Clinical trial NCT04540627
Conditions: Healthy Adult Participants
Sponsor: mAbxience Research S.L.
Start date: 2020-07-06; Completion date: 2020-10-23
Enrollment: 56 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Double-Blind, Randomised, Placebo-Controlled Exploratory Study to Estimate the Prophylactic Efficacy of Palivizumab in Healthy Adult Participants Inoculated with Respiratory Syncytial Virus (RSV).

Detailed description:
As no data exists for Palivizumab in the RSV human challenge model, this exploratory study is therefore planned to establish the margins of effect and variance of prophylactically administered Palivizumab within the RSV-A Memphis 37b challenge model in healthy adult volunteers.

The study will be performed in adults aged 18-55 years, in two parts.

• Part 1: All participants will be administered Palivizumab (8mg/Kg, intravenously). Pharmacokinetic (PK), safety will be measured.

If there are no safety concerns in Part 1, and PK analysis of Palivizumab treated participants confirm the modelling of 8mg/Kg to be appropriate, Part 2 will commence with the planned 8mg/Kg treatment dose. However, if PK analysis of Part 1 suggests that 8mg/kg may be insufficient dose to provide suitable efficacious coverage in Part 2, then Part 2 will proceed with a dose of 15mg/Kg.

• Part 2: Participants will be either administered Palivizumab (8mg/Kg or 15mg/Kg, as determined in Part ) or a placebo and they will subsequently be challenged with an RSV-A strain (Memphis 37b). The margin of effect and variance between groups will be measured, as well as safety and reactogenicity.

Arms: arm 1: Sodium Chloride 0.9% Solution (Normal Saline) arm 2: Sterile vial 50mg/0.5mL
Interventions: intervention 1: Palivizumab intervention 2: Placebo intervention 3: RSV-A Memphis 37b virus
Intervention descriptions: intervention 1: Liquid solution in sterile water for injection (final concentration of 20mg/mL), intravenous infusion, single dose of 8mg/kg or 15mg/kg, administered at a rate of 1mL/min intervention 2: Sodium Chloride 0.9% Solution (Normal Saline), intravenous infusion, single dose of 0mg/Kg, administered at a rate of 1mL/min intervention 3: Single Intranasal Virus Dose (challenge dose is approximately 4.5log10 PFU)

Protocol documents:
Prot_000.pdf: 
Protocol Title: 
A Double-Blind, Randomised, Placebo-Controlled 
Exploratory Study to Estimate the Prophylactic 
Efficacy of Palivizumab in Healthy Adult 
Participants Inoculated with Respiratory Syncytial 
Virus (RSV) 
NCT Number: 
NCT04540627 
Protocol version 
date: 
Version 2.0, 22 May 2020 
 
 


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CLINICAL STUDY PROTOCOL 
A Double-Blind, Randomised, Placebo-Controlled Exploratory Study to Estimate the Prophylactic 
Efficacy of Palivizumab in Healthy Adult Participants Inoculated with Respiratory Syncytial Virus 
(RSV) 
Short title: 
An RSV Human Challenge Study of Palivizumab in Healthy Adult 
Participants 
Version and Date of Protocol: 
Final V2.0 _Date 22 May 2020 
Sponsor Protocol Number: 
MB05-P-01-20 
hVIVO Protocol Number: 
HVO-CS-001 
Sponsor: 
mAbxience Research S.L. 
Manuel Pombo Angulo 28, 3rd floor 
Madrid Spain 
Postal Code: 28050 
Phone: +34 917 711 500 
Compound Number: 
Palivizumab (Synagis ™) 
EudraCT number: 
2020-001044-26 
Confidentiality and Protections Statement: 
This document is the property of mAbxience and contains confidential information of hVIVO and 
mAbxience. 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 mAbxience. 
Personal data included in the protocol is subject to General Data Protection Regulation (GDPR:  EU 
2016/679) considerations and protections. 


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Sponsor Statement: 
This protocol was subjected to critical review. The information it contains is consistent with current 
knowledge of the risks and benefits of the study intervention, and with the moral, ethical and scientific 
principles governing clinical research as set out in the current Declaration of Helsinki and the principles 
of International Council for Harmonisation (ICH) Good Clinical Practice (GCP). 
 
Sponsor Signatory: 
[Name] 
[Title] 
 
Date (DD MMM YYYY) 
 
 
 


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Investigator Agreement: 
I have read the protocol, and agree to conduct the study in accordance with the approved protocol and 
any future amendments, the Declaration of Helsinki ,the principles of ICH GCP, the current regulatory 
requirements as detailed in the Medicines for Human Use (Clinical Trial) Regulations (Statutory 
Instrument 2004/1031) and all subsequent amendments, the UK Data Protection Act 2018, any other 
applicable laws and guidance.  
I agree to conduct the procedures described in this protocol according to these guidelines and to 
appropriately direct and assist the staff under my control. 
Principal Investigator (PI) Signatory: 
Name (typed or printed): 
Institution and Address: 
 
 
 
Signature: 
Date: 
(DD MMM YYYY) 
Note: In this protocol, the terms hVIVO and ‘Investigator’ distinguish between the Principal Investigator 
(PI)’s responsibility, and actions required by the organisation (hVIVO). The term ‘Investigator’ includes 
appropriately qualified persons to whom the PI has formally delegated his/her Investigator roles and 
responsibilities. 




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Study Personnel Contact Information  
CONTACT 
DETAILS 
Sponsor 
mAbxience Research S.L. 
Manuel Pombo Angulo 28, 3rd floor 
Madrid Spain 
Postal Code: 28050 
Phone: 
 
Sponsor’s Representative 
 
mAbxience Research S.L. 
C/ Manuel Pombo Angulo 28, 4th Floor 
28050, Madrid 
Phone:
 
Email: 
  
Principal Investigator (PI) and 
Clinical Trial Unit 
 
hVIVO Services Limited 
Queen Mary BioEnterprises Innovation Centre 
London E1 2AX, United Kingdom  
Phone:
 
Email:
  
Sponsor’s Medical Monitor 
 
mAbxience Research S.L. 
C/ Manuel Pombo Angulo 28, 4th Floor 
28050, Madrid 
Phone:
 
Email: 
 
Key Protocol Contributors 
Refer to the local study contact list document 
 
 


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Protocol Amendment Summary of Changes Table 
PROTOCOL HISTORY 
Document 
Date 
Amendment Type 
Initial Clinical Trial Protocol 
(v1.0) 
 24 Mar 2020 
Not applicable. First Version. 
Protocol Amendment 01 (v2.0) 
22 May 20202 
Substantial Amendment  
Amendment 01 (22-May-2020) 
Overall Rationale for the Amendment: 
Section # and Name 
Description of Change 
Brief Rationale 
7.1 Participant 
Withdrawal; 
1.3.2 Part 2 SOA 
Assessments to be performed at the Early 
Withdrawal Visit (EWV) have been updated to 
clarify the assessments that should be performed, 
where possible, and the optional assessments that 
are performed at the PI’s discretion.  
Section 7.1 updated to incorporate specific text to 
clarify that, in the scenario where a Participant 
withdraw from the quarantine phase, EWV 
assessments will not be repeated for assessments 
already performed on the day as part of the study 
SOA unless clinically indicated.  
Clarification of the 
assessments 
performed at the 
EWV. 
8.14 Nasal 
Discharge Collection 
from Paper Tissues; 
1.3.2 Part 2 SOA 
Section 8.14 updated to clarify that the distribution 
of paper tissues and bags will start on Day -2, with 
the first collection on Day -1 as stated in the study 
protocol SOA. Thereafter distribution and collection 
of tissues will occur daily until the discharge from 
quarantine.  
Part 2 SOA has been revised to resolve the 
inadvertent inclusion of paper tissues collection on 
Day 28 Follow-up Visit due to administrative error. 
Text revised to 
resolve an 
administrative error. 
 
8.20.1.2 Respiratory 
Pathogen Screen, 
1.3.2 Part 2 SOA 
Section 8.20.1.2 amended to incorporate specific 
text confirming that the nasopharyngeal swab or 
nasal wash collected on entry to quarantine will be 
tested to detect the presence of a set of respiratory 
pathogens, including Covid-19, that could 
potentially contraindicate a participant's 
participation in the study.   
Part 2 SOA updated to specify that the 
nasopharyngeal swab or nasal wash for respiratory 
pathogen screen can be performed on either Study 
Day -3 or Study Day-2. 
Inclusion of Covid-
19 testing as part of 
the Respiratory 
Pathogen Screen 
6.3. Randomisation 
and Blinding 
Section 6.3 amended to incorporate an update to 
the process for emergency unblinding. An individual 
access to a secured website will be provided to the 
Investigator to replace code break envelopes. 
Reference to the code break envelopes has been 
amended throughout the document. 
Process for 
emergency 
unblinding amended  
 
 
 


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Table of Contents 
1. 
Protocol Summary ....................................................................... 10 
1.1. 
Synopsis ........................................................................................ 10 
1.1.1. 
Indication(s): .................................................................................. 10 
1.1.2. 
Rationale: ....................................................................................... 10 
1.1.3. 
Objectives and Endpoints: ............................................................. 11 
1.1.4. 
Overall Design: .............................................................................. 13 
1.1.5. 
Disclosure Statement: .................................................................... 14 
1.1.6. 
Number of Participants: ................................................................. 14 
1.1.7. 
Intervention Groups and Duration: ................................................. 15 
1.2. 
Study Schematic: On-study Participant Progression ..................... 17 
1.3. 
Schedules of Activities (SoA) ........................................................ 18 
1.3.1. 
Part 1 SoA ...................................................................................... 18 
1.3.2. 
Part 2 SoA ...................................................................................... 20 
2. 
Introduction .................................................................................. 25 
2.1. 
Background .................................................................................... 25 
2.2. 
Study Rationale ............................................................................. 26 
2.3. 
Benefit/Risk Assessment ............................................................... 26 
2.3.1. 
Risk Assessment ........................................................................... 27 
2.3.2. 
Benefit Assessment ....................................................................... 30 
2.3.3. 
Overall Benefit: Risk Conclusion ................................................... 31 
3. 
Objectives and Endpoints........................................................... 32 
3.1. 
Part 1 Objectives and Endpoints ................................................... 32 
3.2. 
Part 2 Objectives and Endpoints ................................................... 32 
4. 
Study Design ................................................................................ 36 
4.1. 
Overall Design ............................................................................... 36 
4.1.1. 
Part 1 design .................................................................................. 36 
4.1.2. 
Part 2 design .................................................................................. 36 
4.1.3. 
Part 1 duration ............................................................................... 36 
4.1.4. 
Part 2 duration ............................................................................... 37 
4.2. 
Scientific Rationale for Study Design ............................................ 38 
4.3. 
Justification for Treatment Dose & Route of Administration .......... 38 
4.4. 
End of Study Definition .................................................................. 38 
5. 
Study Population ......................................................................... 39 
5.1. 
Inclusion Criteria ............................................................................ 39 
5.2. 
Exclusion Criteria ........................................................................... 41 
5.3. 
Lifestyle Considerations................................................................. 43 
5.3.1. 
Meals and Dietary Restrictions ...................................................... 43 
5.3.2. 
Caffeine, Alcohol, and Tobacco ..................................................... 43 
5.3.3. 
Activity ............................................................................................ 44 
5.4. 
Screen Failure ............................................................................... 44 
6. 
Study Intervention ....................................................................... 45 
6.1. 
Study Intervention(s) Administered ............................................... 45 
6.2. 
Preparation/Handling/Storage/Accountability ................................ 46 
6.2.1. 
Dose Preparation ........................................................................... 46 
6.2.2. 
Handling, Storage, and Accountability ........................................... 46 
6.3. 
Randomisation and Blinding .......................................................... 48 
6.4. 
Study Intervention Compliance ...................................................... 49 
6.5. 
Concomitant Therapy .................................................................... 49 


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6.6. 
Dose Modification .......................................................................... 50 
7. 
Discontinuation of Study Intervention/Withdrawal .................. 51 
7.1. 
Participant Withdrawal ................................................................... 51 
7.2. 
Participant Discontinuation ............................................................ 51 
7.2.1. 
Temporary Discontinuation/Temporary Delay in Enrolment .......... 52 
7.3. 
Lost to Follow up ............................................................................ 52 
7.4. 
Participant Replacement Strategy ................................................. 52 
7.5. 
Stopping Rules .............................................................................. 53 
8. 
Study Assessments and Procedures ........................................ 54 
8.1. 
Medical and Medication History ..................................................... 54 
8.2. 
Demographics ................................................................................ 54 
8.3. 
Height, Weight and Body Mass Index (BMI).................................. 54 
8.4. 
Complete Physical Examination .................................................... 54 
8.5. 
Direct Physical Examination .......................................................... 54 
8.6. 
Vital Signs ...................................................................................... 55 
8.7. 
Tympanic Temperature .................................................................. 55 
8.8. 
Electrocardiogram .......................................................................... 56 
8.9. 
Spirometry ..................................................................................... 56 
8.10. 
Peak expiratory flow (PEF) ............................................................ 56 
8.11. 
Forced oscillation technique (FOT) ............................................... 56 
8.12. 
Patient Health Questionnaire (PHQ-9) and Generalised Anxiety 
Disorder (GAD-7) Questionnaire ................................................... 57 
8.13. 
Participant Symptom Diary Card ................................................... 57 
8.14. 
Nasal Discharge Collection from Paper Tissues ........................... 58 
8.15. 
Alcohol Breath Testing ................................................................... 58 
8.16. 
Urinalysis ....................................................................................... 59 
8.17. 
Urine Drugs of Abuse and Nicotine Test ....................................... 59 
8.18. 
Pregnancy Test .............................................................................. 59 
8.19. 
Blood Samples ............................................................................... 59 
8.19.1. 
Safety Blood Samples ................................................................... 59 
8.19.2. 
Challenge Virus Serology Samples ............................................... 59 
8.19.3. 
Pharmacokinetic Blood Samples ................................................... 60 
8.19.4. 
Anti-drug Antibody Blood Samples ................................................ 61 
8.19.5. 
Blood Samples for Exploratory Research ...................................... 61 
8.20. 
Upper Respiratory Samples .......................................................... 61 
8.20.1. 
Nasal samples ............................................................................... 61 
8.21. 
Recording of Adverse Events and Serious Adverse Events ......... 62 
8.21.1. 
Time Period and Frequency for Collecting AE and SAE Information
 ....................................................................................................... 63 
8.21.2. 
Method of Detecting AEs and SAEs .............................................. 63 
8.21.3. 
Follow-up of AEs and SAEs ........................................................... 63 
8.21.4. 
Regulatory Reporting Requirements for SAEs .............................. 63 
8.21.5. 
Pregnancy ...................................................................................... 64 
8.21.6. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs ............................................................ 64 
8.22. 
Treatment of Overdose .................................................................. 64 
8.23. 
Pharmacokinetics .......................................................................... 65 
8.24. 
Pharmacodynamics ....................................................................... 65 
9. 
Statistical Considerations........................................................... 66 
9.1. 
Statistical Hypotheses ................................................................... 66 
9.2. 
Sample Size Determination ........................................................... 66 


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9.2.1. 
Part 1 sample size ......................................................................... 66 
9.2.2. 
Part 2 challenge study sample size ............................................... 66 
9.3. 
Populations for Analyses ............................................................... 67 
9.3.1. 
Subgroup Analysis ......................................................................... 68 
9.4. 
Interim Analysis ............................................................................. 68 
9.5. 
Sequence of Analysis .................................................................... 68 
9.6. 
Statistical Analysis ......................................................................... 69 
9.6.1. 
Statistical Analysis Plan ................................................................. 69 
9.6.2. 
General statistical methods ........................................................... 69 
9.6.3. 
Participant accountability ............................................................... 70 
9.6.4. 
Protocol deviations......................................................................... 70 
9.6.5. 
Demographic and baseline characteristics .................................... 70 
9.6.6. 
Compliance to study treatment ...................................................... 70 
9.6.7. 
Efficacy Endpoint(s) ....................................................................... 70 
9.6.8. 
Tertiary/exploratory efficacy endpoint(s) ....................................... 72 
9.6.9. 
Safety Analyse(s) ........................................................................... 72 
9.6.10. 
Other Analyses .............................................................................. 72 
10. 
Supporting Documentation and Operational Considerations 73 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................... 73 
10.1.1. 
Regulatory and Ethical Considerations ......................................... 73 
10.1.2. 
Financial Disclosure ....................................................................... 73 
10.1.3. 
Informed Consent Process ............................................................ 73 
10.1.4. 
Data Protection .............................................................................. 74 
10.1.5. 
Committees Structure .................................................................... 74 
10.1.6. 
Dissemination of Clinical Study Data ............................................. 75 
10.1.7. 
Data Quality Assurance ................................................................. 75 
10.1.8. 
Source Documents ........................................................................ 75 
10.1.9. 
Study Discontinuation .................................................................... 76 
10.1.10. Publication Policy ........................................................................... 76 
10.2. 
Appendix 2: Clinical Laboratory Tests ........................................... 77 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ......................... 78 
10.3.1. 
Adverse Event ................................................................................ 78 
10.3.2. 
Adverse Drug Reaction .................................................................. 79 
10.3.3. 
Unexpected Adverse (Drug) Reaction ........................................... 79 
10.3.4. 
Serious Adverse Event .................................................................. 80 
10.3.5. 
Suspected Unexpected Serious Adverse Reaction ....................... 81 
10.3.6. 
Recording, Assessment and Follow-up of AE and/or SAE ............ 81 
10.3.7. 
Reporting of SAEs ......................................................................... 87 
10.3.8. 
Reporting of SUSARs .................................................................... 88 
10.3.9. 
Adverse Reactions to non-IMPs .................................................... 88 
10.3.10. Post-study AEs and SAEs ............................................................. 88 
10.3.11. Pregnancy ...................................................................................... 88 
10.4. 
Appendix 4: Normal Ranges .......................................................... 90 
10.5. 
Appendix 5: Abbreviations ............................................................. 91 
11. 
References ................................................................................... 93 
 
 


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List of Tables 
Table 1 - Risk Assessment ................................................................................................................... 27 
Table 2 - Study Interventions ................................................................................................................ 45 
Table 3 - Prohibited Medications .......................................................................................................... 49 
Table 4 – Permitted Medication ............................................................................................................ 50 
Table 5 – Study Stopping Rules ........................................................................................................... 53 
Table 6 - Protocol-Required Safety Laboratory Assessments .............................................................. 77 
Table 7 – Classification of Adverse Event Severity .............................................................................. 84 
Table 8- Classification of Adverse Event Relationship ......................................................................... 85 
Table 9 - Classification of Adverse Event Outcome ............................................................................. 86 
Table 10 - Contact Details for Reporting SAEs..................................................................................... 87 
 
 


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1. 
Protocol Summary 
1.1. 
Synopsis 
1.1.1. 
Indication(s): 
Palivizumab is a marketed prophylactic monoclonal antibody (mAb) for the prevention of serious lower 
respiratory tract disease caused by Respiratory Syncytial Virus (RSV) in children at high risk for RSV 
disease. 
1.1.2. 
Rationale: 
There are currently no effective vaccines to prevent RSV in children, and treatment options for RSV-
infected individuals are limited. Palivizumab is licensed for immunoprophylaxis against RSV in young 
high-risk children, requiring 5 monthly doses and is not affordable in Low to Medium Income Countries 
(LMICs). The high costs of Palivizumab (US$9600/per season in the USA, and €5000 in Europe) 
make this biotherapeutic product unaffordable for children in LMICs, which are the areas where the 
virus is most prevalent and the associated mortality rates are the highest. According to data from The 
Lancet, between 66,000 and 199,999 children died from complications stemming from RSV in 2005. 
99% of those deaths were recorded in developing countries. Therefore, in order to provide effective and 
affordable RSV immunoprophylaxis for young high-risk children in LMICs, biosimilars for Palivizumab 
are being developed.  
As no data exists for Palivizumab in the RSV human challenge model, this exploratory study is therefore 
planned to establish the margins of effect and variance of prophylactically administered Palivizumab 
within the RSV-A Memphis 37b challenge model in healthy adult volunteers. This will enable 
subsequent evaluation of biosimilars (such as MB05) for prophylactic equivalence or non-inferiority to 
the reference article (Palivizumab), in the RSV human challenge model. 
The study will be performed in adults aged 18-55 years, in two parts.  
• 
Part 1: All participants will be administered Palivizumab (8mg/Kg, intravenously). 
Pharmacokinetic (PK), safety will be measured. 
o 
If there are no safety concerns in Part 1, and PK analysis of Palivizumab treated 
participants confirm the modelling of 8mg/Kg to be appropriate, Part 2 will commence with 
the planned 8mg/Kg treatment dose. However, if PK analysis of Part 1 suggests that 
8mg/kg may be insufficient dose to provide suitable efficacious coverage in Part 2, then 
Part 2 will proceed with a dose of 15mg/Kg. 
• 
Part 2: Participants will be either administered Palivizumab (8mg/Kg or 15mg/Kg, as determined in 
Part 1) or a placebo and they will subsequently be challenged with an RSV-A strain (Memphis 37b). 
The margin of effect and variance between groups will be measured, as well as safety and 
reactogenicity. 


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1.1.3. 
Objectives and Endpoints: 
1.1.3.1. 
Part 1 Objectives and Endpoints 
Objectives 
Endpoints 
• 
To confirm the planned dose of Palivizumab 
to be given to participants in Part 2 
• 
Evaluation of PK levels after intravenous 
administration of Palivizumab 
• 
To assess safety of Palivizumab in healthy 
adults 
• 
Frequency and severity of Adverse Events 
(AEs) and serious AEs (SAEs) 
• 
Frequency and severity of Treatment 
Emergent Adverse Events (AEs) and 
serious AEs (SAEs) 
• 
Frequency and severity of drug related 
Treatment Emergent Adverse Events 
(AEs) and serious AEs (SAEs) 
1.1.3.2. 
Part 2 Objectives and Endpoints 
Objectives 
Endpoints 
• 
To estimate the margin and variance of 
prophylactic effect of Intravenous (IV) 
treatment with Palivizumab administered 1 
day prior to inoculation in the RSV human 
challenge model in healthy adults compared 
to Placebo [assessed 
by quantitative 
reverse 
transcriptase-polymerase 
chain 
reaction (qRT-PCR)]. 
The margin and variance will be estimated as 
follows: 
• 
Area under the viral load-time curve (VL-
AUC) 
of 
RSV-A 
Memphis 
37b 
as 
determined by qRT-PCR on nasal samples 
collected twice daily starting two days post-
viral challenge (Day +2) up to the end of 
quarantine. 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by cell culture (pfu/mL)]. 
The margin and variance will be estimated as 
follows: 
• 
Area under the viral load-time curve (VL-
AUC) 
of 
RSV-A 
Memphis 
37b 
as 
determined by cell culture on nasal 
samples collected twice daily starting two 
days post-viral challenge (Day +2) up to 
the end of quarantine. 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by total symptom score 
(TSS)]. 
The margin and variance will be estimated as 
follows: 
• 
Area under the total symptom score-time 
curve (TSS-AUC) collected daily in the 
participant symptom diary card starting 
one day post-viral challenge (Day +1) up to 
the end of quarantine. 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by total symptom score 
(TSS)]. 
The margin and variance will be estimated as 
follows: 
o 
Sum Total symptom score-time curve 
(TSS-Sum) collected daily in the 
participant symptom diary card starting 
one day post-viral challenge (Day +1) 
up to the end of quarantine. 


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Objectives 
Endpoints 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by total weight of nasal 
discharge produced and the total number of 
tissues used in each group]. 
The margin and variance will be estimated as 
follows: 
• 
Total weight of nasal discharge produced 
starting one day post-viral challenge (Day 
+1) up to the end of quarantine. 
• 
Total 
number 
of 
tissues 
used 
by 
participants starting one day post-viral 
challenge (Day +1) up to the end of 
quarantine. 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by viral shedding of 
RSV-A Memphis 37b in nasal samples, in 
terms of incidence, duration, and peak]. 
The margin and variance will be estimated as 
follows: 
o 
Occurrence of at least two positive 
“quantifiable” qRT-PCR measurements in 
nasal samples at different timepoints 
reported within two or more consecutive 
days starting two days post-viral challenge 
(Day +2) up to the end of quarantine. 
o 
Occurrence of at least two positive 
“detectable” qRT-PCR measurements in 
nasal samples at different timepoints 
reported within two or more consecutive 
days starting two days post-viral challenge 
(Day +2) up to the end of quarantine. 
o 
Number 
of 
days 
with 
quantifiable 
qRT-PCR measurements in nasal samples 
starting two days post-viral challenge (Day 
+2) up to the end of quarantine. 
o 
Peak viral load of RSV-A Memphis 37b as 
defined by the maximum viral load 
determined by 
quantifiable qRT-PCR 
measurements in nasal samples starting 
two days post-viral challenge (Day +2) up 
to the end of quarantine. 
Similar endpoints may be evaluated based on 
quantitative viral culture assay. 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by symptomatic infection 
in terms of incidence, duration, and peak]. 
The margin and variance will be estimated as 
follows: 
• 
Incidence of symptomatic RSV infection, 
as defined by: 
o 
Incidence of infection, and 
o 
At least one grade 2 symptom 
from one or more respiratory 
categories from the participant 
symptom diary card. 
• 
Number of days with symptoms of grade 2 
or more, starting one day post-viral 
challenge (Day +1) up to the end of 
quarantine. 


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Objectives 
Endpoints 
• 
Peak symptom score defined by the 
maximum daily sum of Symptom score 
starting one day post-viral challenge (Day 
+1) up to the end of quarantine. 
• 
To assess safety of Palivizumab in the RSV 
human challenge model in healthy adults 
• 
Frequency and severity of Adverse Events 
(AEs) and serious AEs (SAEs) 
• 
Frequency and severity of Treatment 
Emergent Adverse Events (AEs) and 
serious AEs (SAEs) 
• 
Frequency and severity of drug related 
Treatment Emergent Adverse Events 
(AEs) and serious AEs (SAEs) 
• 
To 
assess 
the 
pharmacokinetics 
of 
Palivizumab in the RSV human challenge 
model in healthy adults 
• 
Palivizumab serum concentrations and 
serum PK parameters through study Day 
+28 
• 
To assess the Anti-Palivizumab antibody 
(ADA) in the RSV human challenge model in 
healthy adults 
• 
Anti-Palivizumab antibody (ADA) through 
Day 28 
Tertiary/Exploratory 
• 
To assess lung function in relation to RSV 
infection 
• 
Assessments 
of 
spirometry, 
Peak 
Expiratory 
Flow 
(PEF), 
and 
Forced 
Oscillation Technique (FOT) 
• 
To explore the Minimal Clinically Important 
Difference (MCID) in instrument change 
• 
The average amount of instrument-
assessed change for all participants who 
rate themselves as "a little better" or 
"somewhat better" 
• 
To explore the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo in relation to baseline immune 
status. 
The above endpoints may be explored in 
relation to the baseline status of volunteers and 
the response to treatment. Baseline status and 
response can be regarding, but not limited to: 
• 
Immune assays related to Palivizumab 
(e.g. IgG anti-F ELISA, PCA) 
• 
Baseline immunity to RSV 
• 
Response to Palivizumab treatment 
• 
To explore the host-pathogen relationship 
in the RSV human challenge model in 
healthy adults 
• 
Immune assays related to Palivizumab 
• 
RSV baseline immunity and immune 
responses to infection 
*Note that tertiary objectives and endpoints are optional and might be assessed only if needed; 
therefore, not all testing might be performed and reported. 
1.1.4. 
Overall Design: 
This is an exploratory study in healthy adult volunteers aged 18-55 years. The study is formed of two 
parts, Part 1 (PK sentinel Part), and Part 2 (Viral Challenge Part). 


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1.1.4.1. 
Part 1 design 
All participants in part 1 will receive: 
• 
Reference article product 
o 
Palivizumab (Synagis™)  
o 
Dose: 8mg/Kg  
If there are no safety concerns in Part 1, and PK analysis of Palivizumab treated participants confirms 
dose level 8mg/Kg to be appropriate, Part 2 will commence with the planned 8mg/Kg treatment dose. 
However, if PK analysis of Part 1 suggests that 8mg/kg may be an insufficient dose to provide suitable 
efficacious coverage in Part 2, then Part 2 will proceed with a dose of 15mg/Kg. Refer to Appendix 
10.1.5 for details on the Safety Data Review from Part 1. 
1.1.4.2. 
Part 2 design 
Participants in Part 2 will be randomised to receive the following on Day -1: 
• 
Reference article product 
o 
Palivizumab (Synagis™) 
o 
Dose: either 8mg/Kg or 15mg/Kg (as determined from Part 1) 
• 
Placebo product 
o 
Sodium Chloride 0.9% Solution (Normal Saline) matched to reference article product 
All participants in Part 2 will subsequently receive the following on Day 0: 
• 
RSV challenge virus 
o 
RSV-A Memphis 37b, total dose of approximately 4.5 log10 plaque forming unit, given 
intranasally 
The Study Schematic - showing participant progression through the study - is presented in Section 1.2; 
the Schedules of Activities (SoA) are presented in Section 1.3.   
 
1.1.5. 
Disclosure Statement: 
This is an exploratory study to evaluate the prophylactic efficacy of intravenously administered 
Palivizumab protecting heathy 18 to 55-year-old adults from RSV infection/disease after RSV 
inoculation. This study is composed of 2 parts: 
o 
Part 1 is an open label one armed cohort where all participants will receive a single 8mg/kg 
dose of Palivizumab administered intravenously. 
o 
Part 2 is a double-blinded, two-armed cohort where participants will be randomised to receive 
Palivizumab (as either a single 8mg/kg or 15mg/kg dose) or Placebo administered 
intravenously, and subsequently inoculated with RSV-A Memphis 37b.  
1.1.6. 
Number of Participants: 
A total of 56 study participants will be included into the two parts of the study as follows: 


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1.1.6.1. 
Part 1 Participant Numbers 
In Part 1, approximately 6 participants will be given Palivizumab for an estimated total of 6 evaluable 
participants. To ensure the number of evaluable participants is reached in each part of the study, refer 
to the Participant Replacement Policy (Section 7.4),  
1.1.6.2. 
Part 2 Participant Numbers 
In this RSV prophylactic treatment Part 2, it is anticipated that no participants will drop out between 
study intervention treatment on Day -1 and RSV inoculation on Day 0. Approximately 50 participants 
will be randomly assigned to study intervention for an estimated total of 50 evaluable participants. To 
ensure the number of evaluable participants is reached in each part of the study, refer to the Participant 
Replacement Policy (Section 7.4). 
Note: 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, unless otherwise specified by the 
protocol.  
1.1.7. 
Intervention Groups and Duration: 
The study will be performed in two parts: 
1.1.7.1. 
Part 1 Interventions & Duration 
The total duration of study participation for a participant is up to approximately 50 days, with the 
following sequence and duration of study periods:  
• 
Screening phase: from Day -28 to Day -1 pre-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 Unit for 1 days (from Day 0 to Day +1). 
Procedures will include: 
o 
Admission to Unit on Day 0 
o 
Study intervention Intravenous (I.V.) dosing on Day 0 
o 
Post infusion monitoring and PK Day 0 and Day 1 
o 
Participants will be discharged from the Unit on Day 1 (or may remain longer at the 
Principal Investigator’s discretion) 
• 
Outpatient phase: study assessments will be conducted at follow up clinic visits and telephone 
calls as follows: 
o 
Clinic visits: Day 2, Day 3, Day 7 (±1 day) and Day12 
o 
Final safety follow-up by telephone: Day 18 (±3 days). 
1.1.7.2. 
Part 2 Interventions & Duration 
The total duration of study participation for a participant is up to approximately 122 days, with the 
following sequence and duration of study periods:  
• 
Screening phase: from Day -90 to Day -4 pre-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)   


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• 
Inpatient phase: Participants will be resident in the Quarantine Unit for approximately 16 days 
(from Day -3 to Day 12). Procedures will include: 
o 
Pre-human viral challenge (HVC):  
- 
Admission to Quarantine Unit on Day -3 
- 
Study intervention I.V. dosing on Day -1 
o 
HVC:  
- 
Challenge Virus inoculation on Day 0  
o 
Post-HVC 
- 
Day 0 onwards and each day – study assessments will be 
conducted as per Schedule of Activities 
- 
Participants will be discharged from the Quarantine Unit on 
Day 12 (or may remain longer at the Principal Investigator’s 
discretion) 
• 
Outpatient phase: study assessments will be conducted 
o 
Clinic visit for PK sample on Day 20 (±2 days) 
o 
Final safety follow-up visit(s): Day 28 (±3 days) 
 
 
 


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1.2. 
Study Schematic: On-study Participant Progression 
 
 
 
*NOTE: Release from quarantine is foreseen at Day 12 in case no virus is detected by PCR (PCR below Ct cut-
off) and the participant has no clinically significant symptoms. If the participant continues to have clinically 
significant symptoms and/or detectable virus on Day 12, additional extended quarantine stay may be required at 
the discretion of the Investigator. 
 


