confirmed moderately severe 
symptomatic influenza infection  
 
 
X 
X 
 
X 
14.2.18.1, .2 
Culture lab-confirmed symptomatic influenza infection  
 
 
X 
X 
 
 
14.2.19 
Duration of quantifiable influenza qRT-PCR measurements 
 
 
 
X 
 
 
14.2.20 
Duration of quantifiable influenza viral culture 
measurements 
 
 
 
X 
 
 
14.2.21 
Time to peak daily total clinical symptoms score 
 
 
 
X 
 
 
14.2.22 
Total weight of mucus 
 
 
 
X 
 
 
14.2.23 
Total number of tissues used by participants 
 
 
 
X 
 
 
14.2.24 
Participants with symptom scored grade 2 or higher 
 
 
 
X 
 
 
14.2.25 
Participants with symptom scored grade 2 or higher by 
time point 
 
 
 
X 
 
 
14.2.26 
Participants with lab-confirmed infection and fever 
(≥37.9°C) 
 
 
 
X 
 
 


 
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n° 
 
Enrolled 
ITT 
ITT-I 
PP 
SAF 
IA 
14.2.27 
Laboratory-confirmed symptomatic influenza infection 
(community acquired) 
 
 
 
X 
 
 
14.2.28.1 
Cytokine/chemokine levels in nasal samples 
 
 
 
X 
 
 
14.2.28.2 
Cytokine/chemokine levels in nasal samples (subgroup 1) 
 
 
 
X 
 
 
14.2.28.3 
Cytokine/chemokine levels in nasal samples (subgroup 2) 
 
 
 
X 
 
 
14.2.29.1 
Cytokine/chemokine levels in serum samples 
 
 
 
X 
 
 
14.2.29.2 
Cytokine/chemokine levels in serum samples (subgroup 1) 
 
 
 
X 
 
 
14.2.29.3 
Cytokine/chemokine levels in serum samples (subgroup 2) 
 
 
 
X 
 
 
14.2.30 
Viral resistance markers 
 
 
 
X 
 
 
14.2.31.1 
Blood – Serum anti-drug antibodies (ADA) – 
Presence/absence of ADA 
 
X 
 
 
 
 
14.2.31.2 
Blood – Serum anti-drug antibodies (ADA) – titer levels by 
day 
 
X 
 
 
 
 
 
Safety 
 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
X 
 
14.3.1 
Summary of Adverse Events 
 
 
 
 
X 
X 
14.3.2.1 
Any solicited AE by SOC and PT during Period 1 
 
 
 
 
X 
 
14.3.2.2 
Any unsolicited TEAE by SOC and PT across all periods 
 
 
 
 
X 
 
14.3.2.3 
Any unsolicited TEAE by SOC and PT during Period 1 
 
 
 
 
X 
 
14.3.2.4 
Any unsolicited TEAE by SOC and PT during Period 1 and 
Period 2 
 
 
 
 
X 
 
14.3.2.5 
Any unsolicited TEAE by SOC and PT during Period 2 
 
 
 
 
X 
 
14.3.2.6 
Any unsolicited TEAE by SOC and PT during Period 2 and 
Period 3 
 
 
 
 
X 
 
14.3.2.7 
Any unsolicited TEAE by SOC and PT during Period 3 
 
 
 
 
X 
 


 
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n° 
 
Enrolled 
ITT 
ITT-I 
PP 
SAF 
IA 
14.3.2.8 
Any unsolicited TEAE by SOC and PT during Period 3 and 
Period 4 
 
 
 
 
X 
 
14.3.3.1 
Any unsolicited TEAE across all periods by SOC, PT and 
relatedness 
 
 
 
 
X 
X 
14.3.3.2 
Any unsolicited TEAE during Period 1 by SOC, PT and 
relatedness 
 
 
 
 
X 
 
14.3.3.3 
Any unsolicited TEAE during Period 1 and Period 2 by SOC, 
PT and relatedness 
 
 
 
 
X 
 
14.3.3.4 
Any unsolicited TEAE during Period 2 by SOC, PT and 
relatedness 
 
 
 
 
X 
 
14.3.3.5 
Any unsolicited TEAE during Period 2 and Period 3 by SOC, 
PT and relatedness 
 
 
 
 
X 
 
14.3.3.6 
Any unsolicited TEAE during Period 3 by SOC, PT and 
relatedness 
 
 
 
 
X 
 
14.3.3.7 
Any unsolicited TEAE during Period 3 and Period 4 by SOC, 
PT and relatedness 
 
 
 
 
X 
 
14.3.4.1 
Any solicited AE by SOC/PT and maximum severity during 
Period 1 
 
 
 
 
X 
X 
14.3.4.2 
Any unsolicited TEAE by SOC/PT and maximum severity 
across all periods 
 
 
 
 
X 
 
14.3.4.3 
Any unsolicited TEAE by SOC/PT and maximum severity 
during Period 1 
 
 
 
 
X 
 
14.3.4.4 
Any unsolicited TEAE by SOC/PT and maximum severity 
during Period 1 and Period 2 
 
 
 
 
X 
 
14.3.4.5 
Any unsolicited TEAE by SOC/PT and maximum severity 
during Period 2 
 
 
 
 
X 
 


 
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n° 
 
Enrolled 
ITT 
ITT-I 
PP 
SAF 
IA 
14.3.4.6 
Any unsolicited TEAE by SOC/PT and maximum severity 
during Period 2 and Period 3 
 
 
 
 
X 
 
14.3.4.7 
Any unsolicited TEAE by SOC/PT and maximum severity 
during Period 3 
 
 
 
 
X 
 
14.3.4.8 
Any unsolicited TEAE by SOC/PT and maximum severity 
during Period 3 and Period 4 
 
 
 
 
X 
 
14.3.5 
All unsolicited TEAE during Period 1 leading to study 
treatment discontinuation, by SOC and PT 
 
 
 
 
X 
 
14.3.6 
Any unsolicited TEAE leading to study discontinuation, 
across all periods, by SOC and PT 
 
 
 
 
X 
 
14.3.7.1 
Any unsolicited TESAE by SOC and PT across all periods 
 
 
 
 
X 
 
14.3.7.2 
Any SAE by SOC and PT during Period 1 
 
 
 
 
X 
 
14.3.7.3 
Any SAE by SOC and PT during Period 1 and Period 2 
 
 
 
