Screening Protocol for a Dose Finding Human Experimental Infection Study in Healthy Subjects Using a GMP-produced SARS-COV-2 Wild Type Strain
Conditions: Covid19
Sponsor: Imperial College London

CONFIDENTIAL 
 
Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
1 
 
 
 Screening Protocol for a dose finding human experimental infection study in healthy subjects 
using a GMP-produced SARS-COV-2 wild type strain 
 
Short Title: 
SARS-CoV-2 Screening Protocol 
Version and Date of Protocol: 
Version 8 
Date 19-Jul-2021 
hVIVO Protocol Number: 
HVO-vCS-003 Screening Protocol 
Sponsor: 
Imperial College London  
Room 221  
Level 2, Medical School Building  
Norfolk Place,  
London W2 1PG   
Compound Number (if applicable): 
Not applicable 
EudraCT Number: 
Not applicable 
 
Confidentiality and Protections Statement: 
This document contains confidential information. 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. 
Personal data included in the protocol is subject to General Data Protection Regulation 
(GDPR:  EU 2016/679) considerations and protections. 
 
 

CONFIDENTIAL 
 
Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
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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: 
 
 
 
 
 
 
 
 
 
 
23 Jul 2021 
Ruth Nicholson 
Head of Research Governance and Integrity 
 
Date 
 
 
 

CONFIDENTIAL 
 
Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
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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 Signatory:  
Name 
(typed 
or 
printed): 
Christopher Chiu 
 
Institution 
and 
Address: 
Department of Infectious Disease, Imperial College London 
 
Hammersmith Campus, DuCane Road 
 
London W12 0NN, United Kingdom 
 
Signature:
 
Date: 
23 Jul 2021 
 
 
 
(DD MMM YYYY) 
 
 
 

CONFIDENTIAL 
 
Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
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Study Contact Information 
CONTACT 
DETAILS 
Sponsor 
Imperial College London  
Room 221  
Level 2, Medical School Building  
Norfolk Place, London W2 1PG   
Sponsor’s Representative  
hVIVO Services Limited 
Queen Mary BioEnterprises Innovation Centre 
42 New Road, London, E1 2AX, United Kingdom 
Refer to the Trial Master File for a complete list of the study personnel contact details.  

CONFIDENTIAL 
 
Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
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Protocol Amendment Summary of Changes Table 
PROTOCOL HISTORY 
Document 
Date 
Amendment Type 
SA 3
19-Jul-2021
Substantial
SA 2 
22-Feb-2021 
Substantial 
NSA 1
09-Dec-2020
Non-substantial
Original Protocol 
02-Dec-2020 
N/A 
Amendment NSA 1 09-Dec-2021 
Overall Rationale for the Amendment: 
Section 
# 
and Name 
Description of Change 
Brief Rationale 
Inclusion 
Criteria 
Update to inclusion criteria  
Administrative error 
Overall 
document 
Minor administrative corrections 
Administrative error 
Amendment SA 2 16-Feb-2021 
Overall Rationale for the Amendment: 
Section # and 
Name 
Description of Change 
Brief Rationale 
2.2 Exclusion 
Exclusion criterion 27 
Brought in line with main protocol 
3 
Screening 
Process 
7-day isolation and 72 hours 
PCR test 
Stay at home for 7 days required prior to 
quarantine 
to 
follow 
pre-admission 
infection control procedure agreed with 
the RFH. PCR test required 72 hours 
prior to admission. 
4.1.2 Ethics 
Corrected typographical error 
HRA approval is not required for either 
screening or main protocol as there are 
no NHS trusts involved in the study. 
4.1.2 Ethics 
Corrected typographical error 
CCC is not required for either screening 
or main protocol as there are no NHS 
trusts involved in the study. 
4.1.3 Consent 
Remote consent 
Participants 
screened 
prior 
to 
implementation of this amendment will 
require re-consenting. The process for 
this has been described. 
4.1.8 Audits 
Corrected typographical error 
Removed reference to imperial college 
healthcare NHS trust as sponsor. ICL is 
the sponsor only. 
 