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1.3. 
Schedules of Activities (SoA) 
1.3.1. 
Part 1 SoA 
Study Phase ➔ 
Clinic Screening 
Phase* 
Overnight stay 
Clinic visits 
Phone 
call 
Study Day ➔ 
Day -28 to Day -1 
Day 0 
Day 1 
Day 2 
Day 3 
Day 7(± 1day) 
Day 12 
Day 18 (± 
3 days) 
Procedure  
Written consent (a) 
X 
X 
 
 
 
 
 
 
Eligibility criteria (+) 
X 
X 
 
 
 
 
 
 
Medical & medication history 
X 
 
 
 
 
 
 
 
Change In medical & medication history 
 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Height & weight, BMI (b) 
X 
X 
 
 
 
 
 
 
Complete physical examination (c) 
X 
X 
X 
 
 
 
X 
 
Vital signs (HR, RR, SBP, DBP, SpO2 )(d) 
X 
BD 
X 
X 
X 
X 
X 
 
Tympanic temperature (d) 
X 
BD 
X 
X 
X 
X 
X 
 
12-lead ECG 
X 
 
 
 
 
 
X 
 
Spirometry  
X 
 
 
 
 
 
 
 
Urine drugs of abuse screen 
X 
X 
 
 
 
 
 
 
Urine pregnancy test 
X 
X 
 
 
 
 
X 
 
Urinalysis 
X 
 
 
 
 
 
X 
 
Alcohol breath test 
 
X 
 
 
 
 
 
 
Product Administration 
IMP/Placebo Dosing (e) 
 
X 
 
 
 
 
 
 
Collection of blood samples 


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Pharmacokinetic sample (f) 
  
8 X 
X 
X 
X 
X 
X 
  
ADA 
  
X 
X 
X 
  
HIV, Hepatitis A, B, & C 
X 
  
  
  
  
  
 
  
Haematology (h) 
X 
  
  
  
  
 
X 
  
Biochemistry (h) 
X 
  
  
  
  
 
X 
  
Thyroid function test 
X 
  
  
  
  
  
 
  
Serum FSH (post-menopausal women) (i) 
X 
  
  
  
  
  
 
  
Serum β-HCG pregnancy test (all females) (j) 
X 
  
  
  
  
  
 
  
Safety Assessments 
Adverse Events (k) 
 
Concomitant medications(k) 
 
KEY NOTES FOR PART 1 SCHEDULE OF EVENTS 
X 
Once 
BD 
Twice Daily, collected pre and post-dosing. 
+ 
Only the applicable Inclusion/Exclusion criteria will be reviewed at each time point. 
* 
All screening assessments will be performed under hVIVO Generic Screening process. Results of tests or examinations performed under hVIVO Generic Screening process, and within 
28 days prior to study Day 0 may be used to determine eligibility without the need to repeat the assessment following study specific consent. 
a 
Study specific consent may occur on Day 0, providing all required eligibility information has been collected through hVIVO Generic Screening process.  
b 
On Day 0, only weight will be measured pre-dosing as individual doses are defined by weight. 
c 
Day 0 physical examination will be performed pre-dose. 
Day 1 physical examination will be performed pre-discharge. 
d 
Vital signs will be measured pre- and post-dose. 
e 
IV drug delivery (approximately 20minutes infusion). 
f 
PK blood samples are taken before the start of infusion; at end of infusion, 15mins and 0.5, 1, 4, 8, 12 h; and at 1, 2, 3, 7, 12 days after infusion. 
g 
ADA blood samples are taken pre infusion and at 7 and 12 days after infusion. 
h 
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 PI discretion). 
i 
A serum follicle stimulating hormone (FSH) test will be performed in all post-menopausal women. 
i 
Blood serum pregnancy test (ß-HCG) will be performed in all female participants who have been tested positive for urine pregnancy testing 
k 
Adverse events and concomitant mediations are reviewed throughout the study including pre and post dosing with Palivizumab. 


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1.3.2. 
Part 2 SoA 
Study Phase  
Screening 
Phase* 
QUARANTINE ISOLATION 
  
Clinic visit 
  
Early 
withdraw
al visit 
Admission 
to 
quarantine 
Dosing 
Human Viral Challenge 
(HVC) 
Post HVC Days 
Dis 
charge 
  
Study Day  
Day -56 to 
Day -4 
(Day -90 
for RSV 
serology) 
Day 
D
ay 
Day 
Day 0 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
28 (± 
3 
days) 
  
 
Procedure  
 
-3 
-2 
-1 
Pre 
Chall-
enge 
Post 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
20 (± 
2 
days) 
 
  
 
Written 
consent (m) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Eligibility 
criteria (+) 
X 
Xl 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Medical & 
medication 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Change In 
medical& 
medication 
history 
 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Height & 
weight, BMI 
(a) 
X 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
 
(X) 
  
(X) 
Alcohol breath 
test 
X 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
  
X 
Urinalysis 
X 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
  
X 
Urine drugs of 
abuse  
X 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
  
X 
Urine 
pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Complete 
physical 
examination 
X 
Xl 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
X 
 
X 
  
X 
Directed 
physical 
examination 
(inc nasal) 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
  
 
Vital signs 
(HR, RR, 
SBP, DBP, 
SpO2  (b) 
X 
X 
T
D
S 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
X 
 
X 
  
X 


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Study Phase  
Screening 
Phase* 
QUARANTINE ISOLATION 
  
Clinic visit 
  
Early 
withdraw
al visit 
Admission 
to 
quarantine 
Dosing 
Human Viral Challenge 
(HVC) 
Post HVC Days 
Dis 
charge 
  
Tympanic 
temperature 
X 
X 
T
D
S 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
X 
 
X 
  
X 
Symptom 
diary card 
 
X 
T
D
S 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
TDS 
X 
 
 
  
 
24-hour tissue 
count & nasal 
discharge 
weight (c) 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
(X) 
12-lead ECG 
X 
Xl 
X0 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
 
X 
  
X 
Spirometry (d) 
X 
Xl 
X 
X 
 
 
(X) 
(X) 
(X) 
X 
(X) 
(X) 
X 
(X) 
(X) 
(X) 
X 
X 
 
X 
  
X 
PEF (d) 
 
 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
FOT (d) 
 
 
(X
) 
(X) 
(X) 
 
 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
 
 
 
 
Patient Health 
Questionnaire 
(PHQ-9) 
(X) 
(X)l 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Generalised 
Anxiety 
Disorder 
Questionnaire 
(GAD-7) 
(X) 
(X)l 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Product Administration 
 
 
Randomisa-
tion 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
IMP/Placebo 
Dosing 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
Challenge 
Virus 
inoculation 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
Collection of blood samples 
Pharmacokine
tic sample(j) 
 
 
 
8 X 
X 
X 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
  
  
Anti-
Palivizumab 
antibody 
(ADA)(q) 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
  
 
Serum FSH-
(post-
menopausal 
women) (e) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Serum β-HCG 
pregnancy test 
(all females) 
(f) 
 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
(X) 
HIV, Hepatitis 
A, B, & C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Study Phase  
Screening 
Phase* 
QUARANTINE ISOLATION 
  
Clinic visit 
  
Early 
withdraw
al visit 
Admission 
to 
quarantine 
Dosing 
Human Viral Challenge 
(HVC) 
Post HVC Days 
Dis 
charge 
  
Haematology 
(g) 
X 
Xl 
 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
(X) 
 
X 
  
X 
Biochemistry 
X 
Xl 
 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
(X) 
 
X 
  
X 
Coagulation 
X 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
X 
Cardiac 
enzymes 
X 
Xl 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
  
 
Thyroid 
function test 
X 
(X)l 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Blood sample 
for serum 
markers (h) 
X 
Xl 
 
Xn 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
  
X 
Collection of respiratory samples 
Nasopharynge
al swab / 
nasal wash - 
Respiratory 
pathogen 
screen (i) 
T 
Xl 
(X
)n 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
Nasopharynge
al swab / 
nasal wash for 
Rapid viral 
antigen test or 
PCR 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
(X)n 
 
 
 
(X) 
Nasopharynge
al swab / 
nasal wash 
Virology (k)  & 
exploratory 
research 
T 
 
X 
 
 
 
 
 
BD 
BD 
BD 
BD 
BD 
BD 
BD 
BD 
BD 
BD 
X 
 
 
  
X 
Safety Assessments 
Adverse 
events (p) 
X 
 
 
 
X 
Concomitant 
medications 
(p) 
X 
 
  
  
X 
 
KEY NOTES FOR PART 2 SCHEDULE OF EVENTS 
X 
Once 
BD 
Twice Daily, 12 hours between assessments (± 1 hour). 
TDS 
Three Times Daily, at the same time each day (± 1 hour). 
T 
To determine tolerance of the procedure only (sample will not be tested). 


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+ 
Only the applicable Inclusion/Exclusion criteria will be reviewed at each time point. 
* 
 All screening assessments will be performed under hVIVO Generic Screening process. Results of tests or examinations performed under hVIVO Generic Screening 
process, and within 90 days (90 days for viral serology and  56 days for other assessments including safety laboratory test) prior to quarantine admission may be used 
to determine eligibility without the need to repeat the assessment following study specific consent. 
a 
Height will be taken at Screening only. 
b 
Vital signs will be taken at the same time each day (± 1 hour). 
c 
Distribution of paper issues and bags will start on Day -2, with the first collection on Day -1. Thereafter collection of tissues will occur at the same timepoints (± 1 hour) 
with tissues distributed 24 h ahead.  
d 
 Assessments will be performed at the same time each day during quarantine (± 1 hour). Where respiratory assessments timepoints occur together, the order of 
assessments will typically be 1) FOT followed by 2) PEF followed by 3) Spirometry. 
e 
A serum follicle stimulating hormone (FSH) test will be performed in all post-menopausal women 
f 
Blood serum pregnancy test (ß-HCG) will be performed in all female participants 
g 
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 PI discretion). 
h 
Virus serology (RSV neutralisation antibody assay) will be performed to determine eligibility and seroconversion. Exploratory RSV-induced immune responses may 
also be assessed. 
i 
Nasopharyngeal swab or nasal wash for respiratory virus screen to assess for the presence of other respiratory viruses; if found positive the participant will not be 
eligible for the current quarantine.  
j 
PK blood samples are taken before the start of infusion; at end of infusion, 15mins, and 0.5, 1, 4, 8, and 12 h after infusion; and at 1, 2, 3, 7, 13, 21 and 29 days after 
infusion. Allowable time windows are described I section 8.19.3. 
k 
Post inoculation Nasal virology samples will be collected at the same time each day during quarantine (± 1 hour) and used for qRT-PCR and viral culture assay. 
Optional exploratory RSV-induced immune responses may also be assessed.  Nasal wash is optional under PI discretion, if NPS are being collected BD and used for 
viral load assessments. 
l 
Can be performed on Study Day -3 or Study Day -2. 
m 
Study specific consent may occur on the day of admission, providing all required eligibility information has been collected through hVIVO Generic Screening process 
n 
Optional and may be collected or not as per PI discretion for exploratory research 
0 
Post-dose ECG 
p 
Adverse events and concomitant mediations are reviewed throughout the study including pre and post dosing with Palivizumab/Placebo and pre and post inoculation.  
q 
ADA blood samples are taken pre infusion and at 7,13 and 29 days after infusion. Allowable time windows are described I section 8.19.4. 
Notes: 
Parenthesis indicates the assessment may be optional, or at the PI's discretion.  
For all participants TDS assessments will commence on Day 0, the first assessment will be pre-virus challenge. 
The PI may perform additional safety assessments as required. 
Where any nasal sampling time points occur together, the order of sampling will typically be (1) Nasopharyngeal swab followed by (2) Nasal wash.  
 
 


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GENOMIC, TRANSCRIPTOMIC AND PROTEOMIC SAMPLES 
DNA/RNA/proteomic sample collection: 
Yes 
☐ 
No 
☒ 
n/a 
Consent considerations:  
Future use of remaining samples for new ethically approved health research and laboratory testing 
protocols according to the local laws. 
 
 
 
 
 


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2. 
Introduction 
2.1. 
Background  
Respiratory Syncytial Virus (RSV) is the most common cause of acute lower respiratory infection (ALRI) in 
infants and children (Nair et al. 2010; Hall et al. 2009; Bont et al. 2016). Globally, it was estimated in 2005 
that RSV caused 33.8 million episodes of ALRI (~22% of all ALRI) and 3.4 million episodes of severe ALRI 
requiring hospitalization among children <5 years old worldwide (Nair et al. 2010). Mortality from RSV 
infection is significant, with an estimated 66,000-199,000 childhood deaths in 2005 worldwide (Nair et al. 
2010). The overwhelming majority of these deaths occur in children below the age of 2 years and in 
developing countries (Nair et al. 2010; Bont et al. 2016). The most recent estimates of global RSV disease 
burden showed that, in 2015, there were no substantial changes in the number of new episodes of RSV-
ALRI and related hospital admissions compared to 2005, but a lower number of in-hospital deaths (Shi et 
al. 2015). Moreover, for children younger than 6 months, Shi et al reported about 1.4 million hospital 
admissions and 27,300 in-hospital deaths due to RSV-ALRI in 2015 worldwide (Shi et al. 2015). 
It should be noted that RSV is also increasingly being recognised as a significant cause of morbidity and 
mortality in older adults and those with underlying chronic cardiopulmonary disorders (Falsey et al. 1995; 
Agius et al. 1990; Falsey et al. 2005). 
The RSV human challenge model was developed to not only aid understanding of RSV disease, but to also 
assess the efficacy of RSV antivirals, immunomodulators and vaccines. The RSV-A Memphis 37b 
challenge strain has been used for over 10 years by both hVIVO and others and has helped assess the 
efficacy of numerous RSV therapies and vaccines (Lambkin-Williams et al. 2018). Specifically, hVIVO have 
safely and successfully used the RSV challenge strain in over 1220 healthy participants (18 to 55 years of 
age) and have also safely completed inoculation of twenty-four participants between 60 and 75 years of 
age. Additionally, another strain of live RSV (Memphis 37c) has been used as an inoculation agent and 
was shown to be safe in over 77 healthy young adults across three studies. RSV infection was not 
associated with any serious adverse side effects. Healthy RSV challenge study participants have 
approximately 65% to 85% chance of becoming infected with RSV following the administration of the virus 
(DeVincenzo et al. 2010). Typical RSV illness is characterised by an abrupt onset of rhinitis, nasal 
stuffiness, fever, malaise, myalgia (muscle aches), and sore throat. In healthy adults, the illness usually 
resolves without any treatment, with relief of symptoms occurring naturally within 7 to 10 days. 
Palivizumab (Synagis™), a humanised monoclonal antibody directed against RSV, has been shown to be 
effective in reducing hospitalisation due to RSV by approximately 50% in high-risk infants who receive 
monthly immunoprophylaxis. While several clinical studies with Palivizumab were performed in adults, it is 
not currently licensed for use in adults. A full summary of the preclinical and clinical experience with 
Palivizumab (Synagis™). can be found in the Summary of Product Characteristics (SmPC) and 
“PALIVIZUMAB Summary of relevant clinical and non-clinical data to support the use of Investigational 
Medicinal Product (IMP) in the clinical trial” document supplementing the SmPC. 


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2.2. 
Study Rationale 
There are currently no effective vaccines to prevent RSV in children, and treatment options for RSV-infected 
individuals are limited. Palivizumab is currently licensed for immunoprophylaxis against RSV in young high-
risk children, requiring 5 monthly doses and is not affordable in LMICs. The high costs of Palivizumab 
(US$9600/per season in the USA, and €5000 in Europe) make this biotherapeutic product unaffordable for 
children in LMICs, which are the areas where the virus is most prevalent and the associated mortality rates 
are the highest. According to data from The Lancet (Nair et al. 2010), between 66,000 and 199,999 children 
died from complications stemming from RSV in 2005. 99% of those deaths were recorded in developing 
countries. Therefore, in order to provide effective and affordable RSV immunoprophylaxis for young high-
risk children in LMICs, biosimilars for Palivizumab are being developed. Biosimilars are medicines of an 
equivalent nature in terms of quality, effectiveness and safety to their benchmark biologics that are 
developed once the patent on the original product has expired, thereby enabling the price to be lowered 
significantly.  
In 2014, the WHO and the Utrecht University in The Netherlands agreed on a technical collaboration [Memo 
of Understanding (MOU)] which will contribute to the goal in promoting the wide availability of safe, effective, 
and affordable biotherapeutics in particular in the public sector of developing countries. Based on this 
memorandum, Utrecht University established the Utrecht Centre for Affordable Biotherapeutics for Public 
Health (UCAB), as a central hub to facilitate the development of safe and affordable biotherapeutics for 
low- and middle-income countries in a sustainable way. UCAB collaborates with mAbxience and local 
manufacturers in low- and middle-income countries in the development of the palivizumab biosimilar. As 
such, mAbxience together with the Utrecht Centre for Affordable Biotherapeutics for Public Health (UCAB) 
have received the mandate from WHO to develop this biosimilar palivizumab, MB05.   
No data exists for Palivizumab in the RSV human challenge model. Further to scientific advice received 
from the European Medicines Agency (EMA), this exploratory study is intended to establish the margins of 
effect and variance of prophylactically administered Palivizumab within the RSV-A Memphis 37b challenge 
model in healthy adult volunteers. This will enable subsequent evaluation of biosimilars (such as MB05) for 
prophylactic equivalence or non-inferiority to the reference article (Palivizumab), in the RSV human 
challenge model. 
Furthermore, this study will explore the minimal clinically important differences (MCID) between the 
reference article Palivizumab and Placebo treated groups after inoculation with RSV. The MCID is defined 
as the smallest difference in score in the outcome of interest that informed what patients or proxies perceive 
as important, and which would lead the patient or clinician to consider a change in the management 
(Schunemann and Guyatt 2005). The data obtained from this study will aid in developing MCIDs for each 
endpoint measure, as appropriate.  
The rationale for the study design is presented in Section 4.2. 
Please refer to the SmPC for a full summary of the preclinical and clinical experience with Palivizumab 
(Synagis™). 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably expected 
adverse events of Palivizumab may be found in SmPC; although possible. Side effects of Palivizumab have 
been established in paediatric population at high risk of severe RSV infection following an intramuscular 


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(IM) administration of Palivizumab. Historical studies in 48 healthy adults (CDER_FDA 2004) using liquid 
and lyophilised Palivizumab administered as both Intramuscular (IM) and IV injections have reported no 
serious adverse events (SAEs). The most common side effect observed in adults was mild transient 
dizziness and headache.    
 
2.3.1. 
Risk Assessment 
The known risks to participants are detailed in Table 1. However, there may also be risks that are 
unforeseen and not anticipated (e.g., unknown allergies). Every effort will be made to monitor the health of 
the participants to ensure that such risks are minimised. Trained medical personnel and facilities will be 
available to provide medical emergency care. 
Table 1 - Risk Assessment  
Potential Risk 
of Clinical 
Significance 
Rationale for Risk 
Mitigation Strategy 
Study Intervention  
Intravenous 
Dosing with 
Palivizumab 
Local signs and symptoms associated 
with the injection may include: erythema, 
swelling/induration, and pain/tenderness 
at the injection site. 
Local reactions will be monitored but are 
generally short-term and do not require 
treatment. 
Other side effects include rash 
Side effects will be monitored but are 
generally short-term and do not require 
treatment.  
Other less common but serious side 
effects reported include anaphylaxis and 
anaphylactic shock and other severe 
acute hypersensitivity reactions 
Medications (e.g epinephrine) will be 
available in the clinic to treat serious 
allergic reactions promptly. Participants 
with a known allergy, or history of 
anaphylaxis or other serious adverse 
reactions will be excluded from the study. 
The study site should have medical 
treatment available in case of severe 
allergic reactions. 
Systemic exposure to Palivizumab 
To minimise any risks associated with 
systemic exposure to Palivizumab, male 
and female participants must be on 
highly effective contraception methods 
during the study and up to 90 days post 
dosing with Palivizumab. 
 
Lack of pre-clinical reproductive toxicity 
evaluation as well as clinical toxicity 
evaluations in pregnancy due to target 
population indication (high-risk children 
<24 
months) 
of 
Palivizumab 
and 
requirements for licensing for indication. 
Although reproductive toxicity studies are 
Participants will be advised to use 
appropriate methods of contraception 
during the study and for 90 days after 
administration of Palivizumab for male 
participants (equivalent to the sperm life 
cycle) 
and 
30 
days 
for 
female 


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Potential Risk 
of Clinical 
Significance 
Rationale for Risk 
Mitigation Strategy 
not considered appropriate for the study 
intervention. 
participants (equivalent to the length of a 
menstrual cycle). 
 
Palivizumab 
may 
interfere 
with 
immunological-based 
RSV 
diagnostic 
tests such as some antigen detection-
based assays. In addition, Palivizumab 
inhibits virus replication in cell culture, 
and therefore may also interfere with viral 
culture assays. Palivizumab does not 
interfere 
with 
reverse 
transcriptase-
polymerase chain reaction-based assays. 
Assay interference could lead to false-
negative RSV diagnostic test results. 
Therefore, diagnostic test results, when 
obtained, should be used in conjunction 
with clinical findings to guide medical 
decisions 
Discharge from quarantine will utilise a 
PCR based test instead of an antigen 
test. 
 
PCR based tests will be used to confirm 
the incidence of infection and to quantify 
virus shed by infected participants. 
 
Implications 
for 
culture-based 
quantification of RSV will be assessed. 
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 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. 
Nasal sampling 
Collection of nasal wash samples or 
nasopharyngeal 
swabs 
may 
cause 
discomfort, 
sneezing, 
watery 
eyes, 
irritated nose or nose bleeding. 
Sample collection will be performed by 
appropriately qualified and trained study 
staff to minimise the discomfort. 


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Potential Risk 
of Clinical 
Significance 
Rationale for Risk 
Mitigation Strategy 
RSV infection from inoculation 
RSV infection & 
severe 
complications 
65% to 85% chance of becoming infected 
with RSV. Typical RSV illness: abrupt 
onset of rhinitis, nasal stuffiness, fever, 
malaise, myalgia (muscle aches), and 
sore throat. 
 
Severe RSV infections are known to 
occur in both infants and adults. In adult 
populations, multiple factors but not older 
age, are independently associated with 
severe RSV complications including 
persons 
of 
any 
age 
with 
chronic 
co-morbidities and significant immune 
compromise. 
 
The study virus, like many viruses, can 
cause more substantial health issues 
such as myocarditis (inflammation or 
damage to the heart muscle). However, 
the chance of this resulting in serious or 
permanent changes is rare, as most 
cases are minor and resolve without any 
lasting 
changes. 
In 
previous 
virus 
challenge studies at hVIVO, uncommonly 
(3 cases in more than 1000 individuals 
who have received the challenge virus) 
blood tests have shown a change 
suggestive of myocarditis, although in 
these few participants the blood tests 
returned to normal without treatment. 
The safety profile of the RSV-A Memphis 
37b challenge strain is well characterised 
in healthy young adults as this has been 
used for over ten years by hVIVO. At 
hVIVO more than 1000 healthy adults 
aged 18 to 55 years have been 
challenged with the RSV-A Memphis 37b 
strain.  
RSV infection in healthy adults usually 
resolves without treatment within 7 to 
10 days.  
Strict inclusion and exclusion criteria will 
apply to ensure only healthy adults are 
enrolled in this study. 
There will be a daily medical monitoring 
in a quarantine unit for at least 12 days 
post-challenge.  
  
Qualified medical and nursing staff in the 
quarantine unit will monitor for, and 
manage any symptoms 
 
Participants will be closely followed up 
while 
being 
in 
quarantine. 
Electrocardiogram will be performed, and 
cardiac enzymes will be tested at least 4 
days, 7 days and 11 days post-viral 
challenge 
Transient 
increase 
in 
alanine 
aminotransferase (ALT) or aspartate 
aminotransferase (AST) without clinical 
presentation, with a good prognosis upon 
improvement of infection.  
ALT and AST will be monitored. 
 
Transmission of 
RSV to 
participants’ 
close contacts 
RSV virus in nasal secretions can cause 
infection in close contacts. 
Virus is usually absent from the nose by 
the time participants are discharged from 
quarantine.  This will be confirmed by 
testing a nasal sample using PCR to 
determine participants’ suitability for 
departure. 
Passing the RSV Challenge Virus to 
others, including vulnerable people (see 
below 
for 
definition 
of 
vulnerable 
populations). 
To reduce the risk, participants will be 
asked to avoid, where possible, contact 
with vulnerable people for 14 days after 
they leave quarantine (Section 2.3.1.1). 


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Potential Risk 
of Clinical 
Significance 
Rationale for Risk 
Mitigation Strategy 
 
Passing the RSV Challenge Virus to 
study staff. 
Clinic staff in contact with participants in 
the quarantine unit will require to wear 
Personal Protective Equipment (PPE) to 
avoid the transmission of the RSV 
Challenge Virus to study staff and to 
prevent the risk of cross-contamination by 
a viral disease being brought up into the 
unit by staff. 
Risk of 
reactivation of 
herpes 
infection. 
If a participant ever had a herpes infection 
(e.g., cold sores, genital herpes or 
shingles), there is a small possibility that 
this infection could return after challenge. 
Participants will be instructed to inform 
the study staff if they currently have an 
active herpes infection or have had one 
during the 30 days before enrolment. 
Please consult the SmPC for Palivizumab (Synagis) for detailed information. 
2.3.1.1. 
Vulnerable persons 
For the purposes of possible contact, a vulnerable individual is a person who has close or household (i.e., 
share the same apartment or house) high-risk contacts 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 
(COPD))  
o 
Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac 
surgery, ischemic heart disease, known anatomic defects) 
o 
Contacts that required medical follow-up or 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)  
o 
Individuals who are receiving long-term aspirin therapy 
2.3.2. 
Benefit Assessment 
Healthy participants in clinical studies will not receive direct benefit from treatment during their participation. 
Participants may develop some temporary immunity to RSV through treatment with Palivizumab 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. 


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2.3.3. 
Overall Benefit: Risk Conclusion 
Taking into account the measures taken to minimise risk to participants in this study, the potential risks are 
justified by the anticipated benefits linked to the evaluation of the margin and variability of Palivizumab in a 
viral challenge model which will subsequently facilitate future assessment of biosimilars for prophylactic 
bioequivalence or non-inferiority to Palivizumab. 
 


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3. 
Objectives and Endpoints 
3.1. 
Part 1 Objectives and Endpoints 
Objectives 
Endpoints 
• 
To confirm the dose of Palivizumab to be 
given to participants in Part 2 
• 
Evaluation of PK levels after intravenous 
administration of Palivizumab 
• 
To assess safety of Palivizumab in healthy 
adults 
• 
Frequency and severity of Adverse Events 
(AEs) and serious AEs (SAEs) 
• 
Frequency and severity of Treatment 
Emergent Adverse Events (AEs) and 
serious AEs (SAEs) 
• 
Frequency and severity of drug related 
Treatment Emergent Adverse Events 
(AEs) and serious AEs (SAEs) 
 
3.2. 
Part 2 Objectives and Endpoints 
Objectives 
Endpoints 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by quantitative reverse 
transcriptase-polymerase 
chain 
reaction 
(qRT-PCR)]. 
The margin and variance will be estimated as 
follows: 
• 
Area under the viral load-time curve (VL-
AUC) 
of 
RSV-A 
Memphis 
37b 
as 
determined by qRT-PCR on nasal samples 
collected twice daily starting two days post-
viral challenge (Day +2) up to the end of 
quarantine. 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by cell culture (pfu/mL)]. 
The margin and variance will be estimated as 
follows: 
• 
Area under the viral load-time curve (VL-
AUC) 
of 
RSV-A 
Memphis 
37b 
as 
determined by cell culture on nasal 
samples collected twice daily starting two 
days post-viral challenge (Day +2) up to 
the end of quarantine. 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by total symptom score 
(TSS)]. 
The margin and variance will be estimated as 
follows: 
• 
Area under the total symptom score-time 
curve (TSS-AUC) collected daily in the 
participant symptom diary card starting 
one day post-viral challenge (Day +1) up to 
the end of quarantine. 


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Objectives 
Endpoints 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by total symptom score 
(TSS)]. 
The margin and variance will be estimated as 
follows: 
o 
Sum Total symptom score-time curve 
(TSS-Sum) collected daily in the 
participant symptom diary card starting 
one day post-viral challenge (Day +1) 
up to the end of quarantine. 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by total weight of nasal 
discharge produced and the total number of 
tissues used in each group]. 
The margin and variance will be estimated as 
follows: 
• 
Total weight of nasal discharge produced 
starting one day post-viral challenge (Day 
+1) up to the end of quarantine. 
• 
Total 
number 
of 
tissues 
used 
by 
participants starting one day post-viral 
challenge (Day +1) up to the end of 
quarantine. 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo [assessed by viral shedding of 
RSV-A Memphis 37b in nasal samples, in 
terms of incidence, duration, and peak]. 
The margin and variance will be estimated as 
follows: 
o 
Occurrence of at least two positive 
“quantifiable” qRT-PCR measurements in 
nasal samples at different timepoints 
reported within two or more consecutive 
days starting two days post-viral challenge 
(Day +2) up to the end of quarantine. 
o 
Occurrence of at least two positive 
“detectable” qRT-PCR measurements in 
nasal samples at different timepoints 
reported within two or more consecutive 
days starting two days post-viral challenge 
(Day +2) up to the end of quarantine. 
o 
Number 
of 
days 
with 
quantifiable 
qRT-PCR measurements in nasal samples 
starting two days post-viral challenge (Day 
+2) up to the end of quarantine. 
o 
Peak viral load of RSV-A Memphis 37b as 
defined by the maximum viral load 
determined by 
quantifiable qRT-PCR 
measurements in nasal samples starting 
two days post-viral challenge (Day +2) up 
to the end of quarantine. 
Similar endpoints may be evaluated based on 
quantitative viral culture assay. 
• 
To estimate the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
The margin and variance will be estimated as 
follows: 
• 
Incidence of symptomatic RSV infection, 
as defined by: 


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Objectives 
Endpoints 
Placebo [assessed by symptomatic infection 
in terms of incidence, duration, and peak]. 
o 
Incidence of infection, and 
o 
At least one grade 2 symptom 
from one or more respiratory 
categories from the participant 
symptom diary card. 
• 
Number of days with symptoms of grade 2 
or more, starting one day post-viral 
challenge (Day +1) up to the end of 
quarantine. 
• 
Peak symptom score defined by the 
maximum daily sum of Symptom score 
starting one day post-viral challenge (Day 
+1) up to the end of quarantine. 
• 
To assess safety of Palivizumab in the RSV 
human challenge model in healthy adults 
• 
Frequency and severity of Adverse Events 
(AEs) and serious AEs (SAEs) 
• 
Frequency and severity of Treatment 
Emergent Adverse Events (AEs) and 
serious AEs (SAEs) 
• 
Frequency and severity of drug related 
Treatment Emergent Adverse Events 
(AEs) and serious AEs (SAEs) 
• 
To 
assess 
the 
pharmacokinetics 
of 
Palivizumab in the RSV human challenge 
model in healthy adults 
• 
Palivizumab serum concentrations and 
serum PK parameters through study Day 
+28 
• 
Nasal concentrations and serum PK 
parameters through study Day +28 
• 
To assess the Anti-Palivizumab antibody 
(ADA) in the RSV human challenge model in 
healthy adults 
• 
Anti-Palivizumab antibody (ADA) through 
Day 28 
Tertiary/Exploratory 
• 
To explore lung function changes in relation 
to RSV infection 
• 
Assessments of spirometry, PEF, and FOT 
• 
To explore the Minimal Clinically Important 
Difference (MCID) in instrument change 
• 
The average amount of instrument-
assessed change for all participants who 
rate themselves as "a little better" or 
"somewhat better" 
• 
To explore the margin and variance of 
prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to 
inoculation in the RSV human challenge 
model in healthy adults compared to 
Placebo in relation to baseline immune 
status. 
The above endpoints may be explored in 
relation to the baseline status of volunteers and 
the response to treatment. Baseline status and 
response can be regarding, but not limited to: 
• 
Immune assays related to Palivizumab 
(e.g. IgG anti-F ELISA, PCA) 
• 
Baseline immunity to RSV 


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Objectives 
Endpoints 
• 
Response to Palivizumab treatment 
• 
To explore the host-pathogen relationship 
in the RSV human challenge model in 
healthy adults 
• 
Immune assays related to Palivizumab 
• 
RSV baseline immunity and immune 
responses to infection 
 


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4. 
Study Design 
4.1. 
Overall Design 
This is an exploratory study in healthy adult participants aged 18-55 years. The study is formed of two parts, 
Part 1 and Part 2. 
4.1.1. 
Part 1 design 
All participants in Part 1 will receive the following on Day 0: 
• 
Reference article product 
o 
 Palivizumab (Synagis™) Dose: 8mg/Kg  
If there are no safety concerns in Part 1, and PK analysis of Palivizumab treated participants confirm dose 
level 8mg/Kg to be appropriate, Part 2 will commence with the planned 8mg/Kg treatment dose. However, 
if PK analysis of Part 1 suggests that 8mg/kg may be insufficient dose to provide suitable efficacious 
coverage in Part 2, then Part 2 will proceed with a dose of 15mg/Kg. 
4.1.2. 
Part 2 design 
Participants in Part 2 will be pre-screened for susceptibility to RSV infection, i.e., have levels of RSV 
neutralising antibodies compatible with susceptibility to RSV infection (the cut-off is based on the average 
25th percentile of the past 12 months screening results). 
Participants in Part 2 will be randomised to receive the following on Day -1: 
• 
Reference article product 
o 
Palivizumab (Synagis™)   
o 
Dose: either 8mg/Kg or 15mg/Kg (as determined from Part 1) 
• 
Placebo product 
o 
Sodium Chloride 0.9% Solution (Normal Saline) matched to reference article product 
All participants in Part 2 will subsequently receive the following on Day 0: 
• 
RSV challenge virus 
o 
RSV-A Memphis 37b, total dose of approximately 4.5 log10 plaque forming unit, given 
intranasally  
The Study Schematic - showing participant progression through the study - is presented in Section 1.2; the 
Schedules of Activities (SoA) are presented in Section 1.3.  
 
4.1.3. 
Part 1 duration 
The total duration of study participation for a participant is up to approximately 52 days, with the following 
sequence and duration of study periods:  


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• 
Screening phase: from Day -28 to Day -1 pre-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 Unit for 1 days (from Day 0 to Day +1). 
Procedures will include: 
o 
Admission to Unit on Day 0 
o 
Study intervention I.V. dosing on Day 0 
o 
Post infusion monitoring and PK Day 0 and Day1 
o 
Participants will be discharged from the Unit on Day 1 (or may remain longer at the 
Principal Investigator’s discretion) 
• 
Outpatient phase: study assessments will be conducted at follow up clinic visits and telephone calls 
as follows: 
o 
Clinic visits: Day 2, Day 3, Day 7 (±1 day) and Day 12 
o 
Final safety follow-up by telephone: Day 18 (±3 days). 
4.1.4. 
Part 2 duration 
The total duration of study participation for a participant is up to approximately 122 days, with the following 
sequence and duration of study periods:  
• 
Screening phase: from Day -90 to Day -4 pre-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 -3 to Day +12). Procedures will include: 
o 
Pre-HVC:  
- 
Admission to Quarantine Unit on Day -3 
- 
Study intervention I.V. dosing on Day -1 
o 
HVC:  
- 
Challenge Virus inoculation on Day 0 (window 1 to 2 days 
post-treatment) 
o 
Post-HVC 
- 
Day 0 onwards and each day – study assessments will be 
conducted as per Schedule of Activities 
- 
Participants will be discharged from the Quarantine Unit on Day12 
(or may remain longer at the Principal Investigator’s discretion) 
• 
Outpatient phase: study assessments will be conducted 
o 
Clinic visit for PK sample on Day 20 (±2 days) 
o 
Final safety follow-up visit(s): Day 28 (±3 days)  
The study will be conducted by hVIVO which has extensive experience with RSV challenge studies. 
Numerous studies have been performed using experimental RSV infection in human participants. To date, 
in hVIVO’s studies, over 1220 healthy participants (18 to 55 years of age) have been successfully and 
safely inoculated with RSV-A Memphis 37b. These studies demonstrated that adults could be infected by 
nasal inoculation and that experimental infection was safe. This strain has been shown to cause symptoms 
and virus shedding that closely match natural infection. 