 
X 
 
14.3.7.4 
Any SAE by SOC and PT during Period 2 
 
 
 
 
X 
 
14.3.7.5 
Any SAE by SOC and PT during Period 2 and Period 3 
 
 
 
 
X 
 
14.3.7.6 
Any SAE by SOC and PT during Period 3 
 
 
 
 
X 
 
14.3.7.7 
Any SAE by SOC and PT during Period 3 and Period 4 
 
 
 
 
X 
 
14.3.8 
Any SAE by SOC, PT and relatedness across all periods 
 
 
 
 
X 
 
 
Laboratory Safety 
 
 
 
 
X 
 
14.3.9.1.1 
Laboratory Safety: quantitative descriptive statistics 
 
 
 
 
X 
 
14.3.9.1.2 
Laboratory Safety: quantitative descriptive statistics – 
Change from baseline 
 
 
 
 
X 
 
14.3.9.2 
Laboratory Safety: Shift tables 
 
 
 
 
X 
 
14.3.9.3 
Laboratory Safety: Subjects with at least a 2-grade increase 
from baseline at any post-baseline 
 
 
 
 
X 
 


 
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n° 
 
Enrolled 
ITT 
ITT-I 
PP 
SAF 
IA 
14.3.9.4 
Laboratory Safety: Urinalysis 
 
 
 
 
X 
 
 
Vital Signs and Tympanic Temperature 
 
 
 
 
X 
 
14.3.10.1 
Vital Signs and Tympanic Temperature: quantitative 
descriptive statistics 
 
 
 
 
X 
 
14.3.10.2 
Vital Signs and Tympanic Temperature: quantitative 
descriptive statistics – Change from baseline 
 
 
 
 
X 
 
14.3.10.3 
Vital Signs and Tympanic Temperature: qualitative 
descriptive statistics 
 
 
 
 
X 
 
 
12-Lead Electrocardiogram 
 
 
 
 
X 
 
14.3.11.1.1 
12-Lead ECG: quantitative descriptive statistics 
 
 
 
 
X 
 
14.3.11.1.2 
12-Lead ECG: quantitative descriptive statistics – change 
from baseline 
 
 
 
 
X 
 
14.3.11.2 
12-Lead ECG: qualitative descriptive statistics 
 
 
 
 
X 
 
 
 


 
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Table 14.1.1: Participant Disposition 
 
Enrolled Analysis Set 
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
 
 
 
Randomized participants 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Participants receiving treatment 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Participants receiving challenge virus 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Participants who completed the study 
Yes 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
No 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
If discontinued, reason for study 
discontinuation 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
Death 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Adverse event or Serious adverse event 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Withdrawal by subject 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Investigator’s decision 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Non-compliance with study requirements 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Pregnancy 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Study terminated by Sponsor 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Lost to follow-up 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Other 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Study duration (days) 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
S.D 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 


 
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Table 14.1.1: Participant Disposition 
 
Enrolled Analysis Set 
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
S.D = Standard Deviation – Q1 = First Quartile – Q3 = Third Quartile 
Percentages are based on the number of subjects without missing values in the Enrolled analysis set 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
 


 
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Table 14.1.2: Study Populations and Reasons for Exclusion 
 
Enrolled Analysis Set 
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
 
 
 
Enrolled  
N 
XX 
XX 
XX 
XX 
 
 
 
 
Intent-To-Treat (ITT) 
Yes 
N 
Missing 
n (%) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
No 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Reason for exclusion from ITT 
Not Randomized 
N 
Missing 
n (%) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
Not study treatment administered 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Intent-To-Treat Infected (ITT-I) 
Yes 
N 
Missing 
n (%) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
No 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Reason for exclusion from ITT-I 
Not Randomized 
N 
Missing 
n (%)  
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
Not study treatment administered 
n (%)  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Per-Protocol (PP) 
Yes 
N 
Missing 
n (%) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
No 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Reason for exclusion from PP 
Not Randomized 
N 
Missing 
n (%) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
Not study treatment administered 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 


 
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Table 14.1.2: Study Populations and Reasons for Exclusion 
 
Enrolled Analysis Set 
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
Not challenge inoculated 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Not have a valid result at least 80% of 
the planned qRT-PCR nasal samples 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
At least one major protocol 
deviation likely to impact the evaluation 
of the primary endpoint 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Safety Analysis Set (SAF) 
Yes 
N 
Missing 
n (%) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
No 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Reason for exclusion from SAF 
Not study treatment administrated 
N 
Missing 
n (%) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
XX 
XX 
XX (XX.X) 
 
 
 
 
Percentages are based on the number of subjects without missing values in the Enrolled analysis set except for reason for exclusion where the percentages are based on 
subjects not included without missing values in the corresponding population 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
 
 


 
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Table 14.1.3: Protocol Deviations 
 
ITT Analysis Set 
 
Minor or Major 
Deviation Category 
PLACEBO 
(N=XX) 
n (%) [d] 
CD388 XX MG 
(N=XX) 
n (%) [d] 
CD388 150 MG 
(N=XX) 
n (%) [d] 
All 
(N=XX) 
n (%) [d] 
Any protocol deviation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
Major protocol deviation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  Major deviation 1 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  Major deviation 2 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  Major deviation n 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
Minor protocol deviation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  Minor deviation 1 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  Minor deviation 2 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  Minor deviation n 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
d = number of deviations 
Percentages are based on the number of subjects in the Intent to Treat (ITT) analysis set 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
 
 


 
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Table 14.1.4.1: Demographics and Baseline Characteristics 
 
ITT Analysis Set 
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
 
 
 
 
 
Sex 
Male 
Female 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Age 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
S.D 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
Ethnicity 
Hispanic / Latino 
Not Hispanic / Latino 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Race 
Asian 
Black or African American 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
White 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Hawaiian or Pacific Islander 
n (%)  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Native Indian or Alaskan 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Other 
n (% 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Weight (kg) 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 


 
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Table 14.1.4.1: Demographics and Baseline Characteristics 
 
ITT Analysis Set 
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
 
 
 
 
 
S.D 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
Height (cm) 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
S.D 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
BMI (kg/m²) 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
S.D 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
S.D = Standard Deviation – Q1 = First Quartile – Q3 = Third Quartile 
Percentages are based on the number of subjects without missing values in the Intent to Treat (ITT) Analysis Set 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
This mock table is used for the following tables: 