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Amendment SA 3 19 Jul 2021 
Overall Rationale for the Amendment: 
Section # and 
Name 
Description of Change 
Brief Rationale 
2.1.3 Inclusion 
Criteria  
Change to wording – removal 
of Sero-negative to Sero-
suitable subjects  
Wording changed to reflect the purpose 
of the Extension Phase of the current 
protocol 
– 
to 
include 
previously 
vaccinated subjects. 
2.1.4 Inclusion 
Criteria 
Change 
to 
contraception 
wording for women. 
Extension of time for contraception post-
viral challenge – wording changed from 
30 days to 6 months after receipt of study 
virus. 
2.1.5 Inclusion 
Criteria  
Change 
to 
contraception 
wording for men. 
Extension of time for contraception post-
viral challenge – wording changed from 
30 days to 6 months after receipt of study 
virus. 
2.1.8 Inclusion 
Criteria 
Removal of QCOVID tool 
wording – adding requirement 
of evidence of completed 
COVID-19 vaccination course 
Evidence required that subjects have 
received both doses of COVID-19 
vaccine. 
2.2.3 Exclusion 
Criteria 
Addition of wording  
No previous SARS-Cov-2 infection. 
2.2.12 
Exclusion 
Criteria 
Removal of wording Hb1A1C 
Hb1A1C – will be ‘optional’ as random 
glucose also recorded. 
2.2.17 
Exclusion 
Criteria 
Removal of wording stating, 
‘no travel restrictions post D28 
follow-up.’ 
Precaution to advise subjects to restrict 
travel should they be re-infected by D28 
2.3 
Personalised 
risk 
assessment 
using 
the 
QCOVID tool 
Removal of Section. 
QCOVID – no longer part of exclusion 
criteria. 
3 
Screening 
Process  
Include 
new 
wording 
for 
volunteer identification  
Use of ethically-approved volunteer 
database if available. 
3 
Screening 
Process 
Include 
new 
wording 
for 
assessing inclusion/exclusion 
criteria 
Inclusion/exclusion criteria at screening 
will be assessed based on available 
evidence 
3 
Screening 
Process 
7-day isolation amended to ‘up 
to’ 7-day isolation 
Brought in line with main protocol and 
main PIS-ICF, able to follow current 
restrictions in place at the Quarantine 
Unit 
4.1.8 Audits 
Corrected typographical error. 
Corrected wording. 
4.2 Appendix 2
Corrected typographical error 
Typographical error in email address 
corrected 

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4.4 Appendix 4
Table of toxicity grading scale 
replaced  
Brought in line with main protocol 

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Protocol number HVO-vCS-003 Screening 
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Table of Contents 
Sponsor Statement .......................................................................................... 2 
Investigator Agreement: ................................................................................... 3 
Study Contact Information................................................................................ 4 
Protocol Amendment Summary of Changes Table ......................................... 5 
Table of Contents ........................................................................................... 8 
1. 
Introduction .................................................................................... 9 
2. 
Study Population ......................................................................... 10 
2.1. 
Inclusion Criteria ............................................................................ 10 
2.2. 
Exclusion criteria ............................................................................ 11 
2.3. 
Screen failures ............................................................................... 15 
3. 
Screening process ....................................................................... 16 
4. 
Supporting Documentation and Operational Considerations 19 
4.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................... 19 
4.2. 
Appendix 2: Adverse events .......................................................... 22 
4.3. 
Appendix 3: Abbreviations ............................................................. 24 
4.4. 
Appendix 4: Toxicity Grading Scale for Laboratory AEs ............... 26 
 
 
 
 
 

CONFIDENTIAL
 
Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
 
 
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1. 
Introduction 
The aim of this screening protocol is to assess volunteers for their potential eligibility to participate 
in a dose finding human experimental infection study in healthy subjects using a GMP-produced 
SARS-CoV-2 wild type strain.  

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Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
 
 
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2. 
Study Population 
Recruitment will be done through a number of channels: 
- 
Approved advertising, including social medial 
- 
hVIVO volunteer database 
- 
Referral 
- 
Organic search, i.e. where the volunteer has learned of this study by doing a Google 
search or through friends or family rather than due to any advertising 
Following Research Ethics Committee approval of the full study, screened subjects who confirm 
their willingness to participate in the SARS-CoV-2 human infection challenge characterization 
study will be invited to consider the study-specific PIS-ICF and enter the final study consenting 
process. 
The number of subjects who are to be recruited will depend on specific sample-size requirements 
for the SARS-CoV-2 human infection characterization study.  
2.1. 
Inclusion Criteria 
The main inclusion criteria for the SARS-CoV-2 challenge study are listed below.  
NO 
INCLUSION CRITERIA  
1 
An informed consent document signed and dated by the participant and the 
Investigator. 
2 
Male or female, age between 18 and 30 years inclusive (at the time of the study 
consent) 
3 
Sero-suitable i.e. with evidence of SARS-CoV-2 vaccine-induced antibody 
responses but no evidence of previous SARS-CoV-2 infection by an authorised 
serology test. Those with indeterminate levels and no history of laboratory-
confirmed SARS-CoV-2 infection may be included or excluded at the PI’s 
discretion on a case-by-case basis. 
4 
Women of childbearing potential with a documented menstrual period within 28 
days before the first dose (unless using a contraceptive method that suppressed 
menstruation as indicated in the study protocol) and willing and able to use 
contraception as described in the study protocol from 2 weeks before the 
scheduled date of viral challenge until 6 months after receipt of the final dose of 
study virus or intervention treatment (whichever occurs last). Negative urine 
pregnancy test will be required at screening plus, on admission to the quarantine 
unit, a Negative serum beta human chorionic gonadotropin (β-hCG) is a required. 
A negative urinary pregnancy test prior to virus challenge is also required. 
5 
Men who are willing to use one of the contraception methods described in the 
study protocol, from the time of the date of viral challenge, until 6 months after 
receipt of the final dose of study medication. 