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Administration of study intervention and challenge with RSV-A Memphis 37b will take place in hVIVO’s 
specialised Clinical Units, either in the Quarantine Unit or Screening Clinic Units. 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. 
4.2. 
Scientific Rationale for Study Design 
This RSV Memphis 37b strain has been shown to cause symptoms and virus shedding that closely match 
natural infection in otherwise healthy adults. 
Administration of study intervention and challenge with RSV-A Memphis 37b will take place in hVIVO’s 
specialised Clinical Units, either in the Quarantine Unit or Screening Clinic Units. 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. 
4.3. 
Justification for Treatment Dose & Route of Administration 
The dose regimen of 8mg/kg in part 1 and 8mg/kg or 15mg/kg Palivizumab in part 2 of the study is supported 
by data from previous clinical trials and human experience referenced in this protocol, SmPC and the 
accompanied document “PALIVIZUMAB Summary of relevant clinical and non-clinical data to support the 
use of IMP in the clinical trial”. 
Studies performed in adult volunteers showed that the half-life of elimination of the drug was approximately 
17-20 days when administered either IV or IM and was safe through at least three-monthly injections (with 
the upper most test dose of 15 mg/kg). There were no safety signals in the adult volunteer studies. A single 
IV dose in adult volunteers at twice the recommended palivizumab prophylaxis dose has been shown to be 
well tolerated. 
Details of clinical studies to examine the comparability of the human safety, tolerability, immunogenicity and 
pharmacokinetics characteristics of the liquid and the lyophilized preparations of Synagis are listed in 
accompanied document “PALIVIZUMAB Summary of relevant clinical and non-clinical data to support the 
use of IMP in the clinical trial”.  
4.4. 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed all phases of the study 
including the last scheduled procedure shown in the SoA relevant for each part of the study or the last 
unscheduled visit as applicable. If a safety visit is required after the last scheduled visit, this will be at the 
PI’s discretion as a duty of care, e.g., repeat spirometry or laboratory tests. These discretionary follow-up 
visits will not be considered part of the trial data unless they represent follow-up and closure on an AE or 
serious adverse event (SAE) identified during the trial period.  
The end of the study is defined as the date of the last visit 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 of the following criteria apply: 
NO 
INCLUSION CRITERIA  
1 
An informed consent document signed and dated by the participant and the 
Investigator. 
2 
Aged between 18 and 55 years old on the day of signing the consent form. 
3 
In good health with no history, or current evidence, of clinically significant medical 
conditions, and no clinically significant test abnormalities that will interfere with 
participant safety, as defined by medical history, physical examination, (including vital 
signs), Electrocardiogram (ECG), and routine laboratory tests as determined by the 
Investigator. 
4 
A documented medical history prior to enrolment. 
5 
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. Post-menopausal females; defined as having a history of amenorrhea 
for >12 months with no alternative medical cause, and /or by FSH level 
>40mIU/mL, confirmed by laboratory. 
b. Documented status as being surgically sterile (e.g. tubal ligation, 
hysterectomy, bilateral salpingectomy and bilateral oophorectomy). 
6 
The following criteria apply to female and male participants: 
 
a) Female participants of childbearing potential must use one form of highly 
effective contraception. Hormonal methods must be in place from at least 2 
weeks prior to the first study visit. The contraception use must continue until 30 
days after the date of viral challenge/last dosing with IMP (whichever occurs last). 
Highly effective contraception is as described below: 
a. Established use of hormonal methods of contraception described below 
(for a minimum of 2 weeks prior to the first study visit). When hormonal 
methods of contraception are used, male partners are required to use a 
condom with a spermicide:  


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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 (IUD)  
c. Intrauterine hormone-releasing system (IUS)  
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 trial and the preferred and usual lifestyle of the 
participant. 
 
b) Male participants must agree to the contraceptive requirements below at entry to 
quarantine and continuing until 90 days after the date of Viral challenge / last 
dosing with the investigational medicinal product (IMP) (whichever occurs last): 
a. Use a condom with a spermicide to prevent pregnancy in a female 
partner or to prevent exposure of any partner (male and female) to the 
IMP. 
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 child bearing potential, that partner 
must use another form of contraception such as one of the highly 
effective methods mentioned above for female participants.  
d. True abstinence - sexual abstinence is considered a highly effective 
method only if defined as refraining from heterosexual intercourse during 
the entire period of risk associated with the study treatments. The 
reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the 
participant. 
c) In addition to the contraceptive requirements above, male participants must 
agree not to donate sperm following discharge from quarantine until 90 days after 
the date of Viral Challenge/last dosing with IMP (whichever occurs last). 


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5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
NO 
STANDARD EXCLUSION CRITERIA   
Medical History 
1 
History of, or currently active, symptoms or signs suggestive of upper or lower respiratory 
tract infection within 4 weeks prior to the first study visit. 
2 
a) Any history or evidence of any other clinically significant or currently active 
systemic comorbidities including psychiatric disorders (includes participants with 
a history of depression and/or anxiety). 
b) And/or other major disease that, in the opinion of the Investigator, may put the 
participant at undue risk, or interfere with a participant completing the study and 
necessary investigations.  
 
The following conditions apply: 
• 
Participants with clinically mild atopic eczema/atopic dermatitis and clinically mild 
psoriasis may be included at the Investigator's discretion (e.g., if small amounts 
of regular topical steroids are used, no eczema in cubital fossa; moderate to 
large amounts of daily dermal corticosteroids is an exclusion).  
• 
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. 
• 
Participants with a physician diagnosed underactive thyroid who have been 
controlled on treatment for at least 6 months with evidence of a normal thyroid 
function test (TFT) can be included at the discretion of the PI.   
• 
Any concurrent serious illness including history of malignancy that may interfere 
with the aims of the study or a participant completing the study. Basal cell 
carcinoma within 5 years of initial diagnosis or with evidence of recurrence is 
also an exclusion. 
• 
Participants with a history of psychiatric illness including depression and/or 
anxiety of any severity within the last 2 years can be included if the Patient Health 
Questionnaire (PHQ-9) and / or the Generalised Anxiety Disorder Questionnaire 
(GAD-7) is less than or equal to 4. Participants with a PHQ-9 or GAD-7 score of 
7 
For Part 2 of the study:  
Sero-suitable to the challenge virus, as defined in the study Analytical Plan. 


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NO 
STANDARD EXCLUSION CRITERIA   
between 5 and 9 may be included following consultation with a Senior Physician 
(Clinical Lead for Screening) who may advise further consultation with the PI. 
• 
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. 
• 
Participants with physician diagnosed mild Irritable Bowel Syndrome (IBS) not 
requiring regular treatment can be included at the discretion of the PI. 
3 
Participants who have smoked ≥ 10 pack years at any time [10 pack years is equivalent 
to one pack of 20 cigarettes a day for 10 years]). 
4 
A total body weight ≤ 50 kg and Body Mass Index (BMI) ≤18 kg/m2 and ≥30kg/m2. 
5 
Females who: 
a) Are breastfeeding, or 
b) Have been pregnant within 6 months prior to the study. 
6 
History of anaphylaxis-and/or a history of severe allergic reaction or significant 
intolerance to any food or drug, as assessed by the PI. 
7 
Venous access deemed inadequate for the phlebotomy and cannulation demands of the 
study. 
8 
a) For Part 2 of the study:Any significant abnormality altering the anatomy of the 
nose in a substantial way or nasopharynx that may interfere with the aims of the 
study and in particular any of the nasal assessments or viral challenge, (historical 
nasal polyps can be included, but large nasal polyps causing current and 
significant symptoms and/or requiring regular treatments in the last month will be 
excluded). 
b) Any clinically significant history of epistaxis (large nosebleeds) within the last 3 
months of the first study visit and/or history of being hospitalized due to epistaxis 
on any previous occasion.  
c) Any nasal or sinus surgery within 3 months of the first study visit. 
Prior or Concomitant Medications and Assessments 
9 
For Part 2 of the study: 
a) Evidence of vaccinations within the 4 weeks prior to the planned date of viral 
challenge/first dosing with IMP (whichever occurs first). 
b) Intention to receive any vaccination(s) before the last day of Follow-up. (NB. No 
travel restrictions will apply after the Day 28 (±3 days) Follow-up Visit). 
10 
Receipt of blood or blood products, or loss (including blood donations) of 470 mL or more 
of blood during the 3 months prior to the planned date of viral challenge/first dosing with 
IMP (whichever occurs first) or planned during the 3 months after the final visit. 
11 
a) Receipt of any investigational drug within 3 months prior to the planned date of 
viral challenge/first dosing with IMP (whichever occurs first).  


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NO 
STANDARD EXCLUSION CRITERIA   
b) Receipt of three or more investigational drugs within the previous 12 months 
prior to the planned date of viral challenge/first dosing with IMP (whichever 
occurs first). 
 
For Part 2 of the study: 
c) Prior inoculation with a virus from the same virus-family as the challenge virus.  
d) Prior participation in another human viral challenge study with a respiratory virus 
in the preceding 3 months, taken from the date of viral challenge in the previous 
study to the date of expected viral challenge in this study. 
12 
a) Confirmed positive test for drugs of abuse on first study visit. One repeat test 
allowed at PI discretion.  
b) 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 
For Part 2 of the study:  
A forced expiratory volume in 1 second (FEV1) < 80%. 
14 
Positive human immunodeficiency virus (HIV), active hepatitis A (HAV), B (HBV), or C 
(HCV) test. 
Other 
15 
Those employed or immediate relatives of those employed at hVIVO or the Sponsor. 
16 
Any other finding that, in the opinion of the Investigator, deems the participant unsuitable 
for the study. 
 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
No dietary restrictions are required before or after dose administration.  
5.3.2. 
Caffeine, Alcohol, and Tobacco 
Participants must abstain from ingesting caffeine- or xanthine-containing products (e.g., coffee, tea, cola 
drinks, and chocolate) for 48 hours prior and during quarantine and for 48 hours prior to all visits requiring 
spirometry. 
Participants must not consume alcohol for 72 hours prior and during quarantine and for 72 hours prior to 
any clinic visits. 
Participants must not smoke, use tobacco or any nicotine containing products for 72 hours prior to and 
during quarantine  Participants that are current smokers may be continued in the study if, in the opinion of 
the PI, cessation of smoking during quarantine will not lead to withdrawal symptoms which could interfere 
with the accurate recording on the Symptoms Diary Card. 


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5.3.3. 
Activity 
Participants will abstain from strenuous exercise for 48 hours prior and during quarantine and for 48 hours 
prior to each clinic visit (unless it is within the usual activity of the participant).  
5.4. 
Screen Failure 
Screen failures are defined as participants who sign the study specific Informed Consent Form (ICF) but 
are not subsequently randomised to receive the study Intervention.  
For individuals who do not meet the criteria for participation in this study (screen failure), the Investigator 
will decide whether the participant should be permanently excluded from the study or invited back for repeat 
assessments (i.e. repeat clinical laboratory test) if the initial screening assessments are still within the 
allowed screening windows (-28 to -1 days for Part 1 and -56 to -4 days for Part 2) or rescreening for a later 
quarantine, as appropriate. 
 
 


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6. 
Study Intervention 
Study interventions administered to participants are described in Table 2. 
6.1. 
Study Intervention(s) Administered 
Table 2 - Study Interventions 
Intervention 
Name 
Palivizumab 
Placebo 
RSV-A Memphis 37b virus 
Type  
Biologic 
Other 
Virus 
Dose 
Formulation 
Liquid solution (50mg or 
100mg) in sterile water 
for injection to give a 
final concentration of 
20mg/mL 
Sodium Chloride 0.9% 
Solution (Normal Saline) 
 
Cryovial, Liquid 
Unit Dose 
Strength(s) 
• 
8 mg/kg for Part 1 
• 
8mg/kg or 15 mg/kg 
for Part 2 
Not applicable 
The inoculum virus titre is 
determined in an infectivity 
(plaque) assay, the titre is 
reported in plaque forming 
units per mL (PFU/mL). The 
challenge dose is 
approximately 4.5log10 PFU.  
Dosage 
Level(s) 
• 
A single dose of 
8mg/Kg, or  
• 
A single dose of 
15mg/Kg 
• 
A single dose of 
0mg/Kg 
A single dose of virus will be 
delivered. 
Dose volume delivery 
method is provided in the 
Analytical Plan 
 
Route of 
Administration 
Infusion IV 
Infusion IV 
Intranasal 
Use 
Reference article 
Placebo control 
Infectious Challenge agent  
IMP and NIMP 
IMP  
IMP (Placebo)  
NIMP Challenge virus 
Sourcing 
Sponsor 
Provided centrally by 
hVIVO 
Provided centrally by hVIVO  
Packaging and 
Labelling 
Study intervention will 
be provided as 
Study intervention will 
be provided as 
RSV Challenge Inoculum will 
be provided in vials. The 


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individual doses in 
single use sterile 
Latex/DEHP Free 
syringes, prepared, 
labelled and QP 
released by 
Hammersmith 
Medicines Research 
(HMR) Pharmacy 
(London) holding MIA 
(IMP) licence. 
individual doses in 
single use sterile 
Latex/DEHP Free 
syringes, prepared, 
labelled and QP 
released by 
Hammersmith 
Medicines Research 
(HMR) Pharmacy 
(London) holding MIA 
(IMP) licence. 
details of the virus challenge 
agent packaging and 
labelling will be provided in 
the Analytical Plan 
Current/Former 
Name(s) or 
Alias(es) 
Synagis ™ 
n/a 
n/a 
All supplies indicated in Table 2 will be provided per the "Sourcing" row depending upon local country 
operational requirements. If local sourcing, every attempt should be made to source these supplies from a 
single lot/batch number where possible (e.g. not applicable in the case where multiple lots or batches may 
be required due to the length of the study).  
Refer to Section 6.2 and the pharmacy manual for details regarding administration of the study intervention. 
6.2. 
Preparation/Handling/Storage/Accountability 
6.2.1. 
Dose Preparation 
Storage and manufacture of the Investigational product will be based on SmPC. Palivizumab and placebo 
will be prepared by an unblinded pharmacist for each individual participant. Dose preparation procedures 
will be described in the pharmacy manual and as described in Hicks et al. (Hicks, Chemaly, and 
Kontoyiannis 2003).  
6.2.2. 
Handling, Storage, and Accountability 
Interventional Product / Placebo: 
Bulk supplied of the Investigational product will be stored at HMR Pharmacy. Individual ready-to-dispense 
Interventional product / Placebo doses will be prepared by unblinded pharmacist, Qualified Person (QP) 
released and delivered to hVIVO prior to administration of the treatment to the participant.  
HMR Pharmacy and hVIVO will maintain drug accountability as detailed in the Pharmacy Manual.  
The Investigator will ensure that all supplies are received by a responsible person, all deliveries and returns 
are documented and signed for, and the condition of the Interventional product / Placebo is monitored. 
Accurate records will be kept of when and how much Interventional product / Placebo is dispensed and 
used in the study. Any reasons for departure from the protocol dispensing regimen must 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 Interventional product / Placebo. 


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Challenge Virus 
The RSV-A Memphis 37b challenge virus was produced via a nasal aspirate collected from a paediatric 
patient infected with RSV. The Challenge Virus stock, RSV-A Memphis 37b, was manufactured under 
current good manufacturing practices (cGMP). The Challenge Virus 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 virus is stored in a secure -80oC freezer (normal temperature range -60°C to -90°C).  
Challenge Virus inoculum will be prepared according to the hVIVO Analytical Plan (AP) and administered 
in accordance with hVIVO's standard operating procedures (SOPs). Each participant will be allocated a 
unique vial containing the Challenge Virus and will receive the inoculum intranasally.  
The time from the Challenge Virus inoculum thawing to inoculation should be no longer than 2 hours. All 
administrations will be made by a member of the clinical team and witnessed by a second member of the 
team. The exact time of inoculation will be recorded in the administration log. Accurate records will be kept 
of when and how much study inoculum is prepared and used. The oversight process will be signed off prior 
to administration of the Challenge Virus. Any non-compliance or problems with the inoculation will be 
recorded in the participant’s source notes and reported to the PI. 
Following inoculation, participants will be closely observed specifically for potential allergic reactions and 
any AEs for the following 24 hours. Post inoculation participants will lie flat for 10 min then sit up with nose 
pegs on for 20 min. Participants will continue to be monitored throughout the clinical phase of the study. 
All study interventions: 
1. The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are reported and 
resolved before use of the study intervention 
2. Only participants enrolled in the study may receive study intervention and only authorised site staff 
may supply or administer study intervention. All study intervention must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labelled storage conditions with access limited to the Investigator and authorised site staff 
3. The 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) 
4. Disposal of used and unused Challenge Virus inoculum vials will be in accordance with hVIVO’s 
SOPs 
5. Unless specifically instructed by Sponsor, the Investigator will not destroy any partly used or 
unused IMP supply. On written authorisation from the Sponsor, the Investigator will send unused 
and partly used IMP supplies and any empty containers for destruction to the address provided at 
the time of authorisation. Alternatively, the destruction of unused and partly used drug supplies and 
any empty containers may be facilitated by the Investigator using a partner service, according to 
local procedures, and a destruction certificate will be provided.  


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6.3. 
Randomisation and Blinding 
hVIVO assigns a unique 6 digits number to each participant in the hVIVO database. This number will be 
used to identify a participant up to the point of randomisation, on source documents, on all study 
correspondence and in the study database. In Part 2 of the study, a separate randomisation number will be 
allocated to the participants at randomisation and will be used for allocation of study intervention 
(Palivizumab or Placebo). 
In Part 2, a computer-generated randomisation schedule will be generated using SAS. Once assigned, that 
randomisation number shall not be reassigned. 
Randomisation numbers will follow a 3-digit format e.g., [001]. A copy of the randomisation code list will be 
sent to the unblinded pharmacist preparing the study intervention, so that study intervention/placebo can 
be prepared for each participant as appropriate. The randomisation number encodes the participant’s 
assignment to receive Palivizumab or Placebo in a 1:1 ratio.  
Each participant will be dispensed blinded study intervention, labelled with his/her unique randomisation 
number, throughout the study. With the exception of the unblinded  pharmacist, the unblinded statistician 
preparing the randomisation code list, the unblinded Clinical Research Associate (CRA) and the Quality 
Assurance (QA) auditors where necessary, the Investigator and all other clinical and non-clinical staff, 
(including the Study Statistician, data management staff), and the participants will remain blinded to the 
treatment allocation until after the database has been locked and approval for study unblinding has been 
given. 
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. 
Participants who are replaced as per Section 7.4 Participant Replacement Strategy  will be replaced and 
assigned a new, unique randomisation number equaling the randomisation number of the replaced 
participant, plus 100. This will ensure that the replacement participant receives the same allocated, blinded 
treatment as the participant who is being replaced. 
 An individual access to a secured website will be provided to the Investigator. The website, compliant with 
21CFR part 11 guidelines, will be used in the event that unblinding is required. In case of an emergency, 
the Investigator has the sole responsibility for determining if unblinding of a participant’s intervention 
assignment is warranted. 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, they will have to 
indicate on the website the reason for unblinding. The person who carried out the unblinding and the date 
and time of code breaking will be automatically recorded. After confirmation of the code break, the treatment 
allocation will appear on the screen. A notification with the treatment allocation will also be provided by 
email. A notification, without the treatment allocation, will be provided to the study team. Furthermore, the 
Sponsor must be notified within 24 hours after breaking the blind. Once the study is complete, the unblinded 
database will be provided to the Sponsor. 
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 as long as doing so will not 
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The study intervention must be discontinued after unblinding, but the participant will be followed up until 
resolution of any AEs. 
6.4. 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention and challenge virus directly 
from the Investigator or designee, under medical supervision.  The date and time of each dose administered 
in the clinic will be recorded in the source documents and recorded in the case report form (CRF).  The 
dose of study intervention and study participant identification will be confirmed at the time of dosing by a 
member of the study site staff other than the person administering the study intervention.  
Any non-compliance 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 from the time the participant signing the study specific 
informed consent, up to final study contact Day 28 (±3 days) will be recorded in the source data. Any 
medication (including over-the-counter or prescription medicines, vitamins, and/or herbal supplements) or 
other specific categories of interest) 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 Investigator and must notify the site as soon as possible if they are prescribed any medication. All 
medications must be stopped prior to the planned date of dosing with IMP/viral challenge (whichever occurs 
first) unless in the opinion of the Investigator and/or Sponsor’s Medical Expert (SME), the medication will 
not interfere with the study procedures or compromise participant safety. 
Medications prohibited throughout the study are shown in Table 3. 
Table 3 - Prohibited Medications 
Prohibited medication 
Washout 
Systemic (oral and parenteral) antiviral drugs. 
 4 weeks prior to first study visit. 
Use or anticipated use during conduct of the study 
of concomitant medications (prescription and non-
prescription), including vitamins or herbal and 
dietary supplements within the specified windows, 
unless in the opinion of the Investigator the 
medication will not interfere with the study 
procedures or compromise participant safety. 
7 days prior to the planned date of viral challenge: 
•Herbal supplements 
•Any medication or product (prescription or over 
the counter) for symptoms of nasal congestion  
•Short and long-acting antihistamines. 
 
Within 21 days prior to the planned date of viral 
challenge: 
•Chronically used medications, vitamins or dietary 
supplements, including any medication known to 


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Prohibited medication 
Washout 
be moderate/potent inducers or inhibitors of 
CYP450 enzyme. 
Any concomitant medication required for the participant’s welfare may be given by the Investigator. 
However, it is the responsibility of the Investigator to ensure that details regarding the medication and the 
reason for its use are recorded appropriately in the source notes to permit their transfer to the clinical 
database.  
The use of paracetamol and/or other allowed medications is permissible within 7 days before the date of 
first dosing with IMP/viral challenge (whichever occurs first) at PI discretion. During the study periods, the 
Investigator may permit a limited amount of paracetamol (no more than 4 g per day i.e. maximum daily 
dose) or topical medication, as clinically required for the treatment of headache or any other pain. Other 
medication to treat AEs may be prescribed if required. 
Medications which are permitted throughout the study are shown in Table 4 below: 
Table 4 – Permitted Medication 
Permitted medication 
Time period 
Paracetamol 
Maximum 4g daily throughout the study duration 
at PI discretion. 
Oral contraceptives 
Allowed at any time during the study. 
Prescription and non-prescription medications, including vitamins or herbal and dietary supplements, 
not listed in prohibited medications are subject to approval by the PI. 
 
6.6. 
Dose Modification  
Modification to the Palivizumab dose from 8mg/kg to 15mg/kg may be required for Part 2 of the study. 
Dose selection for Part 2 will be made by the Sponsor based on a review of the PK data obtained from at 
least  6 participants dosed with 8mg/kg of Palivizumab in Part 1; and a confirmation of no safety or 
tolerability concerns from the Safety Data Review Meeting as described in Section 10.1.5. 
The PK assessment up to and including Day 12 exposure will be used as a decision information for the 
dose for Part 2. PK exposure data from at least 5 out of 6 participants is required for dose decision making 
with a projected exposure of ≥40 µg/mL on Day 12. 


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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 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 (EWV) should be carried out, and if clinically indicated, the 
participant should be invited back for a final follow up visit. If a participant withdraws from the study during 
the quarantine phase, an EWV will be completed on the day where possible prior to the participant leaving 
the unit. It is likely that some of the assessments required as part of the EWV will already have been 
performed for the study day as per SOA, in this case the completed assessments will not be repeated on 
the same day unless clinically indicated. 
The sponsor should be notified of all study withdrawals in a timely manner, and in cases where the 
withdrawal is due to a medical reason the participant would be referred to his/her GP.  
Participants will be counselled that early withdrawal from the viral challenge phase of the study is strongly 
discouraged, as it may pose a risk both to the participant and his/her contacts. In the event of a participant 
insisting on early withdrawal during the challenge isolation period, the participant will be encouraged to stay 
and would be advised of the potential risks of carrying RSV infection into the community, and to vulnerable 
groups in particular as described in Section 2.3.1 
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 Investigator must document this in the site study records. 
7.2. 
Participant Discontinuation 
Participants will be withdrawn from study intervention for the reasons listed below. These participants must 
not receive any additional intervention but should continue to be followed for safety. Additional unscheduled 
visits may be performed for safety reasons.  
• 
Non-compliance with the study requirements and restrictions. 
• 
Clinically significant abnormal laboratory findings, which in the opinion of the Investigator(s) 
and/or Sponsor, precludes further participation in the study. 
• 
Development of inter-current illness which, in the opinion of the Investigator would compromise 
the health of the participant or the study objectives. 
• 
The 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 Investigator(s) or Sponsor for safety, behavioural, 
or administrative reasons. 
• 
The wish of the participant. 


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• 
Any intervention related SAEs.  
• 
Anaphylactic reaction following dosing. 
• 
The participant becomes pregnant (if pregnancy is specified as an exclusion criterion). 
  
Participants who are withdrawn from the study, will be requested to attend an Early Withdrawal Visit, with 
assessments as detailed in the SoA. 
7.2.1. 
Temporary Discontinuation/Temporary Delay in Enrolment 
At the first study visit, if a participant is found to be ineligible due to transient circumstances (such as acute 
disease and/or fever), dosing with Palivizumab will be postponed until transient circumstances have been 
resolved and the participant will be re-invited to a later quarantine group within the allowed time window. 
For participant rescreening refer to Section 5.4  
7.3. 
Lost to Follow up 
A participant will be considered lost to follow-up if he or 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 clinic 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 or not the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow up, the 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.  
7.4. 
Participant Replacement Strategy 
Participants who withdraw or are discontinued from the study may be replaced in order to achieve the 
planned evaluable number of participants as follows, if deemed appropriate by the PI and with the approval 
of the Sponsor: 
• 
In Part 1, withdrawals or early discontinuation prior to the completion of all scheduled clinic visits up to 
and including Day 12 Visit may be replaced.  
• 
In Part 2, participants who have been dosed but not inoculated may be replaced. The replacement 
participant will be assigned to the same group as the original (discontinued) participant.  
Participants who have been dosed and inoculated but did not complete the study may be replaced. 


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7.5. 
Stopping Rules 
The PI and the SME will perform safety reviews on available clinical and virology data as appropriate during 
the quarantine period.  
Three clinical scenarios relating to the incidence of SAEs/SUSAR during the study and the procedures that 
should be performed in each case are presented in Table 5. 
Table 5 – Study Stopping Rules 
Status 
Criterion 
Procedure 
 
1 
A report has been received of one (or 
more) SUSAR in anyone (or more) 
participant(s). 
If such a status occurs at any point during the 
study, then further administration of 
Palivizumab will not take place. The PI and 
the SME will review the data and make 
decisions on whether it is appropriate to 
recommence dosing (via a substantial 
amendment, if indicated) or terminate the 
study.  
2 
No SUSAR 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, but which 
collectively represent a concern for 
safety. 
 
If such a status occurs at any point during the 
study, then further administration of IMP will 
not take place. The PI and the SME will 
review the data and make a decision on 
whether it is appropriate to recommence 
dosing (via a substantial amendment, if 
indicated) or terminate the study.  
3 
Unexpected virus-related SAE or 
Unexpected virus-related AEs of clinical 
concern have been reported following 
Human Viral Challenge. 
*Expectedness will be assessed by 
referring to the challenge virus dossier 
 
If such a status occurs at any point during the 
study, then the PI and the SME will review the 
data and make a decision based on 
expectedness* of the viral event.  
If the event is unexpected, further 
administration of the virus will not take place. 
The PI and the SME will review the data and 
make a decision on whether it is appropriate 
to recommence inoculation (via a substantial 
amendment, if indicated) or terminate the 
study.  
In any event, participant follow-up should continue until resolution or stabilisation of AEs and final follow-
up on Day 28 (± 3 days). 
 
 


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8. 
Study Assessments and Procedures  
Study procedures and their timing are summarised in the SoA. Protocol waivers or exemptions are not 
allowed. Adherence to the study design requirements, including those specified in the SoA, 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 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 value obtained nearest to dosing will be used as the baseline measure for 
assessments, unless stated otherwise.  
Procedures conducted as part of the hVIVO Generic Screening process and obtained before signing of the 
study specific Informed Consent Form (ICF) may be utilised for screening or baseline purposes provided 
the procedures met the protocol-specified criteria and were performed within the time frame defined in the 
SoA.  
Where applicable, unless otherwise stated, normal ranges will be identified in the Investigator Trial Master 
File (TMF).  
8.1. 
Medical and Medication History 
Medical and medication histories including any allergies will be recorded at screening, including, but not 
limited to, detailed histories on allergies [e.g. rhinitis, dermatitis, food, aspirin/non-steroidal anti-
inflammatory drugs (NSAIDs) and asthma]. 
8.2. 
Demographics 
Demographic data will be recorded at screening. 
8.3. 
Height, Weight and Body Mass Index (BMI) 
Height and weight measurements will be recorded in compliance with hVIVO’s standard procedures. 
BMI will be calculated as: BMI (kg/m2) =  
Weight (kg) 
 
 
 
 
 
 
 
 
 
 
 
Height (m)2 
8.4. 
Complete Physical Examination 
A complete physical examination to include a full systemic assessment. 
8.5. 
Direct Physical Examination 
Directed physical examinations will be conducted as deemed appropriate by the Investigator and will 
include examination of the 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] 
and on chest auscultation [wheezing or rhonchi, crepitations] will be performed. Physician-reported 


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assessments of viral challenge related illness will be graded in accordance with their intensity and 
documented in the source data. 
Following viral challenge, URT and LRT symptoms (as described above) will be expected and presumed 
to represent virus infection consequent to viral challenge and will not be additionally captured as AEs unless 
they meet the definition of an AE, and are deemed to be clinically significant (in the opinion of the 
Investigator) to be classed as AEs. 
Following viral challenge all unexpected (in the opinion of the Investigator) directed physical examination 
findings will be captured as AEs, along with all other occurrences that meet the criteria for an AE. 
8.6. 
Vital Signs 
Vital signs assessments will be recorded as follows: 
• 
Heart rate (HR) will be recorded in beats per minute. 
• 
Respiratory rate (RR): respirations will be counted and recorded as breaths per minute. 
• 
BP: systolic BP and diastolic BP will be measured in millimeters of mercury (mmHg); 
measurements will be made supine. 
• 
Peripheral arterial oxygen saturation (SpO2%) will be assessed using pulse oximetry. 
In the event of a participant having an unexpected abnormal or out of normal range result, the assessment 
may be repeated after at least 2 minutes to exclude a technical fault and confirm the original reading. The 
assessment may then be repeated at the PI’s discretion and in accordance with hVIVO’s SOPs. 
Study specific normal ranges are provided in Appendix 4. If a result is out of the normal range and meets 
the criteria for an AE, the severity of the AE will be guided by the Division of Microbiology and Infectious 
Diseases (DMID) Adult Toxicity Table November 2007. 
Deterioration in a vital sign (compared to baseline) should only be reported as an AE if the deterioration 
fulfils the criteria for an AE. If deterioration in a vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated vital sign will be considered as additional 
information 
8.7. 
Tympanic Temperature 
The study specific normal range for tympanic temperature is detailed in Appendix 4.The severity of out of 
normal range values will be assigned using the DMID toxicity scale as a guide. 
Temperature may be more frequently monitored in quarantine if appropriate. 
Following viral challenge, pyrexia will be expected and presumed to represent virus infection consequent 
to viral challenge and will not be additionally captured as an AE unless it meets the definition of an AE, and 
is deemed to be clinically significant (in the opinion of the Investigator) to be classed as an AE. 
Following viral challenge all unexpected (in the opinion of the Investigator) pyrexia will be captured as an 
AE, along with all other occurrences that meet the criteria for an AE. 
Febrile illness (FI) is defined as any occurrence of temperature ≥ 37.9 oC 


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8.8. 
Electrocardiogram 
Study specific normal ranges are provided in Appendix 4. 
Twelve-lead ECGs will be obtained to evaluate the electrical activity of the heart. ECGs will be read on site 
by an appropriately qualified Investigator. Wherever possible the same Investigator will review subsequent 
ECGs from the same participant for the assessment of any change from baseline. 
Any changes from baseline during the study will be assessed for their clinical significance. Clinically 
significant changes will be reported as AEs. The PI or delegate will assess non-clinically significant changes 
to determine whether they should be recorded. 
8.9. 
Spirometry 
Spirometry will be performed according to hVIVO’s procedures. Height at screening will be used as the 
baseline measurement for all spirometry assessments. 
Spirometry should meet the ATS/ERS guidelines criteria(Miller et al. 2005). For FEV1 and FVC, the highest 
value from a minimum of 3 technically satisfactory attempts will be considered. For FEV1 and FVC the 
highest and the second highest value should not exceed more than 150 mL or 5% (whichever is greater). 
If the difference is larger, up to 8 technically acceptable measurements will be made with repeatability 
assessed after each additional attempt. If after 8 technically acceptable attempts the difference remains 
greater than 150 mL or 5% (whichever is greater) the highest values will be reported, and an operator 
comment will be made to the source data. FEV1 and FVC will be assessed and reported as the highest 
values regardless of curve. 
Predicted values will be calculated according to the formula of the European Coal and Steel Community 
(ECCS).  
Spirometry may be repeated at any time in the event of respiratory signs or symptoms (repeated coughing, 
bradypnoea, tachypnoea, rales and rhonchi) or respiratory difficulties. 
8.10. 
Peak expiratory flow (PEF) 
All participants will self-test their PEF using portable, hand-held Peak Flow Meters (PFMs). The PEF self-
test must be observed by quarantine staff when recorded during quarantine to ensure compliance and 
technique. 
8.11. 
Forced oscillation technique (FOT) 
Forced oscillation technique (FOT) is a versatile, non-invasive assessment of respiratory mechanics based 
on tidal breathing analysis. Airwaves of multiple frequencies (typically 5 to 30 Hz) are applied to the 
respiratory tract during relaxed breathing. The test involves participants breathing through a breathing 
handle in a seated position, wearing a nose-clip, with cheeks supported. Breathing is recorded for 
approximately 1 minute. During this time the instantaneous pressure-flow relationship, measured at the 
mouth at varying frequencies, are analysed in order to measure Respiratory Impedance (Zrs). Zrs is made 
up of an in-phase, termed resistance (Rrs) and out-phase, referred to as reactance (Xrs). Resistance at 
5Hz penetrates the periphery of the lung, providing information of the entire respiratory tract. Resistance > 
20Hz represents respiratory resistance of the proximal airways. Distal lung resistance can be calculated by 


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subtracting total airway resistance from proximal airway resistance (R5-R20). Xrs comprises of 2 elements 
that are dependent upon frequency. At higher frequencies (>20 Hz) Xrs is positive in sign and represents 
the inertive force needed to move air in the conducting airways. At low frequencies of 5 Hz (X5) is negative 
in sign and indicates the capacitance of the lung periphery. A minimum of 3 tests will be performed and the 
mean values reported. Testing will take approximately 5 minutes  
FOT is an exploratory measure of small airway lung function and may be measured on a subset of 
volunteers. 
8.12. 
Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorder 
(GAD-7) Questionnaire 
PHQ-9 and GAD-7 questionnaire will be used at the discretion of the investigator at screening and/or 
quarantine admission to assess participants’ eligibility in terms of ability to tolerate isolation in the 
quarantine unit. 
8.13. 
Participant Symptom Diary Card 
Participants will report and assess the severity of any challenge virus-related signs and symptoms three 
times/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 4: Symptoms at rest 
o 
Runny nose 
o 
Stuffy nose 
o 
Sneezing 
o 
Sore throat 
o 
Earache 
o 
Malaise/tiredness 
o 
Headache 
o 
Muscle and/or joint ache 
o 
Chilliness/Feverishness 
o 
Cough 
o 
Chest tightness 
o 
Shortness of breath 
o 
Wheeze 
Additional to the categorical symptom diary card, a Visual Analogue Scale dairy card using a 100mm scale, 
with the same symptoms, will be completed by the participants. 


