Efficacy of MVA-NP+M1 in the Influenza H3N2 Human Challenge Model
Phase: PHASE2
Conditions: Influenza
Sponsor: Barinthus Biotherapeutics

 
 
 
 
Efficacy of MVA-NP+M1 in the Influenza H3N2 Human 
Challenge Model 
 
NCT03883113 
 
Document Title: FLU010 Protocol Version 5.0 
 
Document Date: 10Jul2019 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
1 
Efficacy of MVA-NP+M1 in the influenza H3N2 Human Challenge 
model 
 
Product MVA-NP+M1 
Protocol Number FLU010 
EudraCT Number 2018-004015-49 
OR IND Number 018827 
Clinical Phase 2 
Clinical Indication Protection against influenza disease 
Issue Date (Version) 10-July-2019 (Version 5.0) 
 
 
Sponsor Vaccitech Ltd. 
Sponsor Representative  
 
EU Legal Representative* 
Contact 
Tom Evans, MD 
 
Venn Life Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
* Vaccitech is the EU Legal Representative until Brexit date 
 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
4 
PROTOCOL HISTORY 
Protocol History 
VACCITECH - CLINICAL STUDY PROTOCOL – FLU010 
Document  
Issue Date 
Amendment Type 
Comments 
Initial Clinical Study 
Protocol – v1.0 
19-Dec-2018 
NA 
 
Clinical Study Protocol - 
v2.0 
27-Feb-2019 
Contraception requirements as per EC’s request 
i.e. 6 months prior vaccination and 6 months 
post-challenge 
 
Contraception methods have been changed to 
highly effective methods as per FAMHP’s 
request 
Following sections have been impacted by this 
amendment: 
 
• 
Eligibility Criteria / Inclusion Criteria, Bullet point 
4b, page 10, 
• 
Section 4.1 Inclusion Criteria, Bullet point 4b, page 
28 
Vaccination start date has been changed from 
March 1, 2019 to April 2, 2019 
Following sections have been impacted by this 
amendment: 
• 
Protocol synopsis: Study/treatment duration, page 
12, 
• 
Section 3.1, page 27. 
Blood volumes removed from protocol; they are 
detailed in the laboratory manuals 
Following sections have been impacted by this 
amendment: 
• 
Time and Events Schedule, Period 1, page 14, 
• 
Section 7.1.5, page 36, 
• 
Section 7.2.3, page 39. 
Clarification regarding samples collection pre-
vaccination (PBMC, Serum & whole blood in 
Trizol) 
Time and Events Schedule, Period 1, page 14. 
Randomization list to Bioanalytical Laboratory 
was removed 
Section 5.5, page 32. 
Serum/ urine pregnancy test was clarified. 
Serum pregnancy test is to be performed at 
screening visit only for female subjects’ 
eligibility in the study. Urine test is to be 
performed in all subsequent visits 
Following sections have been impacted by this 
amendment: 
• 
Section 7.1.2.1, page 35, 
• 
Section 7.2.3, page 39. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
5 
Protocol History 
VACCITECH - CLINICAL STUDY PROTOCOL – FLU010 
Document  
Issue Date 
Amendment Type 
Comments 
Reference to Plasma samples was removed 
everywhere in the protocol 
Following sections have been impacted by this 
amendment: 
• 
Section 7.1.5, page 36, 
• 
Section 7.1.6, page 37. 
Clinical Study Protocol – 
v3.0 
02-Apr-2019 
Exclusion criteria reorganised: 
- #10 & 18 moved to Exclusion (Challenge 
Period Only) where they are respectively 
numbered # 4 & 6. 
- #19 deleted as already present in the challenge 
exclusion list. 
- #3 & 5 in the challenge exclusion list have 
been added to ensure participants safety 
 
Exclusion criterion #3 clarified 
• 
Synopsis – Sections Exclusion Criteria & Exclusion 
(Challenge Period Only) respectively pages 13 & 14  
Sections 4.2 & 4.3 respectively pages 32 & 33  
Endpoints section: 
Secondary endpoints: clarified (deletion of 
“regardless of take rate” in endpoint 2 & 4 and 
“consecutive” in endpoint 6) 
Exploratory endpoints:  
- qPCR and culture results were added 
- Transcriptomic analysis, initially part of the 
protocol, but omitted in the endpoints, has been 
added 
- Epigenetic response of T-Cells has been added 
 
Synopsis – pages 14 & 15 
Sections 2.2 & 2.3 page 29 
Section 7.1.6 – page 40 
Section 9.1.2.3. page 48 
- Statistical Methods: removal of participants 
with virologically confirmed influenza in the 
symptom severity total AUC 
- IDMC analysis and timing were removed in 
section 9.1 
- Section 9.1.2 reorganised for better 
understanding. Subsections 9.1.2.1, 9.1.2.2 & 
9.1.2.3 have been created. The information 
Synopsis - Section Efficacy – page 15 
Section 9.1.2.2 page 47 
 
Section 9.1 page 46 
 
Section 9.1.2 and its subsections – pages 47 & 48 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
6 
Protocol History 
VACCITECH - CLINICAL STUDY PROTOCOL – FLU010 
Document  
Issue Date 
Amendment Type 
Comments 
initially under section 9.1.2 has been placed 
accordingly in appropriate new subsections. 
Time and Events Schedules (Periods 1 & 2) 
have been clarified: 
- footnotes have been added or amended 
- Month 6 post-vaccination follow-up call was 
moved from the challenge period to Period 1 
- Hep B was removed as redundant; HBsAg is 
being measured 
- Trizol samples have been renamed with the 
appropriate test name i.e. transcriptomics 
- PBMC, serum and transcriptomics have been 
split into 2 rows for better clarity 
- Transcriptomics timepoints in Period 2 have 
been added on Days 2, 5 and 8. 
- The blood tests in Period 2 have been 
combined to allow the site to withdraw blood on 
Day -2 or Day -1 
- NP swabs sample line in Period 2 has been 
deleted as repeated 
- Clarification that MNT can be tested at 
screening visit 1 or screening visit 2 
Section Periods 1 & 2 – pages 16 to 19 
New members of the team have been added: 
- Vaccitech new Head of Clinical Operations, 
Elizabeth Eagling-Vose (replacing Chris Ellis) 
- Approved EU Legal Representative, Venn Life 
Sciences 
Section: Study Administrative Structure and Investigators 
– pages 1 & 22 
Randomization and Blinding section has been 
amended to describe the process put in place to 
maintain the study double blind 
Section 3.2 – page 30 
- The number of MVA-NP+M1 vials number 
per box has been changed in the Packaging and 
labelling section. “50 or 10 vials” has been 
replaced by “25 vials”. 
Section 5.3 – page 34 
 
 
Section 5.4 – pages 34 & 35 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
7 
Protocol History 
VACCITECH - CLINICAL STUDY PROTOCOL – FLU010 
Document  
Issue Date 
Amendment Type 
Comments 
- The study drug accountability process has 
been clarified  
HRT added to the Permitted Concomitant 
Therapies section 
Section 6.1 – page 36 & 37 
Solicited symptoms have been updated in the 
Assessments section 
Clarification of MNT performed at screening 
visit 1 or screening visit 2 
A subsection relating to Transcriptomics was 
added under section 7  
Transcriptomics initially referred to as Trizol 
was already part of the protocol 
Section 7 – page 37 
 
Section 7.1.1 - pages 37 & 38 
 
Section 7.1.7 – page 40 
Sodium and potassium tests were added to the 
biochemistry assessment in Period 2 
Section 7.2.3 – pages 42 & 43 
The Stopping Rules or Discontinuation Criteria 
section has been renamed “Stopping Rules or 
Non-Vaccination Criteria”. This section has 
been slightly reworded to provide clarity. 
Temperature has been changed to be consistent 
with the toxicity grading scale in Appendix 2. 
The stopping rules have been amended by 
removing the time limit in the solicited and 
unsolicited AEs  
Section 8.3 – pages 45 & 46 
A causality assessment has been added “Not 
Related” 
Section 10.3 – page 51 
A number of changes implemented for 
clarification, consistency and typo corrections 
with no substantial amendment to previous 
protocol version 
Throughout the protocol 
The period between vaccination and challenge 
has been changed from “2 months post 
vaccination and no later than 6 months” to 
“6 weeks post vaccination and not later than 
6 months” 
Throughout the protocol - added to improve recruitment 
rates with no major change in overall window 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
8 
Protocol History 
VACCITECH - CLINICAL STUDY PROTOCOL – FLU010 
Document  
Issue Date 
Amendment Type 
Comments 
Clinical Study Protocol – 
v4.0 
14-May-2019 
The 
challenge 
virus 
atomiser 
Teleflex 
VaxINatorTM kit has been replaced by Teleflex 
MAD301 and MAD130. 
 
Section 3.1 – page 30 
Sections 5.2.2 & 5.4 – page 34 
Clinical Study Protocol – 
v5.0 
10-Jul-2019 
MNT increase from ≤10 to <20 
 
 
 
 
 
Attack rate change from 90% to 83% 
 
 
A clarification added the challenge risk section 
 
Synopsis – Inclusion Criteria – page 15 
Section 1.1 – page 28 
Section 3.1 – page 32 
Section 3.2 – page 33 
Section 4.1 – page 34 
 
Synopsis – Statistical Methods – page 17 
Section 9.1.2.3 – page 49 
 
Section 7.2.1 – page 44 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
9 
TABLE OF CONTENTS 
Title Page 
 ..................................................................................................................... 1 
Signatures 
 ..................................................................................................................... 2 
Protocol History ................................................................................................................ 4 
Table of Contents .............................................................................................................. 9 
Protocol Amendment: Summary of Changes............................................................... 12 
Protocol Synopsis ............................................................................................................ 14 
Time and Events Schedule ............................................................................................. 18 
List of Abbreviations and Definitions of Terms .......................................................... 21 
Study Administrative Structure and Investigators ..................................................... 23 
1. 
Introduction ............................................................................................. 25 
 
Background Information .................................................................................... 25 
 
Clinical Studies ................................................................................................... 28 
 
Overall Rationale for the Study .......................................................................... 30 
2. 
Study Objectives ...................................................................................... 30 
 
Primary Objective ............................................................................................... 30 
 
Secondary Objectives ......................................................................................... 30 
 
Exploratory Objectives ....................................................................................... 30 
3. 
Study Design ............................................................................................ 31 
 
Overview of Study Design ................................................................................. 31 
 
Discussion of Study Design ................................................................................ 31 
4. 
Selection of Study Population ................................................................ 32 
 
Inclusion Criteria ................................................................................................ 32 
 
Exclusion Criteria ............................................................................................... 33 
 
Exclusion (Challenge Period only) ..................................................................... 34 
5. 
Treatment ................................................................................................ 34 
 
Physical Description of the Study Drug ............................................................. 34 
 
Other Medication Administered in the Study ..................................................... 35 
5.2.1 
Placebo ................................................................................................. 35 
5.2.2 
Challenge Product [H3N2] ................................................................... 35 
 
Packaging and Labelling .................................................................................... 35 
 
Storage and Study Drug Accountability ............................................................. 35 
 
Randomization and Blinding .............................................................................. 36 
 
Dose and Administration .................................................................................... 37 
 
Safety Monitoring ............................................................................................... 37 
5.7.1 
Safety Monitoring Committee .............................................................. 37 
5.7.2 
Independent Data Monitoring Committee ............................................ 37 
6. 
Prior and Concomitant Therapy ........................................................... 38 
 
Permitted Concomitant Therapies ...................................................................... 38 
 
Prohibited Concomitant Therapies ..................................................................... 38 
7. 
Assessments.............................................................................................. 38 
 
Timing of Assessments ....................................................................................... 38 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
10 
7.1.1 
Screening Period .................................................................................. 39 
7.1.2 
Treatment Period .................................................................................. 39 
7.1.3 
Follow-up Period .................................................................................. 40 
7.1.4 
Unscheduled Visits ............................................................................... 41 
7.1.5 
Sample Collection and Handling .......................................................... 41 
7.1.6 
Immunogenicity ................................................................................... 41 
7.1.7 
Transcriptomics .................................................................................... 42 
7.1.8 
Efficacy Variables ................................................................................ 42 
7.1.9 
Efficacy Criteria ................................................................................... 42 
 
Safety Evaluations .............................................................................................. 42 
7.2.1 
Study Products Potential Risks ............................................................ 42 
7.2.2 
Adverse Events ..................................................................................... 43 
7.2.3 
Clinical Laboratory Tests ..................................................................... 43 
7.2.4 
Vital Signs ............................................................................................ 44 
7.2.5 
Spirometry ............................................................................................ 44 
7.2.6 
Electrocardiogram ................................................................................ 44 
7.2.7 
Physical Examination ........................................................................... 45 
7.2.8 
Other Assessments ............................................................................... 45 
 
Total Volume of Blood Sampling ...................................................................... 45 
8. 
Study Termination/Completion ............................................................. 45 
 
Study Completion ............................................................................................... 45 
 
Removal of Participants From Study ................................................................. 45 
 
Stopping Rules or Non-Vaccination Criteria ..................................................... 46 
9. 
Statistical Methods .................................................................................. 47 
 