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Protocol number HVO-vCS-003 Screening 
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* No radiological assessments will be conducted as part of this screening process.  Chest X-Ray 
may only be performed after volunteer signs main PIS-ICF.  
2.2. 
Exclusion criteria 
The main exclusion criteria for the SARS-CoV-2 challenge study are listed below. 
NO 
STANDARD EXCLUSION CRITERIA   
Any potential subject who meet any of the criteria below will be excluded from participating 
in this study. 
Clinical history 
1.  
History or evidence of any clinically significant or currently active cardiovascular, 
(including thromboembolic events), respiratory, dermatological, gastrointestinal, 
endocrine, haematological, hepatic, immunological, rheumatological, metabolic, 
urological, renal, neurological, psychiatric illness. Specifically: 
a) Subjects with any history of physician diagnosed and/or objective test 
confirmed asthma, chronic obstructive pulmonary disease, pulmonary 
hypertension, reactive airway disease, or chronic lung condition of any 
aetiology or who have experienced: 
o Significant/severe wheeze in the past 
o Respiratory symptoms including wheeze which has ever resulted 
in hospitalisation 
o Known bronchial hyperreactivity to viruses 
6 
In good health with no history of clinically significant medical conditions (as 
described in Exclusion criteria) that would interfere with subject safety, as defined 
by medical history, physical examination and routine laboratory tests, ECG, and 
Chest X-Ray* and determined by the Investigator at a screening evaluation 
and/or at admission to the Quarantine Unit.  
7 
Subjects will have a documented medical history either prior to entering the study 
and/or following medical history review with the study physician at screening 
8 
Evidence of having had a complete COVID-19 vaccination course (as one or 
two intramuscular injections depending on the authorisation schedule) with the 
last injection at least 14 days before enrolment 
9 
Willing and able to commit to participation in the study 

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Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
 
 
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NO 
STANDARD EXCLUSION CRITERIA   
b) History of thromboembolic, cardiovascular or cerebrovascular disease 
c) History or evidence of diabetes mellitus 
d) Any concurrent serious illness including history of malignancy that could 
interfere with the aims of the study or a subject completing the study. 
Basal cell carcinoma within 5 years of treatment or with evidence of 
recurrence is also an exclusion 
e) Migraine with associated neurological symptoms such as hemiplegia or 
vision loss. Cluster headache/migraine or prophylactic treatment for 
migraine 
f) History or evidence of autoimmune disease or known immunodeficiency 
of any cause. 
g) Other major disease that, in the opinion of the Investigator, could interfere 
with a subject completing the study and necessary investigations. 
h) Immunosuppression of any type. 
2.  
Any significant abnormality altering the anatomy of the nose in a substantial way 
or nasopharynx, a clinically significant history of epistaxis (large nosebleeds) 
within the last 3 months, nasal or sinus surgery within 6 months of inoculation. 
3.  
Clinically active rhinitis (including hay fever) 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. 
4.  
History of anaphylaxis and/or a history of severe allergic reaction or significant 
intolerance to any food or drug, as assessed by the PI. 
5.  
History or presence of alcohol addiction, or excessive use of alcohol (average 
weekly intake in excess of 28 units alcohol; one unit being a half glass of beer, a 
small glass of wine or a measure of spirits). 
6.  
Psychiatric illness including subjects with a history of depression and/or anxiety 
with associated severe psychiatric comorbidities, for example psychosis. 
Specifically,  
a) Subjects with history of anxiety-related symptoms of any severity within 
the last 2 years if the Generalized Anxiety Disorder-7 score is ≥4 
b) Subjects with a history of depression of any severity within the last 2 years 
if the Patient Health Questionnaire-9 score is ≥4 
 
7.  
Current smokers or subjects who have smoked ≥5 pack years at any time [5 pack 
years is equivalent to one pack of 20 cigarettes a day for 5 years]. 
 