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The Investigator will assess and review challenge virus-related symptoms that are recorded on the diary 
card following each scheduled completion. 
Following viral challenge all unexpected (in the opinion of the Investigator) post viral challenge symptoms 
will be captured as AEs, along with all other occurrences that meet the criteria for an AE. 
Participant cold perception questions 
Two additional cold-related questions will be answered by the participant each morning. The first question 
asks whether the participant’s perception of whether they have a cold or not, the second asks the 
participant’s perception of improvement/worsening of the cold. 
1. Do you have a cold: Yes/No 
If the participant selects Yes to having a cold, then the second 7-point Likert scale “global change since 
yesterday” question is completed by the participant, as below. 
2. Compared to yesterday, I feel that my cold is: 
• 
Very much better 
• 
Somewhat better 
• 
A little better 
• 
The same 
• 
A little worse 
• 
Somewhat worse 
• 
Very much worse 
8.14. 
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 bag (for that participant only). 
A daily 24-hour collection will take place throughout the quarantine period. Distribution of paper tissues and 
bags will start on Day -2, with the first collection on Day -1. Thereafter distribution and collection of tissues 
will occur at 08:00h (± 1 hour). Tissues will be handed out daily and collection will occur until the discharge 
from quarantine. 
In the event of a participant staying in quarantine beyond the planned day of discharge, the 24-hour 
distribution and collection of tissues and bags will continue until the participant is finally discharged from 
quarantine. 
24-hour paper tissue collections will be analysed to determine the following over the quarantine period: 
• 
24-hour nasal discharge weight. 
• 
The number of paper tissue used for nasal discharge over 24-hour period. 
8.15. 
Alcohol Breath Testing 
Breath alcohol testing will be conducted to determine compliance with the study alcohol restrictions. 
Additional tests may be conducted for assessing eligibility at the discretion of the investigator. Results will 
be recorded in the source documents. 


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8.16. 
Urinalysis 
Clinical urine safety analysis will be undertaken using commercially available urine test strips that provide 
an instant result that will be documented in the source data. 
Urinalysis will be performed to evaluate the parameters described in Appendix 2. 
If the dipstick yields abnormal results, a urine sample may be sent for microscopy, culture and sensitivity 
(MCS), at the Investigator’s discretion. MCS will include but is not limited to RBC, WBC, epithelial cells, 
crystals, casts, and bacteria. 
Urine safety analysis values will be evaluated by the Investigator for clinical relevance. Those deemed to 
be clinically significant will be reported as AEs. 
8.17. 
Urine Drugs of Abuse and Nicotine Test 
Urinalysis will be performed for drugs of abuse and cotinine using commercially available kits that provide 
an instant result, which will be documented in the source data. 
Drugs of abuse screen will include (but is not limited to) amphetamines, barbiturates, cocaine, opiates, 
cannabinoids and benzodiazepines. 
 
8.18. 
Pregnancy Test 
Female participants of childbearing potential are to have a urine pregnancy test at screening. Participants 
will only be enrolled if the pregnancy test is negative. 
Note: Pregnancy test must be performed even if the participant is menstruating at the time of the study visit. 
Blood samples will be tested for serum FSH in post-menopausal women only. 
8.19. 
Blood Samples 
A maximum volume of 470 mL of blood may be taken from each participant from screening through to the 
final study contact. If additional samples are required in excess of this amount, e.g., to monitor 
abnormalities, these will be collected at the discretion of the Investigator. 
8.19.1. 
Safety Blood Samples 
Appendix 2 describes the safety blood tests that will be performed including, but not limited to, haematology, 
biochemistry and cardiac enzymes. Additional safety assessments (e.g. coagulation) will be conducted at 
the discretion of the PI/Investigator, as required 
8.19.2. 
Challenge Virus Serology Samples 
Participants in Part 2 must be sero-suitable to take part in the study; i.e. he/she must have no or low pre-
existing serum levels of antibodies specific to the Challenge Virus. This antibody titre cut-off for sero-
suitability will be described in the AP. 


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Serum levels of pre-existing RSV specific antibodies to the Challenge Virus will be determined as described 
in the AP. 
8.19.3. 
Pharmacokinetic Blood Samples 
Blood (plasma) samples for the evaluation of PK parameters of Palivizumab will be collected as outlined in   
the PK Sampling Schedules below: 
Part 1 PK Sampling Schedule: 
Before the start of infusion; at end of infusion,15min, and 0.5, 1, 4, 8, and 12 h after infusion; and at 1, 2, 
3, 7, 12 days after infusion. 
The allowable time windows for the sampling are as follows: 
▪ 
± 5 minutes from the scheduled time for time points ≤ 1 hour from infusion; 
▪ 
± 15 minutes from the scheduled time for time points > 1 hour from infusion, with NOTE below: 
o 
1 day timepoint: +/- 1 hour window 
o 
2 days timepoint: +/- 2 hours window 
o 
3 days timepoint: +/- 2 hours window 
o 
7 days timepoint: +/- 1 day window 
o 
12 days timepoint: +/- 3 hours window 
▪ 
There is no time window requirement for the pre-infusion sample. The pre-infusion PK sample must 
be taken on the same day prior to infusion. 
Part 2 PK Sampling Schedule: 
Before the start of infusion; at end of infusion, 15mins and 0.5, 1, 4, 8, and 12 h after infusion; and at 1, 2, 
3, 7, 13, 21 and 29 days after infusion. 
The allowable time windows for the sampling are as follows: 
▪ 
± 5 minutes from the scheduled time for time points ≤ 1 hour from infusion; 
▪ 
± 15 minutes from the scheduled time for time points > 1 hour from infusion, with NOTE below: 
o 
1 day timepoint: +/- 1 hour window 
o 
2 days timepoint: +/- 2 hours window 
o 
3 days timepoint: +/- 2 hours window 
o 
7 days timepoint: +/- 2 hours window 
o 
13 days timepoint: +/- 2 hours window 
o 
21 days timepoint: +/- 2 days window 
o 
29 days timepoint: +/- 3 days window (and with at least 5 days after the previous PK 
sampling timepoint) 


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▪ 
There is no time window requirement for the pre-infusion sample. The pre-infusion PK sample must 
be taken on the same day prior to infusion. 
Blood samples will be transported, processed and stored in accordance with the AP, and analysed using a 
bioanalytical assay. 
8.19.4. 
Anti-drug Antibody Blood Samples 
Blood (plasma) samples for the evaluation of anti-Palivizumab antibodies will be collected as outlined in the 
ADA Sampling Schedules bellow: 
Part 1 ADA Sampling Schedule: 
Before the infusion, and at 7 and 12 days after infusion. 
The allowable time windows for the sampling are as follows: 
▪ 
 7 days timepoint: +/- 1 day window 
▪ 
12 days timepoint: +/- 3 hours window 
Part 2 ADA Sampling Schedule: 
Before the infusion, and at 7, 13 and 29 days after infusion. The allowable time windows for the sampling 
are as follows: 
▪ 
 7 days timepoint: +/- 2 hours window 
▪ 
13 days timepoint: +/- 2 hours window 
▪ 
29 days timepoint; +/- 3 days window 
There is no time window requirement for the pre-infusion sample.  
Blood samples will be transported, processed and stored in accordance with the AP, and analysed using a 
bioanalytical assay. 
8.19.5. 
Blood Samples for Exploratory Research 
Remaining aliquots of blood may be stored and used for exploratory immunology analysis related to viral 
infection and the response to treatment. These analyses may include but are not limited to: 
• 
immunology assays related to baseline immunity and response to infection with RSV  
• 
Immune assays related to Palivizumab (e.g. IgG anti-F ELISA, PCA) 
8.20. 
Upper Respiratory Samples 
The following exploratory upper respiratory sampling procedures will be performed during the study: 
• 
Nasopharyngeal FLOQ swab or nasal wash, as appropriate 
8.20.1. 
Nasal samples 
Nasopharyngeal FLoQ swabs or nasal wash, as appropriate, will be performed to collect samples of 
nasopharyngeal cells and epithelial lining fluid for: 


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• 
Respiratory Pathogen Screen 
• 
RSV discharge test 
• 
Viral loads 
• 
Exploratory purposes 
Tolerance of the procedure may be determined at the screening visit. 
8.20.1.1. Viral Load 
Viral load will be determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) 
and/or a viral culture assay to investigate the following parameters: 
• 
Infectivity status and rate. 
• 
viral dynamics (e.g. duration, peak, time to peak). 
8.20.1.2. Respiratory Pathogen Screen 
On entry to quarantine, a nasopharyngeal swab or nasal wash will be collected and tested to detect the 
presence of a set of respiratory pathogens, including Covid-19, that could potentially contraindicate a 
participant's participation in the study.  The methodology to be used to conduct the respiratory virus screen 
will be documented in the Analytical Plan. Additional test may be conducted if the results from the first test 
were invalid to support study eligibility prior to virus inoculation, or if a community acquired infection is 
suspected during quarantine. 
Any additional screening tests will be conducted at the discretion of the PI.  
8.20.1.3. RSV discharge test 
A PCR based test will be used to determine the presence of RSV in a nasopharyngeal swab or nasal wash 
sample taken prior to discharge from the Quarantine Unit on Day 12 (and subsequent days if, at the 
discretion of the PI, an extended quarantine stay is required due to the PCR test result and/or the presence 
of clinical symptoms).  
8.20.1.4. Exploratory purposes 
Remaining aliquots of nasal samples may be stored and used for exploratory immunology analysis related 
to viral infection and the response to treatment. These analyses may include but are not limited to: 
• 
immunology assays related to baseline immunity and response to infection with RSV  
• 
Immune assays related to Palivizumab (e.g. IgG anti-F ELISA, PCA) 
8.21. 
Recording of Adverse Events and Serious Adverse Events 
The Investigator (PI) is responsible for ensuring that all AEs, SAEs and pregnancies are identified, 
evaluated, recorded and reported in a timely manner as per Regulatory requirements and hVIVO’s SOPs. 
The Investigator’s responsibility is to ensure that the medical management of AEs, SAEs and pregnancy 
events (participant/partner of male participant) is delegated to adequately trained, competent Investigator 
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The Sponsor of the study will also perform an evaluation of seriousness, causality and expectedness of all 
SAEs.  
The definitions of an AE or 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 10.3. 
8.21.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs/SAEs will be collected from the signing of the ICF until the last Follow-up Visit at the time points 
specified in the SoA (Section 1.3). 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study participation. 
However, if the 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 Investigator must promptly notify the sponsor. 
8.21.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures for 
completing and transmitting SAE reports are provided in Appendix 10.3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about AE occurrences. 
8.21.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each participant at 
subsequent visits/contacts. Additional Information/clarification may be required to ensure accurate 
completion of safety reports. The follow up reports should include a detailed Investigator’s clinical 
assessment. All AEs/SAEs, will be followed until resolution, stabilisation, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3). Further information on follow-up procedures 
is provided in Appendix 10.3. 
8.21.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator (PI) to the Sponsor of a SAE is essential so that legal obligations 
and ethical responsibilities towards the safety of participants and the safety of a study intervention under 
clinical investigation are met. 
The following reporting process will be followed: 
- 
PI will send SAE/pregnancy forms to mAbxience PV (sponsor) within 24 hours of becoming 
aware of the event 
- 
mAbxience PV will assess expectedness to determine if the SAE requires expedited reporting  
- 
mAbxience PV will send query to the PI if additional information is needed 
- 
mAbxience PV will report the case to the Medicines and Healthcare Regulatory Agency (MHRA) 
via the EudraVigilance Database Management System EVWEB (or alternatively using MHRA 
eSUSAR tool) 


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- 
PI (or hVIVO) will report SUSAR and other relevant safety information to the Ethics Committee in 
accordance with REC guidelines.  
The sponsor has a legal responsibility to ensure that the local regulatory authority and other regulatory 
agencies duly informed about the safety of a study intervention under clinical investigation. The sponsor 
ensures compliance with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
Investigators. 
An Investigator who receives an investigator safety report describing a SAE or other specific safety 
information (e.g., summary or listing of SAEs) from the sponsor will review and will notify the IRB/IEC, if 
appropriate according to local requirements. 
Further information on regulatory reporting requirements is provided in Appendix 10.3. 
8.21.5. 
Pregnancy 
Details of all pregnancies in female participants and, if indicated, female partners of male participants will 
be collected from study specific informed consent and until the last study assessment as outlined in the 
SoA. If a pregnancy is reported, the Investigator should inform the sponsor within 24 hours of learning of 
the pregnancy and should follow the procedures outlined in  Appendix 10.3. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, foetal death, stillbirth, congenital anomalies, 
ectopic pregnancy) are considered SAEs. 
8.21.6. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs 
Not applicable. 
8.22. 
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 Investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities associated with 
overdose and participants will be clinically followed up until the AE has resolved. 
3. Document the quantity of the excess dose as well as the duration of the overdose in the CRF. 
The Sponsor is responsible for notifying the MHRA and REC of the potential serious breach within 7 days 
of becoming aware of it.  
 


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8.23. 
Pharmacokinetics 
Blood (plasma) samples for the evaluation of PK parameters of Palivizumab will be collected as outlined in 
section 8.19.3. 
Blood samples will be transported, processed and stored in accordance with the AP, and analysed using a 
bioanalytical assay. 
Drug concentration information that may unblind the study will not be reported to investigative site or blinded 
personnel until the study has been unblinded. 
8.24. 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 


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9. 
Statistical Considerations 
Venn Life Sciences will perform the statistical analysis for the study. Full details of the planned statistical 
analysis (including the Part 1 analysis) will be presented in the Statistical Analysis Plan (SAP). Any 
deviations from the SAP will be documented in the Clinical Study Report (CSR). 
Part 1 data analysis will be reported after completion of Part 1, and based on these results, Part 2 of the 
study will commence.  
9.1. 
Statistical Hypotheses 
There are no statistical hypotheses for Part 1. For Part 2, the main hypothesis is that Intravenous (IV) 
treatment with Palivizumab will have a prophylactic effect on RSV disease, that will translate to a lower 
infection rate and/or lower clinical symptomatology and/or lower viral titres compared to placebo. 
Considering that the objectives of Part 2 are not for demonstration of statistically significant differences 
between groups, formal hypothesis testing will be performed for the main endpoints, as described in Section 
1.1.6. All tests will be two-sided, using a type-one error probability of 0.05. p-values between 0.05 and 0.10 
will be considered as indicative of a trend. As this is an exploratory study, no adjustment for multiple testing 
will be performed. 
9.2. 
Sample Size Determination 
9.2.1. 
Part 1 sample size 
Approximately 6 participants will be enrolled in Part 1 of the study for an estimated total of 6 evaluable 
participants. Six evaluable participants are considered sufficient to achieve the objectives of Part 1. 
9.2.2. 
Part 2 challenge study sample size 
Approximately 50 participants will be enrolled in Part 2 of the study for an estimated total of 25 evaluable 
participants per intervention group. 
The sample size of 50 challenged and evaluable participants (25 Palivizumab treated participants and 25 
placebo participants) in Part 2 of the study was calculated based on the assumptions of an infection rate of 
73.7%,  (infection rate obtained from  placebo group participants from 7 studies totalling 216 RSV 
challenged participants, with 160 infected), a mean area under the viral load-time curve (VL-AUC) of RSV-
A Memphis 37b as determined by qRT-PCR on nasal samples in the placebo arm of 20.3 hours*Log10 
copies/mL with corresponding SD of 17.8 and CV of 87.9%. Based on these assumptions, and using a 0.05 
two-sided type one error probability, the 50 challenged and evaluable participants will ensure a power of 
80% to the detection of a reduction of at least 70% in VL-AUC. 
Using a 0.1 two-sided type one error probability, the 50 challenged participants will ensure a power of 80% 
to the detection of a reduction between 60 and 65% in VL-AUC. 
Reduction in VL-AUC 
50% 
55% 
60% 
65% 
70% 
75% 
80% 
N/group for 80% power, 5% 
two-sided 
49 
40 
34 
29 
25 
22 
19 


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Power,  5% two-sided with 
25 participants 
0.522 
0.601 
0.660 
0.729 
0.800 
0.843 
0.886 
Power, 10 % two sided with 
25 participants 
0.644 
0.716 
0.781 
0.835 
0.881 
0.916 
0.940 
 
9.3. 
Populations for Analyses 
The following populations are defined: 
Part 1 
Population 
Description 
Enrolled  
All participants who signed the informed consent. 
Evaluable 
All participants assigned to study intervention and who take a dose of 
study treatment and who complete visit Day 12 Except those participants 
with protocol deviations that lead to exclusion. 
Safety Analysis Set 
All participants assigned to study intervention and who take a dose of 
study treatment.  
PK Analysis 
The PK Analysis set is defined as all participants with at least one post-
dose PK result. 
 
Part 2 
Population 
Description 
Enrolled  
All participants who signed the informed consent and randomised to 
study treatment. 
Evaluable 
All participants randomly assigned to study intervention and who take a 
dose of study treatment, are given viral challenge, and who complete 
quarantine. Except those participants with protocol deviations that lead 
to exclusion.  
Safety Analysis  
All participants randomly assigned to study intervention and who take a 
dose of study intervention, regardless of whether they received the 
challenge virus or not. Participants will be analysed according to the 
intervention they actually received. 
PK Analysis  
The PK Analysis set is defined as all participants with at least one post-
dose PK result. 
The primary analysis will be on the evaluable population. The safety evaluation will be performed on the 
Safety Analysis population. 


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9.3.1. 
Subgroup Analysis 
A ‘Laboratory confirmed infected’ subgroup will be identified and certain pre-specified analyses (to be 
documented in the SAP) will also be performed. 
9.4. 
Interim Analysis 
The Statistical Analysis Plan will describe the planned interim analyses in greater detail. 
Interim analyses in Part 2 will only assess the Placebo group infectivity, that impacts powering assumptions.  
9.5. 
Sequence of Analysis 
A specific statistician (name ‘unblinded statistician’ in the remainder of this document) will be dedicated to 
performing all unblinded analyses conducted before the final database lock and unblinding. As soon as the 
first unblinded analysis, the unblinded statistician will remain independent from the project to maintain the 
study team blinded.  
Part 1 
• 
The analysis of the PK data obtained from Part 1 of the study, confirming the dose to be used in 
Part 2 will be conducted as soon as part 1 will be completed. The PK assessment to progress from Part 1 
into Part 2 is as described in Section 9.6.10 
Part 2 
• 
An interim analysis aiming at reassessing the sample size will be performed once at least 50% of 
the planned number of challenged participants have been challenged and released from the quarantine 
unit. This analysis will be performed by the unblinded statistician. This analysis will be solely to confirm the 
powering assumptions (i.e. infection rate) within the Placebo group and may allow for additional participants 
to be included into the study, if needed to ensure the study is not underpowered. A second interim look to 
the placebo infection rate may be conducted when the targeted enrolment is reached, to further consider 
increasing the sample-size.  
As the interim look(s) will not compare the two treatment groups on the efficacy endpoints, and as the study 
is exploratory and statistical testing is not its primary goal, no adjustment to the type I error rate will be 
made.  
• 
The main analysis will be performed when efficacy (qRT-PCR and categorical symptom scores) 
clean data up to discharge from quarantine (Day 12) are available from all participants. In addition, PK data 
that may become available at that time might be analysed as well. The unblinded statistician will be 
unblinded for these analyses (i.e., will have access to the individual participant treatment assignment). The 
remaining study personnel will remain blinded (i.e., will not have access to the individual participant 
treatment assignment) until study end and database lock. No individual listings are expected to be required 
until End of Study (EOS) and the Investigator will not have access to the treatment allocation up to study 
end and database lock. This analysis will be considered as final for key efficacy endpoints. 
• 
 A final EoS analysis will be performed when all endpoint data (safety and efficacy) up to study end 
(Day 28) are available and locked. All available tertiary endpoints available at that time may also be 
analysed in this step. An integrated CSR containing all data will be written and made available to the 
sponsor and the Investigator. Individual listings will only be provided at this stage.  


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The final CSR will contain at least the final analyses of endpoints. If the data for tertiary endpoints become 
available at a later stage, (an) additional analysis/analyses will be performed. These analyses will be 
documented separately to the CSR and will be made available to the Sponsor and Investigators at that 
time. 
9.6. 
Statistical Analysis 
This section is a summary of the planned statistical analyses of the most important endpoints including key 
endpoints. 
9.6.1. 
Statistical Analysis Plan 
Data will be analysed and reported using SAS® version 9.4 or later.  
The detailed SAP will be developed by Venn Life Sciences and approved by the Sponsor prior to any look 
at unblinded data. The SAP will give a more detailed description of the report presentations to be produced 
for Parts 1 and 2 of the study, respectively, expanding on the protocol specified analysis. Any deviation(s) 
from the original statistical plan should be described and justified in an amendment to the protocol and/or 
SAP as appropriate and referenced also in the final clinical study report (CSR).  
Further post-hoc evaluations of any exploratory endpoints may be conducted and reported separately.  
9.6.2. 
General statistical methods 
9.6.2.1. 
Descriptive statistics 
Continuous variables will be summarised using the following statistics: number of available data, number 
of missing values, mean (and/or geometric mean where applicable), standard deviation, median, Q1, Q3, 
minimum and maximum values. When relevant, confidence intervals will be computed for the mean or the 
median. 
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, 
confidence intervals will be computed. 
9.6.2.2. 
Inferential statistics and significance testing 
Between group comparisons will be performed using appropriate two-sided hypothesis tests at the 5% two-
sided significance level.  
For normally distributed continuous variables (either raw variable or log-transformed variables) the 
difference in means, the standard error and the 95% two-sided confidence interval (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% two-sided CI for the original variable will be 
presented. The t-test, analysis of covariance, or linear mixed-models for repeated measures will be used, 
depending on the endpoint. For endpoints that are not normally distributed (such as total symptom scores), 
the Wilcoxon Rank-Sum test will be used. Details on the method used for each endpoint will be provided in 


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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% two-sided CIs will be presented. Except otherwise specified in the SAP, the Chi-square test will be 
used to compare frequencies between groups. 
As the study is explorative by nature, there will be no attempt to adjust for the multiplicity of endpoints. 
9.6.3. 
Participant accountability 
The number of participants receiving Palivizumab or Placebo, receiving Challenge Virus, withdrawing 
from (also split by reason for withdrawal), and completing the study, and the numbers in each analysis 
set, will be summarised. 
9.6.4. 
Protocol deviations 
Participant data will be reviewed for major protocol deviations prior to database lock and decisions will be 
documented within the meeting minutes. At this meeting, participants will be reviewed for their 
inclusion/exclusion from the analysis sets. 
9.6.5. 
Demographic and baseline characteristics 
Descriptive statistics of demographics (age, sex, height, weight, BMI, and ethnicity) will be presented by 
treatment group and across all participants. Medical history information will be listed. Other baseline 
characteristics will be defined in the SAP.  
9.6.6. 
Compliance to study treatment 
Compliance with study drug will be computed for each patient as proportion of prescribed study drug 
actually taken. 
9.6.7. 
Efficacy Endpoint(s) 
Endpoints 
Planned Inferential 
Analysis 
Area under the viral load-time curve (VL-AUC) of RSV-A Memphis 37b as 
determined by qRT-PCR on nasal samples collected twice daily starting two 
days post-viral challenge (Day +2) up to the end of quarantine. 
t-test if assumptions 
valid 
Area under the viral load-time curve (VL-AUC) of RSV-A Memphis 37b as 
determined by cell culture on nasal samples collected twice daily starting 
two days post-viral challenge (Day +2) up to the end of quarantine. 
Area under the total symptom score-time curve (TSS-AUC) collected daily 
in the participant symptom diary card starting one day post-viral challenge 
(Day +1) up to the end of quarantine. 


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Endpoints 
Planned Inferential 
Analysis 
Sum Total symptom score-time curve (TSS-Sum) collected daily in the 
participant symptom diary card starting one day post-viral challenge (Day 
+1) up to the end of quarantine. 
MMRM for repeated 
measures, if underlying 
assumptions valid 
Total weight of nasal discharge produced starting one day post viral 
challenge (Day +1) up to the end of quarantine. 
t-test if assumptions 
valid 
Total number of tissues used by participants starting one day post viral 
challenge (Day +1) up to the end of quarantine. 
Occurrence of at least two positive “quantifiable” qRT PCR measurements 
in nasal samples at different timepoints reported within two or more 
consecutive days starting two days post viral challenge (Day +2) up to the 
end of quarantine. 
Chi-square test 
Occurrence of at least two positive “detectable” qRT PCR measurements 
in nasal samples at different timepoints reported within two or more 
consecutive days starting two days post viral challenge (Day +2) up to the 
end of quarantine 
Number of days with quantifiable qRT PCR measurements in nasal 
samples starting two days post viral challenge (Day +2) up to the end of 
quarantine. 
t-test if assumptions 
valid 
Peak viral load of RSV-A Memphis 37b as defined by the maximum viral 
load determined by quantifiable qRT PCR measurements in nasal samples 
starting two days post viral challenge (Day +2) up to the end of quarantine. 
t-test if assumptions 
valid 
Incidence of symptomatic RSV infection, as defined by: 
o 
Incidence of infection, and 
o 
At least one grade 2 symptom from one or more respiratory 
categories from the participant symptom diary card. 
Chi-square 
test 
(on 
both the composite and 
each component) 
Number of days with symptoms of grade 2 or more, starting one day post 
viral challenge (Day +1) up to the end of quarantine. 
-test 
if 
assumptions 
valid 
Peak symptom score defined by the maximum daily sum of Symptom score 
starting one day post viral challenge (Day +1) up to the end of quarantine. 
-test 
if 
assumptions 
valid 
 


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9.6.8. 
Tertiary/exploratory efficacy endpoint(s) 
No formal statistical testing will be conducted for tertiary and exploratory endpoints. Only the descriptive 
statistics, as presented in Section 9.6.2.1 will be computed. 
9.6.9. 
Safety Analyse(s) 
AEs will be coded using the most current version of the Medical Dictionary for Regulatory Activities 
(MedDRA) and summarized by system organ class, preferred term, and treatment group for the number of 
AEs reported and the number and percentage of patients reporting each AE.   
A by-patient AE data listing including onset and resolution dates, verbatim term, preferred term, blinded 
treatment, severity, relationship to treatment, action taken, and outcome will be provided. 
Other safety data, including laboratory evaluations (biochemistry, haematology, coagulation (if required), 
cardiac enzymes and urine analysis)), vital signs assessments, physical examinations, 12-lead ECG and 
Spirometry will be summarized by time of collection and by treatment group. In addition, change from 
Baseline will be summarized for vital signs and clinical laboratory results. 
The frequency of patients with abnormal safety laboratory results will be tabulated by treatment. 
9.6.10. 
Other Analyses  
The analysis of the PK data obtained from Part 1 of the study, confirming the dose to be used in Part 2 will 
be conducted as soon as part 1 will be completed. The PK assessment up to and including Day 12 exposure 
will be used as a decision information for the dose for Part 2. PK exposure data from at least 5 out of 6 
participants is required for dose decision making with a projected exposure of ≥40 µg/mL on Day 12. 
The following pharmacokinetic endpoints will be presented by treatment group: 
• 
Serum PK parameters of Palivizumab following dose administration in healthy adult 
participants inoculated with RSV-A Memphis 37b will be defined in the PK Analysis Plan. 
PK parameters will be calculated using non-compartmental methods. Parameters will be summarised 
descriptively. Exploratory PKPD modelling may be performed to inform the exposure response for 
subsequent studies. 
 


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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: 
o 
Consensus ethical principles derived from international guidelines including the Declaration of 
Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International 
Ethical Guidelines 
o 
Applicable ICH Good Clinical Practice (GCP) Guidelines 
o 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF and other relevant documents (e.g., advertisements) 
must be submitted to an IRB/IEC by the Investigator and reviewed and approved by the IRB/IEC 
before the study is initiated. 
• 
Any amendments to the protocol will require IRB/IEC approval before implementation of changes 
made to the study design, except for changes necessary to eliminate an immediate hazard to 
study participants. 
• 
The Investigator will be responsible for the following: 
o 
Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/IEC 
o 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures 
o 
Providing oversight of the conduct of the study at the site and adherence to requirements of 21 
CFR, ICH guidelines, the IRB/IEC, 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 course of the study. 
10.1.3. 
Informed Consent Process 
The Investigator will obtain a signed ICF from each participant before any study specific procedures are 
performed.  
When historical screening data collected through the hVIVO generic screening process is used for 
screening, the study specific ICF will be obtained at quarantine admission (Day -3/-2) from each participant 
before any study specific procedures are performed.  


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Potential participants will typically be sent a copy of the ICF when their Screening Visit/Quarantine 
admission visit (as applicable) is arranged 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 ICF is discussed by the Investigator, and they will be given the opportunity to ask any 
questions and may take the information sheet away to consider their participation. 
All participants will be required to have a good understanding of English and the Investigator will be 
responsible for ensuring that the participant understands the information contained in the ICF. Once the 
Investigator has confirmed that the participant has understood the study, including the benefits and risks of 
participation, the participant and the Investigator can sign and date the ICF.  
The ICF must be signed and dated by the participant and countersigned by the Investigator (whoever 
conducted the consent discussion). A copy of the ICF will be given to the participant, and the original will 
be held in the hVIVO TMF. 
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 ICF.  
The ICF will contain a separate section that addresses the use of samples for future research. The 
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 and may withdraw their consent 
at any time and for any reason.  
10.1.4. 
Data Protection 
Participants will be assigned a unique identifier by the sponsor. 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 
who will be required to give consent for their data to be used as described in the informed consent  
The participant must be informed that his/her medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the sponsor, by appropriate IRB/IEC 
members, and by inspectors from regulatory authorities. 
10.1.5. 
Committees Structure 
The decision on the dose level (8mg/kg or 15mg/kg) to be used for Part 2 of the study will be based on the 
outcome of PK data from Part 1 and a review of the safety and tolerability of the 8mg/kg dose level.  
A Safety Data Review meeting between the Sponsor and the Investigator is required prior to Part 2 for a 
formal assessment of all safety data up to and including Day 12. The meeting will at a minimum consist of 
the Sponsor’s Medical Monitor and the PI.  
Clinical safety data required for review are Vital Signs (heart rate, blood pressure, respiratory rate, and 
pulse oximetry), Tympanic temperature, Physical examination, Safety laboratory values, Urinalysis, 
Adverse events, Serious Adverse events and Concomitant medication use.  


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10.1.6. 
Dissemination of Clinical Study Data 
The key design elements of this Protocol will be posted on publicly accessible registers, such as 
ClinicalTrials.gov. Where required, protocol summaries will also be posted on national or regional clinical 
trial registers or databases (e.g., EudraCT database) in compliance with the applicable regulations. 
It is the Sponsor’s (or Sponsor delegate) responsibility to send the Clinical Trial Summary Report to the 
REC and Medicines and Healthcare Regulatory Agency (MHRA) (if required) within 1 year of the end of the 
trial. In addition, the Sponsor or Sponsor delegate is responsible for entering appropriate data into the 
EudraCT results database within 1 year of the end of the trial.  
The PI/Investigator shall provide assurance to participants that their confidentiality will be maintained 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. 
10.1.7. 
Data Quality Assurance 
Participant data will be collected at site using paper source casebooks which will then be data entered 
into the electronic case report form (eCRF) database unless transmitted to the sponsor or designee 
electronically (e.g., laboratory data). The Investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the CRF. 
The Investigator must maintain accurate documentation (source data) that supports the information entered 
in the CRF.  
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory agency 
inspections and provide direct access to source data documents. Monitoring details describing strategy 
(e.g., risk-based initiatives in operations and quality such as Risk Management and Mitigation Strategies 
and Analytical Risk-Based Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (remote or on-site monitoring) are provided in the 
Monitoring Plan. 
Study monitors will perform ongoing source data verification to confirm that data entered into the CRF by 
authorized site personnel are accurate, complete, and verifiable from source documents; that the safety 
and rights of participants are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all applicable regulatory 
requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be retained by 
the Investigator during the retention period as agreed with the sponsor and as required by local regulations 
or institutional policies. No records may be destroyed during the retention period without the written 
approval of the Sponsor. No records may be transferred to another location or party without written 
notification to the Sponsor. 
10.1.8. 
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. 


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Data reported on the CRF or entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The Investigator may need 
to request previous medical records or transfer records, depending on the study. Also, current medical 
records must be available. 
Definition of what constitutes source data can be found in the Source Data Agreement. 
10.1.9. 
Study Discontinuation 
The Sponsor reserves the right to temporarily suspend or discontinue the study for any reason at any time. 
In addition, the study may be stopped at any time if, in the opinion of the PI, 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, and 
will also inform the regulatory authorities of the suspension or termination of the study and the reason(s) 
for the action.  
The PI/Investigator is responsible for promptly informing the REC and providing the reason(s) for the 
suspension or termination of the study. 
If the study is prematurely terminated, all study data must be returned to the Sponsor. In addition, the site 
must conduct final disposition of all unused IMPs in accordance with the Sponsor's procedures for the 
study. 
Termination of the clinical trial may also be initiated by the MHRA or the REC.  
 