Statistical Analysis ............................................................................................. 47 
9.1.1 
Baseline Characteristics ....................................................................... 48 
9.1.2 
Efficacy Data ........................................................................................ 48 
9.1.3 
Safety Data ........................................................................................... 49 
 
Determination of Sample Size ............................................................................ 50 
10. 
Adverse Event Reporting ....................................................................... 51 
 
Definitions  ....................................................................................................... 51 
 
Intensity of Adverse Events ................................................................................ 51 
 
Causality Assessment ......................................................................................... 52 
 
Action Taken Regarding the Study Drugs .......................................................... 52 
 
Outcome 
 ....................................................................................................... 53 
 
Recording of Adverse Events ............................................................................. 53 
 
Reporting of Serious Adverse Events ................................................................. 53 
 
Pregnancy 
 ....................................................................................................... 54 
 
Reporting of Serious Adverse Events to Competent Authorities/Ethics 
Committees  ....................................................................................................... 54 
11. 
Ethical Aspects ........................................................................................ 54 
 
Study-Specific Design Considerations ............................................................... 54 
 
Regulatory Ethics Compliance ........................................................................... 54 
11.2.1 
Investigator Responsibilities ................................................................ 54 
11.2.2 
Independent Ethics Committee or Institutional Review Board 
(IEC/IRB) ............................................................................................. 55 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
11 
11.2.3 
Informed Consent ................................................................................. 56 
11.2.4 
Privacy of Personal Data ...................................................................... 57 
12. 
Administrative Requirements ................................................................ 57 
 
Protocol Amendments ........................................................................................ 57 
 
Participant Identification, Enrolment, and Screening Logs ................................ 57 
 
Source Documentation ....................................................................................... 57 
 
Case Report Form Completion ........................................................................... 58 
 
Monitoring  ....................................................................................................... 58 
 
Data Management ............................................................................................... 59 
 
Data Quality Assurance ...................................................................................... 59 
 
On-Site Audits .................................................................................................... 59 
 
Study Termination .............................................................................................. 60 
 
Record Retention ................................................................................................ 60 
 
Use of Information and Publication ................................................................... 60 
 
Registration of Clinical Studies and Disclosure of Results ................................ 61 
 
Confidentiality .................................................................................................... 61 
13. 
References ................................................................................................ 62 
Appendix 1:  ................................................................................................................... 64 
Appendix 2: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials .................................... 64 
A. 
Tables for Clinical Abnormalities ...................................................................... 64 
B. 
Tables for Laboratory Abnormalities ................................................................. 67 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
12 
List of Tables 
Table 1: Previous MVA-NP+M1 trials  ......................................................................... 23 
Table 2: Treatment Overview: Challenge number (+ additional vaccination) ............... 37 
 
List of Figures 
Figure 1: 
Immunogenicity of MVA-NP+M1 in older adults (FLU001) ....................... 24 
 
PROTOCOL AMENDMENT: SUMMARY OF CHANGES 
Overall Reason for Amending the Protocol:  
Version 2.0 dated 27-Feb-2019: 
Further to Belgian Ethics Committee request dated 13-Feb-2019 the contraception period 
has been extended to 6 months pre-vaccination and 6 months post-challenge. 
FAMHP’s request dated 26-Feb-2019 was implemented; i.e. highly effective contraception 
methods. 
Additional changes were made to provide clarity in the protocol and correct some 
discrepancies that will impact vaccination period. 
Version 3.0 dated 02-Apr-2019: 
This substantial amendment includes: 
• Additional timepoints in the challenge period to measure transcriptonics. The Time 
and Events Schedule has been reshuffled to allow clarity regarding the assessments 
to be performed. Sodium and potassium tests have been added to the biochemistry 
test in the challenge period. 
• The exclusion criteria have been split in two categories i.e. study entry and 
challenge period entry. 
• The process that maintains the double blind throughout the study has been amended 
to provide a robust procedure. 
 
Further clarifications have been made throughout the protocol. These are considered 
minor. 
Version 4.0 dated 14-May-2019: 
This amendment is to specify that the Teleflex MAD301 and MAD130 are being used in 
the study, rather than the Teleflex VaxINatorTM. 
Version 5.0 dated 10-Jul-2019: 
This amendment is to increase MNT value at study entry. The rate of seronegativity in the 
screened population as defined by an MNT < 10 units has declined since previous studies, 
but in general a twofold dilution is within the assay variability and should have a minor 
effect of take rates. As a value below 20 represents the geometric mean of one duplicate 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
13 
sample reading 10 and one reading 20, this value should not impact the take rate after 
challenge but will increase the pool of potentially eligible participants. 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL - PROTOCOL SYNOPSIS 
14 
PROTOCOL SYNOPSIS 
Study Title 
Efficacy of MVA-NP+M1 in the influenza H3N2 Human Challenge 
model 
Product 
MVA-NP+M1 
Clinical Phase 
2 
Protocol Number 
FLU010 
Indication 
Prevention of influenza-
related disease 
EudraCT Number 
2018-004015-49 
IND Number 
018827 
 
Sponsor 
Vaccitech Ltd 
Sponsor Representative 
Tom Evans, MD 
Clinical Centre 
SGS Antwerp Clinical Challenge Unit 
 
Objectives: 
The primary objective of this study is to show that MVA-NP+M1 decreases the viral shedding of influenza 
virus, as measured by the cumulative area under the curve, following human challenge.  
Secondary objectives are to show safety, the effect on the incidence of laboratory-confirmed influenza-like 
illness (ILI), total and individual symptom scores, and mucous production (measured by tissue weight). 
Immune T cell responses and correlation of these responses with efficacy will also be investigated. 
Overview of Study Design: 
This is a single centre, randomized, double blind study. The study consists of an outpatient vaccination phase, 
and at least 6 weeks later an inpatient challenge phase. 155 participants will be randomized 93:62 to receive 
either MVA-NP+M1 or Placebo. Up to 20 participants will be challenged over several 3-week blocks, and the 
remainder at the final 3-week block for a total of 80 MVA-NP+M1 and 54 Placebo recipients challenged. 
Study Population: 
Healthy adult volunteers ages 18-55, male and female. 
155 participants will be enrolled and vaccinated, and 134 will be challenged at least 6 weeks later. 
Eligibility Criteria: 
Inclusion Criteria: 
1. Healthy males and females aged ≥18 and ≤55 years of age at the point of enrolment. 
2. Non-smokers or those who stopped smoking ≥ 3 months prior to screening 1 visit.  
3. Willingness to remain in isolation for the duration of the study. 
4. A female participant is eligible for this study if she is not pregnant or breast feeding and 1 of the 
following: 
a. 
Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal 
ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 
year). 
b. Of childbearing potential but has been, and agrees to continue practicing, highly 
effective contraception or abstinence (if this is the preferred and usual lifestyle of the 
participant) from 6 months prior to vaccination to 6 months after administration of the 
influenza challenge virus. Highly effective methods of contraception include 1 or more 
of the following:  
i. male partner who is sterile (vasectomised) prior to the female participants 
entry into the study and is the sole sexual partner for the female participant;  
ii. hormonal (oral, intravaginal, transdermal, implantable or injectable);  
iii. an intrauterine hormone-releasing system (IUS);  
iv. an intrauterine device (IUD) with a documented failure rate of < 1%;  

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL - PROTOCOL SYNOPSIS 
15 
v. bilateral tubal occlusion. 
5. Pre-challenge serum microneutralization (MNT) against A/Belgium/4217/2015 (H3N2) 
challenge strain <20.  
 
Exclusion Criteria: 
1. Body Mass Index (BMI) < 19 and > 32. 
2. Presence of any significant acute or chronic, uncontrolled medical (or psychiatric) illness 
including a history of chronic respiratory illness.  
3. History of seasonal hay fever or clinically significant seasonal allergic rhinitis (SAR), including 
the use of symptomatic prescription only medication and non-prescription medication. 
4. History or evidence of autoimmune disease or known immunodeficiency of any cause - with the 
exception of atopic dermatitis/eczema and atopic rhinitis. 
5. Any history of anaphylaxis in reaction to vaccination or history of allergic reactions likely to be 
exacerbated by any component of the vaccine.  
6. History of lung disease (Asthma, COPD). 
7. Current smokers or those who stopped smoking < 3months prior to screening 1 visit. 
8. Positive diagnostic tests for HIV, Hepatitis B or Hepatitis C indicating active infection. 
9. Evidence of drug abuse or a positive urine drug screen or alcohol breath test. 
10. Chronic use of any medication or other product (prescription or over-the-counter), for symptoms 
of rhinitis or nasal congestion or for any chronic nasopharyngeal complaint, or chronic use of 
any intranasal medication for any indication that has not cessed within 30 days prior to screening 
1. 
11. Receipt of any investigational drug within 3 months prior to vaccination, or prior participation 
in a clinical trial of any influenza vaccine, or any investigational vaccine or experimental 
influenza viral challenge delivered directly to the respiratory tract within 1 year prior to 
challenge. 
12. Receipt of the 2018/2019 seasonal flu vaccine.  
13. Receipt of any live vaccines within the 4 weeks prior to vaccination. 
14. Any laboratory test which is abnormal and which is deemed by the Investigator(s) to be clinically 
significant.  
15. Receipt of any systemic chemotherapy agent at any time. 
16. Physician reported influenza or a syndrome consistent with influenza (as judged by the 
investigator) in the previous 6 months. 
17. Known allergy to treatments for influenza (including but not limited to oseltamivir). 
18. History of frequent epistaxis (nose bleeds). 
19. Any nasal or sinus surgery within 6 months of Viral Challenge or any significant abnormality, 
either of which results in alteration of the anatomy of the nose or nasopharynx (including 
significant nasal polyps). 
20. Volunteers with household contacts who are at risk for serious or severe complications of 
influenza disease including, but not limited to: persons ≥ 65 years; presence of significant 
chronic cardiopulmonary, metabolic, renal, or neurological conditions; immunosuppression due 
to any condition or therapies; BMI >40.  
21. Participants that are an employee or family member of the Investigator or study site personnel 
may not be enrolled. 
22. Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for 
the study. 
 
Exclusion (Challenge Period only) 
1. Abnormal spirometry assessed to be clinically significant. 
2. Known close contact with anyone known to have influenza in the past 7 days at the time of 
quarantine. 
3. ILI symptoms as assessed at the admission to clinic on Day -2 prior to challenge. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL - PROTOCOL SYNOPSIS 
16 
4. Presence of fever, defined as participant presenting with a temperature reading of > 38.0°C 
on admission to quarantine.  
5. Qualitative PCR results positive for viral infection. However, participants may be re-tested 
and included into later challenge cohort, if they later test negative for viral infection. 
6. Acute use of any medication or other product, prescription or over-the-counter, for 
symptoms of rhinitis or nasal congestion within 7 days prior to challenge. This includes any 
oral corticosteroid or beta agonist containing nasal spray. 
Test Product, Dose, Mode of Administration: 
Vaccination (one dose):  
Single dose of MVA-NP+M1 at 1.5 x 108 pfu, 0.5mL given intramuscularly in the deltoid 
Challenge Virus:  
A/Belgium/4217/2015 [H3N2] will be used as the challenge virus at 1.0 x 106 TCID50/mL given by 
intranasal spray, 0.25 mL per nostril 
 
Reference Product, Dose, Mode of Administration: 
Vaccination (one dose):  
Saline Placebo (0.5 mL given intramuscularly) in the deltoid 
 
Study/Treatment Duration: 
The study consists of a screening phase, followed by vaccination of 155 participants starting in April 2019. In 
the challenge phase, cohorts up to 20 participants will begin inoculations and will remain in quarantine for 13 
days. A new cohort of up to 20 participants is then challenged every 3 weeks thereafter until all 134 
participants are enrolled. The total study length is approximately 8 months, excluding an initial screening 
phase.  
 
Criteria for Evaluation: 
Elicited local and systemic symptoms following vaccination will be collected for 7 days by diary card. 
Unsolicited adverse events (AEs) are collected throughout the study from consent form signature. Immune 
response will be measured using both T cell-related (ELISpot, ICS) and antibody (Hemagglutination 
Inhibition (HI) and MNT) assays. Samples will also be stored for potential future correlate of protection 
analysis. 
Nasal swabs for influenza virus are collected twice a day (at least 8 hours apart) from Day 2 to Day 10 
following intranasal challenge, which are tested for influenza PCR and culture. Symptoms of influenza-related 
infection will be collected from Day 1 to Day 11 of challenge, as will total nasal tissue weight.  
 
Efficacy: Total viral area under the curve (vAUC) for virologic shedding as measured by quantitative PCR 
(qPCR) for MVA-NP+M1 vs. Placebo groups. 
 