 
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Table 14.1.4.2: Demographics and Baseline Characteristics – ITT-I Analysis Set 
Table 14.1.4.3: Demographics and Baseline Characteristics – PP Analysis Set 
Table 14.1.4.4: Demographics and Baseline Characteristics – SAF Analysis Set  
 


 
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Table 1.4.5: Medical History 
 
ITT Analysis Set 
 
System Organ Class 
  Preferred Term 
PLACEBO 
(N=XX) 
n (%)  
CD388 XX MG 
(N=XX) 
n (%)  
CD388 150 MG 
(N=XX) 
n (%)  
All 
(N=XX) 
n (%)  
Any Medical History 
XX (XX.X)  
XX (XX.X)  
XX (XX.X)  
XX (XX.X) 
 
 
 
 
SOC A 
XX (XX.X)  
XX (XX.X)  
XX (XX.X) 
XX (XX.X)  
  PT a 
XX (XX.X)  
XX (XX.X)  
XX (XX.X) 
XX (XX.X)  
  PT b 
XX (XX.X)  
XX (XX.X) 
XX (XX.X)  
XX (XX.X)  
  … 
XX (XX.X)  
XX (XX.X)  
XX (XX.X) 
XX (XX.X) 
 
 
 
 
SOC B 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X)  
  PT c 
XX (XX.X)  
XX (XX.X)  
XX (XX.X)  
XX (XX.X)  
  PT d 
XX (XX.X)  
XX (XX.X)  
XX (XX.X)  
XX (XX.X)  
 
 
 
 
… 
 
 
 
 
Percentages are based on the number of subjects in the Intent to Treat (ITT) Analysis Set 
Subjects with the same System Organ Class and Preferred Term will be counted only once within the SOC and PT 
Coding dictionnary: MedDRA version xx.x (Month year) 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
 
 


 
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Table 1.4.6.1: Prior Medication 
 
ITT Analysis Set 
 
ATC Level 2 
  Preferred Name 
PLACEBO 
(N=XX) 
n (%) 
CD388 XX MG 
(N=XX) 
n (%) 
CD388 150 MG 
(N=XX) 
n (%) 
All 
(N=XX) 
n (%) 
Any Prior Medication 
XX (XX.X)  
XX (XX.X)  
XX (XX.X)  
XX (XX.X) 
 
 
 
 
ATC Level 2 A 
XX (XX.X)  
XX (XX.X)  
XX (XX.X) 
XX (XX.X)  
  PN a 
XX (XX.X)  
XX (XX.X)  
XX (XX.X) 
XX (XX.X)  
  PN b 
XX (XX.X)  
XX (XX.X) 
XX (XX.X)  
XX (XX.X)  
  … 
XX (XX.X)  
XX (XX.X)  
XX (XX.X) 
XX (XX.X) 
 
 
 
 
ATC Level 2 B 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X)  
  PN c 
XX (XX.X)  
XX (XX.X)  
XX (XX.X)  
XX (XX.X)  
  PN d 
XX (XX.X)  
XX (XX.X)  
XX (XX.X)  
XX (XX.X)  
… 
 
 
 
 
Percentages are based on the number of subjects in the Intent to Treat (ITT) Analysis Set 
Subjects with the same Anatomical Term Class and Preferred Name will be counted only once within the ATC and PN 
Coding Dictionary: WHODrug Global version (Month day, year) 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
This mock table is used for the following tables: 
Table 14.1.6.2: Concomitant Medications – PP Analysis Set 
Table 14.1.7.1: Concomitant Medications – ITT Analysis Set 
Table 14.1.7.2: Concomitant Medications – PP Analysis Set 
 
 
 


 
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Table 14.1.8.1: Compliance to Study Intervention 
 
ITT Analysis Set 
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
 
 
 
 
 
Administration completed in full 
No 
Yes 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Percentages are based on the number of subjects without missing values in the Intent-To-Treat (ITT) Analysis Set 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
Table 14.1.8.2: Compliance to Study Intervention – SAF Analysis Set 
 
 


 
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 Table 14.2.1.1: Primary efficacy - Area Under the Viral Load-time Curve (VL-AUC) from qRT-PCR 
 
PP Analysis Set 
 
 
Description 
 Statistics 
 
PLACEBO 
(N=XX) 
 
CD388 XX MG 
(N=XX) 
 
CD388 150 MG 
(N=XX) 
 
ALL 
(N=XX) 
 
 
Area under the viral load-time 
curve (VL-AUC) from qRT-PCR 
 N 
 
XX 
 
XX 
 
XX 
 
XX 
 
 Missing 
 
XX 
 
XX 
 
XX 
 
XX 
 
 Mean 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
 S.D 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
 Median 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
 Q1, Q3 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
 Min, Max 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
 95% CI Mean 
 
[XX.XX ; XX.XX] 
 
[XX.XX ; XX.XX] 
 
[XX.XX ; XX.XX] 
 
[XX.XX ; XX.XX] 
 
 
CD388 doses vs. Placebo 
comparison 
 Hodges-Lehmann estimation of 
the location shift 
 
 
 
XX.X 
 
XX.X 
 
 
 
 (95% CI) 
 
 
 
[XX.X; XX.X] 
 
[XX.X; XX.X] 
 
 
 
 P-value for one-sided Wilcoxon 
rank sum test 
 
 
 
X.XXXX 
 
X.XXXX 
 
 
 
 
S.D = Standard Deviation – Q1 = First Quartile – Q3 = Third Quartile – CI = Confidence Interval 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
This mock table is used for the following tables: 
Table 14.2.1.2.1: Primary efficacy, supplementary analysis - Area Under the Viral Load-time Curve (VL-AUC) from qRT-
PCR- ITT Analysis Set 
Table 14.2.1.2.2: Primary efficacy, supplementary analysis - Area Under the Viral Load-time Curve (VL-AUC) from qRT-
PCR- ITT-I Analysis Set 
Table 14.2.5.1: Area Under the Viral Load-time Curve (VL-AUC) from Viral Culture - PP Analysis Set 


 
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Table 14.2.5.2: Area Under the Viral Load-time Curve (VL-AUC) from Viral Culture – ITT-I Analysis Set 
 


 
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Table 14.2.2.1: Peak Viral Load from qRT-PCR 
 
PP Analysis Set 
 
 
Description 
 Statistics 
 
PLACEBO 
(N=XX) 
 