Subjects who have smoked <5 pack years - at any time in the 3 months prior 
to admission to the quarantine unit they have used tobacco in any form (e.g., 

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Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
 
 
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NO 
STANDARD EXCLUSION CRITERIA   
smoking or chewing) or other nicotine-containing products in any form (e.g., 
gum, patch) or electronic cigarettes. 
8.  
Family history of 1st degree relative aged 50 years or less with sudden cardiac 
or unexplained death  
9.  
Family History of Severe COVID or response to any other viral disease 
e.g. Guillain–Barré 
Measurements and investigations 
10.  
A total body weight of ≤ 50g and a Body Mass Index (BMI) ≤18 kg/m2 and ≥28 
kg/m2. The upper limit of BMI may be increased to ≤ 30kg/m2 at the PI’s 
discretion, in the case of physically fit muscular individual 
11.  
Venous access deemed inadequate for the phlebotomy and cannulation 
demands of the study. 
12.  
Any clinically significant abnormal finding on screening biochemistry, 
haematology and microbiology blood tests or urinalysis i.e. grade 1 lab 
abnormalities (or above, see Appendix 4 Toxicity Grading Scale for Laboratory 
AEs) apart from minor deviations which are clinically acceptable and approved 
by the Principal Investigator 
a) Elevated random glucose.  
b) Positive HIV, active/chronic hepatitis A, B or C test. 
c) Confirmed positive test for drugs of abuse on admission and urinary 
cotinine at quarantine. 
13.  
A forced expiratory volume in 1 second (FEV1) and a forced vital capacity (FVC) 
<80% of predicted value calculated using ATS/ERS guidance 
14.  
Twelve-lead ECG recording with clinically relevant abnormalities as judged by 
the study physician/PI. 
Recent respiratory infection 
15.  
History of, or currently active symptoms suggestive of upper or lower respiratory 
tract infection (including reduced sense of taste and smell, raised body 
temperature and/or persistent cough) within 6 weeks prior to viral challenge. 
16.  
Presence of cold-like symptoms and/or fever (defined as subject presenting with 
a temperature reading of >37.9ºC)  
17.  
History of previous SARS-CoV-2 infection at any time 
Receipt of medications and interventions 

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Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
 
 
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NO 
STANDARD EXCLUSION CRITERIA   
18.  
Evidence of a live vaccine within 60 days prior to the planned date of viral 
challenge, a non-live vaccine within 30 days prior to the planned date of viral 
challenge (except for COVID-19 vaccines), or intention to receive any 
vaccination(s) before the day 28 follow-up visit.  
19.  
Receipt of blood or blood products, or loss (including blood donations) of 550 mL 
or more of blood during the 3 months prior to the planned date of viral challenge 
or planned during the 3 months after the final visit. 
20.  
Medications 
a) Use of any medication or product (prescription or over-the-counter), for 
symptoms of hayfever, nasal congestion or respiratory tract infections or 
dermatitis/eczema including the use of regular nasal or medium-high 
potency dermal corticosteroids, antibiotics and First Defence™ (or 
generic equivalents) within 7 days prior to the planned date of viral 
challenge apart from those described and allowed in Permitted 
Medication or agreed by the Principle Investigator 
b) Receipt of any investigational drug within 3 months prior to the planned 
date of viral challenge. 
c) Receipt of three or more investigational drugs within the previous 12 
months prior to the planned date of viral challenge. 
d) Prior inoculation with a virus from the same virus-family as the challenge 
virus. 
e) Receipt of systemic (intravenous and/or oral) glucocorticoids or systemic 
antiviral drugs within 6 months prior to the planned date of viral challenge.
f) Over the counter medications (e.g. paracetamol or ibuprofen) where the 
dose taken over the preceding 7 days prior to the planned date of viral 
challenge had exceeded the maximum permissible 24-hour dose (e.g., 
>4g per day of paracetamol over the preceding week). 
g) Use or anticipated use within 7 days prior to the planned date of viral 
challenge and during the conduct of the study of concomitant medications 
(prescription and/or non-prescription), including vitamins or herbal and 
dietary supplements within the specified windows. 
h) Chronically used medications, vitamins or dietary supplements, including 
any medication known to be a moderate/potent inducer or inhibitor of 
cytochrome P450 enzymes, within 21 days prior to the planned date of 
viral challenge. 
i) Subjects who have received any systemic chemotherapy agent, 
immunoglobulins, or other cytotoxic or immunosuppressive drugs at any 
time. 
21.  
Prior participation in another human viral challenge study in the preceding 12 
months taken from the date of viral challenge in the previous study to the date of 
expected viral challenge in this study. 
22.  
Any nasal sampling procedure in the 6 months before date of expected viral 
challenge in this study. Nasal swabs are allowed. 

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Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
 
 
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NO 
STANDARD EXCLUSION CRITERIA   
General 
23.  
Subject was mentally or legally incapacitated in the opinion of the Investigator. 
 