Secondary endpoints include: 
- 
Incidence in each group (MVA-NP+M1 and saline Placebo) of laboratory-confirmed ILI (qPCR or 
culture) 
- 
Total AUC for total symptom score for MVA vs. Placebo 
- 
Total days of fever for MVA-NP+M1 vs. Placebo 
- 
Total mucus weight for MVA vs. Placebo 
- 
Correlation of T cell responses (as defined by ELISpot assay) to the primary endpoint, symptom 
scores, and influenza incidence 
- 
The attack rate, defined as percentage of inoculated participants with at least two positive swabs as 
determined by qPCR 
 
Exploratory endpoints 
- 
Time to start; time to peak and duration of qPCR and quantitative culture results 
- 
Time to start, time to peak, and duration for total symptoms for MVA vs. Placebo  
- 
Severity of individual symptoms for MVA-NP+M1 vs. Placebo 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL - PROTOCOL SYNOPSIS 
17 
- 
Correlation of antigen specific T cell phenotypes to the primary endpoint, symptom scores, and 
influenza incidence 
- 
Effect of vaccination on the antibody responses to influenza following the intranasal challenge  
- 
Transcriptional response to vaccination and viral challenge assessed by deep sequencing of RNA 
- 
Potential assessment of epigenetic responses of T-Cells during the study. 
 
Safety  
-  
Frequency and severity of participant-recorded local and systemic adverse events recorded for the 
7 days following vaccination 
-  
Frequency and severity of non-solicited adverse events captured throughout the study after 
vaccination 
-  
Frequency and types of serious adverse events  
-  
Severity of adverse events in each study group following intranasal challenge with H3N2 
 
Statistical Methods: 
Sample size: determined by the challenge cohort of N=134  
 
Immune response:  
Primary immune endpoint will be the T cell response measured by ELISpot and recorded as the mean spot 
forming units per million peripheral blood mononuclear cells (PBMCs) in the peptide-stimulated wells 
minus the mean dimethyl sulfoxide (DMSO) control wells for the given sample. 
 
Efficacy: 
The primary endpoint upon which the powering analysis is performed using the vAUC from the qPCR for 
all collected samples, compared between groups using a Mann-Whitney U Test (Wilcoxon rank sum). The 
assumptions are based on the Placebo data from two prior challenge studies with this H3N2 virus. The study 
is powered to detect as low as a 20% efficacy of the vaccine using this endpoint at a power of 80%, and 
approximately 25% efficacy at a 90% power. This allows for up to 20% drop out without prejudicing the 
goal of the study. 
Secondary endpoints include the rate of virologically confirmed ILI (symptoms of either an upper or lower 
respiratory illness along with two positive PCR or culture) measured between groups. Another key 
secondary endpoint of relevance to the biologic effect of this vaccine will be the comparison of the symptom 
severity as a total Area Under the Curve (AUC). This endpoint takes into account both the severity and the 
duration of symptoms. Mucosal secretions will be collected, and the weight of the sample tissues compared 
between groups.  
Importantly, with a 83% attack rate and 30% efficacy, approximately 20 of the 80 vaccinated participants 
will have a zero AUC, and these participants can be compared to those with the highest vAUC in correlate 
of protection analyses.  
Safety will be reported using standard frequency and severity tables.  
At the protocol sample size, there is a 93% chance that a Serious Adverse Event (SAE) with a 3% incidence 
will be observed in at least one participant.  
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
20 
Period 2 
In-Clinic Confinement  
Unscheduled 
Visit3 
Out- 
patient 
Day -2 
Day -1 
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
Day 
8 
Day 
9 
Day 
10 
Day 
11 
Day 285 
±3 
Transcriptomics - whole blood collection 
(PAXgene® RNA) 
x10 
x10 
  
x  
  
 
x  
  
 
x  
  
  
  
 
x 
 
1  
Admission to clinic is possible on Day -1, in which case Day -2 assessments may be performed on Day -1. Pre-challenge assessments may be performed on Day -2 or Day -1.  
2  
Multiplex PCR tests are to be performed to determine whether participants are incubating other viruses at the time of inoculation. Participants with positive results should not enter the challenge 
group and could be offered to be part of one of the subsequent groups if their infection is cleared. 
3  
Assessments during Unscheduled Visits will be performed at the discretion of the Investigator 
4  
Symptom Score Questionnaire to be administered b.i.d. from Day 1 to Day 10 but only once prior discharge on Day 11 
4a  During the challenge period the biochemistry test will include creatinine, glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma 
glutamylaminotransferase (GGT), C-reactive protein (CRP), bilirubin, sodium and potassium 
5  
Month 6 visit post-vaccination day (180 days ±14) will be performed for all vaccinated participants if it is greater than Day 28 post-Challenge  
6  
ECG performed on Day -1 pre-vaccination will be considered as study Baseline. Any change from Baseline considered significant by the Investigator is to be recorded as AE 
7  
Tissue collection to start 12 hours post-Challenge 
8  
Additional sera collected for future correlate work 
9  
PBMCs to be sent to Viroclinics for processing 
10  Transcriptomics baseline samples are required on Day -2 and Day -1. For participants who replace challenge drop-outs, only Day -1 sample will be collected which is acceptable. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
21 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse event 
AESI 
Adverse Events of Special Interest 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
b.i.d. 
Bis in die; twice daily 
BMI 
Body mass index 
CEF 
Chicken Embryo Fibroblasts 
CI 
Confidence interval 
CPU  
Clinical Pharmacology Unit  
CRP 
C-reactive protein 
CTCAE 
DBP 
DMSO 
Common Terminology Criteria for Adverse Events 
Diastolic Blood Pressure 
Dimethyl sulfoxide 
ECG 
Electrocardiogram 
ELISpot 
Enzyme-linked immunosorbent assay 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
Gamma glutamyltransferase 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
GMT 
Geometric mean titre 
HBsAg 
Hepatitis B surface antigen 
HI 
Hemagglutination Inhibition assay 
HCV 
Hepatitis C virus 
HCT 
Hematopoietic Cell Transplant 
HIV 
Human immunodeficiency virus 
HLA-I 
Human leukocyte antigen I 
HLA-II 
Human leukocyte antigen II 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization 
ICS 
Intracellular Cytokine Staining 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IFN 
Interferon 
ILI 
Influenza-like illness 
IMP 
IND 
Investigational medicinal product 
Investigational New Drug  
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IUD 
Intrauterine Device 
IUS 
Intrauterine hormone-releasing system 
LPLV 
Last Participant Last Visit 
MCH 
mean corpuscular haemoglobin 
MCHC 
Mean corpuscular haemoglobin concentration 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
22 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intention-To-Treat 
MNT 
Microneutralization Test 
NA 
Not applicable 
NP 
Nasopharyngeal 
PBMCs 
Peripheral Blood Mononuclear Cells 
PBS 
Phosphate-buffered saline 
PCR 
Polymerase Chain Reaction 
QC 
Quality control 
qPCR  
Quantitative PCR (can be a reverse transcriptase PCR) 
RBC 
Red Blood Cell 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic Blood Pressure 
SD 
Standard deviation 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TCID50 
50% Tissue culture Infective Dose 
TMF 
Trial Master File 
vAUC 
Viral area under the curve (as determined by qPCR) 
WBC 
White blood cell 
WHO 
World Health Organization 
 
 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
24 
2800 Mechelen 
Belgium 
CLINICAL LABORATORY 
ZNA Klinisch Laboratorium 
Campus Middelheim 
Lindendreef 1 
2020 Antwerpen 
Belgium 
BIOANALYTICAL LABORATORY 
Viroclinics 
Rotterdam Science Tower 
Marconistraat 16 
3029 AK Rotterdam 
Netherlands 
PHARMACOVIGILANCE 
SGS Life Sciences, Medical Affairs 
Department 
Generaal De Wittelaan 19A B5 
2800 Mechelen 
Belgium 
MANUFACTURING FACILITY 
Emergent BioSolutions 
5901 East Lombard Street 
Baltimore 
MD 21224 
US 
PACKAGING AND LABELLING 
Fisher BioServices 
Woodside Industrial Estate 
Unit 1 
Bishop's Stortford 
Hertfordshire, CM23 5RG 
UK 
 
Fisher Clinical Services  
Langhurst Wood Road 
Horsham 
West Sussex, RH12 4QD 
UK 
 
 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
25 
 
1. INTRODUCTION  
 
 BACKGROUND INFORMATION 
Influenza is an orthomyxovirus and encodes a segmented Ribonucleic acid (RNA) genome. Influenza is divided 
into 3 groups- A, B and C. Most seasonal influenza and all known pandemics are caused by Influenza A, whilst 
B causes seasonal influenza and influenza C infection is seen in sporadic outbreaks [1]. Influenza A is subdivided 
further on the basis of haemagglutinin (H or HA) and neuraminidase (N or NA) activity e.g., H1N1 subtype. 
There are at least 16 different types of HA and 9 of NA. These proteins are found as spiked surface projections 
on the Influenza A virus [2]. Other genes encode proteins vital for structure, reproduction and virulence including 
nucleoprotein (NP), Matrix 1 (M1), M2 (ion pore), NS1, NS2, PA, PB1, PB1-F2 and PB2, which are found in 
the virion core [1, 2]. 
Seasonal influenza has a significant annual global impact accounting for an estimated 1 billion illnesses and 
290,000 – 650,000 deaths [3] with an estimated annual economic cost of $87.1 billion in the US alone [4]. 
Influenza pandemics also occur occasionally with significant health and economic burden [5]. In addition, the 
unpredictable risk of sporadic outbreaks of human infections with avian influenza (H5N1) could trigger a new 
pandemic if the virus acquires the ability to transmit from person to person [6] and make influenza a major 
global public health issue. The major demographic groups at highest risk of influenza infection, severe disease 
and death remain young children, older individuals, pregnant women and those with co-morbid conditions such 
as asthma, chronic respiratory disease, diabetes and immunosuppressive conditions.  
Vaccination remains the most cost-effective strategy available to combat influenza. Current influenza vaccines 
work by inducing strain-specific antibodies against the highly polymorphic surface proteins (haemagglutinin, 
neuraminidase) of the influenza virus. Inactivated or live vaccines are made up of proteins from viruses or live 
viruses, respectively, covering four influenza virus strains (H1N1, H3N2 and two strains of influenza B). The 
composition of virus strains used in the production of vaccines is based on a prediction of strains likely to 
circulate in the population in the upcoming influenza season. As the circulating virus strains change, current 
vaccines need to be reformulated annually to match new strains arising through genetic drift in the surface 
proteins of these seasonal viruses. As these surface proteins to which vaccine-induced antibodies are targeted 
are highly polymorphic, there is little protection against strains of a new subtype and limited protection even 
across strains within the same subtype.  Approximately one year in 20, vaccine efficacy is much lower than 
expected owing to antigenic drift away from the vaccine strain [7]. This need for constant redesign and 
remanufacture increases the vaccine cost, places limitations on supply [8] and critically delays vaccine 
production when new strains arise until the HA and NA sequences have been identified leaving large populations 
susceptible to infection and illness from the new strains. Furthermore, the efficacy of current vaccines is limited 
in the face of antigenic mismatch between circulating strains and those in the vaccine and it is also substantially 
reduced in older adults.  Vaccination in older adults, who are a major target group for vaccination, prevents 
laboratory-confirmed influenza in only 30–40% compared to 70–90% in young adults [9]. Thus, there is a major 
demand for improved vaccination strategies that can provide protection against a broad spectrum of virus strains 
particularly for older groups.  
In situations where individuals are exposed to a newly arisen influenza virus strain against which they lack 
protective neutralising antibodies, cross-reactive T-cells against conserved internal antigens of influenza have 
been shown to be associated with limiting viral shedding, reduced duration of symptoms and minimising severity 
of symptomatic illness [10, 11]. Thus, a vaccine against influenza that induced protective T cell responses against 
conserved internal antigens could provide lasting immunity against not only human seasonal influenza, but also 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
26 
other subtypes currently found in avian species or swine which have the potential to cause a new pandemic. 
Since adults have been primed by prior exposure to influenza, a vaccine expressing conserved internal antigens 
of influenza such as NP and M1 could be used to boost cross-reactive T-cell responses to protective levels, 
providing durable broad immunity to all subtypes of influenza A. 
The internal proteins of the influenza virus are more conserved compared to the external surface glycoproteins. 
There are two reasons for selecting NP and M1 as a target for T-cell inducing vaccines. First, there is very little 
polymorphism of NP and M1 between influenza A isolates. NP is 92% identical between H3N2 and H1N1 
strains, and 91% identical between H3N2 and H5N1 strains. M1 is 95% identical between H3N2 and H1N1 
strains, and 93% identical between H3N2 and H5N1 strains. This low level of variation appears to allow strong 
T cell cross-reactivity. In the local population more than 70% of individuals generate a T cell response to these 
two antigens [12]. Second, analysis of T-cell response to all the proteins of influenza have shown that the T-cell 
response to NP and M1 is the strongest and 80% of individuals have responses to these two proteins (Figure 1). 
Furthermore, recent studies have shown that T-cells specific to M1 and NP are associated with protecting 
individuals against influenza by limiting viral shedding, reduced duration of symptoms and minimising severity 
of symptomatic illness [10, 11]. 
Recombinant viral vectored vaccines have been used in humans to induce high frequencies of CD4+ and CD8+ 
T cell responses to a wide range of antigens. One such recombinant viral vector is Modified Vaccinia Ankara 
(MVA) which has been used to generate strong T-cell responses to a wide range of antigens, including antigens 
from plasmodium, tuberculosis, hepatitis C, HIV and influenza. We have constructed MVA-NP+M1 which is a 
recombinant, replication-deficient MVA vector expressing the influenza antigens NP and M1 as a fusion protein 
[13].  
MVA is an attractive candidate orthopox vaccine vector for safety and immunogenicity reasons. The successful 
worldwide eradication of smallpox using vaccination with vaccinia virus highlighted vaccinia as a candidate 
vaccine vector. Although millions of humans have been vaccinated with conventional replication-competent 
vaccinia virus, its small but definite risk to both researchers and future patients led to the development of several 
attenuated strains of vaccinia during smallpox eradication. MVA was originally derived from the vaccinia strain 
Ankara by over 500 serial passages in primary chicken embryo fibroblasts (CEF cells). MVA has six major 
genomic deletions compared to the parental Ankara genome and is severely compromised in its ability to 
replicate in mammalian cells. No replication has been documented in non-transformed mammalian cells.   
MVA has an excellent safety record. It was administered intradermally to approximately 120,000 people during 
the smallpox eradication campaign [14]. MVA is currently in development as a vector for multiple diseases 
including HIV-1[15, 16], tuberculosis[17], HCV [18], influenza [13] and melanoma [19]. MVA vectored 
vaccines developed at the University of Oxford have been administered to over 4500 individuals including 
infants, young children, elderly adults, HIV-infected adults and children and patients with cancer in Europe and 
Africa without any safety concerns. Clinical studies have shown intramuscular administration, as compared to 
intradermal, to be associated with fewer and short-lived local AEs and no reduction in immunogenicity [20]. 
Vaccination with MVA-NP+M1 results in a rapid increase in influenza-specific cross-reactive IFN-γ-secreting 
effector T cells which are maintained at protective levels over the course of a year [13]. In the older age groups, 
MVA-NP+M1 can boost pre-existing levels of influenza-specific T-cells and maintain them for up to 6 months 
post-vaccination [21]. MVA-NP+M1 in combination with licensed inactivated influenza vaccine induced 
influenza-specific T-cells and in addition, increase the magnitude and breadth of the antibody response induced 
by the inactivated influenza vaccine [22].  Furthermore, in a small Phase 2a challenge study of MVA-NP+M1 
alone, MVA-NP+M1 vaccinated individuals experimentally challenged with live influenza virus trended to less 
severe symptoms and shorter duration of viral shedding compared to unvaccinated controls [23]. These studies 
demonstrated the safety of MVA-NP+M1 in older adults and in combination with seasonal influenza vaccine, 
the immunogenicity of MVA-NP+M1 in older adults and in combination with licensed inactivated seasonal 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
27 
influenza vaccine and the potential efficacy of MVA-NP+M1 in limiting the severity of influenza illness in 
adults.  
[H3N2] Challenge background  
The A/Belgium [H3N2] challenge strain is a live, wild-type influenza A virus that was initially isolated from a 
nasopharyngeal swab from a paediatric patient in Antwerp, 2015. The first-in-human study was a non-controlled, 
open-label, single-centre, dose-escalation study to determine the safety, infectivity and immunology of the 
potential novel influenza virus H3N2 challenge strain. The primary objective was to determine the viral 
challenge strain dose that had an acceptable safety profile and an observed attack rate (on symptom and positive 
viral confirmation after day 2) of >60% (i.e. at least 8 out of 12 participants had to be infected).  36 participants 
were allocated to 3 cohorts. Each cohort consisted of 12 participants.  
 