CD388 XX MG 
(N=XX) 
 
CD388 150 MG 
(N=XX) 
 
ALL 
(N=XX) 
 
 
Peak viral load from qRT-PCR 
 N 
 
XX 
 
XX 
 
XX 
 
XX 
 
 Missing 
 
XX 
 
XX 
 
XX 
 
XX 
 
 Mean 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
 S.D 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
 Median 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
XX.XX 
 
 Q1, Q3 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
 Min, Max 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
XX.X, XX.X 
 
 95% CI Mean 
 
[XX.XX ; XX.XX] 
 
[XX.XX ; XX.XX] 
 
[XX.XX ; XX.XX] 
 
[XX.XX ; XX.XX] 
 
 
CD388 doses vs. Placebo 
comparison 
 Difference in means vs. Placebo  
 
 
XX.XX 
 
XX.XX 
 
 
 
 95% CI 
 
 
 
[XX.XX ; XX.XX] 
 
[XX.XX ; XX.XX] 
 
 
 
 P-value for one-sided Wilcoxon 
rank sum test  
 
 
 
X.XXXX 
 
X.XXXX 
 
 
 
 
S.D = Standard Deviation – Q1 = First Quartile – Q3 = Third Quartile – CI = Confidence Interval 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
 
This mock table is used for the following tables: 
Table 14.2.2.2: Peak Viral Load from qRT-PCR – ITT-I Analysis Set 
Table 14.2.6.1: Peak Viral Load from Viral Culture- PP Analysis Set 
Table 14.2.6.2: Peak Viral Load from Viral Culture – ITT-I Analysis Set 


 
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Table 14.2.9.1: Area Under the Curve over time of Total Clinical Symptoms Score (TSS-AUC)- PP Analysis Set 
Table 14.2.9.2: Area Under the Curve over time of Total Clinical Symptoms Score (TSS-AUC)– ITT-I Analysis Set 
Table 14.2.10.1: Peak of Total Clinical Symptoms Score (TSS) - PP Analysis Set 
Table 14.2.10.2: Peak of Total Clinical Symptoms Score (TSS) - ITT-I Analysis Set 
Table 14.2.11.1: Individual Peak Daily Total Clinical Symptoms Score (TSS) - PP Analysis Set 
Table 14.2.11.2: Individual Peak Daily Total Clinical Symptoms Score (TSS) - ITT-I Analysis Set 
 
 


 
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Table 14.2.3.1: Time to Confirmed Negative Test by qRT-PCR 
 
PP Analysis Set 
 
Description 
 Statistics 
 
PLACEBO 
(N=XX) 
 
CD388 XX MG 
(N=XX) 
 
CD388 150 MG 
(N=XX) 
 
 
Number of subjects 
  With event 
  Censored 
 
n (%) 
n (%) 
 
 
XX (XX.X) 
XX (XX.X) 
 
 
XX (XX.X) 
XX (XX.X) 
 
 
XX (XX.X) 
XX (XX.X) 
 
 
Number of subjects who do not 
have a detectable qRT-PCR 
value 
 n (%) 
 
XX (XX.X) 
 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
Kaplan-Meier Estimates of 
Time to confirmed negative 
test by qRT-PCR (hours) 
 25th Percentile  (95% CI) 
 
XX [XX ; XX] 
 
XX [XX ; XX] 
 
XX [XX ; XX] 
 Median (95% CI) 
 
XX [XX ; XX] 
 
XX [XX ; XX] 
 
XX [XX ; XX] 
 75th Percentile (95% CI) 
 
XX [XX ; XX] 
 
XX [XX ; XX] 
 
XX [XX ; XX] 
 
 
 
 
 
 
 
Kaplan-Meier estimates (%) 
(95% CI) of the cumulative 
proportion of subjects with 
an event: 
 0 hour 
12 hours 
24 hours 
36 hours 
48 hours 
… 
 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
XX.X (XX.X; XX.X) 
 P-value for one-sided Gehan-Wilcoxon 
test  
 
 
 
X.XXXX 
 
X.XXXX 
 
 
 
 
 
 
 
CI = Confidence Interval 
Percentages are based on the number of subjects in the Per Protocol (PP) Analysis Set 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 


 
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This mock table is used for the following tables: 
Table 14.2.3.2: Time to Confirmed Negative Test by qRT-PCR – ITT-I Analysis Set 
Table 14.2.7.1: Time to Confirmed Negative Test by Viral Culture – PP Analysis Set 
Table 14.2.7.2: Time to Confirmed Negative Test by Viral Culture – ITT-I Analysis Set 
Table 14.2.12.1: Time to Symptom Resolution – PP Analysis Set 
Table 14.2.12.2: Time to Symptom Resolution – ITT-I Analysis Set 
 
 
 


 
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Table 14.2.4.1: Viral Load from qRT-PCR by day and by timepoint 
 
PP Analysis Set  
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
 
 
 
 
 
Visit X* 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
S.D 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
Visit X* 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
S.D 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
Min, Max 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
……….. 
 
 
 
 
 
 
 
 
S.D = Standard Deviation – Q1 = First Quartile – Q3 = Third Quartile 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
Note: * Visit X can be “Day X – Timepoint X” or “Day X” 
 
This mock table is used for the following tables: 
Table 14.2.4.2: Viral Load from qRT-PCR by day and by timepoint – ITT Analysis Set 
Table 14.2.4.3: Viral Load from qRT-PCR by day and by timepoint – ITT-I Analysis Set 