10.1.10. Publication Policy 
By signing the study protocol, the PI agrees that the results of this study may be used for the purposes of 
national and international registration, publication, and information for medical and pharmaceutical 
professionals by the Sponsor. 
If necessary, the authorities will be notified of the PI's name, address, qualifications, and extent of 
involvement. In order to allow the use of the information derived from this clinical study, the PI understands 
that he 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 trial. In the case the Sponsor acts as fully responsible for the publication, 
the Sponsor agrees to allow the PI time to review all manuscripts and abstracts prior to submission for 
publication. mAbxience 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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10.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Table 6 will be performed The Doctor’s Laboratory (TDL). 
• 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5 
of the protocol. 
• 
Additional tests may be performed at any time during the study as determined necessary by the 
Investigator or required by local regulations. 
• 
Pregnancy Testing  
Table 6 - Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Haematology 
Platelet Count. 
White blood cell (WBC) count (absolute) 
WBC differential: 
Neutrophils 
Lymphocyte 
Monocytes 
Eosinophils 
Basophils 
Red blood cell (RBC) count 
 
Reticulocyte count (% and absolute) 
 
Haemoglobin 
Haematocrit 
Mean corpuscular volume (MCV) 
Mean corpuscular haemoglobin (MCH) 
MCH concentration (MCHC). 
Coagulation 
Prothrombin Time (PT) 
Activated Partial Thromboplastin Time (APTT) 
Biochemistry 
Sodium 
Potassium 
Glucose (random) 
Albumin 
Chloride 
Bicarbonate 
Calcium 
Uric acid 
Total protein 
Creatinine 
Total, direct, and indirect bilirubin 
Inorganic phosphate 
Blood urea nitrogen 
C-reactive protein (CRP) 
Gamma glutamyl transferase 
Alkaline phosphatase (ALP) 


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Laboratory 
Assessments 
Parameters 
Alanine transaminase (ALT) 
Lactate dehydrogenase (LDH) 
Aspartate transaminase (AST) 
Urea. 
Thyroid function 
Thyroid Stimulating Hormone (TSH) 
Thyroxine 
Cardiac enzymes 
Creatine Kinase (CK) 
CK-MB 
Troponin (T) 
Routine urinalysis 
Colour 
Specific gravity 
Appearance 
pH 
Presence of blood, glucose, leukocytes, ketones, nitrites, proteins, 
urobilinogen, bilirubin by dipstick 
Microscopy, culture and sensitivity examination (If the dipstick 
yields abnormal results) 
Other 
screening/eligibility 
tests 
Follicle stimulating hormone (FSH)* 
β-human chorionic gonadotrophin (β-hCG) 
Total cholesterol 
Thyroid function test [thyroid stimulating hormone (TSH), free 
thyroxine (T4)] 
Antibodies against HIV-1 and HIV-2 
Hepatitis A immunoglobulin M (HepA) 
Hepatitis B surface antigen (HBsAg) 
Hepatitis C antibodies (HepC) 
*Only for post-menopausal women 
 
Investigators must document their review of each laboratory safety report. 
Laboratory results that could unblind the study will not be reported to investigative sites or other blinded 
personnel until the study has been unblinded. 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
10.3.1. 
Adverse Event 
AE Definition 
An AE is defined as any untoward medical occurrence in participants. An AE can therefore be any 
unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of an investigational medicinal product, whether or not considered 


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related to the investigational medicinal product, or for the purposes of Human Viral Challenge studies, 
the Challenge Virus. 
 
Events Meeting the AE Definition 
• 
Exacerbation of a pre-existing illness. 
• 
Increase in frequency or severity of a pre-existing episodic condition. 
• 
A condition detected or diagnosed after IMP or inoculum administration even though it may have 
been present prior to the start of the study. 
• 
A complication that occurs during a hospitalisation. 
• 
A clinically significant change in laboratory parameter. 
 
Events NOT Meeting the AE Definition 
• 
Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion); the 
condition that leads to the procedure is an AE. 
• 
Pre-existing disease or conditions present or detected prior to start of IMP or Challenge Virus 
inoculation administration that does not worsen (including screening findings such as abnormal 
laboratory results). 
• 
Hospitalisation for elective surgery, social and/or convenience admissions provided they are 
arranged before the start of IMP administration. 
• 
Over-administration of either the challenge virus, IMP or concomitant medication without any 
signs or symptoms. 
• 
An uncomplicated pregnancy or an induced elective abortion to terminate a pregnancy without 
medical reason. 
• 
Typical/normal viral symptoms on symptom diary cards. 
10.3.2. 
Adverse Drug Reaction 
An adverse drug reaction (ADR) 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 judged by either the reporting Investigator or the Sponsor as having a reasonable causal 
relationship to a medicinal product qualify as ADRs. The expression ‘reasonable causal relationship’ 
means to convey in general that there is evidence or argument to suggest a causal relationship. 
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: 


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(a) In the case of a product with a marketing authorisation, in the Summary of Product Characteristics for 
that product, which is applicable for this study 
(b) In the case of any other investigational medicinal product, in the Investigator’s Brochure relating to the 
trial in question’, not applicable for this study. 
For this study the option (a) is applicable. 
10.3.4. 
Serious Adverse Event 
SAE Definition  
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. 
Results in death 
b. 
Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the participant was at 
risk of death at the time of the event. It does not refer to an event, which hypothetically might have 
caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
In general, hospitalisation signifies that the participant has been detained (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment 
that would not have been appropriate in the physician’s office or outpatient setting. 
Complications that occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfils any other serious criteria, the event is serious. When in doubt as to 
whether “hospitalisation” occurred or was necessary, the AE should be considered serious. 
• 
Hospitalisation for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. 
Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhoea, influenza, and accidental 
trauma (e.g., sprained ankle) which may interfere with or prevent everyday life functions but do 
not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Is an important medical event: 
• 
Important medical events’ - some medical events may jeopardise the participant or may require 
an intervention to prevent one of the above characteristics/consequences. Such events should 
also be considered as ‘serious’ in accordance with the above definition.  


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• 
Medical judgement should be exercised in deciding whether an adverse event/reaction is 
serious. Important adverse events/reactions that are not immediately life threatening or do not 
result in death or hospitalisation but may jeopardise the participant or may require intervention 
to prevent one of the other outcomes listed in the definition above occurring, should also be 
considered serious. Details of the SAE must be provided. 
10.3.5. 
Suspected Unexpected Serious Adverse Reaction 
A suspected unexpected serious adverse reaction (SUSAR) is ‘a serious adverse reaction, the nature and 
severity* of which is not consistent with the information about the medicinal product in question, as defined 
in the Summary of Product Characteristics (SmPC), included in this clinical trial application package.   
Expectedness of adverse events will be determined by the sponsor. The Reference Safety Information 
(RSI) document for this study is the Summary of Product Characteristics (SmPC), section 4.8.  
Any changes to the referenced safety information will be deemed as a change to the risk/benefit profile and 
will require a substantial amendment to be submitted to the MHRA. This amendment must be approved 
before the changes are implemented in the study. 
*The term ‘severity’ is used here to describe the intensity of a specific event. This is not the same as ‘serious’ 
which is based on participant/event outcome or action criteria. 
10.3.6. 
Recording, Assessment and Follow-up of AE and/or SAE 
10.3.6.1. AE and SAE Recording  
All AEs and SAEs will be collected from the date of signed written informed consent until study 
completion/final study contact or until the resolution of the AE. AEs will be fully recorded in the source 
documents as they are reported whether spontaneously volunteered by a participant or in response to 
questioning about wellbeing at each face to face study visit and during telephone calls. Enquiries about 
AEs should cover the period between the previous and current visit. 
The following are examples of open ended, non-leading questions that may be used to obtain this 
information:  
• 
How are you feeling? 
• 
Have you had any medical problems since your last visit/assessment?  
• 
Have you taken any new medicines, other than those given to you in this study, since your 
last visit/assessment? 
Following the reporting of AEs and concomitant medication, the Investigator should assess the 
participant’s eligibility to continue in the study.  
The PI will record all relevant information regarding an AE/SAE in the source documents and evaluate 
AEs using the following guidelines:  
• 
Description of events (if the event consists of a cluster of signs and symptoms, a diagnosis 
should be recorded) 
• 
Seriousness 
• 
Severity (or grade) 


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• 
Onset date and time 
• 
Frequency 
• 
Date and time of resolution (or ‘continuing’ if unresolved) 
• 
Action taken  
• 
Concomitant medication 
• 
Clinical outcome 
• 
Relationship or causality (IMP/Challenge Virus/ study procedures/ concomitant 
medication/other). 
Any clinically significant abnormal laboratory result, vital sign or other measure will be followed until it 
returns to normal or baseline values, stabilises, or is judged by the Investigator to be no longer clinically 
significant.  
If an AE is not resolved at the end of the study, the AE should be followed until it has resolved or (in the 
case of pregnancy) the pregnancy has been terminated (including spontaneous abortion), resulted in a 
birth, or a decision has been made by the Sponsor that no further follow-up is required. 
Even if the AE or SAE is assessed by the PI as not reasonably attributable to the challenge virus, its 
occurrence must be fully documented in the source notes 
10.3.6.2. Assessment 
Description 
If the event consists of a cluster of signs and symptoms, a diagnosis should be recorded (e.g. 
gastroenteritis) rather than each sign and symptom.  
Onset and end 
The dates and times of the onset and end of the event should be recorded.  
Assessment  
Challenge Virus Symptoms 
The Investigator will assess and review Challenge Virus related symptoms recorded in participants’ 
hVIVO Symptom Diary Cards. Symptoms greater than Grade 0 will be expected and presumed to 
represent virus infection consequent to Viral Challenge, and will not be additionally captured as AEs 
unless they meet the definition of an AE, and are deemed to be clinically significant (in the opinion of 
the Investigator) to be classed as AEs.  
Following Viral Challenge all unexpected (in the opinion of the Investigator) symptoms post inoculation 
will be captured as AEs, along with all other occurrences that meet the criteria for an AE. 
Physical Examination 
Any clinically significant change in complete physical examination findings during the study will be 
documented as an AE. 
Direct Physical Examination 
Following Viral Challenge, upper and lower respiratory symptoms (nasal discharge, otitis, pharyngitis, 
sinus tenderness, new wheezes, rales and rhonchi) will be expected and presumed to represent virus 


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infection consequent to Viral Challenge, and will not be additionally captured as AEs unless they meet 
the definition of an AE, and are deemed to be clinically significant (in the opinion of the Investigator) to 
be classed as AEs. 
Vital Signs 
Deterioration in a vital sign (compared to baseline) should only be reported as an AE if the deterioration 
fulfils the criteria for an AE. If deterioration in a vital sign is associated with clinical signs and 
symptoms, the sign or symptom will be reported as an AE and the associated vital sign will be 
considered as additional information. 
Temperature 
Following Viral Challenge, pyrexia will be expected and presumed to represent virus infection 
consequent to Viral Challenge, and will not be additionally captured as an AE unless it meets the 
definition of an AE, and is deemed to be clinically significant (in the opinion of the Investigator) to be 
classed as an AE.  
Following Viral Challenge all unexpected (in the opinion of the Investigator) pyrexia post inoculation will 
be captured as an AE, along with all other occurrences that meet the criteria for an AE. 
Spirometry 
A 15% drop in a spirometry value (compared to baseline) confirmed by a repeat on the same day, will 
be a Grade 1 (mild) AE. The PI/Investigator will use his/her clinical judgement to assign severity grades 
above Grade 1, based on evaluation of clinical signs and symptoms. If the repeated value has returned 
to normal an AE will not be raised. 
Laboratory Values 
Deterioration in a laboratory value (compared to baseline) should only be reported as an AE if the 
deterioration fulfils the criteria for an AE. If deterioration in a laboratory result is associated with clinical 
signs and symptoms, the sign or symptom will be reported as an AE and the associated laboratory 
result will be considered as additional information. 
The Investigator and/or SME will judge whether abnormal laboratory values are clinically significant or 
not clinically significant, and record this in the source document. This entry should be signed and dated 
by the relevant Investigator. Laboratory abnormalities detected at screening will be considered as part 
of the medical history and will not be reported as AEs 
Challenge Virus associated laboratory abnormalities (e.g.: elevated ALT, AST or GGT; decreased 
neutrophils) may be recorded as AEs (at the discretion of the Investigator).   
C-reactive Protein 
Any value above 5 mg/L but less than 60 mg/L will be a Grade 1 (mild) AE (unless deemed non 
clinically significant by the PI or delegate. The PI or delegate will use his/her clinical judgement to 
assign severity grades above Grade 1, based on evaluation of clinical signs and symptoms.  
 


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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 will use the [grading scale for AEs] as a reference when collecting, reporting and clarifying 
database queries of AEs, SAEs and ARs.  
The severity of an AE that does not appear in the [grading scale for AEs] should be determined according 
to the definitions in Table 7  
Table 7 – 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 that intermittently interferes with regular 
activities 
Grade 3 
Severe 
Significant level of discomfort and prevents regular activities 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described in the 
definition of an SAE, NOT when it is rated as severe. It is important to distinguish between serious and 
severe AEs. An AE of severe intensity needs not necessarily be considered serious. For example, a 
migraine headache that incapacitates a participant for many hours may be severe, whereas a stroke that 
results in a limited degree of disability may be considered mild, but should be reported as a SAE. 
10.3.6.4. Frequency 
The frequency of the AE should be categorised as one of the following: 
• 
Single 
• 
Intermittent 
• 
Continuous 
10.3.6.5. Assessment of Causality 
• 
The Investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. 
• 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or arguments 
to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study intervention administration will be considered 
and investigated. 


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• 
The Investigator will also reference the Reference Safety Information (RSI) section in the SmPC, 
in his/her assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the Investigator has minimal information 
to include in the initial report to Sponsor’s Pharmacovigilance provider. However, it is very important 
that the investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and send 
a SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
• 
The relationship of an AE to the IMP will be categorised as shown in Table 8: 
Table 8- Classification of Adverse Event Relationship 
Classification 
Definition 
Not related 
The AE is related to an aetiology other than the IMP (the alternative 
aetiology must be documented in the participant’s medical record). 
Unlikely to be related 
The AE is unlikely to be related to the IMP and likely to be related to 
factors other than IMP. 
Possibly related 
There is an association between the AE and the administration of the 
IMP, and there is a plausible mechanism for the AE to be related to the 
IMP, but there may also be alternative aetiology, such as characteristics 
of the participant’s clinical status or underlying disease. 
Probably related 
 
A reasonable temporal sequence of the AE and the IMP administration 
exists and, based upon the known pharmacological action of the drug, 
known or previously reported adverse reactions to the drug or class of 
drugs, or judgment based on the Investigator’s clinical experience, the 
association of the AE with the IMP seems likely. 
Definitely related 
 
A definite causal relationship exists between the AE and the 
administration of the IMP, and other conditions do not appear to explain 
the AE. 
 
Unless an AE is ‘definitely related’ to the IMP, a causal relationship to one of the following should be 
considered, and full details provided on the AE reporting form as appropriate. 
• 
Challenge Virus 
• 
Study procedures 
• 
Concomitant medication 
• 
Other 


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10.3.6.6. Action Taken 
The Investigator should ensure that adequate medical care is provided to participants for any AEs, including 
clinically significant laboratory values related to the IMP. In addition, the Investigator will describe whether 
any treatment was given for the AE. 
The Investigator will classify the action taken with regard to the AE. The action taken should be classified 
according to the following categories and full details provided as appropriate: 
• 
None 
• 
Non-drug therapy given 
• 
Concomitant medication taken 
• 
IMP dose not changed 
• 
IMP dose adjusted 
• 
IMP administration temporarily interrupted 
• 
IMP administration permanently discontinued 
• 
Participant withdrawn 
• 
Participant hospitalised 
• 
Other 
10.3.6.7. Outcome 
An AE should be followed until the Investigator has determined and recorded the outcome or an 
alternative explanation. The outcome should be classified according to the categories shown in Table 9. 
Table 9 - Classification of Adverse Event Outcome 
Classification 
Definition 
Resolved 
Resolution of the AE with no residual signs or symptoms 
Resolved with sequelae 
Resolution of the AE with residual signs or symptoms 
Ongoing 
Either incomplete improvement or no improvement of the AE, 
such that it remains on-going 
Fatal 
Outcome of the AE was death. ‘Fatal’ should be used when 
death was at least possibly related to the AE. 
Unknown (e.g. Lost to follow-up) 
Outcome of the AE is not known (e.g. the participant is lost to 
follow-up). 
 
10.3.6.8. Follow-up 
All AEs and SAEs must be followed-up by the Investigator, or where appropriate, be referred to the 
participant’s GP or other healthcare professional for follow-up until they are: 
• 
Resolved (return to normal or baseline values), or 
• 
Stabilised, or 


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• 
Judged by the PI/Investigator to be no longer clinically significant, or 
• 
An alternative explanation has been provided. 
Additional measurements and/or evaluations may be necessary to investigate the nature and/or causality 
of an AE or SAE. This may include additional laboratory tests, diagnostic procedures, or consultation with 
other healthcare professionals. If the participant dies, any post-mortem findings (including histopathology) 
will be provided to the Sponsor if possible. 
10.3.7. 
Reporting of SAEs 
SAEs must be documented and reported as per hVIVO’s SOPs.  
Prompt notification of SAEs by the Investigator to the Sponsor is essential so that the Sponsor can meet 
its regulatory reporting obligations for the study. If the Investigator does not have all of the details regarding 
the SAE he/she will not wait until this information becomes available before making the initial report to 
Sponsor. Contact details are detailed in Table 10. 
Notification should be made: 
• 
In a detailed written SAE form report within 24 hours of the Investigator becoming aware of the 
event.  
All reports should be directed to the pharmacovigilance mailbox. The Investigator at the site is responsible 
for ensuring that a member of the Sponsor study team is made aware of any SAE reports that have been 
transmitted. 
 
Table 10 - Contact Details for Reporting SAEs 
Contact  
Details 
Pharmacovigilance reporting email 
pharmacovigilance@mabxience.com 
Pharmacovigilance fax number reporting  
0034 917711590 
SAE e-mail address:  
pharmacovigilance@mabxience.com 
In addition, any AE resulting in permanent study discontinuation for a participant, even if not serious and 
regardless of expectedness or causality, must be reported by telephone, email or fax to the Sponsor within 
7 calendar days of the PI or any other site personnel’s knowledge of the event. 
The SAE form, AE record and relevant concomitant medication record should be faxed/emailed to the 
Sponsor within 24 hours of the Investigator or any site personnel’s knowledge of a SAE. An updated SAE 
report form should be forwarded to the Sponsor within 24 hours of receipt of the new/updated information 
as relevant.  


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Information relating to the participant’s subsequent medical progress must be submitted to the Sponsor as 
available, until the SAE has subsided or, in the case of permanent impairment, until it stabilises and the 
overall clinical outcome has been ascertained.  
The Investigator will also provide additional information, including a copy of the following documents (where 
applicable): 
• 
Copies of test results, as available  
• 
Hospital discharge summary (as soon as it is available to the PI) 
• 
Autopsy report (as soon as it is available to the PI). 
The Investigator must report SAEs/SUSARs to the relevant REC in accordance with applicable regulatory 
requirements and within the relevant timelines.  
The REC will be sent annual safety updates in order to facilitate their continuing review of the study. 
10.3.8. 
Reporting of SUSARs 
The Sponsor is responsible for assessing SUSARs, unblinding potential SUSARs, and reporting SUSARs 
to the MHRA.  
The Sponsor shall ensure that all relevant information about a SUSAR that occurs during the course of a 
clinical trial in the UK and is fatal or life threatening, is reported as soon as possible to the MHRA. This 
needs to be done within 7 calendar days after the Sponsor became aware of the event. Any additional 
relevant information should be sent within 8 days of the first report being sent. 
The Sponsor shall ensure that a SUSAR which is not fatal or life-threatening is reported as soon as 
possible and in any event within 15 calendar days after the Sponsor became aware of the event. 
10.3.9. 
Adverse Reactions to non-IMPs 
Any AEs and SAEs which are related to/caused by a concomitant medication or Challenge agent, should 
not be classed as ARs, SARs, or SUSARs (ARs, SARs, SUSARs relate only to IMP by definition). However, 
an SAE caused by a non-IMP would need to be reported to the MHRA/REC for the appropriate action to 
be taken. 
10.3.10. Post-study AEs and SAEs 
All SAEs that occur during the [specify period] time period must be reported by the Investigator to the SME 
as soon as possible, in accordance with hVIVO’s SOPs, and at the latest within 24 hours of becoming 
aware of the event.  
10.3.11. Pregnancy  
If a female participant or partner of a male participant becomes pregnant during [specify time period], this 
must be reported by the Investigator to the medical monitor and Study Monitor by telephone as soon as 
possible, in accordance with hVIVO’s SOPs, and at the latest within 24 hours of becoming aware of the 
event.  


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Following the telephone notification, the Investigator must fully and accurately complete the appropriate 
pregnancy reporting form, which must be e-mailed to the pharmacovigilance department and the Study 
Monitor at the latest within 24 hours of becoming aware of the pregnancy.  
Participants will be advised to contact their GP or a specialist, as appropriate.  
Consent for follow-up of the pregnancy and pregnancy outcome will be sought from the pregnant study 
participant or the pregnant partner of the male study participant as applicable. Consent for follow-up will be 
documented on an hVIVO Pregnancy Follow-up ICF.  
Provided that the appropriate consent is in place, information related to the pregnancy will be collected as 
per hVIVO’s SOPs and the Sponsor’s requirements. The completed reporting form(s) will be sent to the 
Sponsor for review and assessment, and subsequent reporting as required. 
• 
A complete evaluation will be documented in the source data to permit transfer to the clinical 
database.  
• 
An emergency request (Section 6.3) to break the blind for the appropriate study participant to 
ensure that further care can be based on the actual identity of the study treatment that the 
participant received. 
• 
hVIVO will maintain contact with the participant for a protracted period of time, but certainly until 
after the birth, in order to assess for outcomes that may be reportable as related AEs, and for 
reporting to the Sponsor as appropriate.  
• 
hVIVO in consultation with the participant will keep the participant’s GP informed.  
• 
All cases of foetal drug exposure via the parent as a study participant will be reported to the Sponsor 
and the REC.  
 


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10.4. 
Appendix 4: Normal Ranges 
Vital Signs 
 
Vital sign Parameters 
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 
50 
100 
beats per minute 
Systolic BP 
90 
140 
mmHg 
Diastolic BP 
50 
90 
mmHg 
 
ECG 
 
ECG Parameters 
Lower limit 
Higher limit 
Units 
HR 
50 
100 
bpm 
QRS 
60 
120 
ms 
PR interval 
120 
220 
ms 
QT 
320 
450 
ms 
QTc 
Normal for females is < 470  
ms 
Normal for males is < 450 
QTcF 
320 
450 
ms 
QTcB 
320 
450 
ms 
RR 
600 
1200 
ms 
 
Spirometry 
 
Spirometry parameters 
Lower limit 
Higher limit 
Units 
FEV1  
Normal if ≥ 80% of the predicted value 
litres 
FEV1/FVC 
Normal if ≥70% (≥ 0.7) of the base value  
litres  
 
 


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10.5. 
Appendix 5: Abbreviations 
ADA 
Anti-Palivizumab Antibody 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ALRI 
Acute Lower Respiratory Infection 
ALT 
Alanine Aminotransferase 
AP 
Analytical Plan 
APTT 
Activated Partial Thromboplastin Time 
AR  
Adverse Reaction 
AST 
Aspartate Aminotransferase 
AST 
Aspartate Transaminase 
ATS 
American Thoracic Society  
AUC 
Area Under the Curve 
BD 
Twice Daily 
BMI 
Body Mass Index 
cGMP 
Current Good Manufacturing Practices 
CK 
Creatine Kinase 
CONSORT 
Consolidated Standards of Reporting Trials 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
CRP 
C-reactive Protein 
CYP450 
Cytochrome 450 
DNA 
Deoxyribonucleic acid 
DMID 
Division of Microbiology and Infectious Disease 
ECG 
Electrocardiogram  
ECSC 
European Coal and Steel Community ( 
ELISA 
Enzyme-linked Immunosorbent Assay 
EMA 
European Medicines Agency 
ERS 
European Respiratory Society  
EU 
European Union  
FEV 
Forced Expiratory Volume 
FOT 
Forced oscillation technique 
FSH 
Follicle Stimulating Hormone 
FVC 
Forced Vital Capacity 
GAD 
Generalised Anxiety Disorder 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GP 
General Practitioner  
HAV 
Hepatitis A 
HbA1c 
Haemoglobin A1c 
HBV 
Hepatitis B 
HCV 
Hepatitis C 
HIV 
Human Immunodeficiency Virus 
HVC 
Human Viral Challenge  
ICF 
Inform Consent Form 
ICH 
International Council for Harmonisation 
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Independent Ethics Committees 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G  
IM 
Intramuscular 
IMP 
Investigational Medicinal Product 


CONFIDENTIAL 
MB05-P-01-20 Protocol Final V2.0 
 
hVIVO template identifier: (G_0687) v3.0  
 
92 
IRB 
Institutional Review Boards 
IUD 
Intrauterine Device  
IV 
Intravenous 
LMIC 
Low to Medium Income Country 
LRT 
Lower Respiratory Tract 
MCH 
Mean Corpuscular Haemoglobin 
MCHC 
Mean Corpuscular Haemoglobin Concentration 
MCID 
Minimal Clinically Important Difference 
MCV 
Mean Corpuscular Volume 
MHRA 
Medicines and Healthcare products Regulatory Agency 
MOI 
Monoamine Oxidase Inhibitors 
NIMP 
Non-Investigational Medicinal Product 
NPS 
Nasopharyngeal Swab 
PBMC 
Peripheral Blood Mononuclear Cell  
PCA 
Principal Component Analysis 
PCR 
Polymerase Chain Reaction 
PEF 
Peak expiratory flow 
PFM 
Peak flow meter 
PFU 
Plaque Forming Unit 
PHQ 
Patient Health Questionnaire 
PI 
Principal Investigator 
PK  
Pharmacokinetic 
PT 
Prothrombin Time 
qRT-PCR 
Quantitative Reverse Transcriptase-Polymerase Chain Reaction 
RBC 
Red Blood Cell 
REC 
Research Ethics Committee 
RNA 
Ribonucleic acid 
RSI 
Reference Safety Information  
RSV 
Respiratory Syncytial Virus 
SAE 
Serious Adverse Event 
SME 
Sponsor’s Medical Expert 
SmPC 
Summary of Product Characteristics  
SoA 
Schedule of Activities  
SOP 
Standard Operating Procedure  
SUSAR 
Suspected Unexpected Adverse Reaction 
T 
Troponin 
TDS 
Three Times Daily 
TMF 
Trial Master File 
TSH 
Thyroid Stimulating Hormone 
TSH 
Thyroid Stimulating Hormone 
TSS 
Total Symptoms Score 
UK 
United Kingdom 
URT 
Upper Respiratory Tract 
WBC 
White Blood Cell 
WHO 
Word Health Organisation 
β-HCG 
β-human chorionic gonadotrophin 
 
 
 


CONFIDENTIAL 
MB05-P-01-20 Protocol Final V2.0 
 
hVIVO template identifier: (G_0687) v3.0  
 
93 
11. 
References 
 
Agius, G., G. Dindinaud, R. J. Biggar, R. Peyre, V. Vaillant, S. Ranger, J. Y. Poupet, M. F. Cisse, and M. 
Castets. 1990. 'An epidemic of respiratory syncytial virus in elderly people: clinical and serological 
findings', J Med Virol, 30: 117-27. 
Bont, L., P. A. Checchia, B. Fauroux, J. Figueras-Aloy, P. Manzoni, B. Paes, E. A. Simoes, and X. 
Carbonell-Estrany. 2016. 'Defining the Epidemiology and Burden of Severe Respiratory Syncytial 
Virus Infection Among Infants and Children in Western Countries', Infect Dis Ther, 5: 271-98. 
CDER_FDA. 2004. "Approval package for: Synagis (Palivizumab) BLA 103770/S-5059." In. 
DeVincenzo, J. P., T. Wilkinson, A. Vaishnaw, J. Cehelsky, R. Meyers, S. Nochur, L. Harrison, P. 
Meeking, A. Mann, E. Moane, J. Oxford, R. Pareek, R. Moore, E. Walsh, R. Studholme, P. 
Dorsett, R. Alvarez, and R. Lambkin-Williams. 2010. 'Viral load drives disease in humans 
experimentally infected with respiratory syncytial virus', Am J Respir Crit Care Med, 182: 1305-
14. 
Falsey, A. R., C. K. Cunningham, W. H. Barker, R. W. Kouides, J. B. Yuen, M. Menegus, L. B. Weiner, C. 
A. Bonville, and R. F. Betts. 1995. 'Respiratory syncytial virus and influenza A infections in the 
hospitalized elderly', J Infect Dis, 172: 389-94. 
Falsey, A. R., P. A. Hennessey, M. A. Formica, C. Cox, and E. E. Walsh. 2005. 'Respiratory syncytial 
virus infection in elderly and high-risk adults', N Engl J Med, 352: 1749-59. 
Hall, C. B., G. A. Weinberg, M. K. Iwane, A. K. Blumkin, K. M. Edwards, M. A. Staat, P. Auinger, M. R. 
Griffin, K. A. Poehling, D. Erdman, C. G. Grijalva, Y. Zhu, and P. Szilagyi. 2009. 'The burden of 
respiratory syncytial virus infection in young children', N Engl J Med, 360: 588-98. 
Lambkin-Williams, R., N. Noulin, A. Mann, A. Catchpole, and A. S. Gilbert. 2018. 'The human viral 
challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel 
diagnostics', Respir Res, 19: 123. 
Miller, M. R., J. Hankinson, V. Brusasco, F. Burgos, R. Casaburi, A. Coates, R. Crapo, P. Enright, C. P. 
van der Grinten, P. Gustafsson, R. Jensen, D. C. Johnson, N. MacIntyre, R. McKay, D. Navajas, 
O. F. Pedersen, R. Pellegrino, G. Viegi, J. Wanger, and Ats Ers Task Force. 2005. 
'Standardisation of spirometry', Eur Respir J, 26: 319-38. 
Nair, H., D. J. Nokes, B. D. Gessner, M. Dherani, S. A. Madhi, R. J. Singleton, K. L. O'Brien, A. Roca, P. 
F. Wright, N. Bruce, A. Chandran, E. Theodoratou, A. Sutanto, E. R. Sedyaningsih, M. Ngama, P. 
K. Munywoki, C. Kartasasmita, E. A. Simoes, I. Rudan, M. W. Weber, and H. Campbell. 2010. 
'Global burden of acute lower respiratory infections due to respiratory syncytial virus in young 
children: a systematic review and meta-analysis', Lancet, 375: 1545-55. 
Schunemann, H. J., and G. H. Guyatt. 2005. 'Commentary--goodbye M(C)ID! Hello MID, where do you 
come from?', Health Serv Res, 40: 593-7. 
Shi, T., E. Balsells, E. Wastnedge, R. Singleton, Z. A. Rasmussen, H. J. Zar, B. A. Rath, S. A. Madhi, S. 
Campbell, L. C. Vaccari, L. R. Bulkow, E. D. Thomas, W. Barnett, C. Hoppe, H. Campbell, and H. 
Nair. 2015. 'Risk factors for respiratory syncytial virus associated with acute lower respiratory 
infection in children under five years: Systematic review and meta-analysis', J Glob Health, 5: 
020416. 
 

SAP_001.pdf: 
 
Document Number or Project Identification: VH0001 / MB05-P-01-20 
Document Version: v3 
Statistical Analysis Plan 
 
Confidential 
 
Page 1 of 54 
 
 
                                                                                                       
 
 
 
 
 
mAbxience Research S.L 
 
MB05-P-01-20 (VH0001 / HVO-CS-001) 
 
A Double-Blind, Randomised, Placebo-Controlled Exploratory Study to Estimate the 
Prophylactic Efficacy of Palivizumab in Healthy Adult Participants Inoculated with 
Respiratory Syncytial Virus (RSV) 
 
Version: 3  
Date: 03/Dec/2020 
 
 
 
 
 
 
 
 
 
 
 
 
Alice Tourneroche 
Statistics Department 
Venn Life Sciences 
63 Boulevard Haussmann 
75008 PARIS 
 
 
 
 
This document is to be considered CONFIDENTIAL and is for the sole use and review by Client 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. 