Challenge agent dose levels increased per cohort and dosing started at a titre of approximately 105TCID50 (50% 
tissue culture infective dose/mL). In vivo toxicity, as determined by the established ferret model for Influenza 
A pathogenesis, suggested that A/Belgium/4217/2015 (H3N2) could be used at similar dosing titres (starting 
from 105 TCID50/mL to 6.76x106 TCID50/mL) as those previously used in human challenge trials. Based on 
international literature, comparing HI titres to MNT, a provisional cut-off for participant inclusion based on a 
MNT of ≤20 was chosen. Since the influence of low MNT (≥10) was unknown, volunteers with low MNT were 
equally distributed over the cohorts  
While the lower bound of the required attack rate (>60%) was reached in all cohorts, none of the participants 
experienced an SAE or cytokine-related AE during the study even at the highest inoculation dose tested. The 
observed attack rate in all cohorts was well above the lower bound of the required attack rate. The signs and/or 
symptoms of Influenza infection similar to community acquired disease. Taken together, the data from the first 
in human dose escalation study show that A/Belgium/4217/2015 (H3N2) is a truly wild-type Influenza A H3N2 
strain which, when used as challenge agent, results high attack rates and significant host changes with relatively 
low variation in virological, haematological, clinical laboratory and symptom efficacy parameters. The choice 
of challenge dose is dependent on several factors but an intermediate dose (106 TCID50/mL) in volunteers with 
MNT ≤10 is adequate given the relatively low variation of essential efficacy parameters observed. Combining 
all data from further and ongoing studies, the attack rate for this dose with those participants with MNT ≤10 has 
been approximately 90%. Increasing this cut-off to <20 should have a minimal effect on the predicted attack rate 
based on previous evidence. 
Non-Clinical Studies 
MVA NP+M1 has been shown to be immunogenic in BALB/c mice. Biodistribution studies were not conducted 
with MVA-NP+M1. However, distribution studies in mice showed no evidence of replication of the virus or 
presence of disseminated infection 1 week after intradermal (ID) and intramuscular (IM) injections using similar 
MVA vaccines (MVA85A, MVA ME-TRAP, MVA AMA1 and MVA MSP1). A distribution study was 
therefore not thought to be necessary for MVA-NP+M1. Previous toxicology studies in mice showed no 
evidence of systemic MVA-related toxicity after administration (either intradermal or intramuscular). A low 
level of local irritation at the site of injection after intradermal administration is normally noted in these 
toxicology studies.  
Single and repeat dose toxicology studies were performed on BALB/c mice using the MVA-NP+M1 produced 
in chicken embryo fibroblasts and revealed that repeated administration of MVA-NP+M1 had no effect on 
mortality, cage side observations or bodyweights. Mice gained weight and had normal food consumption during 
the study. Clinical observations, inoculation site reactogenicity, clinical chemistry, clinical haematology, gross 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
30 
 OVERALL RATIONALE FOR THE STUDY 
Vaccination remains the most cost-effective strategy available to combat influenza. Current influenza vaccines 
work by inducing strain-specific antibodies against the highly polymorphic surface proteins of the influenza 
virus. The need for constant redesign and remanufacture increases the vaccine’s cost, places limitations on 
supply and critically delays vaccine production when new strains arise. Thus, there is a major demand for 
improved vaccination strategies that can provide protection against a broad spectrum of virus strains.  
Previous MVA-NP+M1 trials have shown satisfactory immunogenicity across different age groups with 
tolerable reactogenicity. A Phase 2a influenza challenge study has shown the MVA-NP+M1 may improve 
protection against viral shedding and reduce severity of influenza symptoms. Importantly, this trial will show 
that a T-cell inducing vaccine, when given alone, can ameliorate the degree of viral shedding and the total 
number and severity of symptoms following challenge with a replicating H3N2 influenza A virus. This MVA-
NP+M1 produced in the novel immortalized duck retinal cell line AGE1.CR.pIX also addresses the scalability 
issues of CEF produced vaccines. 
2. STUDY OBJECTIVES 
 PRIMARY OBJECTIVE 
The primary objective of the study is to determine the efficacy of MVA-NP+M1 vaccine administered in a 
human influenza challenge model to reduce the degree of nasopharyngeal viral shedding (recorded as viral AUC 
as determined by qPCR).  
Hypothesis: The primary hypothesis tested in this study is that the induction of influenza-specific CD4+ and 
CD8+ T cells by MVA-NP+M1 will result in a decrease of the viral replication and symptoms associated with 
influenza following challenge with an H3N2 influenza A virus in healthy volunteers. 
 SECONDARY OBJECTIVES 
Secondary objectives are to determine: 
- 
The incidence in each group (MVA-NP+M1 and saline Placebo) of laboratory-confirmed influenza 
(qPCR or culture) (and time to start; time to peak and duration of qPCR and quantitative culture results) 
- 
The attack rate, defined as percentage of inoculated participants with at least two positive swabs as 
determined by qPCR 
- 
Total AUC for total symptom score for MVA-NP+M1 vs. Placebo  
- 
Total days of fever for MVA-NP+M1 vs. Placebo  
- 
Total mucus weight for MVA-NP+M1 vs. Placebo 
- 
Correlation of T cell responses (as defined by ELISpot assay) to the primary endpoint, symptom scores, 
and influenza incidence 
- 
Safety of MVA-NP+M1 vaccination  
- 
Safety of H3N2 challenge in the setting of MVA-NP+M1 vaccination 
 
 EXPLORATORY OBJECTIVES 
Exploratory objectives are to determine:  
- 
Time to start; time to peak and duration of qPCR and quantitative culture results 
- 
Severity of individual symptoms for MVA-NP+M1 vs. Placebo 
- 
Time to start, time to peak, and duration for total symptom score for MVA-NP+M1 vs. Placebo  
- 
Correlation of antigen specific T cell phenotypes with illness outcomes 
- 
Effect of vaccination on the antibody responses to influenza following the intranasal challenge 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
31 
- 
Transcriptional response to vaccination and viral challenge assessed by deep sequencing of RNA 
- 
Determine epigenetic response of T-Cells during the study. 
3. STUDY DESIGN 
 OVERVIEW OF STUDY DESIGN 
This is a randomized, single-centre, double blind study. The study will screen healthy volunteers and only enrol 
those with MNT <20. The study consists of an outpatient vaccination phase, and at least 6 weeks later an 
inpatient challenge phase.  
155 participants will be randomized 3:2 to receive either MVA (N=93) or Placebo (N=62) by intramuscular 
injection in the non-dominant arm deltoid. Vaccination-related local and systemic symptoms will be followed 
by participant-directed diary cards for 7 days, and unsolicited adverse events will be followed throughout the 
study from consent signature. The vaccinations will be administered starting in April 2019. Blood for 
immunogenicity and storage of samples for correlates of protection will be drawn at five time points: Days 1, 8, 
28 post-vaccination, on entry to the quarantine facility for challenge (Day -1), and 27 days post-challenge 
(Day 28).  
Up to 20 participants with no intercurrent ILI will be challenged during each of the challenge periods lasting 
three weeks (approximately 12 MVA-NP+M1 recipients and 8 Placebo recipients per three-week block), to 
achieve a total of 80 participants from the MVA-NP+M1 group and 54 from the saline Placebo group being 
challenged. Participants will enter the quarantine facility on Day -2 or Day -1 and be discharged the morning of 
Day 11. The grouping of participants undergoing challenge will be as consistent as possible with the grouping 
used during the randomization process; i.e., the first participants vaccinated will be the first quarantined and 
challenged, but in all cases at least 6 weeks will have passed between vaccination and challenge. 
Participants will receive a single intranasal administration of the H3N2 challenge agent (A/Belgium/4217/2015) 
as a nasal spray via the Teleflex MAD301 and MAD130. The MAD301 hard plastic atomizer will be combined 
with the MAD130 syringe and vial adaptor to constitute components that are the most similar to the VaxINatorTM 
kit, used in previous studies for H3N2 inoculation. 
Participants will be in a semi-recumbent (45°) position, lying in bed and will receive 0.25 mL of the challenge 
agent solution into each nostril. 
After viral inoculation, participants are to remain in a supine position for 2 hours. Participants are not allowed 
to blow their noses during this period. All administrations will be performed by a member of the clinical site 
staff. 
The assessments performed are summarized per visit in the Time and Events Schedule. 
 DISCUSSION OF STUDY DESIGN 
Dose Selection 
The dose of MVA-NP+M1 to be used in this study will be 1.5 x108 pfu (4.3 x108 TCID50) 0.5 mL administered 
intramuscularly, based on previous Phase 1 and 2a clinical trials, which have shown the vaccine is safe and 
immunogenic at this dose (FLU001, FLU002, FLU003, FLU004 and FLU005). Participants received the 
proposed 1.5 x 108 pfu dose in FLU001 which was less reactogenic and better tolerated than the 2.5 x 108 pfu 
used in one group. The immune responses were not significantly different between the two doses.  
The 1.5 x 108 pfu dose was thus chosen to balance reactogenicity and immunogenicity. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
32 
Placebo Control 
Placebo saline control given as 0.5 mL intramuscularly in the deltoid will be used to establish the frequency and 
magnitude of solicited and non-solicited adverse events, as well as to control for the laboratory and clinical 
assessments used as endpoints. All such recordings will be performed in a blinded fashion.  
Dose of challenge agent 
The choice of challenge dose is dependent on several factors but an intermediate dose (106 TCID50/mL) in 
volunteers with MNT <20 is adequate given the relatively low variation of essential efficacy parameters 
observed. Combining all data from previous and ongoing studies, the attack rate for this dose with those 
participants with MNT <20 has been approximately 83%.  
Randomization and Blinding 
Randomization will be used to avoid bias in the assignment of participants to treatment, to increase the likelihood 
that known and unknown participant attributes (e.g., demographic and baseline characteristics) are evenly 
balanced across treatment groups, and to enhance the validity of statistical comparisons across treatment groups. 
Participants are blinded to study allocation. 
Since MVA-NP+M1 has a cloudy appearance compared to saline Placebo and regular transparent syringes will 
be used, a label will surround the syringes to maintain the blind. The syringes will be transported from the 
pharmacy to the vaccination room in opaque containers to keep the study treatment blinded from the site staff 
and the study participants. The dedicated unblinded dosing team will be assigned for the vaccine administration. 
The participant receiving the vaccine/placebo will be asked to look away from the injection site to keep the blind 
and will not be unblinded during the trial. After administration, the unblinded dosing team will lift the label to 
ensure the full dose has been given to the participant. The used syringes will then be returned to the pharmacy 
in the opaque transport containers. Detailed procedural instructions will be made in the study execution 
documents.  
The pharmacist will confirm that the vaccine has been completely injected. Since the person administering the 
vaccine might become unblinded due to spillback of the solution from the skin outwards, only the assigned 
unblinded team will be responsible for the vaccination. Further instructions are provided in the pharmacy manual 
to ensure the syringes have no residue left when returned to the pharmacy and the study blinding during this 
procedure is preserved. All personnel that record adverse events throughout the study and all personnel involved 
in the challenge will remain blinded to treatment allocation.  This will be assured to reduce potential bias during 
safety data collection and evaluation of clinical endpoints. All laboratory personnel conducting immunology 
assays will receive blinded samples and will report these values back to the data management and statistics group 
in a blinded fashion.  
4. SELECTION OF STUDY POPULATION 
Screening for eligible participants will be performed within approximately 1 month prior to randomization and 
the administration of either MVA-NP+M1 or saline Placebo. 
Approximately 155 participants are planned to be enrolled into the vaccination phase. They will be randomized 
to one of 2 treatment groups, A or B, in a 93:62 ratio. 134 of these participants will be included in the challenge 
phase. 
For details on the sample size calculation, please refer to Section 9.2. 
 INCLUSION CRITERIA 
1. Healthy males and females aged ≥18 and ≤55 years of age at the point of enrolment. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
33 
2. Non-smokers or those who stopped smoking ≥ 3 months prior to screening 1 visit.  
3. Willingness to remain in isolation for the duration of the study. 
4. A female participant is eligible for this study if she is not pregnant or breast feeding and 1 of the 
following: 
a. Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are 
postmenopausal, as defined by no menses in greater than or equal to 1 year). 
b. Of childbearing potential but has been and agrees to continue practicing highly effective 
contraception or abstinence (if this is the preferred and usual lifestyle of the participant) from 
6 months prior to vaccination to 6 months after administration of the influenza challenge virus. 
Highly effective methods of contraception include 1 or more of the following:  
i. male partner who is sterile (vasectomised) prior to the female participants entry into the 
study and is the sole sexual partner for the female participant;  
ii. hormonal (oral, intravaginal, transdermal, implantable or injectable);  
iii. an intrauterine hormone-releasing system (IUS);  
iv. an intrauterine device (IUD) with a documented failure rate of < 1%;  
v. bilateral tubal occlusion. 
5. Pre-challenge serum MNT against A/Belgium/4217/2015 (H3N2) challenge strain <20.  
 