 
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Table 14.2.8.1: Viral Load from Viral Culture by day and by timepoint – PP Analysis Set 
Table 14.2.8.2: Viral Load from Viral Culture by day and by timepoint – ITT Analysis Set 
Table 14.2.8.3: Viral Load from Viral Culture by day and by timepoint – ITT-I Analysis Set 
Table 14.2.13.1: Total Clinical Symptoms Score by day and by timepoint – PP Analysis Set 
Table 14.2.13.2: Total Clinical Symptoms Score by day and by timepoint – ITT Analysis Set 
Table 14.2.13.3: Total Clinical Symptoms Score by day and by timepoint – ITT-I Analysis Set 
Table 14.2.28.1: Cytokine/Chemokine Levels in Nasal Samples – PP Analysis Set 
Table 14.2.28.2: Cytokine/Chemokine Levels in Nasal Samples (subgroup 1) – PP Analysis Set 
Table 14.2.28.3: Cytokine/Chemokine Levels in Nasal Samples (subgroup 2) – PP Analysis Set 
Table 14.2.29.1: Cytokine/Chemokine Levels in Serum Samples – PP Analysis Set 
Table 14.2.29.2: Cytokine/Chemokine Levels in Serum Samples (subgroup 1) – PP Analysis Set 
Table 14.2.29.3: Cytokine/Chemokine Levels in Serum Samples (subgroup 2) – PP Analysis Set 
Table 14.2.31.2: Blood – Serum Anti-drug Antibodies (ADA) – Titer Levels by day - ITT Analysis Set 
Table 14.3.9.1.1: Laboratory Safety: quantitative descriptive statistics – SAF Analysis Set 
Table 14.3.9.1.2: Laboratory Safety: quantitative descriptive statistics – Change from Baseline – SAF Analysis Set 
Table 14.3.9.4: Laboratory Safety: Urinalysis: quantitative descriptive statistics – SAF Analysis Set 
Table 14.3.10.1: Vital Signs and Tympanic Temperature: quantitative descriptive statistics – SAF Analysis Set 
Table 14.3.10.2: Vital Signs and Tympanic Temperature: quantitative descriptive statistics – Change from Baseline – 
SAF Analysis Set 
Table 14.3.11.1.1: 12-Lead ECG: quantitative descriptive statistics – SAF Analysis Set 
Table 14.3.11.1.2: 12-Lead ECG: quantitative descriptive statistics – Change from Baseline – SAF Analysis Set 
 
 
 


 
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Table 14.2.14.1: Incidence of Confirmed Influenza Infection by qRT-PCR 
 
PP Analysis Set 
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
 
 
 
 
 
qRT-PCR-confirmed influenza  
infection 
No 
Yes 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
n (%) 
95% CI  
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
n (%) 
95% CI 
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
 
 
 
 
CD388 doses vs. Placebo 
comparison 
One-sided Fisher’s 
exact p-value 
 
X.XXXX 
X.XXXX 
 
 
 
 
 
CI = Confidence Interval 
Percentages are based on the number of subjects without missing values in the Per Protocol (PP) Analysis Set 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
 
This mock table is used for the following tables: 
Table 14.2.14.2: Incidence of Confirmed Influenza Infection by qRT-PCR – ITT-I Analysis Set 
Table 14.2.15.1: Incidence of Occurrence of At Least 1 Positive Quantitative (≥LLOQ) Cell Culture – PP Analysis Set 
Table 14.2.15.2: Incidence of Occurrence of At Least 1 Positive Quantitative (≥LLOQ) Cell Culture – ITT-I Analysis 
Set 
Table 14.2.16.1: Incidence of qRT-PCR-Confirmed Symptomatic Influenza Infection – PP Analysis Set 
Table 14.2.16.2: Incidence of qRT-PCR-Confirmed Symptomatic Influenza Infection – ITT-I Analysis Set 


 
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Table 14.2.17.1: Incidence of qRT-PCR-Confirmed Moderately Severe Symptomatic Influenza Infection – PP Analysis Set 
Table 14.2.17.2: Incidence of qRT-PCR-Confirmed Moderately Severe Symptomatic Influenza Infection – ITT-I Analysis 
Set 
Table 14.2.18.1: Incidence of Culture Lab-Confirmed Symptomatic Influenza Infection – PP Analysis Set 
Table 14.2.18.2: Incidence of Culture Lab-Confirmed Symptomatic Influenza Infection – ITT-I Analysis Set 
 
 
 


 
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Table 14.2.19: Duration of Quantifiable Influenza qRT-PCR Measurements 
 
PP Analysis Set  
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
 
 
 
 
 
Duration of quantifiable influenza 
qRT-PCR measurements (hours) 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
Mean 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
S.D 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Median 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
XX.XX, XX.XX 
Min, Max 
95% CI Mean 
XX.X, XX.X 
[XX.XX ; XX.XX] 
XX.X, XX.X 
[XX.XX ; XX.XX] 
XX.X, XX.X 
[XX.XX ; XX.XX] 
XX.X, XX.X 
[XX.XX ; XX.XX] 
 
 
 
 
S.D = Standard Deviation – Q1 = First Quartile – Q3 = Third Quartile – CI = Confidence Interval 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
This mock table is used for the following tables: 
Table 14.2.20: Duration of Quantifiable Influenza Viral Culture Measurements – PP Analysis Set 
Table 14.2.21: Time to Peak Daily Total Clinical Symptoms Score – PP Analysis Set 
Table 14.2.22: Total Weight of Mucus – PP Analysis Set 
Table 14.2.23: Total Number of Tissues Used by Participants – PP Analysis Set 
 
 
 


 
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Table 14.2.24: Participants with Symptom Scored Grade 2 or higher 
 
PP Analysis Set 
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
 
 
 
 
 
Participants with symptom 
scored grade 2 or higher 
No 
Yes 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
n (%) 
95% CI  
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
n (%) 
95% CI 
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
XX (XX.X) 
[XX.XX ; XX.XX] 
 
 
 
 
CI = Confidence Interval 
Percentages are based on the number of subjects without missing values in the Per Protocol (PP) Analysis Set 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
This mock table is used for the following tables: 
Table 14.2.26: Participants with Lab-Confirmed Infection and Fever (≥37.9°C)– PP Analysis Set 
Table 14.2.27: Laboratory-Confirmed Symptomatic Influenza Infection (community acquired) – PP Analysis Set 
 
 
 


 
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Table 14.2.25: Participants with Symptom Scored Grade 2 or higher by day 
 
PP Analysis Set 
Description 
Statistics 
PLACEBO 
(N=XX) 
CD388 XX MG 
(N=XX) 
CD388 150 MG 
(N=XX) 
All 
(N=XX) 
 
 
 
 
 
Visit X 
No** 
Yes** 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
n (%)  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Visit X 
N 
XX 
XX 
XX 
XX 
Missing 
XX 
XX 
XX 
XX 
No** 
n (%)  
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
Yes** 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
……… 
 
 
 
 
 
 
 
 
Percentages are based on the number of subjects without missing values in the Per Protocol (PP) Analysis Set 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
Note: * Visit X can be “Day X – Timepoint X” or “Day X” 
Note: ** Modalities updated according to analysis 
 