 
Document Number or Project Identification: VH0001 / MB05-P-01-20 
Document Version: v3 
Statistical Analysis Plan 
 
Confidential 
 
Page 3 of 54 
 
 
Document version history  
 
Version 
Date 
Author 
Modifications since previous version 
V1 
05/Oct/2020 
Alice Tourneroche 
NA for initial release 
V2 
27/Oct/2020 
Alice Tourneroche 
 Section 4.2.1.4: Note added for 
Laboratory-confirmed virus-like-
illness definition 
 Section 6: Precision added for the 
definition of the subgroup 
 Section 7.1: Definition of the 
Infection Rate for Interim Analysis 
updated to be consistent with the 
assumptions used in the Sample Size 
calculation: Variant 2 used instead of 
Variant 1  
V3 
03/Dec/2020 
Alice Tourneroche 
 Section 4.2.1.4: Precision added in 
URTI, LRTI definition 
 Section 5.1.2: Normality checks 
updated 
 Section 5.3.3: Table number updated 
 Section 5.4.1: Graphical 
representation updated 
 Section 5.4.2.1:  
o Graphical representation 
updated 
o Graphical representation added 
for Peak Viral Load (for both 
qPCR and cell culture) 
o Analysis rule added for Number 
of days analysis (for both qPCR 
and cell culture) 
o Analysis rule updated for Time 
to Peak Virus Shedding analysis 
 Section 5.4.2.2:  
o Graphical representation 
updated 
o Graphical representation added 
for Peak Symptom score 
o Analysis rule added for Number 
of days analysis 
Section 11.2: update Figures table 
according to changes listed above 
 
 


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Page 4 of 54 
 
 
Table of Contents 
ABBREVIATIONS AND DEFINITIONS .................................................................................................................. 7 
 
INTRODUCTION ...................................................................................................................................... 10 
 
HIGHLIGHTS FROM STUDY PROTOCOL ................................................................................................... 10 
2.1 
BACKGROUND/RATIONALE .......................................................................................................................... 10 
2.2 
STUDY OBJECTIVES ..................................................................................................................................... 10 
2.2.1 
PART 1 .................................................................................................................................................... 10 
2.2.2 
PART 2 .................................................................................................................................................... 10 
2.3 
INVESTIGATIONAL PLAN ............................................................................................................................... 11 
2.3.1 
Study design ..................................................................................................................................... 11 
2.3.1.1 
PART 1 ................................................................................................................................................ 11 
2.3.1.2 
PART 2 ................................................................................................................................................ 12 
2.3.2 
Determination of sample size ........................................................................................................... 12 
2.3.2.1 
PART 1 ................................................................................................................................................ 12 
2.3.2.2 
PART 2 ................................................................................................................................................ 12 
2.3.3 
Study assessments and study plan ................................................................................................... 13 
2.3.3.1 
PART 1 ................................................................................................................................................ 13 
2.3.3.2 
PART 2 ................................................................................................................................................ 16 
 
ANALYSIS DATASETS .............................................................................................................................. 21 
3.1 
REASONS FOR EXCLUDING SUBJECTS FROM ANALYSIS DATASETS ........................................................................... 21 
3.2 
STUDY DISCONTINUATIONS .......................................................................................................................... 21 
3.2.1 
PARTICIPANT WITHDRAWAL ........................................................................................................................ 21 
3.2.2 
PARTICIPANT DISCONTINUATION .................................................................................................................. 21 
3.2.3 
TEMPORARY DISCONTINUATION/TEMPORARY DELAY IN ENROLMENT .................................................................. 22 
3.2.4 
PARTICIPANT REPLACEMENT STRATEGY .......................................................................................................... 22 
3.3 
ANALYSIS DATASET DEFINITIONS.................................................................................................................... 22 
3.3.1 
Part 1 ................................................................................................................................................ 22 
3.3.1.1 
Enrolled ........................................................................................................................................ 22 
3.3.1.2 
Evaluable ...................................................................................................................................... 22 
3.3.1.3 
Safety Analysis Set (SAF) .............................................................................................................. 22 
3.3.1.4 
PK Analysis Set ............................................................................................................................. 22 
3.3.2 
Part 2 ................................................................................................................................................ 23 
3.3.2.1 
Enrolled ........................................................................................................................................ 23 
3.3.2.2 
Evaluable ...................................................................................................................................... 23 
3.3.2.3 
Safety Analysis Set (SAF) .............................................................................................................. 23 
3.3.2.4 
PK Analysis Set ............................................................................................................................. 23 
3.3.2.5 
Protocol deviations....................................................................................................................... 23 
 
ENDPOINTS/VARIABLES/ASSESSMENTS FOR ANALYSIS ......................................................................... 23 
4.1 
PART 1 .................................................................................................................................................... 23 
4.1.1 
PHARMACOKINETIC ENDPOINTS .................................................................................................................... 23 
4.1.2 
SAFETY ENDPOINTS .................................................................................................................................... 24 
4.2 
PART 2 .................................................................................................................................................... 24 
4.2.1 
EFFICACY ENDPOINTS .................................................................................................................................. 24 
4.2.1.1 
VIRAL LOADS/SHEDDING EVALUATIONS ...................................................................................................... 24 
4.2.1.2 
SYMPTOMS EVALUATION ......................................................................................................................... 24 
4.2.1.3 
WEIGHT OF MUCUS PRODUCED ................................................................................................................ 25 
4.2.1.4 
INCIDENCE OF INFECTION & ILLNESS .......................................................................................................... 25 
4.2.1.5 
TEMPERATURE ...................................................................................................................................... 29 
4.2.2 
SAFETY .................................................................................................................................................... 29 


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4.2.2.1 
Adverse events ............................................................................................................................. 29 
4.2.2.2 
Laboratory endpoints ................................................................................................................... 30 
4.2.2.3 
Other safety endpoints ................................................................................................................. 30 
4.2.3 
PHARMACOKINETIC ENDPOINTS .................................................................................................................... 31 
4.2.4 
OTHER ENDPOINTS – TERTIARY/EXPLORATORY ................................................................................................ 31 
 
STATISTICAL AND ANALYTICAL METHODS .............................................................................................. 31 
5.1 
GENERAL STATISTICAL CONSIDERATIONS ......................................................................................................... 31 
5.1.1 
Presentation of results ...................................................................................................................... 32 
5.1.2 
Significance testing and estimation.................................................................................................. 32 
5.2 
DATA HANDLING CONVENTIONS .................................................................................................................... 33 
5.2.1 
Definitions ........................................................................................................................................ 33 
5.2.1.1 
Baseline ........................................................................................................................................ 33 
5.2.1.2 
Quarantine discharge ................................................................................................................... 33 
5.2.2 
Retest, Outliers ................................................................................................................................. 33 
5.2.3 
Missing data and analysis rules ........................................................................................................ 33 
5.2.3.1 
Missing data ................................................................................................................................. 33 
5.2.3.2 
Analysis rules ................................................................................................................................ 34 
5.2.4 
Windows for time points .................................................................................................................. 35 
5.2.5 
Unscheduled visits ............................................................................................................................ 35 
5.3 
PLANNED ANALYSIS .................................................................................................................................... 35 
5.3.1 
Subject disposition and study discontinuations ................................................................................ 35 
5.3.2 
Protocol deviations ........................................................................................................................... 36 
5.3.3 
Demographics and baseline characteristics ..................................................................................... 36 
5.3.4 
Medical history – Previous medications ........................................................................................... 36 
5.4 
EFFICACY ANALYSES .................................................................................................................................... 36 
5.4.1 
PRIMARY EFFICACY ANALYSIS ........................................................................................................................ 36 
5.4.2 
SECONDARY EFFICACY ANALYSES ................................................................................................................... 37 
5.4.2.1 
VIRAL LOADS/SHEDDING EVALUATIONS ...................................................................................................... 37 
5.4.2.2 
SYMPTOMS EVALUATION ......................................................................................................................... 38 
5.4.2.3 
WEIGHT OF MUCUS PRODUCED ................................................................................................................ 39 
5.4.2.4 
INCIDENCE OF INFECTION & ILLNESS .......................................................................................................... 40 
5.4.2.5 
TEMPERATURE ...................................................................................................................................... 41 
5.4.3 
TERTIARY/EXPLORATORY EFFICACY ANALYSES .................................................................................................. 41 
5.5 
PHARMACOKINETIC (PK) ANALYSES ............................................................................................................... 42 
5.6 
SAFETY ANALYSES ...................................................................................................................................... 42 
5.6.1 
Extent of exposure and compliance .................................................................................................. 42 
5.6.2 
Adverse events.................................................................................................................................. 42 
5.6.3 
Laboratory safety variables .............................................................................................................. 43 
5.6.4 
12-Lead Electrocardiogram (ECG) .................................................................................................... 43 
5.6.5 
Physical examinations ...................................................................................................................... 44 
5.6.6 
Vital signs ......................................................................................................................................... 44 
5.6.7 
Concomitant medications ................................................................................................................. 44 
5.6.8 
ADA ................................................................................................................................................... 44 
5.6.9 
Other safety variables ...................................................................................................................... 44 
 
SUBGROUP ANALYSIS ............................................................................................................................ 45 
 
SEQUENCE OF ANALYSIS ........................................................................................................................ 45 
7.1 
INTERIM ANALYSIS ...................................................................................................................................... 45 
7.2 
FINAL ANALYSIS ......................................................................................................................................... 45 
7.3 
UNBLINDED STATISTICIAN ............................................................................................................................ 45 
 
DEVIATIONS FROM TRIAL PROTOCOL .................................................................................................... 46 


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SOFTWARE DOCUMENTATION ............................................................................................................... 47 
 
DERIVED DATA ....................................................................................................................................... 48 
 
TABLES, FIGURES AND LISTINGS ............................................................................................................. 49 
11.1 
LIST OF TABLES .......................................................................................................................................... 49 
11.2 
LIST OF FIGURES......................................................................................................................................... 52 
11.3 
LIST OF LISTINGS ........................................................................................................................................ 53 
 
REFERENCES ........................................................................................................................................... 54 
 
 
 
 


 
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Abbreviations and definitions 
ADA 
Anti-Palivizumab antibody  
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
APTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC 
Area Under the Curve 
BD 
Twice Daily 
BMI 
Body Mass Index 
BP 
Blood Pressure 
CI 
Confidence Interval 
CK 
Creatine Kinase 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CRP 
C-reactive Protein 
CS 
Clinically Significant 
CSR 
Clinical Study Report 
CV 
Coefficient of variation 
DBP 
Diastolic Blood Pressure 
ELISA 
Enzyme-linked Immunosorbent Assay 
EWV 
Early Withdrawal Visit  
ECG 
Electrocardiogram 
EOS 
End Of Study 
FEV 
Forced Expiratory Volume 
FOT 
Forced Oscillation Technique 
FSH 
Follicle Stimulating Hormone 
FVC 
Forced Vital Capacity 
FI 
Febrile Illness 
GAD 
Generalised Anxiety Disorder 
GP 
General Practitioner  


 
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HAV 
Hepatitis A 
HbA1c 
Haemoglobin A1c 
HBV 
Hepatitis B 
HCV 
Hepatitis C 
HIV 
Human Immunodeficiency Virus 
HR 
Heart Rate 
HVC 
Human Viral Challenge  
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G  
IMP 
Investigational Medical Product 
IV 
Intravenous  
LLOD 
Lower Limit Of Detection 
LLOQ 
Lower Limits Of Quantification 
LRT 
Lower Respiratory Tract 
LRTI 
Lower respiratory tract illness 
MCH 
Mean Corpuscular Haemoglobin 
MCHC 
Mean Corpuscular Haemoglobin Concentration 
MCID 
Minimal Clinically Important Difference 
MCV 
Mean Corpuscular Volume 
MCID 
Minimal Clinically Important Difference 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed Model for Repeated measures 
NA 
Not Applicable 
NCS 
Non-Clinically Significant 
NDA 
No Detectable Antibody 
NPS 
Nasopharyngeal Swab 
PCA 
Principal Component Analysis 
PCR 
Polymerase Chain Reaction 
PEF 
Peak expiratory flow 
PFU 
Plaque Forming Units 
PHQ 
Patient Health Questionnaire 
PK 
Pharmacokinetic 
PT 
Prothrombin Time 


 
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PT 
Preferred Term 
qRT-PCR 
quantitative Reverse Transcriptase-Polymerase Chain Reaction 
RBC 
Red Blood Cell 
RR 
Respiratory Rate 
RSV 
Respiratory Syncytial Virus  
SAE 
Serious Adverse Event 
SAF 
Safety dataset 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SI 
Systemic Illness 
SoA 
Schedule of Activities  
SOC 
System Organ Class 
SBP 
Systolic Blood Pressure 
T 
Troponin 
TDS 
Three Times Daily 
TEAE 
Treatment-Emergent Adverse Event 
TSH 
Thyroid Stimulating Hormone 
TSS 
Total Symptom Score  
ULOQ 
Upper Limit Of Quantification 
URT 
Upper Respiratory Tract 
URTI 
Upper respiratory tract illness 
VL 
Viral Load 
WBC 
White Blood Cell 
WHO 
Word Health Organization 
β-HCG 
β-human chorionic gonadotrophin 
 
 
 


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Introduction 
This document is the statistical analysis plan (SAP) for the MB05-P-01-20 study. The purpose of this 
SAP is to provide a comprehensive and detailed description of the statistical analyses that will be 
carried out to assess the clinical safety, pharmacokinetics/pharmacodynamics, immunogenicity, and 
efficacy of the study treatment, as outlined in the study protocol version 2 dated 22 May 2020. The 
SAP pre-specifies the statistical approaches to be used and is validated prior to the study database lock 
or to any unblinded interim look at the data. 
 
 
Highlights from study protocol 
2.1 
Background/Rationale 
Full details of the background and rationale for the study are provided in Section 1.1.2 of the protocol. 
2.2 
Study Objectives 
2.2.1 Part 1 
 
Objective 1: To confirm the planned dose of Palivizumab to be given to participants in Part 2 
 
Objective 2: To assess safety of Palivizumab in healthy adults 
 
2.2.2 Part 2 
 
Objective 1: To estimate the margin and variance of prophylactic effect of Intravenous (IV) 
treatment with Palivizumab administered 1 day prior to inoculation in the RSV human 
challenge model in healthy adults compared to Placebo [assessed by quantitative reverse 
transcriptase-polymerase chain reaction (qRT-PCR)]. 
 
 
Objective 2: To estimate the margin and variance of prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to inoculation in the RSV human challenge model in 
healthy adults compared to Placebo [assessed by cell culture (pfu/mL)]. 
 
 
Objective 3: To estimate the margin and variance of prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to inoculation in the RSV human challenge model in 
healthy adults compared to Placebo [assessed by total symptom score (TSS) Area-Under-the-
Curve (AUC)]. 
 
 
Objective 4: To estimate the margin and variance of prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to inoculation in the RSV human challenge model in 
healthy adults compared to Placebo [assessed by total symptom score (TSS)]. 
 
 
Objective 5: To estimate the margin and variance of prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to inoculation in the RSV human challenge model in 
healthy adults compared to Placebo [assessed by total weight of nasal discharge produced and 
the total number of tissues used in each group]. 
 


 
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 
Objective 6: To estimate the margin and variance of prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to inoculation in the RSV human challenge model in 
healthy adults compared to Placebo [assessed by viral shedding of RSV-A Memphis 37b in nasal 
samples, in terms of incidence, duration, and peak]. 
 
 
Objective 7: To estimate the margin and variance of prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to inoculation in the RSV human challenge model in 
healthy adults compared to Placebo [assessed by symptomatic infection in terms of incidence, 
duration, and peak symptom score]. 
 
 
Objective 8: To assess safety of Palivizumab in the RSV human challenge model in healthy 
adults 
 
 
Objective 9: To assess the pharmacokinetics of Palivizumab in the RSV human challenge model 
in healthy adults 
 
 
Objective 10: To assess the Anti-Palivizumab antibody (ADA) in the RSV human challenge 
model in healthy adults 
 
 
Objective 11: To assess lung function in relation to RSV Infection (optional) 
 
 
Objective 12: To explore the Minimal Clinically Important Difference (MCID) in instrument 
change (optional) 
 
 
Objective 13: To explore the margin and variance of prophylactic effect of IV treatment with 
Palivizumab administered 1 day prior to inoculation in the RSV human challenge model in 
healthy adults compared to Placebo in relation to baseline immune status. (optional) 
 
 
Objective 14: To explore the host-pathogen relationship in the RSV human challenge model in 
healthy adults (optional) 
 
2.3 Investigational plan 
2.3.1 
Study design 
This is an exploratory study in healthy adult volunteers aged 18-55 years. The study is formed of two 
parts, Part 1 (PK sentinel Part), and Part 2 (Viral Challenge Part). 
 
2.3.1.1 Part 1 
All participants in part 1 will receive: 
 
Reference article product 
o Palivizumab (Synagis™) 
o Dose: 8mg/Kg 
If there are no safety concerns in Part 1, and PK analysis of Palivizumab treated participants confirms 
dose level 8mg/Kg to be appropriate, Part 2 will commence with the planned 8mg/Kg treatment 
dose. 


 
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However, if PK analysis of Part 1 suggests that 8mg/kg may be an insufficient dose to provide suitable 
efficacious coverage in Part 2, then Part 2 will proceed with a dose of 15mg/Kg. 
 
2.3.1.2 Part 2 
Participants in Part 2 will be randomised to receive the following on Day -1: 
 
Reference article product 
o Palivizumab (Synagis™) 
o Dose: either 8mg/Kg or 15mg/Kg (as determined from Part 1) 
 
Placebo product 
o Sodium Chloride 0.9% Solution (Normal Saline) matched to reference article product 
 
All participants in Part 2 will subsequently receive the following on Day 0: 
 
RSV challenge virus 
o RSV-A Memphis 37b, total dose of approximately 4.5 log10 plaque forming unit, 
given intranasally 
 
2.3.2 
Determination of sample size  
2.3.2.1 Part 1 
Approximately 6 participants will be enrolled in Part 1 of the study for an estimated total of 6 
evaluable participants. Six evaluable participants are considered sufficient to achieve the objectives 
of Part 1. 
 
2.3.2.2 Part 2 
Approximately 50 participants will be enrolled in Part 2 of the study for an estimated total of 25 
evaluable participants per intervention group. 
 
The sample size of 50 challenged and evaluable subjects (25 Palivizumab treated subjects and 25 
placebo subjects) in part 2 of the study was calculated based on the assumptions (obtained from the 
placebo group of prior publications of RSV challenge studies) of an infection rate of 73.7%, a mean 
area under the viral load-time curve (VL-AUC) of RSV-A Memphis 37b as determined by qRT-PCR on 
nasal samples in the placebo arm of 20.3 hours*Log10 copies/mL with corresponding SD of 17.8 and 
CV of 87.9%. Based on these assumptions, and using a 0.05 two-sided type one error probability, the 
50 challenged and evaluable subjects will ensure a power of 80% to the detection of a reduction of at 
least 70% in VL-AUC. 
Using a 0.1 two-sided type one error probability, the 50 challenged subjects will ensure a power of 
80% to the detection of a reduction between 60 and 65% in VL-AUC. 
 
Reduction in VL-AUC 
50% 
55% 
60% 
65% 
70% 
75% 
80% 
N/group for 80% power, 
5% two-sided 
49
40
34
29
25
22
19
Power,  5% two-sided with 
25 subjects 
0.522 
0.601 
0.660 
0.729 
0.800 
0.843 
0.886 
Power, 10 % two sided 
with 25 subjects 
0.644 
0.716 
0.781 
0.835 
0.881 
0.916 
0.940 


 
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Document Version: v3 
Statistical Analysis Plan 
 
Confidential 
 
Page 13 of 54 
 
 
 
2.3.3 Study assessments and study plan 
2.3.3.1 Part 1 
The total duration of study participation for a participant is up to approximately 50 days, with the following 
sequence and duration of study periods:  
 
Screening phase: from Day -28 to Day -1 pre-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 Unit for 1 days (from Day 0 to Day +1). 
Procedures will include: 
o Admission to Unit on Day 0 
o Study intervention Intravenous (I.V.) dosing on Day 0 
o Post infusion monitoring and PK Day 0 and Day 1 
o Participants will be discharged from the Unit on Day 1 (or may remain longer at the 
Principal Investigator’s discretion) 
 
Outpatient phase: study assessments will be conducted at follow up clinic visits and telephone 
calls as follows: 
o Clinic visits: Day 2, Day 3, Day 7 (±1 day) and Day12 
o Final safety follow-up by telephone: Day 18 (±3 days). 
 
 


 
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Statistical Analysis Plan 
 
Confidential 
 
Page 14 of 54 
 
 
Study Phase  
Clinic Screening Phase* 
Overnight stay 
Clinic visits 
Phone call 
Study Day 
Day -28 to Day -1 
Day 0 
Day 1 
Day 2 
Day 3 
Day 7(± 1day) 
Day 12 
Day 18 (± 3 days) 
Procedure 
Written consent (a)
X
X
Eligibility criteria (+)
X
X
Medical & medication history 
X 
 
Change In medical & medication history 
 
X 
 
 
 
 
 
 
Demographics
X
Height & weight, BMI (b)
X
X
Complete physical examination (c)
X
X
X
X
Vital signs (HR, RR, SBP, DBP, SpO2 )(d)
X
BD
X
X
X
X
X
Tympanic temperature (d)
X
BD
X
X
X
X
X
12-lead ECG 
X 
X 
Spirometry  
X 
 
Urine drugs of abuse screen
X
X
Urine pregnancy test
X
X
X
Urinalysis
X
X
Alcohol breath test
X
Product Administration
IMP/Placebo Dosing (e)
X
Collection of blood samples 
Pharmacokinetic sample (f)
8 X
X
X
X
X
X
ADA
X
X
X
HIV, Hepatitis A, B, & C
X
Haematology (h)
X
X
Biochemistry (h)
X
X
Thyroid function test
X
Serum FSH (post-menopausal women) (i)
X
Serum β-HCG pregnancy test (all females) (j) 
X 
  
  
  
  
  
 
  
Safety Assessments
Adverse Events (k)
Concomitant medications(k)
 
 
 


 
Document Number or Project Identification: VH0001 / MB05-P-01-20 
Document Version: v3 
Statistical Analysis Plan 
 
Confidential 
 
Page 15 of 54 
 
 
KEY NOTES FOR PART 1 SCHEDULE OF EVENTS 
X 
Once 
BD 
Twice Daily, collected pre and post-dosing. 
+ 
Only the applicable Inclusion/Exclusion criteria will be reviewed at each time point. 
* 
All screening assessments will be performed under hVIVO Generic Screening process. Results of tests or examinations performed under hVIVO Generic Screening process, and within 28 days prior to 
study Day 0 may be used to determine eligibility without the need to repeat the assessment following study specific consent. 
a 
Study specific consent may occur on Day 0, providing all required eligibility information has been collected through hVIVO Generic Screening process.  
b 
On Day 0, only weight will be measured pre-dosing as individual doses are defined by weight. 
c 
Day 0 physical examination will be performed pre-dose.
Day 1 physical examination will be performed pre-discharge. 
d 
Vital signs will be measured pre- and post-dose. 
e 
IV drug delivery (approximately 20minutes infusion). 
f 
PK blood samples are taken before the start of infusion; at end of infusion, 15mins and 0.5, 1, 4, 8, 12 h; and at 1, 2, 3, 7, 12 days after infusion. 
g 
ADA blood samples are taken pre infusion and at 7 and 12 days after infusion. 
h 
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 PI discretion). 
i 
A serum follicle stimulating hormone (FSH) test will be performed in all post-menopausal women. 
i 
Blood serum pregnancy test (ß-HCG) will be performed in all female participants who have been tested positive for urine pregnancy testing 
k 
Adverse events and concomitant mediations are reviewed throughout the study including pre and post dosing with Palivizumab. 
 
 


 
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Document Version: v3 
Statistical Analysis Plan 
 
Confidential 
 
Page 16 of 54 
 
 
2.3.3.2 Part 2 
The total duration of study participation for a participant is up to approximately 122 days, with the 
following sequence and duration of study periods:  
 
Screening phase: from Day -90 to Day -4 pre-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 -3 to Day 12). Procedures will include: 
o Pre-human viral challenge (HVC):  
- 
Admission to Quarantine Unit on Day -3 
- 
Study intervention I.V. dosing on Day -1 
o HVC:  
- 
Challenge Virus inoculation on Day 0  
o Post-HVC 
- 
Day 0 onwards and each day – study assessments will be 
conducted as per Schedule of Activities 
- 
Participants will be discharged from the Quarantine Unit on 
Day 12 (or may remain longer at the Principal Investigator’s 
discretion) 
 
Outpatient phase: study assessments will be conducted 
o Clinic visit for PK sample on Day 20 (±2 days) 
Final safety follow-up visit(s): Day 28 (±3 days) 
 
 
*NOTE: Release from quarantine is foreseen at Day 12 in case no virus is detected by PCR (PCR below Ct cut-off) and the 
participant has no clinically significant symptoms. If the participant continues to have clinically significant symptoms and/or 
detectable virus on Day 12, additional extended quarantine stay may be required at the discretion of the Investigator 


 
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Document Version: v3  
Statistical Analysis Plan 
 
Confidential 
 
Page 17 of 54 
 
 
Study Phase  
Screening 
Phase* 
QUARANTINE ISOLATION 
  
Clinic visit 
  Early 
withdrawal 
visit 
Admission 
to 
quarantine 
Dosing 
Human Viral Challenge 
(HVC) 
Post HVC Days 
Dis 
charge 
  
Study Day  
Day -56 to 
Day -4 
(Day -90 for 
RSV 
serology) 
Day 
Day 
Day 
Day 0 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 28 
(± 3 
days) 
  
 
Procedure  
 
-3 
-2 
-1 
Pre 
Chall-
enge 
Post 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
20 (± 2 
days) 
 
  
 
Written consent 
(m) 
X 
X 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
  
 
Eligibility criteria 
(+) 
X 
Xl 
X 
X 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
  
 
Medical & 
medication 
history 
X 
  
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
  
 
Change In 
medical& 
medication 
history 
 
Xl 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Height & 
weight, BMI (a) 
X 
Xl 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
 
(X) 
 
(X) 
  
(X) 
Alcohol breath 
test 
X 
Xl 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
X 
  
X 
Urinalysis 
X 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
  
X 
Urine drugs of 
abuse  
X 
Xl 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
X 
  
X 
Urine pregnancy 
test 
X 
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
X 
 
X 
Complete 
physical 
examination 
X 
Xl 
X 
X 
 
  
  
  
  
X  
  
  
X  
  
  
  
  
X 
 
X 
  
X 
Directed 
physical 
examination (inc 
nasal) 
 
 
 
 
 
X  
X  
X  
X 
 
X  
X 
 
X  
X  
X  
X 
 
 
 
  
 
Vital signs (HR, 
RR, SBP, DBP, 
SpO2  (b) 
X 
X  
TDS 
TDS 
TDS 
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
X 
 
X 
  
X 
Tympanic 
temperature 
X 
X  
TDS 
TDS 
TDS 
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
X 
 
X 
  
X 
Symptom diary 
card 
 
X  
TDS 
TDS 
TDS 
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
TDS  
X 
 
 
  
 


 
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Statistical Analysis Plan 
 
Confidential 
 
Page 18 of 54 
 
 
Study Phase  
Screening 
Phase* 
QUARANTINE ISOLATION 
  
Clinic visit 
  Early 
withdrawal 
visit 
Admission 
to 
quarantine 
Dosing 
Human Viral Challenge 
(HVC) 
Post HVC Days 
Dis 
charge 
  
24-hour tissue 
count & nasal 
discharge 
weight (c) 
 
  
 
X 
X 
X  
X  
X  
X 
X 
 
X  
X  
X  
X  
X  
X  
X 
 
 
 
(X) 
12-lead ECG 
X 
Xl 
X0 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
 
 
X 
  
X 
Spirometry (d) 
X 
Xl 
X 
X 
 
 
(X)  
(X)  
(X)  
X  
(X)  
(X)  
X  
(X)  
(X)  
(X)  
X  
X 
 
X 
  
X 
PEF (d) 
 
  
X 
X 
X 
 
  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X 
 
X 
 
X 
FOT (d) 
 
  
(X) 
(X) 
(X) 
 
  
(X)  
(X)  
(X)  
(X)  
(X)  
(X)  
(X)  
(X)  
(X)  
(X)  
(X)  
(X) 
 
 
 
 
Patient Health 
Questionnaire 
(PHQ-9) 
(X) 
(X)
l 
 
 
  
  
  
  
  
  
  
  
  
  
  
 
 
 
  
 
Generalised 
Anxiety Disorder 
Questionnaire 
(GAD-7) 
(X) 
(X)
l 
 
 
  
  
  
  
  
  
  
  
  
  
  
 
 
 
  
 
Product Administration 
  
Randomisa-tion 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
IMP/Placebo 
Dosing 
 
  
 
X 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
    
Challenge Virus 
inoculation 
 
  
 
 
 
X 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
    
Collection of blood samples 
  
Pharmacokinetic 
sample(j) 
 
 
 
8 X 
X 
X 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
    
Anti-
Palivizumab 
antibody 
(ADA)(q) 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
  
 
Serum FSH-
(post-
menopausal 
women) (e) 
X 
  
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
  
 
Serum β-HCG 
pregnancy test 
(all females) (f) 
 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
(X) 
HIV, Hepatitis A, 
B, & C 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Haematology (g) 
X 
Xl 
 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
(X) 
 
X 
  
X 
Biochemistry 
X 
Xl 
 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
(X) 
 
X 
  
X 
Coagulation 
X 
Xl 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
X 
Cardiac 
enzymes 
X 
Xl 
 
 
 
 
 
  
 
X 
 
 
X 
 
 
 
X 
 
 
 
  
 


 
Document Number or Project Identification: VH0001 / MB05-P-01-20 
Document Version: v3  
Statistical Analysis Plan 
 
Confidential 
 
Page 19 of 54 
 
 
Study Phase  
Screening 
Phase* 
QUARANTINE ISOLATION 
  
Clinic visit 
  Early 
withdrawal 
visit 
Admission 
to 
quarantine 
Dosing 
Human Viral Challenge 
(HVC) 
Post HVC Days 
Dis 
charge 
  
Thyroid function 
test 
X 
(X)
l 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Blood sample 
for serum 
markers (h) 
X 
Xl 
 
Xn 
 
 
  
  
  
  
  
  
  
  
  
  
  
 
 
X 
  
X 
Collection of respiratory samples 
  
Nasopharyngeal 
swab / nasal 
wash - 
Respiratory 
pathogen 
screen (i) 
T  
Xl  
(X)
n 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
Nasopharyngeal 
swab / nasal 
wash for Rapid 
viral antigen 
test or PCR 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
(X)n 
 
 
 
(X) 
Nasopharyngeal 
swab / nasal 
wash Virology 
(k)  & 
exploratory 
research 
T 
 
X 
 
 
 
 
 
BD 
BD 
BD 
BD 
BD 
BD 
BD 
BD 
BD 
BD  
X 
 
 
  
X 
Safety Assessments 
 
 
Adverse events 
(p) 
X 
 
 
 
X 
Concomitant 
medications (p) 
X 
 
  
  
X 
 
KEY NOTES FOR PART 2 SCHEDULE OF EVENTS 
X  
Once 
BD  
Twice Daily, 12 hours between assessments (± 1 hour). 
TDS  
Three Times Daily, at the same time each day (± 1 hour). 
T  
To determine tolerance of the procedure only (sample will not be tested). 
+  
Only the applicable Inclusion/Exclusion criteria will be reviewed at each time point. 


 
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Statistical Analysis Plan 
 
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Page 20 of 54 
 
 
* 
All screening assessments will be performed under hVIVO Generic Screening process. Results of tests or examinations performed under hVIVO Generic Screening process, and within 90 days (90 days for 
viral serology and  56 days for other assessments including safety laboratory test) prior to quarantine admission may be used to determine eligibility without the need to repeat the assessment following 
study specific consent. 
a 
Height will be taken at Screening only. 
b 
Vital signs will be taken at the same time each day (± 1 hour). 
c 
Distribution of paper issues and bags will start on Day -2, with the first collection on Day -1. Thereafter collection of tissues will occur at the same timepoints (± 1 hour) with tissues distributed 24 h 
ahead.  
d 
 Assessments will be performed at the same time each day during quarantine (± 1 hour). Where respiratory assessments timepoints occur together, the order of assessments will typically be 1) FOT 
followed by 2) PEF followed by 3) Spirometry. 
e 
A serum follicle stimulating hormone (FSH) test will be performed in all post-menopausal women 
f 
Blood serum pregnancy test (ß-HCG) will be performed in all female participants 
g 
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 PI discretion). 
h 
Virus serology (RSV neutralisation antibody assay) will be performed to determine eligibility and seroconversion. Exploratory RSV-induced immune responses may also be assessed. 
i 
Nasopharyngeal swab or nasal wash for respiratory virus screen to assess for the presence of other respiratory viruses; if found positive the participant will not be eligible for the current quarantine.  
Nasopharyngeal swab or nasal wash for respiratory virus screening includes a Covid-19 test 
j 
PK blood samples are taken before the start of infusion; at end of infusion, 15mins, and 0.5, 1, 4, 8, and 12 h after infusion; and at 1, 2, 3, 7, 13, 21 and 29 days after infusion.  
k 
Post inoculation Nasal virology samples will be collected at the same time each day during quarantine (± 1 hour) and used for qRT-PCR and viral culture assay. Optional exploratory RSV-induced immune 
responses may also be assessed.  Nasal wash is optional under PI discretion, if NPS are being collected BD and used for viral load assessments. 
l 
Can be performed on Study Day -3 or Study Day -2. 
m 
Study specific consent may occur on the day of admission, providing all required eligibility information has been collected through hVIVO Generic Screening process 
n 
Optional and may be collected or not as per PI discretion for exploratory research 
0 
Post-dose ECG 
p 
Adverse events and concomitant mediations are reviewed throughout the study including pre and post dosing with Palivizumab/Placebo and pre and post inoculation.  
q 
ADA blood samples are taken pre infusion and at 7,13 and 29 days after infusion.  
Notes: 
Parenthesis indicates the assessment may be optional, or at the PI's discretion.  
For all participants TDS assessments will commence on Day 0, the first assessment will be pre-virus challenge. 
The PI may perform additional safety assessments as required. 
Where any nasal sampling time points occur together, the order of sampling will typically be (1) Nasopharyngeal swab followed by (2) Nasal wash.  


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Document Version: v3 
Statistical Analysis Plan 
 
Confidential 
 
Page 21 of 54 
 
 
 
Analysis datasets 
3.1 Reasons for excluding subjects from analysis datasets 
The final selection of subjects for the analysis populations will be discussed in the Data Review Meeting 
(DRM). Reasons for exclusion of subjects from analysis sets will be documented in the DRM minutes. 
 
3.2 
Study discontinuations 
3.2.1 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 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 (EWV) should be carried out, 
and if clinically indicated, the participant should be invited back for a final follow up visit. If a 
participant withdraws from the study during the quarantine phase, an EWV will be completed on the 
day where possible prior to the participant leaving the unit. It is likely that some of the assessments 
required as part of the EWV will already have been performed for the study day as per SOA, in this 
case the completed assessments will not be repeated on the same day unless clinically indicated. 
The sponsor should be notified of all study withdrawals in a timely manner, and in cases where the 
withdrawal is due to a medical reason the participant would be referred to his/her GP. 
Participants will be counselled that early withdrawal from the viral challenge phase of the study is 
strongly discouraged, as it may pose a risk both to the participant and his/her contacts. In the event 
of a participant insisting on early withdrawal during the challenge isolation period, the participant 
will be encouraged to stay and would be advised of the potential risks of carrying RSV infection into 
the community, and to vulnerable groups in particular. 
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 Investigator must document this in the site study records. 
 
3.2.2 Participant Discontinuation 
Participants will be withdrawn from study intervention for the reasons listed below. These 
participants must not receive any additional intervention but should continue to be followed for 
safety. Additional unscheduled visits may be performed for safety reasons. 
 
Non-compliance with the study requirements and restrictions. 
 
Clinically significant abnormal laboratory findings, which in the opinion of the Investigator(s) 
and/or Sponsor, precludes further participation in the study. 
 
Development of inter-current illness which, in the opinion of the Investigator would 
compromise the health of the participant or the study objectives. 
 
The 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 Investigator(s) or Sponsor for safety, 
behavioural, or administrative reasons. 
 
The wish of the participant. 


 
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Statistical Analysis Plan 
 
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Page 22 of 54 
 
 
 
Any intervention related SAEs. 
 
Anaphylactic reaction following dosing. 
 
The participant becomes pregnant (if pregnancy is specified as an exclusion criterion). 
Participants who are withdrawn from the study, will be requested to attend an Early Withdrawal 
Visit, with assessments as detailed in the SoA. 
 
3.2.3 
Temporary Discontinuation/Temporary Delay in Enrolment 
At the first study visit, if a participant is found to be ineligible due to transient circumstances (such as 
acute disease and/or fever), dosing with Palivizumab will be postponed until transient circumstances 
have been resolved and the participant will be re-invited to a later quarantine group within the 
allowed time window. 
 