24.  
Females who: 
a) Are breastfeeding within 6 months of study commencement, or 
b) Had been pregnant within 6 months prior to the study, or 
c) Had a positive pregnancy test at any point during screening or prior to 
inoculation with challenge virus
25.  
Those in close domestic contact (i.e. sharing a household with, caring for, or daily 
face to face contact) with children under 3 years, the elderly (>65 years), 
immunosuppressed persons, or those with chronic respiratory disease 
Other 
26.  
Was employed or was a first-degree relative of anyone employed by the 
Sponsor, a participating clinical trial site, or any Contract Research Organisation 
involved in the study. 
27.  
Any other reason that the Investigator considered made the subject unsuitable 
to participate. 
28.  
Participants with no knowledge of their family history 
2.3. 
Screen failures 
Volunteers that do not enroll on HVO-vCS-003 will be recorded as screen failures and may be 
eligible to participate in other studies.  

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Protocol number HVO-vCS-003 Screening 
Protocol version 8.0, 19-Jul-2021 
 
 
 
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3. 
Screening process 
The screening process will consist of several stages: 
Volunteers interested in participating will be asked to register their details on a SARS-CoV-2 
specific web page UKcovidchallenge.com unless they have previously registered via the hVIVO 
volunteer database or other ethically-approved volunteer database. All advertising and media will 
direct volunteers to this web page to register their interest. Volunteers already registered with any 
other hVIVO database or ethically-approved volunteer database may be contacted to determine 
their interest in participating in SARS-CoV-2 research. 
On the registration form, they will Agree with the Privacy Policy. When beginning the application, 
they will enter the following details: 
- 
Full Name 
- 
Gender 
- 
Date of Birth 
- 
Email 
- 
Phone number 
If they fit the age criteria, they will be contacted and guided to a short webform questionnaire to 
be performed prior to a follow-up telephone questionnaire or will be asked to complete a telephone 
questionnaire where the following details will be collected. All volunteer communications and 
appointment scheduling are managed by the Flucamp recruitment team. Flucamp are the 
volunteer recruitment function within hVIVO. 
Webform Questionnaire (to be followed with a telephone questionnaire): 
- 
Do you have a valid photo ID, UK Driving license or Passport? 
 
- 
Are you registered with a GP in the UK? 
 
- 
Do you currently have asthma? 
 
- 
Do you have COPD as diagnosed by a doctor? 
 
- 
Are you or your partner pregnant or trying to get pregnant? 
- 
Have you ever been diagnosed with anxiety or depression? 
 
- 
Do you have any viral blood conditions such as HIV, Hepatitis A, B or C?  
- 
Are you currently suffering from any illness or health related condition (e.g. coughs 
& colds, stomach problems, chest complaints, dizziness, headaches, eczema 
etc.)? 
- 
Are you taking any medicines, either prescribed by a doctor, or bought from a 
chemist/pharmacy (This includes contraception, vitamins and supplements)? 
- 
Height & Weight 
Telephone Questionnaire (prior Webform Questionnaire completion is not compulsory): 
- 
Home Address 
- 
Ethnicity 
- 
BMI 
- 
Have you suffered from cold or flu symptoms in the last two weeks? 
- 
Are you available to take part in a clinical trial in the next 12 months? 

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Protocol number HVO-vCS-003 Screening 
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- 
Can you read and write in English? 
- 
Do you have photo ID? 
- 
Are you registered with a GP? 
- 
Have you used recreational drugs in the last 3 months? 
- 
Are you a smoker or ex-smoker? If so, how many cigarettes per day and how long 
for? 
- 
Are you currently suffering from any illness or health-related condition? (coughs, 
colds, stomach problems, chest complaints, dizziness, eczema, headaches etc.) 
- 
Have you ever been diagnosed with anxiety or depression? 
- 
Are you taking medicines prescribed by a doctor or bought from chemist/pharmacy 
(includes contraception, vitamins, supplements)? 
- 
Are you or your partner trying to get pregnant? 
- 
Do you have any viral blood conditions (e.g. HIV, Hepatitis A, B or C)? 
- 
Are you employed or related to anybody at hVIVO? 
- 
Do you have asthma? 
- 
Have you had Asthma in childhood? 
- 
Do you have COPD as diagnosed by a doctor? 
- 
Complete a COVID-19 symptom assessment 
If inclusion/exclusion criteria are provisionally met based on answers to these questions, an 
appointment for a first screening visit will be scheduled and a confirmation email and a screening 
Participant Information Sheet (PIS)/Informed Consent Form (ICF) will be sent to volunteers.  
Screening appointments will be conducted at hVIVO. First, the screening process will be 
discussed with the participant by the study doctor or nurse. When the subject has had enough 
time to consider their participation in screening, ask any questions they may have, and only when 
they have agreed to take part will they be asked to read, sign and date a consent form in the 
presence of the study doctor or nurse who will also sign the consent form.  Written consent for 
screening will be obtained prior to any history-taking, examination or tests are carried out. A copy 
will be kept in the research file, a copy given to the patient and a copy put into their medical notes. 
Following informed consent, the following assessments will be completed. 
- 
Confirmation of name, age, gender, and contact details 
- 
Full medical history including questions about past and present health including 
clinically significant family history 
- 
Optional - Quality of life questionnaires including the GAD-7 Anxiety Test 
questionnaire and PHQ-9 Depression Test questionnaire. 
- 
Questions about current weekly alcohol and/or smoking consumption and an 
alcohol breath test will be performed. 
- 
Check of any previous participation in clinical trials via The Over-Volunteering 
Prevention System (TOPS). 
- 
Examination for signs of illness or disease (a medical examination). 
- 
Height and weight 
- 
Pulse rate, blood pressure, temperature and breathing rate checked (Vital Signs). 
- 
Electrocardiogram (ECG) 
- 
Urine samples for: 