This mock table is used for the following tables: 
Table 14.2.30: Viral Resistance Markers – PP Analysis Set 
Table 14.2.31.1: Blood – Serum Anti-Drug Antibodies (ADA) – Titer Levels by day - ITT Analysis Set 
Table 14.3.9.2: Laboratory Safety: Shift tables – SAF Analysis Set 
Table 14.3.9.3: Laboratory Safety: Subjects with at least a 2-grade increase from baseline at any post-baseline – 
SAF Analysis Set 
Table 14.3.9.4: Laboratory Safety: Urinalysis: qualitative descriptive statistics – SAF Analysis Set 


 
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Table 14.3.10.3: Vital Signs and Tympanic Temperature: qualitative descriptive statistics – SAF Analysis Set 
Table 14.3.11.2: 12-Lead ECG: qualitative descriptive statistics – SAF Analysis Set 
 
 
 


 
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Table 14.3.1: Summary of Adverse Events  
 
SAF Analysis Set  
 
Description 
PLACEBO 
(N=XX) 
n (%) [e] 
CD388 XX MG 
(N=XX) 
n (%) [e] 
CD388 150 MG 
(N=XX) 
n (%) [e] 
ALL 
(N=XX) 
n (%) [e] 
 
 
 
 
Any AE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Period 1: 
 
 
 
 
 
 
 
 
Any TEAE (solicited and unsolicited) 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any solicited AE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE - leading to study treatment 
discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE leading to study discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE considered as related to study 
treatment (at least possibly related) 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any SAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Period 1 and Period 2: 
 
 
 
 
 
 
 
 
Any unsolicited TEAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE leading to study discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE considered as related to study 
treatment (at least possibly related) 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any SAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 


 
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Table 14.3.1: Summary of Adverse Events  
 
SAF Analysis Set  
 
Description 
PLACEBO 
(N=XX) 
n (%) [e] 
CD388 XX MG 
(N=XX) 
n (%) [e] 
CD388 150 MG 
(N=XX) 
n (%) [e] 
ALL 
(N=XX) 
n (%) [e] 
 
 
 
 
Period 2: 
 
 
 
 
 
 
 
 
Any unsolicited TEAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE leading to study discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE considered as related to study 
treatment (at least possibly related) 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any SAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Period 2 and Period 3: 
 
 
 
 
 
 
 
 
Any unsolicited TEAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE leading to study discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE considered as related to study 
treatment (at least possibly related) 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any SAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Period 3: 
 
 
 
 
 
 
 
 
Any unsolicited TEAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE leading to study discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE considered as related to study 
treatment (at least possibly related) 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 


 
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Table 14.3.1: Summary of Adverse Events  
 
SAF Analysis Set  
 
Description 
PLACEBO 
(N=XX) 
n (%) [e] 
CD388 XX MG 
(N=XX) 
n (%) [e] 
CD388 150 MG 
(N=XX) 
n (%) [e] 
ALL 
(N=XX) 
n (%) [e] 
 
 
 
 
Any SAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Period 3 and Period 4: 
 
 
 
 
 
 
 
 
Any unsolicited TEAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE leading to study discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE considered as related to study 
treatment (at least possibly related) 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any SAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Period 4 
 
 
 
 
 
 
 
 
Any unsolicited TEAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE leading to study discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE considered as related to study 
treatment (at least possibly related) 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any SAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Across all Periods: 
 
 
 
 
 
 
 
 
Any unsolicited TEAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any unsolicited TEAE leading to study discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 


 
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Table 14.3.1: Summary of Adverse Events  
 
SAF Analysis Set  
 
Description 
PLACEBO 
(N=XX) 
n (%) [e] 
CD388 XX MG 
(N=XX) 
n (%) [e] 
CD388 150 MG 
(N=XX) 
n (%) [e] 
ALL 
(N=XX) 
n (%) [e] 
Any unsolicited TEAE considered as related to study 
treatment (at least possibly related) 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any SAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any TESAE leading to study treatment permanent 
discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any TESAE leading to study discontinuation 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Any TESAE considered related to the study treatment 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
Death 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
e = number of events 
Percentages are based on the number of subjects in the Safety (SAF) Analysis Set 
Presented: number of subjects (percent of subjects) [number of events] 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
 


 
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Table 14.3.2.1: Any Solicited AE by SOC and PT during Period 1 
 
SAF Analysis Set  
 
System Organ Class 
  Preferred Term 
PLACEBO 
(N=XX) 
n (%) [e] 
CD388 XX MG 
(N=XX) 
n (%) [e] 
CD388 150 MG 
(N=XX) 
n (%) [e] 
All 
(N=XX) 
n (%) [e] 
Any solicited AE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
SOC A 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  PT a 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  PT b 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  … 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
SOC B 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  PT c 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  PT d 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
… 
 
 
 
 
e = number of events 
Percentages are based on the number of subjects in the Safety (SAF) Analysis Set 
Subjects with the same System Organ Class and Preferred Term will be counted only once within the SOC and PT 
Coding dictionnary: MedDRA version xx.x (Month year) 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
This mock table is used for the following tables: 
Table 14.3.2.2: Any Unsolicited TEAE by SOC and PT across all Periods – SAF Analysis Set 
Table 14.3.2.3: Any Unsolicited TEAE by SOC and PT during Period 1 – SAF Analysis Set 
Table 14.3.2.4: Any Unsolicited TEAE by SOC and PT during Period 1 and Period 2 – SAF Analysis Set 


 
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Table 14.3.2.5: Any Unsolicited TEAE by SOC and PT during Period 2 – SAF Analysis Set 
Table 14.3.2.6: Any Unsolicited TEAE by SOC and PT during Period 2 and Period 3 – SAF Analysis Set 
Table 14.3.2.7: Any Unsolicited TEAE by SOC and PT during Period 3 – SAF Analysis Set 
Table 14.3.2.8: Any Unsolicited TEAE by SOC and PT during Period 3 and Period 4 – SAF Analysis Set 
Table 14.3.5: All Unsolicited TEAE during Period 1 Leading to Study Treatment Discontinuation, by SOC and PT – SAF 
Analysis Set 
Table 14.3.6: Any Unsolicited TEAE Leading to Study Discontinuation, across all Periods, by SOC and PT – SAF 
Analysis Set 
Table 14.3.7.1: Any Unsolicited TESAE by SOC and PT across all Periods – SAF Analysis Set 
Table 14.3.7.2: Any SAE by SOC and PT during Period 1 – SAF Analysis Set 
Table 14.3.7.3: Any SAE by SOC and PT during Period 1 and Period 2 – SAF Analysis Set 
Table 14.3.7.4: Any SAE by SOC and PT during Period 2 – SAF Analysis Set 
Table 14.3.7.5: Any SAE by SOC and PT during Period 2 and Period 3 – SAF Analysis Set 
Table 14.3.7.6: Any SAE by SOC and PT during Period 3 – SAF Analysis Set 
Table 14.3.7.7: Any SAE by SOC and PT during Period 3 and Period 4 – SAF Analysis Set 
 