3.2.4 Participant Replacement Strategy 
Participants who withdraw or are discontinued from the study may be replaced in order to achieve the 
planned evaluable number of participants as follows, if deemed appropriate by the PI and with the 
approval of the Sponsor: 
 
In Part 1, withdrawals or early discontinuation prior to the completion of all scheduled clinic 
visits up to and including Day 12 Visit may be replaced.  
 
In Part 2, participants who have been dosed but not inoculated may be replaced. The 
replacement participant will be assigned to the same group as the original (discontinued) 
participant.  
Participants who have been dosed and inoculated but did not complete the study may be 
replaced. 
 
 
3.3 
Analysis dataset definitions 
3.3.1 
Part 1 
3.3.1.1 
Enrolled 
All participants who signed the informed consent. 
3.3.1.2 
Evaluable 
All participants assigned to study intervention and who take a dose of study treatment and who 
complete visit Day 12 except those participants with protocol deviations that lead to exclusion. 
3.3.1.3 
Safety Analysis Set (SAF) 
All participants assigned to study intervention and who take a dose of study treatment. 
3.3.1.4 
PK Analysis Set 
The PK Analysis set is defined as all participants with at least one postdose PK result. 
 


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Statistical Analysis Plan 
 
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Page 23 of 54 
 
 
3.3.2 
Part 2 
3.3.2.1 
Enrolled 
All participants who signed the informed consent and randomised to study treatment. 
3.3.2.2 
Evaluable 
All participants randomly assigned to study intervention and who take a dose of study treatment, are 
given viral challenge, and who complete quarantine. Except those participants with protocol 
deviations that lead to exclusion. 
3.3.2.3 
Safety Analysis Set (SAF) 
All participants randomly assigned to study intervention and who take a dose of study intervention, 
regardless of whether they received the challenge virus or not. Participants will be analysed 
according to the intervention they actually received. 
3.3.2.4 
PK Analysis Set 
The PK Analysis set is defined as all participants with at least one post-dose PK result. 
3.3.2.5 
Protocol deviations 
All deviations will be reviewed and adjudicated as either major with potential impact on efficacy 
evaluation, major deviations without impact on efficacy evaluation or minor deviations during the blind 
review meeting, before database lock and code break. 
 
Major protocol deviations are defined as deviations liable to either impact the rights, safety or well-
being of the patient or to prevent or change the interpretation of the results of the primary efficacy 
analysis of the study. 
The following deviations will be considered as major (this list is not exhaustive and will be reviewed at 
the time of the blind review meeting): 
 
 
non compliance with the inclusion or non inclusion criteria 
 
non compliance with the randomisation procedure 
 
non compliance with study treatment 
 
non compliance with challenge virus inoculation 
 
no post-baseline data for the primary efficacy endpoint 
 
intake of forbidden medication 
 
All other deviations will a priori be considered as minor deviations. 
 
 
Endpoints/Variables/Assessments for analysis 
4.1 
Part 1 
4.1.1 Pharmacokinetic endpoints 
 
Objective 1: 
o Evaluation of PK levels after intravenous administration of Palivizumab 
 


 
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Statistical Analysis Plan 
 
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Page 24 of 54 
 
 
4.1.2 Safety endpoints 
 
Objective 2: 
o Frequency and severity of Adverse Events (AEs) and serious AEs (SAEs) 
o Frequency and severity of Treatment Emergent Adverse Events (AEs) and serious AEs 
(SAEs) 
o Frequency and severity of drug related Treatment Emergent Adverse Events (AEs) and 
serious AEs (SAEs) 
 
4.2 
Part 2 
4.2.1 Efficacy endpoints 
4.2.1.1 Viral loads/shedding evaluations 
 
Obective 1:  
o Area under the viral load-time curve (VLAUC) of RSV-A Memphis 37b as determined by 
qRT-PCR on nasal samples collected twice daily starting two days postviral challenge 
(Day +2) up to the end of quarantine 
 
Objective 2:  
o Area under the viral load-time curve (VLAUC) of RSV-A Memphis 37b as determined by 
cell culture on nasal samples collected twice daily starting two days post-viral challenge 
(Day +2) up to the end of quarantine. 
 
Objective 6: 
o Peak 
 
Peak viral load of RSV-A Memphis 37b as defined by the maximum viral load 
determined by quantifiable qRT-PCR measurements in nasal samples starting 
two days post-viral challenge (Day +2) up to the end of quarantine. 
 
Peak viral load of RSV-A Memphis 37b as defined by the maximum viral load 
determined by quantifiable cell culture measurements in nasal samples 
starting two days post-viral challenge (Day +2) up to the end of quarantine. 
o Duration 
 
Number of days with quantifiable qRT-PCR measurements in nasal samples 
starting two days post-viral challenge (Day +2) up to the end of quarantine. 
 
Number of days with quantifiable cell culture measurements in nasal samples 
starting two days post-viral challenge (Day +2) up to the end of quarantine. 
 
Duration of virus shedding : The time (hours) from first detectable until first 
confirmed undetectable assessment after their peak measure (after which no 
further virus is detected).  
 
Time to Peak Virus Shedding: The time (days) from inoculation until the peak of 
virus shedding (qPCR) 
4.2.1.2 Symptoms evaluation 
 
Objective 3:  
o Area under the total symptom score-time curve (TSS-AUC) collected daily in the 
participant symptom diary card starting one day post-viral challenge (Day +1) up to 
the end of quarantine. 
 
Objective 4:  


 
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o Total symptom score sum-time curve (TSS-Sum) collected daily in the participant 
symptom diary card starting one day post-viral challenge (Day +1) up to the end of 
quarantine. 
 
Objective 7:  
o Peak symptom score defined by the maximum daily sum of Symptom score starting 
one day post-viral challenge (Day +1) up to the end of quarantine. 
o Number of days with symptoms of grade 2 or more, starting one day post-viral 
challenge (Day +1) up to the end of quarantine. 
 
4.2.1.3 Weight of mucus produced 
 
Objective 5: 
o Total weight of nasal discharge produced starting one day post-viral challenge (Day 
+1) up to the end of quarantine. 
o Total number of tissues used by participants starting one day post-viral challenge 
(Day +1) up to the end of quarantine. 
 
4.2.1.4 Incidence of infection & illness 
o Objective 6: 
o Incidence of laboratory-confirmed infection (variant 1 as below) 
o Incidence of laboratory-confirmed infection (variant 2 as below) 
o Objective 7: 
o “Laboratory-confirmed virus-like-illness” (variant 3, as below), as defined by: 
 
Incidence of “laboratory-confirmed infection”, and 
 
At least one grade 2 symptom from one or more respiratory categories from 
the participant symptom diary card 
o “Laboratory-confirmed virus-like-illness” (variant 1, as below) 
o “Laboratory-confirmed virus-like-illness” (variant 2, as below) 
o Upper respiratory tract illness (URTI) 
o Lower respiratory tract illness (LRTI) 
o Systemic illness (SI) 
o Febrile Illness (FI) 
o Fold seroconversion 
 
 
 


 
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Laboratory-confirmed infection 
“Laboratory-confirmed infection” is defined as the presence of “viral shedding”, measured in nasal 
samples. Subjects with incomplete qPCR data and no recorded data meeting the definition will be 
treated as not having met the criteria for Laboratory-confirmed RSV infection. 
 
Viral shedding (variant 1) 
One or both of the following definitions must be met: 
 
At least 2 positive quantifiable detections by viral load qPCR assay specific for the challenge virus, 
reported within 4 consecutive scheduled assessments and from 2 independent samples from Day 
+2 until discharge (For clarification, see some examples in table below) 
 
Examples of Viral Load qPCR Assay Values (only) and Evidence of Viral Shedding. 
Assessment n# 
Assessment n+1* 
Assessment n+2* 
Assessment n+3* 
Viral shedding? 
Detected 
Detected 
Detected 
Detected 
No 
1.456 
2.359 
Any value 
Any value 
Yes 
0.956 
Detected 
3.647 
Any value 
Yes 
3.452 
Not detected 
Detected 
0.956 
Yes 
Not Detected 
2.359 
Not detected 
4.852 
Yes 
Not Detected
1.128
3.647
Not detected
Yes
1.567
Not detected
Not detected
Detected
No
1.5567 
Not detected 
Not detected 
2.434 
Yes 
 
qPCR data are scheduled to be collected twice daily (morning and evening). 
# Assessment n may be on the morning or evening of any given day. 
* n+1, n+2 and n+3 are the scheduled assessments following assessment n and independent of study day. For 
example, Assessment n could be Day 2 evening and Assessment n+3 could be Day 4 morning. 
 
 
One positive detection by viral load qPCR assay, specific for the challenge virus, in which an aliquot 
of the same sample has also tested positive in a viral culture assay appropriate for detecting the 
challenge virus (i.e. cell-based infectivity assay) from Day +2 until discharge. 
 
For qPCR and the cell-based infectivity assay, a positive detection is any positive numeric or ‘Detected’ 
value. A quantifiable detection value is any numeric value and will exclude ‘Detected’ and ‘Not 
detected’ values. 
 
Viral shedding (variant 2) 
One or both of the following definitions must be met: 
 
At least 2 positive detectable assessments by viral load qPCR assay specific for the challenge virus, 
reported within 4 consecutive scheduled assessments and from 2 independent samples from Day 
+2 until discharge 
 
 
One positive detection by viral load qPCR assay, specific for the challenge virus, in which an aliquot 
of the same sample has also tested positive in a viral culture assay appropriate for detecting the 
challenge virus (i.e. cell-based infectivity assay) from Day +2 until discharge. 
 
Laboratory-confirmed virus-like-illness (variant 1) 
Virus-like-illness (variant 1) is defined as the occurrence of laboratory-confirmed infection AND any of 
the following: 
 
Upper respiratory tract illness (defined below) 


 
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 
Lower respiratory tract illness (defined below) 
 
Systemic illness (defined below) 
 
Febrile illness (defined below). 
 
Laboratory-confirmed virus-like-illness (variant 2) 
Virus-like-illness (variant 2) is defined as the occurrence of laboratory-confirmed infection AND 
symptoms of either of the following: 
 
any two different self-reported diary card symptoms (≥ Grade 1), or 
 
at least one Grade 2 self-reported symptom from one or more respiratory categories (URTI and 
LRTI symptoms defined below). 
 
Laboratory-confirmed virus-like-illness (variant 3) 
Incidence of symptomatic RSV infection, as defined by occurence of “laboratory-confirmed infection”, 
AND at least one grade 2 symptom from one or more respiratory categories from the participant 
symptom diary card 
 
Note: Laboratory-confirmed virus-like-illness definitions will be derived with both Viral shedding 
definitions.  
 
Upper respiratory tract illness (URTI) 
A subject will be considered to have upper respiratory tract illness (URTI) if he/she has any one of 
thefollowing URT (diary card) self-reported symptom or any one of the following URT (directed physical 
examination (DPE)) sign on two consecutive scheduled assessments (from the last assessment on Day  
0 to quarantine discharge (including any extended quarantine period)), at least one must attain  Grade 
2 severity, or if any of the following attain Grade 3 severity once. URT (diary card) symptoms and URT 
(DPE) signs will not be combined in this algorithm and will be assessed and used separately. 
Self-reported symptoms (taken from symptom diary card): 
 
Rhinorrhea (runny nose) 
 
Nasal congestion (stuffy nose) 
 
Sore throat 
 
Sneezing. 
Physician findings (taken from DPE): 
 
Nasal discharge 
 
Otitis 
 
Pharyngitis 
 
Sinus tenderness. 
 
Lower respiratory tract illness (LRTI) 
A subject will be considered to have lower respiratory tract illness (LRTI) if he/she has any one of the 
following LRT (diary card) self-reported symptom or any one of the following LRT (DPE) sign on two 
consecutive scheduled assessments (from the last assessment on Day 0 to quarantine discharge 
(including any extended quarantine period)), at least one must attain Grade 2 severity, or if any of the 
following attain Grade 3 severity once. LRT (diary card) symptoms and LRT (DPE) signs should not be 
combined in this algorithm and should be assessed separately. 
Self-reported symptoms (taken from symptom diary card): 
• 
Cough 
• 
Shortness of breath 
• 
Chest tightness 


 
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• 
Wheezing. 
The individual LRT (physicians DPE) signs are: 
• 
New wheezes, rhonchi. 
 
Systemic illness (SI) 
A subject will be considered to have SI if he/she fulfils the criteria for any of the following; 
• 
febrile illness (defined below), 
• 
upper respiratory tract illness (defined above) 
• 
lower respiratory tract illness (defined above). 
AND 
• 
has any one of the following self-reported symptoms (diary card) on two consecutive 
scheduled assessments (from the last assessment on Day 0 to quarantine discharge (including 
any extended quarantine period)), at least one of which must attain grade 2 severity, or if any 
of the following attain grade 3 severity once: 
o Malaise 
o Headache 
o Muscles and/or joint ache 
o Chilliness / feverishness. 
 
Febrile Illness (FI) 
Febrile illness (FI) is defined as a tympanic temperature of ≥ 37.9oC occurring any time from the last 
assessment on Day 0 to quarantine discharge (including any extended quarantine period)). 
 
Fold seroconversion 
Seroconversion is defined as a ≥ 4-fold increase in RSV specific antibodies (measured by RSV 
Neutralisation Assay) from baseline to follow-up post-quarantine. 
 
Proportion (on any occasion, and on two separate occasions) of subjects with grade 2 or worse 
symptoms at any day and at each day post-Viral Challenge 
Subjects with incomplete data and no recorded symptoms meeting the definition for these endpoints 
will be treated as not having met the endpoint (i.e. did not experience symptoms of grade 2 or 
higher). 
 
Any Occasion 
o The proportion of subjects who develop any of the 13 individual symptoms of grade 2 or 
higher (on any occasion, from the last assessment on Day 0 to quarantine discharge 
(including any extended quarantine period)) will be calculated. A single occurrence of any 
of these individual symptoms (of grade 2 or higher) anytime in this period corresponds to 
meeting the endpoint.  
o In addition, the proportion of subjects who develop any of the 13 individual symptoms of 
grade 2 or higher, on any occasion for each day separately, will be calculated.  
 
Two Separate Occasions 
o The proportion of subjects who develop any of the 13 individual symptoms of grade 2 or 
higher (on two separate occasions on any day, from the last assessment on Day 0 to 
quarantine discharge (including any extended quarantine period)) will be calculated. Two 
occurrences of any of these individual symptoms (of grade 2 or higher) in this period 
corresponds to meeting the endpoint.  
o In addition, the proportion of subjects who develop any of the 13 individual symptoms of 
grade 2 or higher, on any two occasions for each day separately, will be calculated.  
 


 
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Proportion (on any occasion, and on two separate occasions) of subjects with any grade (i.e. grade 
≥1) at any day and at each day post-Viral Challenge 
Subjects with incomplete data and no recorded symptoms meeting the definition for these endpoints 
will be treated as not having met the endpoint (i.e. did not experience symptoms of any grade). 
 
Any Occasion 
o The proportion of subjects who develop any of the 13 individual symptoms of any grade 
i.e. grade ≥1 (on any occasion, from the last assessment on Day 0 to quarantine discharge 
(including any extended quarantine period)) will be calculated. A single occurrence of any 
of these individual symptoms of any grade anytime in this period corresponds to meeting 
the endpoint.  
o In addition, the proportion of subjects who develop any of the 13 individual symptoms of 
any grade on any occasion for each day separately, will be calculated.  
 
Two Separate Occasions 
o The proportion of subjects who develop any of the 13 individual symptoms of any grade 
i.e. grade ≥1 (on two separate occasions on any day, from the last assessment on Day 0 to 
quarantine discharge (including any extended quarantine period)) will be calculated. Two 
occurrences of any of these individual symptoms (i.e. grade ≥1) in this period corresponds 
to meeting the endpoint.  
o In addition, the proportion of subjects who develop any of the 13 individual symptoms of 
any grade i.e. grade ≥1, on any two occasions for each day separately, will be calculated.  
 
4.2.1.5 Temperature 
Using the scheduled protocol assessments from the last assessment on Day 0 to quarantine discharge 
(including any extended quarantine period), this endpoint corresponds to the highest tympanic 
temperature.  
 
 
4.2.2 Safety 
 The safety and tolerability will be evaluated by the monitoring of the occurrence of AEs and SAEs, 
clinical laboratory results, physical examinations, vital signs, electrocardiogram and concomitant 
medications.  
 
4.2.2.1 Adverse events 
Adverse events (AE) 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 Events (TEAE) will be defined as any adverse event that occurs from 
the time of first study treatment dose administered to the subject until last study visit, i.e. an AE that 
was not present prior to receiving the first dose of IMP. 
 
Serious adverse events (SAE) are those AE that put the life of the subject at risk or that cause serious 
or permanent damage to the subject's health. An AE is to be recorded and reported as SAE in the event 
of any of the following: 
o AE results in death 
o AE is life-threatening (i.e. constitutes an immediate threat to the subject's life) 


 
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o AE results in hospitalization of the trial participant or prolongs an existing hospitalization 
o AE results in persistent or significant disability or incapacity 
o AE is a congenital anomaly or birth defect. 
o AE is another medically important condition: to be completed 
 
Tolerability/safety will be assessed over the whole study period. 
 
o Objective 8:  
o Frequency and severity of Adverse Events (AEs) and serious AEs (SAEs) 
o Frequency and severity of Treatment Emergent Adverse Events (AEs) and serious AEs 
(SAEs)Frequency and severity of drug related Treatment Emergent Adverse Events 
(AEs) and serious AEs (SAEs) 
 
4.2.2.2 
Laboratory endpoints 
The following clinical laboratory tests are to be performed on collected blood samples: 
o Clinical chemistry: Sodium, Potassium, Glucose (random), Albumin, Chloride, Bicarbonate, 
Calcium, Uric acid, Total protein, Creatinine, Total, direct, and indirect bilirubin, Inorganic 
phosphate, Blood urea nitrogen, C-reactive protein (CRP), Gamma glutamyl transferase, 
Alkaline phosphatase (ALP), Alanine transaminase (ALT), Lactate dehydrogenase (LDH), 
Aspartate transaminase (AST), Urea 
o Hematology: Platelet Count, White blood cell (WBC) count (absolute), WBC differential 
(Neutrophils, Lymphocyte, Monocytes, Eosinophils, Basophils), Red blood cell (RBC) count, 
Reticulocyte count (% and absolute), Haemoglobin, Haematocrit, Mean corpuscular volume 
(MCV), Mean corpuscular haemoglobin (MCH), MCH concentration (MCHC). 
o Coagulation: Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) 
o Cardiac enzymes: Creatine Kinase (CK), CK-MB, Troponin (T)Urinalysis: Colour, Specific gravity, 
Appearance, pH, Presence of blood, glucose, leukocytes, ketones, nitrites, proteins, 
urobilinogen, bilirubin by dipstick, Microscopy, culture and sensitivity examination (If the 
dipstick yields abnormal results) 
4.2.2.3 Other safety endpoints 
4.2.2.3.1 Physical examinations 
A complete physical examination to include a full systemic assessment will be performed (General 
Appearance, Eyes, Ears, Nose, Throat, Head & Neck, Cranial Nerves/ Nervous System, Musculoskeletal 
Skin, Cardiovascular (heart sounds, pulses), Abdomen/GI system, Respiratory System (breath sounds, 
resonance, added sounds), Chest – Ausculation (breath sounds, crepitations, wheeze, pleural rub), 
Chest – Vocal Resonance, Chest – Percussion, Other Findings) 
 
Directed physical examinations will be conducted as deemed appropriate by the Investigator and will 
include examination of the 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] and on chest auscultation [wheezing or rhonchi, crepitations] will be performed. Physician-
reported assessments of viral challenge related illness will be graded in accordance with their intensity 
and documented in the source data. 
 


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Safety will be assessed based on abnormalities (normal, abnormal NCS, abnormal CS) for complete 
examination, and on grades for directed physical examination. 
4.2.2.3.2 Vital signs  
The following vital signs will be performed: 
o Weight (kg), Height (m/cm), BMI 
o Heart rate (HR) will be recorded in beats per minute. 
o Respiratory rate (RR): respirations will be counted and recorded as breaths per minute. 
o BP: systolic BP and diastolic BP will be measured in millimeters of mercury (mmHg); 
measurements will be made supine. 
o Peripheral arterial oxygen saturation (SpO2%) will be assessed using pulse oximetry 
Tympanic temperature (Celsius) 
4.2.2.3.3 Electrocardiograms (ECG) 
Twelve-lead ECGs will be obtained to evaluate the electrical activity of the heart. 
4.2.2.3.4 Concomitant medications 
Safety will also be assessed based on the analysis of Concomitant medications coded according to the 
latest available version of the WHO-Drug dictionary. 
"Concomitant" is defined as a medication which was taken during treatment, e.g. stop date later than 
randomization. 
All others will be considered “Prior”. 
4.2.2.3.5 ADA 
 
Objective 10: 
o Anti-Palivizumab antibody (ADA) through Day 28  
4.2.3 Pharmacokinetic endpoints 
 
Objective 9:  
o Palivizumab serum concentrations and serum PK parameters through study Day +28 
o Nasal concentrations (if done) and serum PK parameters through study Day +28 
 
4.2.4 Other endpoints – Tertiary/Exploratory 
 
Objective 12:  
o Assessments of spirometry, Peak Expiratory Flow (PEF), and Forced Oscillation Technique 
(FOT) 
 
Objective 13:  
o The average amount of instrument-assessed change for all participants who rate 
themselves as "a little better" or "somewhat better” 
 
Statistical and Analytical Methods 
5.1 
General statistical considerations 
The statistical analyses are performed in accordance with the ICH E9 guideline.  


 
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The statistical analyses will be performed by an external Contract Research Organisation (CRO), Venn 
Life Sciences, under the responsibility of the Sponsor. 
5.1.1 Presentation of results 
The following descriptive statistics will be presented: 
o For quantitative variables: number of available values (N), number of missing values, mean 
(Mean), standard deviation (SD), CV (Coeffcient Variation), median (Median), Q1 (or first 
quartiles), Q3 (third quartiles), minimum (Min), maximum (Max) values. When relevant, 
confidence intervals will be calculated for the mean (Student CI) or the median (Hahn & 
Meeker 1991). 
 
o For qualitative variables: number of available values, number of missing values, number and 
percentage of observations in each category of the variable. Except if otherwise specified, 
percentages will be calculated using the number of available values as denominator (i.e., not 
including missing values). When relevant, confidence intervals of proportions will be calculated 
using the Clopper-Pearson exact method (Clopper & Pearson 1934).  
 
All listing will be sorted by treatment group, subject number and time point if applicable.  
 
5.1.2 Significance testing and estimation 
When precised in section 5.3, between group comparisons will be performed using appropriate two-
sided hypothesis tests at the 5% two-sided significance level.  
For normally distributed continuous variables (either raw variable or log-transformed variables) the 
difference in means, the standard error and the 95% two-sided confidence interval (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% two-sided CI for the 
original variable will be presented. The t-test, or Mixed Model for Repeated measures (MMRM) will be 
used, depending on the endpoint. For endpoints that are not normally distributed (such as total 
symptom scores), the Wilcoxon Rank-Sum test will be used.  
The underlying assumptions of the MMRM presented in Section 5.4.2 will be checked by reviewing the 
standardized residuals (’Pearson’) of the model. If necessary, splines (random coefficient linear 
regression spline) models will be computed and their fit compared with the fit of the linear model using 
AICs to address potential departure from linearity. 
The underlying assumptions of the t-test will be checked by reviewing the distribution graphically and 
by reviewing the skewness, the kurtosis and the Shapiro-Wilks test. 
For categorical variables, differences in absolute frequency and/or relative risks will be presented, with 
their 95% two-sided CIs will be presented. Except otherwise specified, the Chi-square test will be used 
to compare frequencies between groups. 
P-values between 0.05 and 0.10 will be considered as indicative of a trend. 
As the study is explorative by nature, there will be no attempt to adjust for the multiplicity of 
endpoints. 
 


 
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5.2 
Data handling conventions 
5.2.1 
Definitions 
5.2.1.1 
Baseline  
Baseline is defined as the last non-missing measurement before dosing. This will usually correspond to 
the measurement performed at Day-1 before first-dose, unless overruled after review of data at the 
DRM or otherwise stated in the appropriate endpoint section(s) below, whatever the reason for that 
assessment (e.g. if it is a repeat assessment, then it should be used as the baseline). However, in case 
of missing value at Day-1 the last available value recorded during previous visits will be used as baseline 
value. 
If all pre-dose measurements are missing then baseline will be considered as missing, and no changes 
from baseline and no percentage reduction from baseline will be computed. 
 
5.2.1.2 
Quarantine discharge 
Unless otherwise specified, Quarantine Discharge refers to actual quarantine discharge regardless of 
whether discharge from quarantine occurred as scheduled on Day 12, or whether the subject entered 
an extended quarantine period. 
 
5.2.2 
Retest, Outliers 
5.2.2.1 Retests 
The retests will be managed as follow: 
o Any retest before baseline: the last available value before baseline will be used as the baseline 
o Any other retest: no value will be used except if otherwise specified during the data review 
meeting. 
5.2.2.2 Outliers 
All available data points will be included in analysis, unless a clear reason is available to exclude data. 
All outlier data will be reviewed during the data-review meeting and decisions regarding their use in 
the statistical analyses will be made. 
 
5.2.3 
Missing data and analysis rules 
5.2.3.1 
Missing data 
Missing or incomplete dates: 
o For calculation / sorting / assignation based on dates (e.g., treatment emergent AEs, 
concomitant medications…), the following rules will apply: 
o The most conservative approach will be considered (i.e., if the onset date of an 
AE/concomitant medication is missing / incomplete, it will be assumed to have occurred during 
the study treatment phase (i.e., a TEAE for AEs) except when the partial onset date or other 
available data indicates differently (e.g., start date day missing, but month before the month 
of baseline date, or stop date before baseline date). 
o 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. 


 
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o Assignations based on dates will be reviewed and confirmed or infirmed during the data review 
meeting 
o Missing or partial start or end dates of IMP administration, if any, will be reviewed during the 
data review meeting. 
 
o No other missing data will be imputed except if otherwise specified in Section 4, Section 5.3to 
5.6. 
 
5.2.3.2 
Analysis rules 
Analysis 
Associated 
Units 
Assay 
LLOD 
Assay 
LLOQ 
Result 
Reported 
results 
Analysis value 
RSV titre 
(qRT-PCR) 
Log10 
Copies/mL 
NA 
2.8* 
Quantifiable 
Titre 
Value 
Reported value 
DETECTED 
DETECTED 
 
LLOQ/2  
NOT 
DETECTED 
NOT 
DETECTED 
0 
INVALID 
INVALID 
Missing data 
point 
NOT TESTED 
NOT TESTED 
Missing data 
point 
RSV titre 
(Plaque 
assay) 
Log10 
PFU/mL 
 
1.7 
Quantifiable 
Titre 
Value 
Reported value 
>6.04 
>6.04 
6.04 (ULOQ) 
DETECTED 
DETECTED 
LLOQ/2 
NOT 
DETECTED 
NOT 
DETECTED 
0 
INVALID 
INVALID 
Missing data 
point 
NOT TESTED 
NOT TESTED 
Missing data 
point 
RSV 
antibody 
titre 
NAb 
10 
156 
NDA  
NDA 
LLOD 
>=10 and 
<156 
<156 
LLOQ/2 
Quantifiable 
Titre 
Value 
Reported value 
≥4209 
≥4209 
4209 (ULOQ) 
INVALID 
INVALID 
Missing data 
point 
NOT TESTED 
NOT TESTED 
Missing data 
point 
*The LLOQ is defined as a cycle threshold (Ct) value of 33.9. This equated to 2.8 Log10 copies/mL by 
utilisation of a target specific copy number standard curve included in each assay run of the assay 
validation.  
NA: Not Applicable 
NDA: No Detectable Antibody 
PFU: Plaque Forming Units 


 
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5.2.4 
Windows for time points 
All visits will be analyzed as entered in the database except if otherwise specified during the data-
review meeting. 
 
5.2.5 
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 
excpet if otherwise specified during data-review meeting. All data will be presented in the individual 
data listings and any relevant safety data will be described in the CSR. 
 
5.3 
Planned analysis 
 
Part 1:  
o PK analysis will be described in the separate PK analysis plan 
o Safety data will be reviewed during a Safety Data Review Meeting between the Sponsor 
and the investigator. The following safety data will be reviewed: Vital Signs (heart rate, 
blood pressure, respiratory rate, and pulse oximetry), Tympanic temperature, Physical 
examination, Safety laboratory values, Urinalysis, Adverse events, Serious Adverse events 
and Concomitant medication use.  
 
Part 2:  
o All statistical analysis are described below. 
o The list of statistical Tables, Figures and Listings are provided in Section 11. 
o Efficacy analysis will be on the evaluable population. The safety evaluation will be 
performed on the SAF population. 
 
5.3.1 
Subject disposition and study discontinuations 
Subject disposition will be described using a table (Statistical table 14.1.1). The following variables will 
be tabulated: 
• 
Number of enrolled patients 
• 
Number of randomized subjects 
• 
Number of randomized subjects per treatment group 
 
Study populations will be tabulated, total and per treatment group (Statistical table 14.1.2.1) along 
with reasons for exclusion from the Evaluable, SAF and PK analysis populations (Statistical tables 
14.1.2.2, 14.1.2.3 and 14.1.2.4 respectively). 
 
Study duration and premature study discontinuation will be summarized using the following variables 
(Statistical table 14.1.3) on SAF population: 
• 
Number of subjects who completed/discontinued the study, total and per treatment group  
• 
Reason of study discontinuation, total and per treatment group 
• 
Study duration, total and per treatment group 
 


 
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All reason for study discontinuation will also be presented in the Listing 16.2.1 along with end of study 
information. 
Visit dates (including date of consent) will be presented in Listing 16.2.4.13. 
Population membership and reason for exclusion will be also provided in Listing 16.2.3. 
 
5.3.2 
Protocol deviations 
All major and minor protocol deviations classified during the data-review meeting will be described in 
Statistical table 14.1.4 on SAF population and also be provided in Listing 16.2.2. 
 
5.3.3 
Demographics and baseline characteristics  
The following demographics variables will be summarized by treatment group on the Evaluable and 
SAF populations (Statistical table 14.1.5 and Listing 16.2.4.1): 
 
Gender 
 
Age 
 
Ethnicity  
The following baseline characteristics will be summarized by treatment group on SAF population: 
 
Weight, Height and BMI (Statistical table 14.1.6 and Listing 16.2.4.2) 
 
Alcohol breath test (Statistical table 14.1.7 and Listing 16.2.4.3) 
 
Urine drugs of abuse (Statistical table 14.1.8 and Listing 16.2.4.4) 
 
Urine pregnancy test (Statistical table 14.1.9 and Listing 16.2.4.5) 
 
Patient Health Questionnaire (PHQ-9) (Statistical table 14.1.10 and Listing 16.2.4.6) 
 
Generalised Anxiety Disorder Questionnaire (GAD-7) (Statistical table 14.1.11 and Listing 
16.2.4.7) 
 
HIV, Hepatitis A, B & C (Statistical table 14.1.12 and Listing 16.2.4.8) 
 
Thyroid function test (Statistical table 14.1.13 and Listing 16.2.4.9) 
 
Eligibility criteria, randomisation information will be presented respectively in Listings 16.2.4.10 and 
16.2.4.11) 
Nasopharyngeal swab / nasal swab respiratory Pathogen Screen data (including COVID-19 test) will be 
presented in listing 16.2.4.14. 
 
5.3.4 
Medical history – Previous medications 
Medical history will be presented by SOC & PT by treatment group (Statistical table 14.1.14). 
Previous medications will be presented by ATC code and Preferred Name by treatment group 
(Statistical table 14.1.15) 
Medical history for each subject will be reported in Listings 16.2.4.12.  
 
5.4 
Efficacy analyses 
5.4.1 Primary efficacy analysis 
Objective 1:  
To estimate the margin and variance of prophylactic effect of Intravenous (IV) treatment with 
Palivizumab administered 1 day prior to inoculation in the RSV human challenge model in healthy 


 
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adults compared to Placebo [assessed by quantitative reverse transcriptase-polymerase chain reaction 
(qRT-PCR)]. 
 
Area under the viral load-time curve (VL-AUC) of RSV-A Memphis 37b as determined by qRT-PCR on 
nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to the end of 
quarantine will be calculated (using the trapezium rule) and tabulated per treatment group. Treatment 
groups will be compared using t-test if assumptions are valid (Statistical Table 14.2.1.1). In case of 
distribution not normal, a data transformation could be used. 
 
qRT-PCR will be also tabulated per visit/timepoint for each treatment group (Statistical Table 14.2.1.2). 
 
Spaghetti plots and mean value over time will be used for graphical presentation of qRT-PCR, boxplot 
will be used for AUC presentation (Statistical Figures 14.2.1.1 to 14.2.1.3). 
 
Individual data for qRT-PCR (included derived data) will be presented on Listing 16.2.6.1. 
 
5.4.2 Secondary efficacy analyses 
5.4.2.1 Viral loads/shedding evaluations 
a) Objective 2:  
To estimate the margin and variance of prophylactic effect of IV treatment with Palivizumab 
administered 1 day prior to inoculation in the RSV human challenge model in healthy adults compared 
to Placebo [assessed by cell culture (pfu/mL)]. 
 
Area under the viral load-time curve (VL-AUC) of RSV-A Memphis 37b as determined by cell culture on 
nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to the end of 
quarantine will be calculated (using the trapezium rule) and tabulated per treatment group. Treatment 
groups will be compared using t-test if assumptions are valid (Statistical Table 14.2.2.1). In case of 
distribution not normal, a data transformation could be used. 
 
Cell culture will be also tabulated per visit/timepoint for each treatment group (Statistical Table 
14.2.2.2). 
Spaghetti plots and mean value over time will be used for graphical presentation of cell culture, boxplot 
will be used for AUC presentation (Statistical Figures 14.2.2.1 to 14.2.2.3). 
 
Individual data for cell culture (included derived data) will be presented on Listing 16.2.6.2. 
 
b) Objective 6 
Peak viral load of RSV-A Memphis 37b as defined by the maximum viral load determined by 
quantifiable qRT PCR measurements in nasal samples starting two days post viral challenge (Day +2) 
up to the end of quarantine will be calculated and presented by treatment group and compared using 
t-test if assumptions are valid (Statistical Table 14.2.3.1). In case of distribution not normal, a data 
transformation could be used. 
Peak viral load of RSV-A Memphis 37b will be also described graphically using boxplot (Statistical Figure 
14.2.1.4). 
 