 EXCLUSION CRITERIA  
1. BMI < 19 and > 32. 
2. Presence of any significant acute or chronic, uncontrolled medical (or psychiatric) illness including 
a history of chronic respiratory illness.  
3. History of seasonal hay fever or a clinically significant seasonal allergic rhinitis (SAR), including 
the use of symptomatic prescription only medication and non-prescription medication.  
4. History or evidence of autoimmune disease or known immunodeficiency of any cause - with the 
exception of atopic dermatitis/eczema and atopic rhinitis. 
5. Any history of anaphylaxis in reaction to vaccination or history of allergic reactions likely to be 
exacerbated by any component of the vaccine.  
6. History of lung disease (Asthma, COPD).  
7. Current smokers or those who stopped smoking < 3months prior to screening 1 visit. 
8. Positive diagnostic tests for HIV, Hepatitis B or Hepatitis C indicating active infection. 
9. Evidence of drug abuse or a positive urine drug screen or alcohol breath test. 
10. Chronic use of any medication or other product (prescription or over-the-counter), for symptoms of 
rhinitis or nasal congestion or for any chronic nasopharyngeal complaint, or chronic use of any 
intranasal medication for any indication that has not cessed within 30 days prior to screening 1.  
11. Receipt of any investigational drug within 3 months prior to vaccination, or prior participation in a 
clinical trial of any influenza vaccine, or any investigational vaccine or experimental influenza viral 
challenge delivered directly to the respiratory tract within 1 year prior to challenge. 
12. Receipt of the 2018/2019 seasonal flu vaccine.  
13. Receipt of any live vaccines within the 4 weeks prior to vaccination. 
14. Any laboratory test which is abnormal and which is deemed by the Investigator(s) to be clinically 
significant.  
15. Receipt of any systemic chemotherapy agent at any time. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
34 
16. Physician reported influenza or a syndrome consistent with influenza (as judged by the investigator) 
in the previous 6 months. 
17. Known allergy to treatments for influenza (including but not limited to oseltamivir). 
18. History of frequent epistaxis (nose bleeds). 
19. Any nasal or sinus surgery within 6 months of Viral Challenge or any significant abnormality, either 
of which results in alteration of the anatomy of the nose or nasopharynx (including significant nasal 
polyps). 
20. Volunteers with household contacts who are at risk for serious or severe complications of influenza 
disease including, but not limited to: persons ≥ 65 years; presence of significant chronic 
cardiopulmonary, metabolic, renal, or neurological conditions; immunosuppression due to any 
condition or therapies; BMI >40.  
21. Participants that are an employee or family member of the Investigator or study site personnel may 
not be enrolled.  
22. Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the 
study. 
 EXCLUSION (CHALLENGE PERIOD ONLY) 
1. Abnormal spirometry assessed to be clinically significant. 
2. Known close contact with anyone known to have influenza in the past 7 days at the time of 
quarantine. 
3. ILI symptoms as assessed at the admission to clinic on Day -2 prior to challenge. 
4. Presence of fever, defined as participant presenting with a temperature reading of > 38.0°C on 
admission to quarantine. 
5. Qualitative PCR results positive for viral infection. However, participants may be included into later 
challenge cohort. 
6. Acute use of any medication or other product, prescription or over-the-counter, for symptoms of 
rhinitis or nasal congestion within 7 days prior to challenge. This includes any oral corticosteroid or 
beta agonist containing nasal spray. 
 
5. TREATMENT 
 PHYSICAL DESCRIPTION OF THE STUDY DRUG 
MVA-NP+M1 is a Modified Vaccinia Ankara virus recombinant, replication-deficient, vector expressing the 
conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1) (H3N2 2007/Panama) as a fusion protein. 
The dose of MVA-NP+M1 to be used in this study will be 1.5 x108 pfu. Each glass vial of MVA-NP+M1 
contains 700 microlitres volume in formulation buffer containing 10% sucrose, 0.1% pluronic acid, 25 mM TRIS 
to a target final concentration of approximately 3 x 108 pfu/mL. The vaccine is not diluted prior to administering.  
MVA-NP+M1 is manufactured in accordance with Good Manufacturing Practice (GMP) by Emergent 
BioSolutions, USA as required by the current Good Clinical Practice (GCP). 
The vaccine has undergone UK and European Qualified Person release. 
A copy of the certificate of analysis of the MVA-NP+M1 drug product will accompany the vials to the clinical 
site. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
35 
 OTHER MEDICATION ADMINISTERED IN THE STUDY 
5.2.1 
Placebo 
Participants who are allocated to the control group will receive a Placebo injection of 0.9% saline (sourced by 
Fisher Clinical Services) instead of MVA-NP+M1. The volume and site of injection will be the same as for 
group A and participants will be blinded as to which injection they are receiving. Each vial of saline will only 
be used for a single participant. A vaccine accountability log of the saline will be maintained at the trial site.  
5.2.2 
Challenge Product [H3N2] 
A/Belgium/4217/2015 (H3N2) is a solution of 6.76x106 TCID50/mL. It is stored as 1.0 mL aliquots between  
-65° and -80°C in 2.0 mL self-standing cryovials.  
Before inoculation it is thawed on ice and diluted to 1.0x106 TCID50/mL with PBS, drawn up into a syringe and 
administered as a nasal spray using the Teleflex MAD301 and MAD130.  
Participants will receive a single intranasal administration of the H3N2 challenge agent (A/Belgium/4217/2015) 
via nasal spray (Teleflex MAD301 and MAD130).  
Participants will be in a semi-recumbent (45°) position, lying in bed and receive 0.25 mL of the challenge agent 
solution into each nostril. 
After viral inoculation, participants are to remain in a supine position for 2 hours. Participants are not allowed 
to blow their noses during this period. All administrations will be performed by a member of the clinical site 
staff. 
 PACKAGING AND LABELLING 
MVA-NP+M1 will be packaged in boxes of 25 vials. MVA-NP+M1 will be labelled according to local law and 
regulatory requirements. The labels will contain the protocol number, reference number, storage caution 
statements, dosing instructions, expiry date, and the notice "keep out of reach of children” and “For Clinical 
Trial Use Only”. 
 STORAGE AND STUDY DRUG ACCOUNTABILITY  
The Investigator (or his/her designee) is responsible for the safe storage of all study products assigned to the 
clinical site, in a locked, secure storage facility with access limited to those individuals authorized to dispense 
the study drugs and maintained within the appropriate ranges of temperature. All study drugs must be stored as 
specified at delivery and in the original packaging. Instructions for the study personnel, regarding the storage 
and handling of the study drugs, will also be provided to the clinical site. 
MVA-NP+M1 must be stored at 2 to 8°C, should not be exposed to freezing temperatures and should be 
protected from light during storage at the clinical site. Saline Placebo can be stored at room temperature or with 
MVA-NP+M1 at 2 to 8°C.  
A/Belgium/4217/2015 (H3N2) is a solution of 6.76 x106 TCID50/mL. It is stored as 1.0 mL aliquots between  
-65° and -80°C in 2.0 mL self-standing cryovials.  
Before inoculation, it is thawed on ice and diluted to 1.0 x106 TCID50/mL with PBS, drawn up into a syringe 
and administered as a nasal spray using the Teleflex MAD301 and MAD130. 
Regular temperature logging of the study product storage room at the clinical site should be performed. In case 
a deviation in storage conditions should occur, the clinical site must not further dispense the affected study drug 
and immediately notify the Sponsor. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
36 
The Investigator is responsible for ensuring that all study products received at the clinical site are inventoried 
and accounted for throughout the study. A vaccine accountability log will be used to record when the 
vaccine/Placebo is removed and used. 
As misallocations of study products may have a detrimental effect on participants’ safety and/or the study 
products’ efficacy and are a potential source of bias, utmost care should be taken to correctly dispense the study 
drugs as assigned by the randomization system. 
Study products should be dispensed under the supervision of the Investigator, a qualified member of the clinical 
staff, or by a hospital/clinic pharmacist. The Investigator must maintain accurate records demonstrating date and 
the number of products supplied to whom and by whom. 
The study unblinded pharmacist will perform the check of study drugs held at the pharmacy to ensure 
accountability and appropriate storage conditions of all study drugs used. The study designated site monitor will 
perform the accountability at the end of the study after Database Lock once the treatments have been unblinded. 
After the last visit of the last participant in the study (LPLV), any unused study drug will be returned to the 
Sponsor or destroyed at the clinical site with the Sponsor’s written permission (in this case a certificate of 
destruction will be provided and filed in the Trial Master File (TMF)). 
Hazardous materials such as used ampoules, needles, syringes and vials containing hazardous liquids, should be 
disposed of immediately in a safe manner and therefore will not be retained for drug accountability purposes. 
 RANDOMIZATION AND BLINDING 
As participants are confirmed to be eligible for the study, they will be assigned a single unique identifier across 
the study. 
At screening, participants receive a unique screening number using the letter S and a number ranging from 001 
to 999. Participants who fail screening and are not enrolled will not be included in the final database but will be 
recorded in a separate screening log. The failure details will be documented in the ‘participants’ file. 
Participants will be assigned to 1 of 2 treatment groups. Allocation of each participant to a given treatment group 
will be determined from a randomization list (to be linked to the unique identifier) prepared prior to study start 
by SGS Life Sciences Secure Data Office using SAS® software (SAS Institute Inc., Cary, NC, USA). 
The randomization list will be generated using randomly permuted blocks and will not be stratified. Participants 
will be randomised 3:2 to receive either MVA-NP+M1 or saline Placebo, with total enrolment of 155 participants 
at an allocation of 93 to 62. Each grouping of up to 20 participants will be given a specific date, approximately 
three weeks apart, to enter the quarantine facility in order to be challenged. If more than 20 participants from a 
vaccination group are eligible and available for challenge, participants who are willing to enter at another date 
will be enrolled with a later cohort to reach the correct allocation of up to 20 participants per challenge. The 
challenge period will include up to approximately 80 participants in the MVA-NP+M1 vs up to approximately 
54 participants in the saline Placebo group. 
The pharmacist or an appropriate qualified member of the study staff, who is unblinded to treatment and assigned 
by the principal Investigator, will prepare the study vaccine that corresponds to the assigned participant 
randomization number. The recruiters calling vaccinated participants back to quarantine, will also be blinded to 
the study status, therefore the Statistical Centre will supply the list of participants to be called to undergo 
challenge and quarantine.  
The randomization list will be retained by SGS Life Sciences Secure Data Office until the end of the study 
(database lock). One copy of the randomization list will be sent in a sealed envelope to the site pharmacist before 
the start of the study. Throughout the study conduct, the monitor needs to check the completeness and status of 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
37 
the envelopes and upon study completion the monitor can retrieve the envelopes and have them destroyed after 
Sponsor’s written approval. 
One copy of code breaking envelopes will be made available to the clinical site, to be used only in case of 
emergency. An additional copy of code breaking envelopes will be kept at SGS Life Sciences Secure Data 
Office. Upon request, SGS Life Sciences Secure Data Office will provide the code-break information to SGS 
Life Science Medical Affairs for SAE reporting purposes. Should a participant experience an adverse event (AE) 
for which it is necessary to break the blind during the study in order to determine the appropriate treatment for 
the event, the principal Investigator or designee will call the Sponsor medical monitor prior to unblinding. The 
reason for unblinding will be documented in the appropriate section of the eSource. Participants who are 
unblinded for any reason during their participation in the study will not be replaced and will be withdrawn 
immediately from the study upon resolution of all SAEs. 
 DOSE AND ADMINISTRATION 
A rationale for the dose of study drug selected in this study is provided in Section 3.2. 
Participants will be randomly and sequentially assigned, according to the randomization schedule and in a 
blinded fashion to 1 of 2 treatments. 
An overview of the treatment in each of the treatment groups is provided in Table 2. 
Table 2: 
Treatment Overview: Challenge number (+ additional vaccination) 
Treatment Group 
Number of 
Subjects 
Treatment 
Group A 
80 (+13) 
MVA-NP+M1  
Group B 
54 (+8) 
Saline Placebo  
 