 
 


 
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Table 14.3.3.1: Any Unsolicited TEAE across all Periods by SOC, PT and Relatedness 
 
SAF Analysis Set  
 
System Organ Class 
  Preferred Term 
     Relatedness 
PLACEBO 
(N=XX) 
n (%) [e] 
CD388 XX MG 
(N=XX) 
n (%) [e] 
CD388 150 MG 
(N=XX) 
n (%) [e] 
ALL 
(N=XX) 
n (%) [e] 
Any unsolicited TEAE 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
     Unrelated 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
     Related 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
SOC A 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  PT a 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
     Unrelated 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
     Related 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
  PT b 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
     Unrelated 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
     Related 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
SOC B 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
  PT c 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
     Unrelated 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
     Related 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
  PT d 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
     Unrelated 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
     Related 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
XX (XX.X) [XX] 
 
 
 
 
… 
 
 
 
 


 
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Table 14.3.3.1: Any Unsolicited TEAE across all Periods by SOC, PT and Relatedness 
 
SAF Analysis Set  
 
System Organ Class 
  Preferred Term 
     Relatedness 
PLACEBO 
(N=XX) 
n (%) [e] 
CD388 XX MG 
(N=XX) 
n (%) [e] 
CD388 150 MG 
(N=XX) 
n (%) [e] 
ALL 
(N=XX) 
n (%) [e] 
e = number of events 
Percentages are based on the number of subjects in the Safety (SAF) Analysis Set 
Subjects with the same System Organ Class and Preferred Term will be counted only once within the SOC and PT 
Coding dictionnary: MedDRA version xx.x (Month year) 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 
 
This mock table is used for the following tables: 
Table 14.3.3.2: Any Unsolicited TEAE during Period 1 by SOC, PT and Relatedness – SAF Analysis Set 
Table 14.3.3.3: Any Unsolicited TEAE during Period 1 and Period 2 by SOC, PT and Relatedness – SAF Analysis Set 
Table 14.3.3.4: Any Unsolicited TEAE during Period 2 by SOC, PT and Relatedness – SAF Analysis Set 
Table 14.3.3.5: Any Unsolicited TEAE during Period 2 and Period 3 by SOC, PT and Relatedness – SAF Analysis Set 
Table 14.3.3.6: Any Unsolicited TEAE during Period 3 by SOC, PT and Relatedness – SAF Analysis Set 
Table 14.3.3.7: Any Unsolicited TEAE during Period 3 and Period 4 by SOC, PT and Relatedness – SAF Analysis Set 
Table 14.3.4.1: Any Solicited AE by SOC/PT and Maximum Severity during Period 1 – SAF Analysis Set 
Table 14.3.4.2: Any Unsolicited TEAE by SOC/PT and Maximum Severity across all Periods – SAF Analysis Set 
Table 14.3.4.3: Any Unsolicited TEAE by SOC/PT and Maximum Severity during Period 1 – SAF Analysis Set 
Table 14.3.4.4: Any Unsolicited TEAE by SOC/PT and Maximum Severity during Period 1 and Period 2 – SAF Analysis Set 
Table 14.3.4.5: Any Unsolicited TEAE by SOC/PT and Maximum Severity during Period 2 – SAF Analysis Set 
Table 14.3.4.6: Any Unsolicited TEAE by SOC/PT and Maximum Severity during Period 2 and Period 3 – SAF Analysis Set 
Table 14.3.4.7: Any Unsolicited TEAE by SOC/PT and Maximum Severity during Period 3 – SAF Analysis Set 
Table 14.3.4.8: Any Unsolicited TEAE by SOC/PT and Maximum Severity during Period 3 and Period 4 – SAF Analysis Set 
Table 14.3.8: Any SAE by SOC, PT and Relatedness across all Periods – SAF Analysis Set 
 


 
Document Number or Project Identification: CIDARA_ CDT-CSP-001 
Document Version: v1 
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List of Figures 
n° 
Efficacy Results 
IA 
14.2.1.1.1 
Primary efficacy analysis – Box Plots for VL-AUC from qRT-PCR – PP Analysis Set 
X 
14.2.1.1.2 
Primary efficacy analysis – Plots of Mean VL-AUC from qRT-PCR over time – PP Analysis 
Set 
X 
14.2.1.2.1.1 
Primary efficacy analysis – Box Plots for VL-AUC from qRT-PCR – ITT Analysis Set 
 
14.2.1.2.1.2 
Primary efficacy analysis – Plots of Mean VL-AUC from qRT-PCR over time – ITT Analysis 
Set 
 
14.2.1.2.2.1 
Primary efficacy analysis – Box Plots for VL-AUC from qRT-PCR – ITT-I Analysis Set 
 
14.2.1.2.2.2 
Primary efficacy analysis – Plots of Mean VL from qRT-PCR over time – ITT-I Analysis Set 
 
14.2.2.1 
Box Plots for Peak Viral Load from qRT-PCR – PP Analysis Set 
X 
14.2.2.2 
Box Plots for Peak Viral Load from qRT-PCR – ITT-I Analysis Set 
 
14.2.3.1 
Time to Confirmed Negative Test by qRT-PCR – PP Analysis Set 
 
14.2.3.2 
Time to Confirmed Negative Test by qRT-PCR – ITT-I Analysis Set 
 
14.2.4.1.1 
Box Plots for VL-AUC from Viral Culture – PP Analysis Set 
 
14.2.4.1.2 
Plots of Mean VL from Viral Culture over time – PP Analysis Set 
 
14.2.4.2.1 
Box Plots for VL-AUC from Viral Culture – ITT-I Analysis Set 
 
14.2.4.2.2 
Plots of Mean VL from Viral Culture over time – ITT-I Analysis Set 
 
14.2.5.1 
Box Plots for Peak Viral Load from Viral Culture – PP Analysis Set 
 
14.2.5.2 
Box Plots for Peak Viral Load from Viral Culture – ITT-I Analysis Set 
 
14.2.6.1 
Time to Confirmed Negative Test by from Viral Culture – PP Analysis Set 
X 
14.2.6.2 
Time to Confirmed Negative Test by from Viral Culture – ITT-I Analysis Set 
 