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Protocol number HVO-vCS-003 Screening 
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o Evidence of infection or kidney/urinary tract conditions 
o Test for pregnancy 
o For drugs of abuse & cotinine 
- 
Provide an airway sample (i.e. nasal swab as a tolerance test for the respiratory 
screen for pathogens and/or immune status). It will be optional to conduct a BioFire 
test at the discretion of the PI. 
- 
Safety blood tests, including full blood count, renal and liver function tests. 
- 
Testing for SARS-CoV-2 virus (COVID-19) antibodies 
- 
Samples for Hepatitis A, B and C and/or HIV (the virus that causes AIDS) 
- 
Lung function tests. 
Inclusion and exclusion criteria will be assessed based on evidence available at the time of 
screening, any non-applicable aspects of the criteria will be checked upon admission.  
The volunteer’s medical history will be requested from their GP and reviewed to assess suitability. 
Subjects may be invited for repeat assessment where / if required at the PI’s discretion. For 
participants contacted via the hVIVO volunteer database, GP medical histories that have been 
previously received by hVIVO may be used for screening purposes if they were obtained within 
the screening window of the study (i.e. within 90 days to -3 days prior to date of virus inoculation). 
As soon as the SARS-CoV-2 human challenge characterization study is approved, potential 
participants who have passed screening up to that point will be given or sent the study specific 
participant information sheet (PIS) detailing the full study and experimental procedures. This will 
be done in advance of the first study specific visit to give participants enough time to read the 
PIS, discuss the study with family and friends, as well as being able to call the hVIVO medical 
team to ask any questions they may have. A follow-up appointment (to be conducted remotely 
due to the COVID-19 pandemic) will be arranged to go through the details of the study with a 
study team member and to answer any questions, if this was not already done at the screening 
visit. Additional calls may be arranged as needed. Participants will be advised that they will be 
required to self-isolate (stay at home) for up to 7 days immediately prior to admission to the 
Quarantine Unit. They will also be asked to take a nasal pharyngeal swab (NPS) 72 hours prior 
to admission to be returned to hVIVO for PCR testing. The samples from this test will be collected 
by a courier and delivered to the hVIVO laboratory to be analysed. 
When the subject has had enough time to consider their participation in this study, ask questions 
and if they are still willing to take part in the study, they will be invited to be admitted to the 
quarantine unit (Day -2). Before any study specific procedures are attempted, the study physician 
will again discuss the study and study procedures with the potential participant and answer any 
questions. After that, participants will be asked to read, sign and date the full study ICF in the 
presence of the study doctor or nurse, who will also sign the consent form.  A copy of the consent 
will be given to the participant and another copy will be filed in their medical notes.  
 
 

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4. 
Supporting Documentation and Operational Considerations 
4.1. 
Appendix 1: Regulatory, Ethical, and Study 
Oversight Considerations 
4.1.1. 
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 
4.1.2. 
Ethics approval 
The Study Coordination Centre has obtained approval from the Specialist Adhoc Research Ethics 
Committee (REC). The study will be conducted in accordance with the recommendations for 
physicians involved in research on human subjects adopted by the 18th World Medical Assembly, 
Helsinki 1964 and later revisions. 
4.1.3. 
Consent 
The Investigator will obtain a signed screening ICF from each participant before any screening or 
study specific procedures are performed as described in section 3. 
Potential participants will be sent a copy of the Screening ICF when their Screening Visit is 
arranged and at least one day prior to the visit, and will be encouraged to read it prior to their 
appointment. Upon arrival at the Screening Visit the Screening ICF is discussed, and they will be 
given the opportunity to ask any questions, and may take the information sheet away to consider 
their participation. Participants will be informed that a further discussion with the full study PIS/ICF 
will be scheduled at a later point (if necessary) and that they will be free to withdraw at any point 
before or after that. 
All participants will be required to have a good understanding of English and the Investigator will 
be responsible for ensuring that the subject understands the information contained in the ICFs. 
Once they have confirmed that the subject has understood the study, including the benefits and 
risks of participation, the subject and the Investigator can sign and date the ICF.  
The ICF must be signed and dated by the subject and countersigned by the Investigator (whoever 
conducted the consent discussion). A copy of the ICF will be given to the subject, and the original 
will be held in the full study TMF. The consent process will be documented in line with hVIVO 
SOPs, which require that documented and signed evidence must be available to confirm staff 
obtaining consent are trained and passed as competent, prior to independently obtaining consent. 
The Investigator will document the consent process in the subject notes and progress notes as 