Any deviation from the treatment regimen defined in the protocol must be documented in the eSource. 
 SAFETY MONITORING 
5.7.1 
Safety Monitoring Committee 
A Safety Monitoring Committee will be made of the CRO Medical Monitor, Sponsor Medical Monitor, and the 
principal Investigator or designated Investigator to review ongoing, blinded, non-cleaned safety data. The 
committee will review any of the ongoing, closely evaluated adverse events that occur after vaccination and 
challenge. As the medical team sees the challenge participants every day, the risk for a meaningful adverse event 
to go unobserved is extraordinarily unlikely, and this will trigger an immediate meeting of the Safety Committee. 
If deemed necessary, the safety committee can stop the study and ask for review by the IDMC, who would have 
access to unblinded information. 
5.7.2 
Independent Data Monitoring Committee  
An Independent Data Monitoring Committee (IDMC) will be set up to monitor and evaluate the safety of the 
study vaccine and challenge virus if required. The IDMC will consist of at least 2 clinical experts, and an 
independent statistician. The IDMC will be convened if any of the Stopping Rules are triggered and to assess 
any SUSARs. For the purpose of these meetings, the treatment code for any requested safety review may be 
provided to the IDMC, but not revealed to the Sponsor. If deemed necessary by the IDMC, treatment codes can 
be fully unblinded to the IDMC. Based on these safety reviews, the IDMC will make recommendations to the 
Sponsor regarding the continuation, modification, or termination of the study. 
Further details will be described in a separate IDMC charter. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
38 
6. PRIOR AND CONCOMITANT THERAPY 
 PERMITTED CONCOMITANT THERAPIES 
After vaccination, due to local soreness at the injection site and potential low-grade fever, paracetamol 
(maximum 4 g/day) and/or ibuprofen (maximum 1800 mg/day) will be allowed. After challenge, medications 
can be used to alleviate symptoms at the decision of the Investigator; however, medications that mask symptoms 
and which are required for comfort only will be discouraged, so that appropriate symptom scoring can take place. 
At the end of Day 8, if the influenza culture (not the qPCR) remains positive, the Investigator may elect to treat 
the participant with oseltamivir at a dose of 75 mg b.i.d. for five days. Participants will not be discharged from 
the quarantine unit until the qPCR is negative or the participant has no fever. All concomitant medications are 
to be collected in the eSource. 
Stable hormone replacement therapy in postmenopausal participants is also permitted. 
Further medication is permitted as per the inclusion criteria [Section 4.1]. 
 PROHIBITED CONCOMITANT THERAPIES 
Oral or nasal steroids will be prohibited and are listed in the challenge exclusion criteria [Section 4.2]. Also, 
refer to Stopping Rules or Non-Vaccination Criteria [Section 8.3].  
7. ASSESSMENTS 
The 
evaluation 
of 
post-vaccination 
solicited 
and 
unsolicited 
events 
will 
use 
a 
standard  
7-day diary card that captures the following local and systemic symptoms. The following local and systemic 
solicited adverse events will be recorded by participants:  
- 
Local: pain, redness, induration, warmth and pruritus at injection site. 
- 
Systemic: feverishness, chills, myalgia, fatigue, headache, nausea, arthralgia, malaise and temperature. 
Participants will also be asked to report any unsolicited adverse events throughout the study after signing the 
consent form. 
The quarantine unit also uses a standardized scoring system which includes the following solicited symptoms:  
- 
Upper respiratory: nasal congestion, runny nose, sneezing, sore throat, sinus pain, difficulty swallowing, 
tearful/watery/painful eyes/aversion to light. 
- 
Lower respiratory: dry cough, productive cough, difficulty breathing. 
- 
General: muscle aches, nausea/vomiting, fever/chills/shivering, sweating, headache, dizziness, tiredness, 
diarrhoea. 
- 
Any suspected cardiac adverse event will be assessed with an ECG and cardiac troponin in consultation 
with a cardiologist. 
 TIMING OF ASSESSMENTS 
An overview of the timing of treatment(s) and assessments is given in the Time and Events Schedule of the 
vaccination period as well as for the challenge phase.  
A 10% deviation from theoretical post dose times will be allowed for all post-dose assessments. The windows 
for follow-up visits post-vaccination will be 7 ±1 day, 27 ±3 days, 55 ±3 days, day from vaccination to challenge 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
39 
> 6 weeks, but less than 6 months. The windows for follow-up visits post-challenge confinement period will be 
27 ±3 days and/ or 6 months post-vaccination (180 ±14 days) whichever is longer. 
7.1.1 
Screening Period 
Screening 
Screening for eligible and consenting participants will be performed within approximately 6 weeks prior to 
randomization/the first administration of study drugs. It will be possible to include participants who are screened 
with the appropriate MNT assay from another protocol or screening test, but the test needs to be performed or 
repeated within 6 weeks of vaccination.  
Some eligibility criteria will be checked prior to assessing MNT in the study. These criteria involve:  
- 
life style questions i.e. smoking, contraception, identify current BMI (upon Investigator discretion), 
recent or planned participation in other studies etc. [inclusion criteria 1 to 4 and exclusion criteria 1 & 7]. 
- 
 current illnesses including current medication.  
Any physical examination, vital signs and laboratory assessments will be completed at Screening 2 visit within 
the 3 weeks leading to the vaccination once MNT is confirmed. However, in order to ensure a sufficient number 
of participants are vaccinated in a given group, MNT may be performed at Screening 2 at the same time as 
Screening 2 assessments. 
Participants will be given a full explanation of the nature of the study and written informed consent (approved 
by the local ethics committee) will be obtained according to local requirements before any study-related 
assessment is carried out. 
At screening, participants will be asked to attend the clinical site to have assessments performed as indicated in 
the Time and Events Schedule. All results from the screening procedure needed to evaluate eligibility, including 
the clinical laboratory results, must be available prior to the first administration of the study drugs on Day 1. 
Any abnormal result at the screening visit will be assessed according to its clinical relevance, and if found 
relevant, the participant will not be included in the study. 
Repeat tests may be performed and participants may be rescreened at the discretion of the Investigator.  
All inclusion/exclusion criteria are to be checked on Screening 2 visit before participant’s vaccination. 
7.1.2 
Treatment Period 
7.1.2.1 
VACCINATION 
Vaccination - Day 1 
Participants will attend the clinic for Vaccination on Day 1 at least 6 weeks before inoculation and challenge. 
This visit will also include a review of inclusion/exclusion criteria, blood draws for PBMCs, Serum and 
Transcriptomics, alcohol breath test, urine drug screen and urine pregnancy test.  
Participants will then be vaccinated with either MVA-NP+M1 or saline Placebo depending on the randomization 
schedule. Following vaccination participants will remain in the clinic for at least 2 hours for monitoring. During 
this time diary cards will be dispensed and explained for completion over the following 7 days for solicited and 
unsolicited events and throughout the study for unsolicited adverse events.  

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
40 
Day 2 
A blood draw for transcriptomics will be taken in the 24 (±3) hours post-vaccination. Participants will return to 
the clinic for safety assessments and transcriptomic blood draw.  
Day 4 
3 days after vaccination, participants will be contacted by phone as a reminder to complete their diary cards.   
Day 8 and Day 28 
7 and 27 days after vaccination participants will attend the clinic for follow-up assessments as per the Time and 
Events Schedule, primarily to assess safety and collect blood for immunogenicity assessments. 
Day 56  
Participants will be called to be assessed for potential intercurrent ILI and possible date of challenge. The 
decision whether to exclude the participant will be at the discretion of the Investigator.  
7.1.2.2 
CHALLENGE 
Day -2 and Day -1 
On Day -2, participants will be admitted to the Clinical Pharmacology Unit (CPU). Eligibility of the participants 
will be confirmed along with the Assessments listed as per Time and Events Schedule.  
Should the participant present a positive Qualitative PCR pre-challenge, the participant will be excluded from 
this challenge group but may enter any of the subsequent challenge groups if the infection is cleared. The 
participant excluded at Day -2 from the challenge period may be replaced with a participant with the same 
treatment on Day -1. 
Day 1 
On Day 1, assessments will be performed as indicated in the Time and Events Schedule. 
After the safety assessments, the participants will be inoculated with challenge virus H3N2 by a trained health 
care worker, followed by repeated blood sampling and NP swab samples as outlined in the Time and Events 
Schedule.  
Day 2 to Day 11  
After inoculation participants will remain in the CPU for a further 10 days. During this time, they will have vital 
signs monitored and targeted physical examinations as well as scoring symptoms twice a day (b.i.d.). Nasal 
swabs are taken twice a day (b.i.d.) at least 8 hours apart on Day 2 to Day 10, as per the Standard Operating 
Procedure (SOP) requirements. Immunogenicity assessments will be performed as indicated in the Time and 
Events Schedule. 
Adverse events and the intake of concomitant medication(s) will be monitored continuously from informed 
consent until the last study-related activity. 
7.1.3 
Follow-up Period 
All participants challenged or vaccinated only, whether they complete the treatment period or are withdrawn 
from the study, will be asked to complete a safety follow-up visit:  
- 
27 days post-vaccination (in-patient visit), if withdrawal occurred before the challenge.  
- 
27 days post-inoculation of challenge virus (in-patient visit), if participant was challenged. 
- 
6 months post-vaccination (180 days ±14), if this is greater than 27 days post-challenge, a phone call will 
be performed to assess any potential interim Serious Adverse Events in all vaccinated participants. This 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
41 
phone call will be preceded by an e-mail. The participant will be called up to 3 times, if there is no 
response, to ensure this last follow-up call is completed, 
except in the case of withdrawal of consent. In order to provide some flexibility for the participants regarding 
the site visits and to maintain the integrity of the study design, a time window of ±3 days is permitted for follow-
up visits at Day 28 and ±14 days for follow-up visit at Month 6 (180 days), in case of time conflict or unforeseen 
circumstances. 
Assessments will be performed as indicated in the Time and Events Schedule. 
7.1.4 
Unscheduled Visits  
Unscheduled visits after randomization can be planned for instance: 
- 
to obtain additional information to ensure safety of the participant. Additional blood and urine samples 
may be taken at the discretion of the Investigator 
- 
to assess, confirm, and follow up on out-of-range clinical laboratory test, vital sign, or ECG values, or in 
case of a positive drug screen, alcohol breath test or pregnancy result. 
Findings made during unscheduled visits should be reported in the eSource. 
7.1.5 
Sample Collection and Handling 
Throughout the study, venous blood samples will be collected for analysis of immune response in blood RNA, 
and blood PBMCs, according to the time points defined in the Time and Events Schedule. The exact date and 
time of blood sampling and handling must be recorded in the source documentation. 
Blood samples will be collected by venipuncture in the forearm into vacuum tubes as specified in the laboratory 
manual. 
Further detailed procedures for PBMC, Transcriptomics and other blood samples collection, shipment, 
processing, and storage are described in the laboratory manual. 
7.1.6 
Immunogenicity 
The whole blood is drawn and processed on the appropriate days will be packaged according to specifications 
and sent by Courier to Viroclinics in Rotterdam for PBMC processing as per Laboratory Manual. 
The viral strains to be possibly used will be determined following the 2018/2019 influenza season but will 
include that of the challenge strain at a minimum. 
ELISpot for interferon gamma/granzyme B will be conducted at Viroclinics and will be performed on 
cryopreserved PBMCs using peptides spanning the NP+M1 antigens of the vaccine, with the peptides of  
15 amino acid length, overlapping by ten. The pools of peptides, and the layout of the plates, including controls, 
can be found in the laboratory manual.  
The stimulation will be as per Laboratory Manual and the plates will be developed and read using a validated 
ELISpot reader. Samples also may be utilized to analyse for T cell responses using a multi-parameter 
intracellular staining (ICS) panel, as per the laboratory manual. The primary assay will be the ELISpot, which 
will take precedence over the ICS assay if the cell yield is limited.  
PBMC samples collected prior to and on Days 8 and 28 after vaccination, and prior to and on Days 8 and 28 
after challenge will be de-identified and may be tested for epigenetic changes such as DNA methylation and 
histone modifications in order to identify reliable epigenetic markers of recent exposure to influenza and 
vaccinia.   