14.2.7.1.1 
Box Plots for TSS-AUC– PP Analysis Set 
X 
14.2.7.1.2 
Plots of Mean TSS over time – PP Analysis Set 
X 
14.2.7.2.1 
Box Plots for TSS-AUC – ITT-I Analysis Set 
 


 
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14.2.7.2.2 
Plots of Mean TSS over time – ITT-I Analysis Set 
 
14.2.8.1 
Box Plots for Peak Total Clinical Symptoms Score – PP Analysis Set 
X 
14.2.8.2 
Box Plots for Peak Total Clinical Symptoms Score – ITT-I Analysis Set 
 
14.2.9.1 
Plots of Mean Peak Daily Total Clinical Symptoms Score over time – PP Analysis Set 
 
14.2.9.2 
Plots of Mean Peak Daily Total Clinical Symptoms Score over time – ITT-I Analysis Set 
 
14.2.10.1 
Time to Symptom Resolution – PP Analysis Set 
X 
14.2.10.2 
Time to Symptom Resolution – ITT-I Analysis Set 
 
14.3.1 
Laboratory Safety: Plots of Mean Raw Values over time – SAF Analysis Set 
 
 
 
 


 
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Figure 14.2.1.1.1: Primary efficacy analysis – Box Plots for VL-AUC from qRT-PCR 
 
PP Analysis Set 
 
 
 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 


 
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Document Template: SOP-CORP-01 AP02 V01 
 
This mock figure is used for the following figures: 
Figure 14.2.1.2.1.1: Primary efficacy analysis – Box Plots for VL-AUC from qRT-PCR – ITT Analysis Set 
Figure 14.2.1.2.2.1: Primary efficacy analysis – Box Plots for VL-AUC from qRT-PCR – ITT-I Analysis Set 
Figure 14.2.2.1: Box Plots for Peak Viral Load from qRT-PCR – PP Analysis Set 
Figure 14.2.2.2: Box Plots for Peak Viral Load from qRT-PCR – ITT-I Analysis Set 
Figure 14.2.4.1.1: Box Plots for VL-AUC from Viral Culture – PP Analysis Set 
Figure 14.2.4.2.1: Box Plots for VL-AUC from Viral Culture – ITT-I Analysis Set 
Figure 14.2.5.1: Box Plots for Peak Viral Load from Viral Culture – PP Analysis Set 
Figure 14.2.5.2: Box Plots for Peak Viral Load from Viral Culture – ITT-I Analysis Set 
Figure 14.2.7.1.1: Box Plots for TSS-AUC – PP Analysis Set 
Figure 14.2.7.2.1: Box Plots for TSS-AUC – ITT-I Analysis Set 
Figure 14.2.8.1: Box Plots for Peak Total Clinical Symptoms Score – PP Analysis Set 
Figure 14.2.8.2: Box Plots for Peak Total Clinical Symptoms Score – ITT-I Analysis Set 
 
 
 
 


 
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Figure 14.2.1.1.2: Primary efficacy analysis – Plots of Mean VL-AUC from RT-qPCR over time 
 
PP Analysis Set 
 
 
 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 


 
Document Number or Project Identification: CIDARA_ CDT-CSP-001 
Document Version: v1 
Mock Tables and Figures  
 
Confidential 
Page 47 of 49 
Document Template: SOP-CORP-01 AP02 V01 
 
This mock figure is used for the following figures: 
Figure 14.2.1.2.1.2: Primary efficacy analysis – Plots of Mean VL-AUC from RT-qPCR over time – ITT Analysis Set 
Figure 14.2.1.2.2.2: Primary efficacy analysis – Plots of Mean VL-AUC from RT-qPCR over time – ITT-I Analysis Set 
Figure 14.2.4.1.3: Plots of Mean VL from Viral Culture over time – PP Analysis Set 
Figure 14.2.4.2.2: Plots of Mean VL from Viral Culture over time – ITT-I Analysis Set 
Figure 14.2.7.1.3: Plots of Mean TSS over time – PP Analysis Set 
Figure 14.2.7.2.2: Plots of Mean TSS over time – ITT-I Analysis Set 
Figure 14.2.9.1: Plots of Mean Peak Daily Total Clinical Symptoms Score over time – PP Analysis Set 
Figure 14.2.9.2: Plots of Mean Peak Daily Total Clinical Symptoms Score over time – ITT-I Analysis Set 
Figure 14.3.1: Laboratory Safety: Plots of Mean Raw Values over time – SAF Analysis Set 
 
 
 


 
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Document Version: v1 
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Confidential 
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Document Template: SOP-CORP-01 AP02 V01 
 
 
 
Figure 14.2.3.1: Time to Confirmed Negative Test by qRT-PCR – PP Analysis Set 
 
PP Analysis Set 
 
 
Data source(s): addmain.xxxx (Date time) 
Analysis dataset(s): adsmain.adxxx (Date time)  adsmain.adxxx (Date time) 
Program: /Study/tlf/tf/pgm/pgm_name.sas Date time / run Date time by Stat_name 


 
Document Number or Project Identification: CIDARA_ CDT-CSP-001 
Document Version: v1 
Mock Tables and Figures  
 
Confidential 
Page 49 of 49 
Document Template: SOP-CORP-01 AP02 V01 
 
 
This mock figure is used for the following figures: 
Figure 14.2.3.2: Time to Confirmed Negative Test by qRT-PCR – ITT-I Analysis Set 
Figure 14.2.6.1: Time to Confirmed Negative Test by from Viral Culture – PP Analysis Set 
Figure 14.2.6.2: Time to Confirmed Negative Test by from Viral Culture – ITT-I Analysis Set 
Figure 14.2.10.1: Time to Symptom Resolution – PP Analysis Set 
Figure 14.2.10.2: Time to Symptom Resolution – ITT-I Analysis Set 


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