 


 
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Peak viral load of RSV-A Memphis 37b as defined by the maximum viral load determined by 
quantifiable cell culture measurements in nasal samples starting two days post viral challenge (Day +2) 
up to the end of quarantine will be calculated and presented by treatment group and compared using 
test test if assumptions are valid (Statistical Table 14.2.3.2). 
Peak viral load of RSV-A Memphis 37b will be also described graphically using boxplot (Statistical Figure 
14.2.2.4). 
 
 
Number of days with quantifiable qRT PCR measurements in nasal samples starting two days post viral 
challenge (Day +2) up to the end of quarantine will be calculated and presented by treatment group 
and compared using t-test if assumptions are valid (Statistical Table 14.2.4.1). In case of distribution 
not normal, a data transformation could be used. In case of missing data on at least one visit, the 
number of days will be considered as missing for the subject, except if quantifiable measurement is 
already recorded on other timepoint for this visit.. 
 
Number of days with quantifiable cell culture measurements in nasal samples starting two days post 
viral challenge (Day +2) up to the end of quarantine will be calculated and presented by treatment 
group and compared using t-test if assumptions are valid (Statistical Table 14.2.4.2). In case of 
distribution not normal, a data transformation could be used. In case of missing data on at least one 
visit, the number of days will be considered as missing for the subject, except if quantifiable 
measurement is already recorded on other timepoint for this visit.. 
 
Duration of virus shedding will be analysed using Kaplan-Meier method. A Kaplan-Meier plot by 
treatment group will be displayed showing the duration of virus shedding (with the time axis as days 
since first virus shedding). A table will accompany the plot and will display the Kaplan-Meier estimates 
of the cumulative proportion of subjects’ event free at specific time points by treatment group. 
Subjects who did not have a confirmed undetectable measure after their peak, will be censored at their 
last detectable assessment. Subjects who do not have a detectable value during quarantine (including 
any extended quarantine period) will be excluded from the analysis (Statistical Table 14.2.4.3 & 
Statistical Figure 14.2.3). 
 
Time to Peak Virus Shedding will be described by treatment group. If the peak value is seen on more 
than one day, the first occurrence is used. Subjects who do not have a detectable value during 
quarantine (including any extended quarantine period) will be excluded from the analysis. (Statistical 
Table 14.2.4.4). 
 
5.4.2.2 Symptoms evaluation 
a) Objective 3:  
To estimate the margin and variance of prophylactic effect of IV treatment with Palivizumab 
administered 1 day prior to inoculation in the RSV human challenge model in healthy adults compared 
to Placebo [assessed by total symptom score (TSS)]. 
 
A total symptom score will be derived for each subject, separately for each assessment (symptom diary 
card) on each day, as the sum of the 13 observed symptom grade values for each symptom diary card 
to obtain a total symptom score for each symptom diary card. If the subject does not have all 13 
observed values on a specific symptom diary card being considered, then total symptom score will not 
be calculated for that symptom diary card. It is expected that subjects will not have missing data. 


 
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Area under the total symptom score-time curve (TSS-AUC) collected daily in the participant symptom 
diary card starting one day post-viral challenge (Day +1) up to the end of quarantine will be calculated 
(using the trapezium rule) and tabulated per treatment group. Treatment groups will be compared 
using t-test if assumptions are valid (Statistical Table 14.2.5.1). In case of distribution not normal, a 
data transformation could be used. 
 
The TSS will be also tabulated per visit/timepoint for each treatment group (Statistical Table 14.2.5.2). 
Spaghetti plots and mean value over time will be used for graphical presentation of TSS, boxplot will 
be used for AUC presentation (Statistical Figures 14.1.4.1 to 14.1.4.3). 
 
Following tables will also be displayed: 
 
Qualitative description for each symptom per visit/timepoint and treatment group (Statistical 
Table 14.2.5.3) 
 
Quantitative description (in mm) for each symptom per visit/timepoint and treatment group 
(Statistical Table 14.2.5.4) 
 
Individual data for Symptom diary cards (included data) will be presented on Listing 16.2.6.3. 
 
b) Objective 4:  
To estimate the margin and variance of prophylactic effect of IV treatment with Palivizumab 
administered 1 day prior to inoculation in the RSV human challenge model in healthy adults compared 
to Placebo [assessed by total symptom score (TSS)]. 
 
Sum Total symptom score-time curve (TSS-Sum) collected daily in the participant symptom diary card 
starting one day post-viral challenge (Day +1) up to the end of quarantine will be analysed using a 
MMRM if underlying assumptions valid (Statistical Table 14.2.5.5). 
 
c) Objective 7 
Peak symptom score defined by the maximum daily sum of Symptom score starting one day post viral 
challenge (Day +1) up to the end of quarantine will be determined and tabulated per treatment group. 
Treatment groups will be compared using t-test if assumptions are valid (Statistical Table 14.2.6.1). In 
case of distribution not normal, a data transformation could be used. 
 
Peak symptom score will be also described graphically using boxplot (Statistical Figure 14.2.4.4). 
 
Number of days with symptoms of grade 2 or more, starting one day post viral challenge (Day +1) up 
to the end of quarantine will be calculated and tabulated per treatment group. Treatment groups will 
be compared using t-test if assumptions are valid (Statistical Table 14.2.6.2). In case of distribution not 
normal, a data transformation could be used. In case of missing data on at least one visit, the number 
of days will be considered as missing for the subject, except if grade 2 or more is already recorded on 
other timepoint for this visit. 
5.4.2.3 Weight of mucus produced 
a) Objective 5:  
To estimate the margin and variance of prophylactic effect of IV treatment with Palivizumab 
administered 1 day prior to inoculation in the RSV human challenge model in healthy adults compared 


 
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to Placebo [assessed by total weight of nasal discharge produced and the total number of tissues used 
in each group]. 
 
Total weight of nasal discharge produced and total number of tissues used by participants starting one 
day post viral challenge (Day +1) up to the end of quarantine will be calculated and tabulated per 
treatment group. Treatment groups will be compared using t-test if assumptions are valid (Statistical 
Table 14.2.7.1). In case of distribution not normal, a data transformation could be used. 
 
In addition, weight of nasal discharge produced and number of tissues used by participants will be also 
tabulated per visit for each treatment group (Statistical Tables 14.2.7.2 and 14.2.7.3 respectively). 
 
Individual data for 24-hour tissue count and nasal discharge weight (included derived data) and will be 
presented on Listing 16.2.6.4. 
 
5.4.2.4 Incidence of infection & illness 
a) Objective 6:  
To estimate the margin and variance of prophylactic effect of IV treatment with Palivizumab 
administered 1 day prior to inoculation in the RSV human challenge model in healthy adults compared 
to Placebo [assessed by viral shedding of RSV-A Memphis 37b in nasal samples, in terms of incidence, 
duration, and peak]. 
 
Incidence of laboratory-confirmed infection (variant 1) and incidence of laboratory-confirmed 
infection (variant 2) will be presented by treatment group and compared using chi-square test 
(Statistical Tables 14.2.8.1 and 14.2.8.2). 
 
b) Objective 7:  
To estimate the margin and variance of prophylactic effect of IV treatment with Palivizumab 
administered 1 day prior to inoculation in the RSV human challenge model in healthy adults compared 
to Placebo [assessed by symptomatic infection in terms of incidence, duration, and peak]. 
 
Incidence of laboratory-confirmed virus-like-illness (Variant 3) will be presented. Treatment group will 
be compared using chi-square test on both the composite and each component (Statistical Table 
14.2.9). 
 
The following infections and illness will be summarised in one Table including data per subject and 
description by treatment group (Statistical Tbales 14.2.10): 
 
“Laboratory-confirmed infection” (variant 1) 
 
“Laboratory-confirmed virus-like-illness” (variant 1) 
 
“Laboratory-confirmed virus-like-illness” (variant 2) 
 
Upper respiratory tract illness (URTI) 
 
Lower respiratory tract illness (LRTI) 
 
Systemic illness (SI) 
 
Febrile Illness (FI) 
 
Fold seroconversion 
 
All Infections data will also be presented in Listing 16.2.6.5. 
 


 
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In addition, the following proportions will be tabulated per treatment group: 
 
Proportion of Subjects with Grade 2 or higher symptoms on any occasion at any time 
(Statistical Table 14.2.11.1) 
 
Proportion of Subjects with Grade 2 or higher Symptoms on any occasion for each day 
separately (Statistical Table 14.2.11.2) 
 
Proportion of Subjects with Grade 2 or higher Symptoms on two separate occasions at any 
time (Statistical Table 14.2.11.3) 
 
Proportion of Subjects with Grade 2 or higher Symptoms on two separate occasions for each 
day separately (Statistical Table 14.2.11.4) 
 
Proportion of Subjects with any symptom (grade >=1) on any cccasion at any time (Statistical 
Table 14.2.11.5) 
 
Proportion of Subjects with any symptom (grade >=1) on any occasion for each day separately 
(Statistical Table 14.2.11.6) 
 
Proportion of Subjects with any symptom (grade >=1) on two separate occasions at any time 
(Statistical Table 14.2.11.7) 
 
Proportion of Subjects with any symptom (grade >=1) on two separate occasions for each day 
separately (Statistical Table 14.2.11.8) 
 
5.4.2.5 Temperature 
The highest tympanic temperature will be calulated and tabulated per treatment group (Statistical 
Table 14.2.12) 
 
5.4.3 Tertiary/Exploratory efficacy analyses 
Tertiary and exploratory objectives are optional and are not included in the list of Tables of this SAP. 
They might be performed as additional analyses depending on the results of the study. 
 
a) Objective 12:  
To explore the Minimal Clinically Important Difference (MCID) in instrument change  
 
The average amount of instrument-assessed change for all participants who rate themselves as "a little 
better" or "somewhat better" may be presented per treatment group.  
 
b) Objective 13:  
To explore the margin and variance of prophylactic effect of IV treatment with Palivizumab 
administered 1 day prior to inoculation in the RSV human challenge model in healthy adults compared 
to Placebo in relation to baseline immune status.  
 
The above endpoints may be explored in relation to the baseline status of volunteers and the response 
to treatment. Baseline status and response can be regarding, but not limited to: 
 
Immune assays related to Palivizumab (e.g. IgG anti-F ELISA, PCA) 
 
Baseline immunity to RSV 
 
Response to Palivizumab treatment 
 
c) Objective 14: 
To explore the host-pathogen relationship in the RSV human challenge model in healthy adults . 


 
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5.5 
Pharmacokinetic (PK) analyses 
Objective 1:  
To assess the pharmacokinetics of Palivizumab in the RSV human challenge model in healthy adults. 
 
Pharmacokinetic analysis will be described in a separate Clinical Pharmacologyanalysis plan. 
Date and time of pharmacokinetic sample will be provided on Listing 16.2.6.6. 
 
5.6 
Safety analyses 
Safety variables will be tabulated and presented for all subjects included in the SAF population. 
 
5.6.1 
Extent of exposure and compliance 
IMP/Placebo dosing and Challenge virus inoculation information will be presented respectively in 
Listings 16.2.5.1 and 16.2.5.2). Compliance, defined as proportion of prescribed study drug actually 
taken (see section 10) will also be presented in Statistical Table 14.3.9 on evaluable and SAF 
populations. 
 
5.6.2 
Adverse events 
Objective 8: To assess safety of Palivizumab in the RSV human challenge model in healthy adults. 
 
Adverse event tabulations: 
Tabulation of adverse events will present for each cell the following information: number of subjects 
with at least one occurrence of the event, corresponding percentage and number of events.  
The following tables will be produced by treatment group: 
• 
Summary table of adverse events (Statistical Table 14.3.1.1): 
o Any AE 
o Any TEAE 
o Any TEAE leading to study discontinuation 
o Any TEAE considered related to the study treatment (at least possibly related) 
o Any SAE 
o Any SAE leading to study discontinuation 
o Any SAE considered related to the study treatment 
o Death (if any) 
 
• 
Detailed Tables:  
o TEAEs by SOC and PT (Statistical Table 14.3.1.2) 
o TEAEs by SOC, PT and severity (Statistical Table 14.3.1.3) 
o At least possibly related TEAEs by SOC, PT and severity (Statistical Table 14.3.1.4) 
o Listing of deaths (Statistical Table 14.3.2) 
o Narrative of deaths, other serious and significant adverse events (Statistical Table 
14.3.3) 
Adverse event listings: 


 
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A by-patient AE data listing including onset and resolution dates, verbatim term, preferred term, 
blinded treatment, severity, relationship to treatment, action taken, and outcome will be provided in 
Listing 16.2.7. 
 
5.6.3 
Laboratory safety variables  
The laboratory values will be directly transferred to the data management department. The laboratory 
report was interpreted by the investigator. Any clinically relevant changes occurring during the trial 
were recorded on the AE Form of the CRF. 
Laboratory evaluations will be summarized by visit and by treatment group on the SAF population 
(Statistical tables 14.3.4.1 to 14.3.4.12). 
For each hematology, chemistry, coagulation and cardiac enzymes variables: 
• 
Quantitative descriptive statistics will be tabulated at each time over the course of the study 
(e.g., at each visit) on raw values and change from baseline 
• 
Qualitative descriptive statistics will be tabulated for each laboratory variable at each time 
over the course of the study by clinical significance (normal, abnormal NCS, abnormal CS) (if 
relevant) 
 
All urinalysis parameters will also be analyzed as qualitative or quantitative variables per visit 
(Statistical table 14.3.4.13). 
 
All laboratory results will be presented in Listings 16.2.8. 
The following listings will be presented: 
• 
Laboratory reference ranges 
• 
Hematology 
• 
Biochemistry 
• 
Coagulation 
• 
Cardiac enzymes 
• 
Urinalysis 
 
5.6.4 
12-Lead Electrocardiogram (ECG) 
Quantitative descriptive statistics will be tabulated for each ECG parameters collected [HR (bpm), QRS 
(ms), PR interval (ms), QT (ms), QTc (ms), QTcF (ms), QTCb (ms), RR (ms)] at each time over the course 
of the study (e.g., at each visit) on raw values and change from baseline by treatment group. Clinical 
significance will also be presented for each ECG parameters. (Statistical tables 14.3.5.1 to 14.3.5.3) 
 
In addition, number of patients for the following categories will be displayed for QTcF and QTcB 
parameters (Statistical Table 14.3.5.4): 
• 
450 ms 
• 
480 ms 
• 
500 ms 
 
• 
< 30 ms increase from baseline 
• 
[30 ms; 60 ms] increase from baseline 
• 
60 ms increase from baseline 
 
All individual measurements will be provided in Listing 16.2.9. 
 


 
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5.6.5 
Physical examinations  
Number of normal, abnormal NCS and abnormal CS values will be presented at each visit by body 
systems for each treatment group to describe complete physical examination (Statistical Table 
14.3.6.1). 
Direct physical examination will also be presented. Upper respiratory tract (URT) (nasal discharge, 
otitis, pharyngitis, sinus tenderness) and lower respiratory tract (LRT) (New Wheezes, 
Rhonchi) symptoms will be tabulated per visit for each treatment group (Statistical Table 14.3.6.2) 
All individual measurements for complete and direc physical examination will be provided respectively 
in Listings 16.2.10.1 and 16.2.10.2. 
 
5.6.6 
Vital signs 
• 
Quantitative descriptive statistics will be tabulated for each vital sign recorded [Heart rate (HR) 
(beats per minutes), Respiratory rate (RR) (breaths per minutes), Systolic BP (SBP) and Diastolic 
BP (DBP) (mmHg), Oxygen saturation (SpO2) (%), Tympanic temparature (°C)] at each time over 
the course of the study (e.g., at each visit) on raw values and change from baseline by 
treatment group (Statistical tables 14.3.7.1 to 14.3.7.2) 
• 
Qualitative descriptive statistics will be presented for each vital sign at each time over the 
course of the study (e.g., at each visit) by treatment group: number of subjects with abnormal 
values beyond clinically important limits (HR<50 or >100 beats per minutes, RR <10 or > 20 
breaths per minutes, SBP <90 or >140 mmHg, DBP <50 or >90 mmHg, SpO2 <95%, Tympact 
temperature <35.5 or >37.8°C) (Statistical table 14.3.7.3) 
All individual measurements will be provided in Listing 16.2.11. 
 
5.6.7 
Concomitant medications 
Concomitant medications will be presented by ATC code and Preferred Name by treatment group 
(Statistical table 14.3.10) 
Previous and concomitant medications for each subject will be reported in Listings 16.2.16.  
 
5.6.8 
ADA 
Objective 10: To assess the Anti-Palivizumab antibody (ADA) in the RSV human challenge model in 
healthy adults. 
 
Analyses for ADA results will be described in a separate Clinical Pharmacology analysis plan. 
Date and time of samples will be provided on Listing 16.2.6.3. 
 
5.6.9 
Other safety variables  
Objective 11: To assess lung function in relation to RSV infection. 
 
Spirometry parameters [FEV1 (L), FEV1/FVC (L)], Peak Expiratory Flow (PEF) and Forced Oscillation 
Technique (FOT) will be presented. Results at each time over the course of the study will be tabulated 
on raw values and change from baseline by treatment group (Statistical Tables 14.3.8.1 to 14.3.8.6). 
 
Individual data will be provided in Listings 16.2.13 to 16.2.15. 
 


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Subgroup analysis 
A “Laboratory confirmed infected” subgroup will be identified and certain pre-specified analyses will 
also be performed. Variant 2 of viral shedding will be used for this subgroup. 
Analyses expected for this subgroup are identified in section 11.1. 
 
Sequence of analysis 
7.1 
Interim analysis 
An interim analysis aiming at reassessing the sample size will be performed once at least 50% of the 
planned number of challenged participants have been challenged and released from the quarantine 
unit. This analysis will be performed by the unblinded statistician. This analysis will be solely to confirm 
the powering assumptions (i.e. infection rate) within the Placebo group and may allow for additional 
participants to be included into the study, if needed to ensure the study is not underpowered. A second 
interim look to the placebo infection rate may be conducted when the targeted enrolment is reached, 
to further consider increasing the sample-size.  
Infection rate is defined as the presence of “viral shedding” measured in nasal sample as defined in 
section 4.2.1.4. Only the first point of the definition variant 2 will be used for the interim analysis to 
estimate the infection rate. 
As the interim look(s) will not compare the two treatment groups on the efficacy endpoints, and as the 
study is exploratory and statistical testing is not its primary goal, no adjustment to the type I error rate 
will be made. 
 
7.2 
Final analysis 
A final analysis will be performed when all endpoint data (safety and efficacy) up to study end (Day 28) 
are available. 
A data-Review meeting (including adjudication of deviations) will be done after Last subject last visit. 
Data that can unblind the subject will not be reviewed during the data-review (PK, ADA).  
The database lock will be done in two steps: 
 
The first database lock will include all data except those that can unblind the subject and those 
with a late availability (Plaque assay, PK, ADA data) 
 
the second database lock will include the remaining data (Plaque assay, PK, ADA data). 
Consequently, TFLs will be produced in two steps. One set after each dabase lock.  
All available tertiary endpoints available at that time may also be analysed in this step. An integrated 
CSR containing all data will be written and made available to the sponsor and the Investigator.  
 
7.3 
Unblinded statistician 
At time of first interim analysis, a statistician from the Venn statistical team will be unblinded. This 
unblinded statistician will not be involved in any discussions related to data (or SAP modifications) with 
the remaining blinded team members. The results will be prepared in a separate network working 
space with specific access rights. Then the interim results will be sent using a ftp site in a dedicated 
folder for people authorised to have access to unblinded results, secured by specific access rights. 
 


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Deviations from trial protocol 
 
The following endpoints have been added: 
o Duration of virus shedding : The time (hours) from first detectable until first confirmed 
undetectable assessment after their peak measure (after which no further virus is 
detected).  
o Time to Peak Virus Shedding: The time (days) from inoculation until the peak of virus 
shedding (qPCR) 
o “Laboratory-confirmed virus-like-illness” (variant 1, as below) 
o “Laboratory-confirmed virus-like-illness” (variant 2, as below) 
o Upper respiratory tract illness (URTI) 
o Lower respiratory tract illness (LRTI) 
o Systemic illness (SI) 
o Febrile Illness (FI) 
o Fold seroconversion 
o Proportion (on any occasion, and on two separate occasions) of subjects with grade 2 or 
worse symptoms at any day and at each day post-Viral Challenge 
o Proportion (on any occasion, and on two separate occasions) of subjects with any grade 
(i.e. grade ≥1) at any day and at each day post-Viral Challenge 
o highest tympanic temperature 
 
 
The first clause of the viral shedding definition (variant 1) has been revised from the protocol. 
The new definition puts emphasis on the importance of the number of assessments as opposed 
to the number of calendar days when confirming the presence of viral shedding. E.g. the SAP 
definition may span over 3 calendar days but is restricted by 4 consecutive assessments.  
The protocol states:  
“At least two positive “quantifiable” qRT PCR measurements in nasal samples at different 
timepoints reported within two or more consecutive days starting two days post viral 
challenge (Day +2) up to the end of quarantine.”  
This SAP states:  
“At least 2 positive quantifiable detections by viral load qPCR assay specific for the challenge 
virus, reported within 4 consecutive scheduled assessments and from 2 independent samples 
from Day +2 until discharge” 
 
 
The first clause of the viral shedding definition (variant 2) has been revised from the protocol. 
The new definition puts emphasis on the importance of the number of assessments as opposed 
to the number of calendar days when confirming the presence of viral shedding. E.g. the SAP 
definition may span over 3 calendar days but is restricted by 4 consecutive assessments.  
The protocol states:  
“At least two positive “detectable” qRT PCR measurements in nasal samples at different 
timepoints reported within two or more consecutive days starting two days post viral 
challenge (Day +2) up to the end of quarantine.”  
This SAP states:  
“At least 2 positive detectable assessments by viral load qPCR assay specific for the challenge 
virus, reported within 4 consecutive scheduled assessments and from 2 independent samples 
from Day +2 until discharge” 
 
 
 
The sequence of analysis has been revised from the protocol. 


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Initially one main analysis (without Data-Review meeting performed) and one final EOS analysis 
(after the Data-Review meeting) were planned. This meant that the evaluable population could 
not be used for the main analysis and led to introducing the “Quarantine completers” population 
for that analysis. Consequently, the efficacy results could have been slightly different between 
the Main Analysis and the Final EOS analysis, might the Evaluable population be different from 
the Quarantine completers, as a result of the data review. 
Given that the time between the main analysis (after Day 12) and the final EOS analysis (after 
Day 28) is very short and due to the delay for avaibility of qRT-PCR data, it is more relevant to 
perform only one final analysis. In this way, a Data-Review meeting (including review of 
populations) will be be performed and the Evaluable population can be used to produce the 
TFLs. 
 
 
Software documentation  
All summaries and statistical analyses will be generated using SAS version 9.4 or higher.  
 
 
 


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 Derived data 
Derived variable
Derivation algorithm
Change 
from 
baseline to visit V 
(continuous) 
Change from baseline of variable X=X(Visit V)-X(Baseline) 
o 
Negative values indicate a decrease in X 
o 
Positive values indicate an increase in X 
 
Treatment
Compliance 
(continuous) 
The compliance Ci for subject i will be computed according to:
𝐶௜= 𝐷௜
௧∗100
𝐷௜
௣
 
where 𝐷௜
௣ mg is the total amount (mg) of IP prescribed to subject i and 𝐷௜
௧ is 
the total amount (mg) of IP actually taken by the subject during the study i.e., 
before the end of study for subject i. 
Event Duration 
(End Date) – (Start Date) + 1 
 
 
 


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 Tables, Figures and Listings 
11.1 List of tables  
 
 
Enrolled 
Evaluable 
SAF 
Laboratory confirmed 
infected subgroup 
14.1 Demographics and Baseline characteristics 
14.1.1 
Subject disposition 
X 
14.1.2.1 
Study populations 
X 
14.1.2.2 
Reason for exclusion from the Evaluable set 
X 
14.1.2.3 
Reason for exclusion from the SAF 
X 
14.1.2.4 
Reason for exclusion from the PK analysis set 
X 
14.1.3 
Study duration and premature study discontinuation 
X 
14.1.4 
Protocol deviations 
X 
14.1.5 
Demographics data 
X 
X 
14.1.6 
Weight, Height and BMI  
X 
14.1.7 
Alcohol breath test 
X 
14.1.8 
Urine drugs of abuse  
X 
14.1.9 
Urine pregnancy test  
X 
14.1.10 
Patient Health Questionnaire (PHQ-9) 
X 
14.1.11 
Generalised Anxiety Disorder Questionnaire (GAD-7)  
X 
14.1.12 
HIV, Hepatitis A, B & C  
X 
14.1.13 
Thyroid function test  
X 
14.1.14 
Medical history 
X 
14.1.15 
Previous medications 
X 
14.2 Efficacy 
14.2.1.1 
Primary efficacy analysis - Area under the viral load-time curve 
(VL-AUC) of RSV-A Memphis 37b as determined by qRT-PCR on 
nasal samples  
  
X 
  
X 
14.2.1.2 
qRT-PCR by visit/timepoint  
  
X 
  
X 
14.2.2.1 
Area under the viral load-time curve (VL-AUC) of RSV-A Memphis 
37b as determined by cell culture on nasal samples 
  
X 
  
X  
14.2.2.2 
Cell culture by visit/timepoint 
  
X 
  
X 
14.2.3.1 
Peak viral load of RSV-A Memphis 37b - qRT PCR 
  
X 
  
X 
14.2.3.2 
Peak viral load of RSV-A Memphis 37b - Cell culture 
  
X 
  
X 
14.2.4.1 
Number of days with quantifiable qRT PCR measurements in 
nasal samples 
  
X 
  
X 
14.2.4.2 
Number of days with quantifiable cell culture measurements in 
nasal samples 
  
X 
  
X 


 
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Statistical Analysis Plan 
 
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Enrolled 
Evaluable 
SAF 
Laboratory confirmed 
infected subgroup 
14.2.4.3 
Duration of virus shedding 
  
X 
  
  
14.2.4.4 
Time to Peak Virus Shedding 
  
X 
  
  
14.2.5.1 
Area under the total symptom score-time curve (TSS-AUC) 
collected daily in the participant symptom diary card 
  
X 
  
X  
14.2.5.2 
TSS by visit/timepoint 
  
X 
  
X 
14.2.5.3 
Symptoms - Qualitative description by visit/timepoint 
  
X 
  
  
14.2.5.4 
Symptoms - Quantitative description by visit/timepoint 
  
X 
  
  
14.2.5.5 
Total symptom score - MMRM 
  
X 
  
X 
14.2.6.1 
Peak symptom score  
  
X 
  
  
14.2.6.2 
Number of days with symptoms of grade 2 or more 
  
X 
  
X 
14.2.7.1 
Total weight of nasal discharge produced 
  
X 
  
X 
14.2.7.2 
Weight of nasal discharge produced by visit 
  
X 
  
  
14.2.7.3 
Number of tissues used by participants by visit 
  
X 
  
  
14.2.8.1 
Laboratory-confirmed infection (Variant 1) 
  
X 
  
  
14.2.8.2 
Laboratory-confirmed infection (Variant 2) 
  
X 
  
  
14.2.9 
Laboratory-confirmed virus-like-illness (Variant 3)  
  
X 
  
  
14.2.10 
Incidence of Illness 
  
X 
  
  
14.2.11.1 
Proportion of Subjects with Grade 2 or Worse Symptoms on Any 
Occasion at any time  
  
X 
  
  
14.2.11.2 
Proportion of Subjects with Grade 2 or higher Symptoms on any 
occasion for each day separately  
  
X 
  
  
14.2.11.3 
Proportion of Subjects with Grade 2 or higher Symptoms on two 
separate occasions at any time  
  
X 
  
  
14.2.11.4 
Proportion of Subjects with Grade 2 or higher Symptoms on two 
separate occasions for each day separately  
  
X 
  
  
14.2.11.5 
Proportion of Subjects with any symptom (grade >=1) on any 
cccasion at any time 
  
X 
  
  
14.2.11.6 
Proportion of Subjects with any symptom (grade >=1) on any 
occasion for each day separately 
  
X 
  
  
14.2.11.7 
Proportion of Subjects with any symptom (grade >=1) on two 
separate occasions at any time 
  
X 
  
  
14.2.11.8 
Proportion of Subjects with any symptom (grade >=1) on two 
separate occasions for each day separately  
  
X 
  
  
14.2.11 
Highest tympanic temperature 
  
X 
  
  
14.3 Safety 
14.3.1.1 
Summary table of adverse events  
X 
X 
14.3.1.2 
TEAEs by SOC and PT 
X 


 
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Enrolled 
Evaluable 
SAF 
Laboratory confirmed 
infected subgroup 
14.3.1.3 
TEAEs by SOC, PT and severity  
X 
14.3.1.4 
At least possibly related TEAEs by SOC, PT and severity  
X 
14.3.2 
Listing of deaths  
X 
14.3.3 
Narrative of deaths, other serious and significant adverse events  
X 
14.3.4.1 
Hematology - Absolute values 
X 
14.3.4.2 
Hematology - Change from baseline 
X 
14.3.4.3 
Hematology - Clinical significance 
X 
14.3.4.4 
Biochemistry - Absolute values 
X 
14.3.4.5 
Biochemistry - Change from baseline 
X 
14.3.4.6 
Biochemistry - Clinical significance 
X 
14.3.4.7 
Coagulation - Absolute values 
X 
14.3.4.8 
Coagulation - Change from baseline 
X 
14.3.4.9 
Coagulation - Clinical significance 
X 
14.3.4.10 
Cardiac enzymes - Absolute values 
X 
14.3.4.11 
Cardiac enzymes - Change from baseline 
X 
14.3.4.12 
Cardiac enzymes - Clinical significance 
X 
14.3.4.13 
Urinalysis 
X 
14.3.5.1 
12-lead ECG - Absolutes values 
X 
14.3.5.2 
12-lead ECG - Change from baseline 
X 
14.3.5.3 
12-lead ECG - Clinical significance 
X 
14.3.5.4 
12-lead ECG - Abnormalities 
X 
14.3.6.1 
Complete physical examination 
X 
14.3.6.2 
Direct physical examination 
X 
14.3.7.1 
Vital signs - Absolute values 
X 
14.3.7.2 
Vital signs - Change from baseline 
X 
14.3.7.3 
Vital signs - Abnormalities 
X 
14.3.8.1 
Spirometry - Absolute values 
X 
14.3.8.2 
Spirometry - Change from baseline 
X 
14.3.8.3 
Peak Exploratory (PEF) - Absolute values 
X 
14.3.8.4
Peak Exploratory (PEF) - Change from baseline
X
14.3.8.5 
Forced Oscillation Technique (FOT) - Absolute values 
X 
14.3.8.6
Forced Oscillation Technique (FOT) - Change from baseline
X
14.3.9 
Compliance 
X 
X 
14.3.11 
Concomitant medications 
X 
 


 
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Statistical Analysis Plan 
 
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11.2 List of figures 
  
  
Evaluable 
Laboratory confirmed 
infected subgroup 
14.2 Efficacy 
14.2.1.1 
qRT-PCR - Spaghetti plots 
X 
X 
14.2.1.2 
qRT-PCR - Mean value over time 
X 
X 
14.2.1.3 
qRT-PCR - VL-AUC- Boxplot 
X 
X 
14.2.1.4 
qRT-PCR - Peak Viral Load - Boxplot 
X 
X 
14.2.2.1 
Cell culture - Spaghetti plots 
X 
X 
14.2.2.2 
Cell culture - Mean value over time 
X 
X 
14.2.2.3 
Cell culture – VL-AUC - Boxplot 
X 
X 
14.2.2.4 
Cell culture - Peak Viral Load - Boxplot 
X 
X 
14.2.3 
Kaplan-Meier Curve 
X 
X 
14.2.4.1 
Total Symptom Score (TSS) - Spaghetti plots 
X 
X 
14.2.4.2 
Total Symptom Score (TSS) - Mean value over 
time 
X 
X 
14.2.4.3 
Total Symptom Score (TSS) – AUC - Boxplot 
X  
X  
14.2.4.4 
Peak symptom score - Boxplot 
X 
X 
  
 


 
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11.3 List of listings 
Demographics and Baseline characteristics 
16.2.1 
End of study information / Discontinued subjects 
16.2.2 
Protocol deviations 
16.2.3 
Population membership and reason for exclusion 
16.2.4.1 
Demographics data 
16.2.4.2 
Weight, Height and BMI  
16.2.4.3 
Alcohol breath test 
16.2.4.4 
Urine drugs of abuse  
16.2.4.5 
Urine pregnancy test  
16.2.4.6 
Patient Health Questionnaire (PHQ-9) 
16.2.4.7 
Generalised Anxiety Disorder Questionnaire (GAD-7)  
16.2.4.8 
HIV, Hepatitis A, B & C  
16.2.4.9 
Thyroid function test  
16.2.4.10 
Eligibility criteria 
16.2.4.11 
randomisation  
16.2.4.12 
Medical history 
16.2.4.13 
Visit dates 
16.2.4.14 
Nasopharyngeal swab / nasal swab respiratory Pathogen Screen 
16.2.5.1 
IMP/Placebo dosing 
16.2.5.2 
Challenge virus inoculation 
Efficacy 
16.2.6.1 
qRT-PCR 
16.2.6.2 
Cell culture 
16.2.6.3 
Symptom diary cards 
16.2.6.4 
24-hour tissue count and nasal discharge weight 
16.2.6.5 
Infections 
16.2.6.6 
Pharmacokinetic samples 
 
 


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Statistical Analysis Plan 
 
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Safety 
16.2.7 
Adverse events 
16.2.8.1 
Laboratory reference ranges 
16.2.8.2 
Hematology 
16.2.8.3 
Biochemistry 
16.2.8.4 
Coagulation 
16.2.8.5 
Cardiac enzymes 
16.2.8.6 
Urinalysis 
16.2.9 
12-Lead ECG 
16.2.10.1 
Complete physical examination  
16.2.10.2 
Direct physical examination  
16.2.11 
Vital signs 
16.2.12 
ADA 
16.2.13 
Spirometry 
16.2.14 
Peak Exploratory (PEF) 
16.2.15 
Forced Oscillation Technique (FOT) 
16.2.16 
Previous and concomitant medications 
 
 References 
Clopper, C. J., & Pearson, E. S. (1934). The use of confidence or fiducial limits illustrated in the case of 
the binomial. Biometrika, 26(4), 404-413. 
Hahn, G. J., & Meeker, W. Q. (2011). Statistical intervals: a guide for practitioners (Vol. 328). John Wiley 
& Sons.