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
42 
7.1.7 
Transcriptomics 
Blood collection by RNA stabilization may be used to evaluate gene expression for correlates of protection or 
correlates of disease. The transcriptomics samples will be collected using PAXgene® RNA tubes that will be 
stored in a monitored -20°C freezer. 
7.1.8 
Efficacy Variables 
The efficacy variables include: 
- 
The qPCR for the challenge H3N2 virus on Day 2 to Day 10 (b.i.d.) 
- 
Influenza culture collected on Day 2 to Day 10 (b.i.d.) (performed only if the PCR is positive)  
- 
Symptoms scores, total and individual collected on Day 1 to Day 11 (twice daily) 
- 
Tissue weights for nasal discharge, collected as needed, from Day 1 to Day 11 
7.1.9 
Efficacy Criteria 
The primary endpoint upon which the powering analysis is performed uses the vAUC for virologic shedding as 
measured by qPCR for all collected samples, compared between groups using a Mann-Whitney U Test 
(Wilcoxon rank sum). The powering is based on the Placebo data from two prior challenge studies with this 
H3N2 virus.  
 SAFETY EVALUATIONS 
The safety assessment in this study will be based on AEs, clinical laboratory tests, ECG, vital signs, and physical 
examination, as described in the following sections. 
7.2.1 
Study Products Potential Risks 
MVA-NP+M1 
Potential risks associated with vaccination include local and systemic reactions.  
Vaccination usually precipitates a local inflammatory reaction. This may include redness, swelling, scaling, 
tenderness, or itching. In previous studies using recombinant MVA vaccines, these local reactions have 
spontaneously resolved within weeks. Systemic reactions that could potentially occur following immunisation 
with a recombinant MVA vaccine include an influenza-like illness with low-grade fever, chills and malaise. In 
general, it appears that the frequency of systemic side effects in response to recombinant MVA vaccines is 
affected by a preceding poxvirus vaccination, with the proportion of volunteers experiencing any systemic side 
effects after the first vaccination being 69%, decreasing to 37% after the second and 22% after a third 
immunisation.  
 
As with any other vaccine, Guillain-Barré syndrome (GBS) or immune mediated reactions that can lead to organ 
damage may occur. However, this has never been seen with a recombinant MVA vaccine to date. Serious allergic 
reactions including anaphylaxis may occur, as also with any vaccine. The incidence of this is unknown but is 
estimated at one per 105 to 106 vaccinations. Volunteers should be vaccinated in a clinical area where Advanced 
Life Support drugs and equipment are immediately available for the management of serious adverse reactions.  
Placebo 
No risk associated. 
Challenge [H3N2] 
All challenged participants will be at risk of becoming infected and developing typical influenza-like illness. 
Only one clinically significant adverse event (AE), “presumed myocarditis”, diagnosed 51 days post inoculation 
and following a subsequent respiratory infection, has been documented amongst all previously reported 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
43 
challenge studies. Nevertheless, because the challenge agent is wild-type (although a seasonal strain which may 
be further passage-attenuated), it is possible that infrequent or rare clinically significant events may occur. A 
number of serious events have been associated with community-acquired Influenza infection [24]. Most were 
seen to occur primarily during pregnancy or in elderly individuals and those with chronic underlying medical 
conditions. Such events have been more frequently observed during pandemic years and have included 
pulmonary complications (including primary viral pneumonia, secondary bacterial pneumonia, and 
exacerbations of underlying chronic obstructive pulmonary disease, and asthma), along with worsening of 
underlying cardiac conditions such as congestive heart failure and ischemic heart disease. Much less frequent 
(and generally rare) complications have also been reported, including myositis, rhabdomyolysis, and neurologic 
complications such as encephalopathy (Reye’s syndrome), encephalomyelitis, transverse myelitis, aseptic 
meningitis, focal neurologic disorders, and Guillain-Barré syndrome. The occurrence of Reye’s syndrome has 
been reported predominately in children less than 14 years of age (90% of cases reported were in this age group) 
and the incidence has dramatically declined during the past 2 decades from a peak of 500 cases per year in the 
1970s. This decline is thought to be related to the understanding of the role of salicylates in Reye’s syndrome. 
Pericarditis and myocarditis have been noted in adults, along with electrocardiographic (ECG) abnormalities in 
up to 53% of infected adults, typically with no cardiac symptoms [25, 26].  However, most of these ECG 
abnormalities resolved within 28 days, and did not result in detectable myocardial damage (as measured by 
creatine kinase isoenzyme MB or troponin I levels) or reduced ejection fractions. 
Because of the potential for severe illness, efforts to minimise this risk are to be implemented during all clinical 
studies with this challenge strain. First, all prospective participants will be carefully evaluated for the presence 
of any known risk factor for severe influenza illness, including underlying pulmonary and cardiac disease, 
pregnancy, and/or immunosuppressive conditions; individuals with such conditions will be excluded from 
participation. Secondly, all enrolled participants will be continuously monitored under quarantine by trained and 
suitably accredited clinical staff for the duration of the study, with qualified physicians available as needed 24h 
a day. Thirdly, the challenge strain has been confirmed to be susceptible to the standard of care antiviral agents 
oseltamivir and zanamivir, in the event that the severity of the illness warrants rescue therapy. 
Because the challenge virus preparation contains egg protein, individuals with known or suspected egg allergies 
should not participate, nor should individuals with a prior history of Guillain-Barré syndrome. 
There is a theoretical risk that inducing influenza-specific T cells might exacerbate disease following challenge. 
No such worsening was observed in the 430 elderly participants who received QIV and MVA-NP+M1 in a 
recent study in the UK.  
7.2.2 
Adverse Events 
Adverse events will be monitored continuously from informed consent until the last study-related activity 
(outpatient visit at 27 days ±3 days post-challenge or 6 months post-vaccination ±14 days, whichever is longer). 
At regular intervals during the study, participants will be asked non-leading questions to determine the 
occurrence of any AEs. All AEs reported spontaneously during the course of the study will be recorded as well. 
For detailed definitions and reporting procedures of AEs, see Section 10. 
AEs will be scored using the modified toxicity tables from the FDA (Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (Appendix 2)). 
7.2.3 
Clinical Laboratory Tests 
Blood samples will be collected by venipuncture at the time points indicated in the Time and Events Schedule. 
Biochemistry and haematology testing will be performed on these samples, as well as immunology testing 
(HBsAg, anti-HCV, and HIV antibodies) on the sample from screening. In female participants of childbearing 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
44 
potential, human chorionic gonadotropin (hCG) using serum pregnancy test will be performed at screening and 
urine pregnancy test at the other study visits as per the Time and Event Schedule. 
Standard laboratory tests will be performed by ZNA Klinisch Laboratorium. The following biochemistry and 
haematology tests will be performed on the safety blood and laboratory samples: 
- 
Biochemistry: creatinine, glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), 
alkaline phosphatase (ALP), gamma glutamylaminotransferase (GGT), C-reactive protein (CRP), 
bilirubin, sodium and potassium. Sodium and potassium tests are only required in the challenge period. 
- 
Haematology: haemoglobin, haematocrit, red blood cell (RBC) count, white blood cell (WBC) count 
with differential, platelet count, mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin 
concentration (MCHC), mean corpuscular volume (MCV) 
A urine drug screen for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates will 
be performed at screening visit 2 and upon admission at the clinical site (Period 1 & 2). A urine drug screen may 
be repeated to check false positive results. 
An alcohol breath test will be performed at screening visit 2 and upon admission at the clinical site on Day 1 for 
Period 1 and on Day -2 (or Day -1) for Period 2. An alcohol breath test may be repeated to check false positive 
results. 
The Investigator must review the laboratory results, document this review, and record any change occurring 
during the study he/she considers to be clinically relevant in the AE section of the eSource. Laboratory values 
outside the normal range will be flagged and their clinical relevance and significance will be assessed, 
documented and signed by the Investigator. A copy of all laboratory reports must be filed in the participant’s 
records. These tests may be repeated at the Investigator’s discretion.  
7.2.4 
Vital Signs 
Vital sign parameters will be assessed after 5 minutes in supine position at the time points indicated in the Time 
and Events Schedule. The vital sign parameters that will be assessed are temperature, supine systolic and 
diastolic blood pressure (SBP and DBP, respectively), pulse rate, and pulse oximetry. 
These parameters will be measured using a completely automated device consisting of an inflatable cuff and an 
oscillatory detection system. All values will be registered on a built-in recorder so that measurements are 
observer-independent. 
Any change from baseline in vital sign values occurring during the study that is considered to be clinically 
relevant by the Investigator should be recorded in the AE section of the eSource system. 
7.2.5 
Spirometry 
Spirometry is to be performed on Day -1 prior to challenge and on Day 10 post-challenge. This assessment may 
be performed during an Unscheduled Visit at the discretion of the Investigator.  
7.2.6 
Electrocardiogram 
Digital twelve-lead ECGs will be recorded in supine position at the time points indicated in the Time and Events 
Schedule. 
The interpretations of the ECGs will be performed and recorded by the Investigator or his/her designee at the 
clinical site. Any change from baseline/pre-vaccination ECG occurring during the study that is considered to be 
clinically relevant by the Investigator should be recorded in the AE section of the eSource system. Specifically, 
the qualified reader will look for signs of myocarditis, which include non-specific ST-segment and  

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
45 
T-wave abnormalities, sinus tachycardia and conduction abnormalities, such as bundle-branch blocks or 
atrioventricular conduction delays. 
7.2.7 
Physical Examination 
Physical examination or symptom-directed examination will be performed at the time points indicated in the 
Time and Events Schedule. 
Physical examination at screening will include height and weight. To obtain the actual body weight, participants 
must be weighed at screening 2 while lightly clothed. The height should be measured barefoot.  
Any change in physical examination occurring during the study that is considered to be clinically relevant by 
the Investigator should be recorded in the AE section of the eSource system. 
7.2.8 
Other Assessments 
Participants will be instructed in the collection of standard issued tissues (according to the laboratory manual) 
used to capture nasal congestion and discharge, and the samples will be collected by the quarantine staff daily, 
weighed, and the result recorded (early AM and in the evening). 
 TOTAL VOLUME OF BLOOD SAMPLING  
The total volume of blood from any single participant will not exceed the maximum allowable volume during 
his/her participation in the entire study as per the Laboratory Manual. 
If necessary, in order to obtain additional information to ensure participant’s safety, additional blood samples 
(up to 10 mL) and/or urine samples may be taken at the discretion of the Investigator. 
8. STUDY TERMINATION/COMPLETION 
 STUDY COMPLETION 
Participants will be considered to have completed the study if they have completed the entire stay of the 
challenge and completed the follow-up visit 27 days post-challenge or 6 months post-vaccination whichever is 
longer.  
 REMOVAL OF PARTICIPANTS FROM STUDY 
Participants have the right to withdraw from the study at any time for any reason, including their future care. 
The Investigator should however try to find out why a participant withdraws from the study and document the 
reason for withdrawal in the eSource. 
Participants may be withdrawn from the study in the event of: 
- 
A severe AE or serious AE (SAE) 
- 
Difficulties in obtaining blood or other samples; 
- 
Failure of the participant to comply with the protocol requirements or to cooperate with the Investigator. 
Participants must be withdrawn from the study in the event of: 
- 
Withdrawal of consent; 
- 
For safety reasons, it being in the best interest of the participant that he/she be withdrawn, in the 
Investigator’s opinion; 
- 
A positive pregnancy test or if the participant is non-compliant with the contraception requirements (see 
Section 4.1); 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
46 
- 
Development of a medical condition that requires concomitant treatment with a prohibited therapy (see 
Section 6.2); 
- 
Breaking of the randomization code during administration of the study drugs, by the Investigator or by a 
member of his/her clinical staff. If the code is broken by the Sponsor, for safety reporting purposes, the 
participant may remain in the study. 
In the event of a participant being withdrawn from the study, the site monitor and Sponsor should be informed. 
In case of withdrawal due to an SAE (for details on AE reporting see Section 10), the Sponsor should be notified 
within 24 hours. In case of withdrawal for other reasons; the Sponsor should be notified within 2 days from the 
event. 
If there is a medical reason for withdrawal, the participant will remain under the supervision of the Investigator 
until satisfactory health has returned. 
Participants who are withdrawn from the study prior to completion of the scheduled study procedures for any 
reason (AE, withdrawal of consent, etc.) should be invited to complete the assessments as much as possible. As 
long as the participant consents, all relevant assessments of the day on which the participant withdrew from the 
study should be completed, at least those related to safety, and the participant should come for a safety  
follow-up visit at Day 28 post-vaccination or Day 28 post-challenge (if challenged) and/ or will receive a call 
6 months post-vaccination whichever is longer. In case of an AE, the appropriate follow-up will be done. 
Participants who withdraw or are withdrawn from the study for reasons other than safety, may be replaced by 
those who underwent vaccination, and added to the final challenge cohort, if vaccinated volunteers are available. 
This decision will be made based upon discussion and mutual agreement between the Sponsor and the 
Investigator. 
Participants who are vaccinated and not entered into the challenge phase will be phoned at 6 months after 
vaccination to assess any potential intercurrent SAEs. 
 STOPPING RULES OR NON-VACCINATION CRITERIA  
The following events constitute contraindications to administration of vaccine at that point in time; if any one 
of these events occurs at the time scheduled for vaccination, the participant may be vaccinated at a later date, or 
withdrawn from the study at the discretion of the Investigator.  
 