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applicable. This documentation will include details of capacity assessment, discussion with 
subject, and when/how consent has been obtained. 
Participants who were consented prior to implementation of Substantial Amendment 2 will require 
re-consent to incorporate the up to 7 day stay at home isolation period and PCR test. This process 
will be done remotely to avoid unnecessary travel by the participants. The process will be as 
follows: 
1) The participant will be emailed (if they have a printer) or posted (if they do not have a 
printer or indicate this as a preference) a copy of the PIS/ICF. 
2) A zoom call will be arranged between the participant and the research physician. 
3) The new procedures will be explained to the participant and the option to ask any 
questions will be presented. 
4) The participant and the research physician will each sign a copy of the PIS/ICF. The 
research team will then arrange for a courier to collect the partially signed PIS/ICF from 
the participant’s home and it will be collated with the partially signed PIS/ICF on site. Once 
the documents are combined the consent will be considered valid. 
5) The participant will be posted a copy of the consent via tracked delivery 
Participants will be assured that they can withdraw from the study at any time and for any reason 
without prejudice to their future medical care, and that they will be informed in a timely manner if 
new information becomes available that may affect their willingness to continue their participation 
in the study. This information will be included within the 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.  
4.1.4. 
Confidentiality 
The Chief Investigator will preserve the confidentiality of participants taking part in the study and 
is registered under the Data Protection Act. 
4.1.5. 
Indemnity 
Imperial College London holds negligent harm and non-negligent harm insurance policies which 
apply to this study. hVIVO holds negligent harm insurance policies which apply to this study. 
4.1.6. 
Sponsor 
Imperial College London will act as the Sponsor for this study.  Delegated responsibilities will be 
assigned to hVIVO Services Ltd.   

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4.1.7. 
Funding 
This study is funded by the UK Vaccines Taskforce and Department of Business, Energy and 
Industrial Strategy. They are acting as sole funders and this agreement is in place. The 
investigators will not receive any additional payment above their normal salaries.  Participants will 
be given a donation of up to £70 to compensate for the time and inconvenience of attending the 
screening visit. Additional visits will be compensated with £20 per visit. 
4.1.8. 
Audits 
The study may be subject to audit by Imperial College London under their remit as sponsor and 
other regulatory bodies to ensure adherence to GCP and the UK Policy Framework for Health 
and Social Care Research.  
4.1.9. 
Sample and data storage and usage 
Samples of tissue, cells and fluids will be stored according to Imperial College London and hVIVO 
SOPs as appropriate. Samples will be pseudoanonymised with participant identification numbers 
only and the anonymisation key kept in a separate locked location accessible only to the hVIVO 
clinical study team. Samples may be used for further assays or in other ethically approved studies. 
Samples and data may be shared with UK and international collaborators in studies that have 
been approved by local ethics committees and subject to a valid Materials Transfer Agreement. 
Data and samples sent outside the UK will be labelled with the identification number only and no 
patient identifiable data transferred. Screening data is recorded on paper case books. Data is 
QC’d and only data for enrolled subjects is transcribed to the study data base, as per the hVIVO 
Data Monument Plan. Data and all appropriate documentation will be stored for a maximum of 25 
years after the completion of the study, including the follow-up period according to Imperial 
College London policy. 
At the end of the study any remaining samples will be either destroyed, transferred to the sponsor 
or subject to consent, transfer to and maintained under hVIVOs HTA licenses.   
4.1.10. 
Data Protection 
Participants will be assigned a unique identifier by hVIVO. Any participant records or datasets 
that are transferred to the Sponsor will contain the identifier only; participant names or any 
information which would make the participant identifiable will not be transferred. 
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law and EU GDPR. The level of disclosure 
including the participant’s rights under the applicable data protection laws must also be explained 
to the participant in the ICF.  
The participant must be informed that his/her medical records may be examined by third parties 
such as Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate REC members, and by inspectors from regulatory authorities. 

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4.2. 
Appendix 2: Adverse events 
4.2.1. 
Definitions   
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study subject.   
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect that: 
 
Results in death 
 
Is life-threatening – refers to an event in which the subject 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 
 
Requires hospitalisation 
 
Results in persistent or significant disability or incapacity 
 
Is a congenital anomaly or birth defect 
Medical judgement should be exercised in deciding whether an AE is serious in other situations.  
Important AEs that are not immediately life-threatening or do not result in death or hospitalisation 
but may jeopardise the subject or may require intervention to prevent one of the other outcomes 
listed in the definition above, should also be considered serious. 
4.2.2. 
Risks and expected adverse events 
4.2.2.1. 
Risk Determination 
All screening procedures involve no more than minimal risk to participants. Similar procedures 
have been used for many years without severe adverse effects. These include blood sampling 
and ECG. Participants will be counselled about the following: 
Blood draws: risks include discomfort as the needle goes through the skin and/or bruising. 
Infection, excess bleeding, clotting, or fainting are also possible, although unlikely. 
ECG: risks include skin irritation due to ECG electrodes. 
4.2.3. 
Reporting procedures 
All adverse events should be reported.  Depending on the nature of the event the reporting 
procedures below should be followed.  Any questions concerning adverse event reporting should 
be directed to the Chief Investigator in the first instance.   
 
5.3.1 Non serious AEs 
All such events, whether expected or not, should be recorded - it should be specified if only some 
non-serious AEs will be recorded. Any reporting should be consistent with the purpose of the trial 
end points.  
 
5.3.2 Serious AEs 
An SAE form should be completed and emailed to the Chief Investigator within 24 hours.   
 

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All SAEs should be reported to the Research Ethics Committee where in the opinion of the Chief 
Investigator, the event was: 
 
‘related’, i.e. resulted from the administration of any of the research procedures; and 
 
‘unexpected’, i.e. an event that is not listed in the protocol as an expected occurrence 
 
Reports of related and unexpected SAEs should be submitted within 15 days of the Chief 
Investigator becoming aware of the event, using the NRES SAE form for non-IMP studies.  The 
Chief Investigator must also notify the Sponsor of all SAEs. 
 
Local investigators should report any SAEs as required by their Local Research Ethics 
Committee, Sponsor and/or Research & Development Office. 
 
 

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Contact details for reporting SAEs 
RGIT@imperial.ac.uk 
CI email (and contact details below) 
Email: c.chiu@imperial.ac.uk for the attention Dr Christopher Chiu 
Please send SAE forms to: Department of Infectious Disease, Imperial College London, 
Commonwealth Building, Hammersmith Campus, Du Cane Road, London W12 0NN 
Tel: 020 8383 2301 (Mon to Fri 09.00 – 17.00) 
 
4.3. 
Appendix 3: Abbreviations 
Abbreviation 
Term
ADA 
Anti-Drug 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  

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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 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G  
IM 
Intramuscular 
IMP 
Investigational Medicinal Product 
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 

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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 
β-HCG 
β-human chorionic gonadotrophin 
 
4.4. 
Appendix 4: Toxicity Grading Scale for Laboratory 
AEs 
Toxicity Grading Scale for Lab 
AEs 
Lab 
Range 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Sodium 
Elevated 
mmol/L
145 
146-147 
148-149 
150-155 
>155 
Sodium 
Low 
mmol/L
135 
132-134 
130-131 
125-129 
<125 
Potassium 
Elevated 
mmol/L
5.1 
5.2-5.3 
5.4-5.5 
5.6-6.5 
>6.5 
Potassium 
Low 
mmol/L
3.5 
3.2-3.3 
3.0-3.1 
2.5-2.9 
<2.5 
Urea 
Elevated 
mmol/L
1.7-8.3 
8.4-9.3 
9.4-11.0 
>11.0 
Requires 
Dialysis 
Creatinine 
(Female) 
Elevated 
µmol/L 
49-92 
101-138 
139-276 
>277 
Requires 
Dialysis 
Creatinine 
(Male) 
Elevated 
µmol/L 
66-112 
123-168 
169-336 
>336 
Requires 
Dialysis 

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Bilirubin 
Normal 
LFTs 
µmol/L 
0-20 
22-30 
31-40 
41-60 
>60 
Bilirubin 
Abnormal 
LFTs 
µmol/L 
0-20 
22-25 
26-30 
31-35 
>35 
ALP 
(Female) 
Elevated 
IU/L 
104 
114-208 
209-312 
313-1040 
>1040 
ALP (Male) 
Elevated 
IU/L 
129 
142-258 
259-387 
388-1290 
>1290 
ALT 
(Female) 
Elevated 
IU/L 
35 
39-88 
89-175 
176-350 
>350 
ALT (Male) 
Elevated 
IU/L 
50 
55-125 
126-250 
251-500 
>500 
AST 
(Female) 
Elevated 
IU/L 
31 
34-78 
79-155 
156-310 
>310 
AST (Male) 
Elevated 
IU/L 
37 
41-93 
94-185 
186-370 
>370 
Albumin 
Low 
g/L  
34-50 
28-31 
25-27 
<25 
-