- 
Acute disease at the time of vaccination. Acute disease is defined as the presence of a moderate or severe 
illness with or without fever. All vaccines can be administered to participants with a minor illness such 
as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e. temperature 
of ≤37.7°C/99.5°F. 
- 
Temperature of >38°C (100.4°F) at the time of vaccination. 
- 
Receipt of a licensed inactivated vaccine (e.g. pneumococcal vaccine) within 2 weeks prior to enrolment. 
There must be a minimum of 2-week interval between the trial vaccination procedures and the use of any 
other licensed inactivated vaccines. Participants with routine/travel vaccinations booked within this 
interval will be either advised to postpone their appointments or will have the trial vaccination postponed 
until the minimum interval required is met. 
- 
Receipt of a licensed live vaccine (e.g. herpes zoster vaccine) within 4 weeks prior to enrolment. There 
must be a minimum of 4-week interval between the trial vaccination procedures and the use of any other 
licensed live vaccines. Volunteers with routine/travel vaccinations booked within this interval will be 
either advised to postpone their appointments or will have the trial vaccination postponed until the 
minimum interval required is met. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
47 
 
If any one of the following halting rules are met, vaccination of participants will be suspended until after a 
review of safety data by the IDMC. Other study activities for safety and immune responses will continue during 
IDMC review. The IDMC will recommend that the study continues as planned, stops, or resumes with 
modification.  
- 
Solicited local AEs: If >10% of doses of a vaccine are followed by the same Grade 3 solicited local AE 
- 
Solicited systemic AEs: If >10% of doses of a vaccine are followed by the same Grade 3 solicited 
systemic AE 
- 
Unsolicited AEs: If 10% (n=15) of subjects develop a Grade 3 unsolicited adverse event of the same type 
that is considered possibly, probably or definitely related to vaccination 
- 
Death occurs that is considered possibly, or definitely related to vaccination 
- 
A life-threatening reaction occurs that is considered possibly, probably, or definitely related to 
vaccination 
- 
Occurrence of a SUSAR 
- 
Occurrence of an acute allergic reaction or anaphylactic shock following the administration of vaccine 
investigational product  
If any one of the following halting rules are met, challenge of participants will be suspended until after a review 
of safety data by the IDMC. Other study activities for safety and immune responses will continue during IDMC 
review. The IDMC will recommend that the study continues as planned, stops, or resumes with modification. 
Occurrence in any participant of: 
- 
A reduction of peak expiratory flow (PEF) below 50% of the baseline value, or moderate or severe lower 
respiratory symptoms occurring within 14 days of challenge 
- 
Pulse oximetry that on repeat monitoring over one hour falls below a value of 90%  
- 
Grade 3 or 4 AE or clinical laboratory abnormality considered related to the challenge agent AND of 
concern to the Investigator or Medical Monitor. Grade 3 headache or fatigue which resolves within 24 
hours will not be a reason for halting unless of concern to the Investigator or Medical Monitor. 
- 
More than three cases of influenza that are sufficiently severe to warrant antiviral therapy  
- 
Laryngospasm, bronchospasm, or anaphylaxis associated with the study drug or challenge within 72 
hours of study drug or challenge administration 
- 
Any SAE for which causality is either unknown or related to challenge 
- 
Any case of suspected myocarditis 
- 
Any death 
9. STATISTICAL METHODS 
 STATISTICAL ANALYSIS 
No formal interim analyses are planned for this trial. 
Statistical analyses will be performed by a qualified vendor under the supervision and responsibility of the 
Sponsor, using SAS® (SAS Institute Inc., Cary, NC, USA; version 9.2 or higher) and/or PhoenixTM WinNonlin® 
(Pharsight Corporation, Palo Alto, CA, USA; version 6.1 or higher). Unscheduled interim analyses may be 
performed at the request of the IDMC to monitor the safety of the investigative vaccine throughout the study 
(also Section 5.7). Details will be described in a separate IDMC charter. 
The following populations will be considered for analysis: 
- 
intent-to-treat (ITT) population, defined as all randomized participants who received the challenge 
inoculation, according to the assigned (randomized) treatment group 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
48 
- 
per-protocol (PP) population, consisting of a subset of the ITT population without any major protocol 
deviations and including those participants who remain in the quarantine facility for the full extent of the 
challenge phase 
- 
safety population, consisting of all participants vaccinated in the vaccine phase, according to the 
vaccination actually received 
- 
challenge safety population, which includes all of those in the above defined ITT, according to the 
vaccination actually received.  
Unless specified otherwise, the ITT population will be used for efficacy and immunogenicity analysis. The safety 
populations will be used for safety/tolerability analysis and analysis of demographics. 
All statistical methods shall be detailed in a Statistical Analysis Plan (SAP) to be issued by SGS statistical team 
and finalized before database lock. The SAP will be approved by the Vaccitech Ltd statistical consultant. 
The final efficacy analysis will be performed once all participants have completed 27 days from the time of 
inoculation (Day 28 post-challenge) or 6 months post-vaccination, whichever is last. 
For continuous variables, descriptive statistics will include mean, standard deviation (SD), median, minimum, 
maximum, and range. For categorical variables, descriptive statistics will include frequencies and percentages. 
9.1.1 
Baseline Characteristics  
For all participants who undergo vaccination, descriptive statistics will be provided per vaccination group for 
demographic (e.g. age, height, weight, BMI, race, sex) and other initial participant characteristics (physical 
examination, medical and surgical history, concomitant diseases).  
Prior and concomitant medications will be coded using the World Health Organization (WHO)_DRUG 
Dictionary. 
9.1.2 
Efficacy Data  
A more detailed description of all efficacy analyses will be included in the trial’s SAP, including planned 
supportive and sensitivity analyses, as well as methods for imputing missing data. 
9.1.2.1 
PRIMARY ENDPOINT 
The trial’s primary endpoint is a comparison of the viral shedding of influenza virus in MVA-NP+M1 versus 
placebo recipients following human challenge, as measured by the cumulative area under the curve (vAUC). 
Difference in vAUC, as measured and quantitated by log-transformed qPCR, will be evaluated using a Mann-
Whitney U Test. AUC will be calculated using the trapezoidal rule. In case no viral load was detected, the log10 
viral load will be imputed. 
Mean (± Standard Error (SE)) viral load over time will be summarized and presented graphically in log10 scale 
by treatment group.  
9.1.2.2 
SECONDARY ENDPOINTS 
The attack rate, defined as percentage of inoculated participants with at least two positive swabs as determined 
by qPCR, will be summarized in percentages and 95% confidence intervals (CIs) by treatment group. The 
difference between the two treatment groups will be compared by a Fisher’s exact test.  
Time to start, time to peak and time to cessation of viral shedding from virus inoculation and duration of viral 
shedding will be summarized by the Kaplan-Meier method. Differences between the treatment groups will also 
be tested using the log-rank test. Differences in peak between treatment groups will be tested using a Mann-
Whitney U test. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
49 
The same analyses as performed for qPCR will be performed on quantitative culture.  
Secondary endpoints include the rate of virologically confirmed ILI (defined as a respiratory or flu-like symptom 
occurring on two consecutive days, along with a positive PCR or culture) measured between groups. Incidence 
of laboratory-confirmed influenza will be compared between vaccine groups using Fisher’s Exact Test. 
Another key secondary endpoint of relevance to the biologic effect of this vaccine will be the comparison of the 
symptom severity as an AUC. This endpoint takes into account both the severity and the duration of symptoms. 
Total and individual symptom scores from Day 1 to Day 11 post-challenge, will be compared by AUC using a 
Mann-Whitney U test.  
T cell responses (as defined by ELISpot assay) will be evaluated in relation to the primary endpoint, symptom 
scores and influenza incidence. 
9.1.2.3 
EXPLORATORY ENDPOINTS 
Time to start, time to peak and time to cessation of total symptoms from virus inoculation and duration of total 
symptoms will be summarized by the Kaplan-Meier method. Differences between the treatment groups will also 
be tested using the log-rank test. 
Total days of fever for MVA-NP+M1 vs. Placebo will be compared by means of a zero-inflated Poisson model. 
Fever is defined as >38.0 degrees Celsius. 
Total mucus production between Days 1 and 11 post-challenge, as measured by total tissue weight, will be 
compared between vaccine groups using a t-test or Mann-Whitney U Test. 
Immunogenicity data, using interferon gamma/granzyme B ELISpot as the primary outcome measure, will be 
compared between vaccine groups using a t-test or Mann-Whitney U Test. Descriptive statistics will be 
calculated including number of observations, mean, median, geometric mean titre (GMT), minimum and 
maximum with 95% confidence interval (CI).  
Transcriptional response to vaccination and viral challenge may be assessed by deep sequencing of RNA using 
PAXgene® RNA tubes. 
Epigenetic responses of T-Cells may be assessed during the study, and the methods will be detailed in the SAP. 
Descriptive comparison of the ratios of the GMTs of the MNT and HI results between the two treatment groups 
will be calculated along with the corresponding 95% CI based on the log10 difference of the two groups. 
Importantly, with a 83% attack rate and 30% efficacy, approximately 20 of the 80 vaccination participants will 
have a zero area under the curve, and these participants can be compared to those with the highest vAUC in 
correlate of protection analyses. An exploratory correlate of protection analysis will be detailed in the SAP prior 
to breaking the blind on the immunogenicity data.  
9.1.3 
Safety Data 
Safety parameters will be tabulated and analysed descriptively. 
Adverse Events 
The original terms used in the eSource documents by Investigators to identify AEs will be fully described and 
coded according to the Medical Dictionary for Regulatory Activities (MedDRA). 
The reported AEs will be allocated to phases based on their start date. All AEs will be listed. All AEs with onset 
after Day 1 of vaccination will be summarized by treatment group. Summaries, listings, and narratives may be 
provided, as appropriate. Summaries will include at a minimum SAEs, and for both solicited and unsolicited 
AEs, the severe (grade 3+ events), related AEs, and AEs following challenge.  

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
50 
Clinical Laboratory Tests 
Each continuous biochemistry and haematology laboratory test will be evaluated by means of descriptive 
statistics (i.e., number of participants, mean, SD, median, minimum, and maximum) on the actual values, at each 
assessment time point and by vaccination group. 
Relative changes in clinical laboratory test values compared to values at baseline will be evaluated according to 
the appended toxicity scale or in accordance with the normal ranges of the clinical laboratory (below, within, or 
above normal range) for parameters for which no toxicity grades are defined. 
A listing of participants with any clinical laboratory test result outside the reference ranges will be provided. 
Vital Signs 
Pulse rate, temperature, SBP, and DBP will be evaluated by means of descriptive statistics (actual values and 
changes from Day 1 to Day 2 of the vaccine phase and from Day 1 of the challenge phase and frequency 
tabulations at each assessment time point and by vaccination group). 
Pulse oximetry will be measured during the entire challenge phase.  
The percentage of participants with values beyond clinically important limits (as defined in the Toxicity Tables) 
will be summarized. 
Electrocardiogram 
ECG variables will be evaluated by means of descriptive analysis by the Investigator at each assessment time 
point. 
The percentage of participants with ECG abnormalities will be summarized. 
The ECG variables that will be analysed by electronic capture from the ECG include heart rate, PR interval, 
QRS interval, QT interval.  
Physical Examination 
Abnormal findings in physical examination will be listed. 
 DETERMINATION OF SAMPLE SIZE 
The sample size was chosen to have sufficient power to detect a 30% difference in the vAUC, assuming a drop 
out of approximately 15-20% from the vaccination group. Since there is 15% over-enrolment during the 
vaccination phase compared to challenge, it is assumed that in a worse-case scenario a 25% reduction, or that 
the final numbers to undergo challenge per group could be as low as 72 MVA-NP+M1 and 48 Placebo recipients. 
The placebo vAUC data were estimated using qPCR data accumulated during two previous challenge studies, 
where vAUC was calculated using the trapezoidal rule. The allocation ratio is chosen not at 2:1 (which would 
be 80:40), but rather at 80:54 to ensure sufficient placebo recipients within each challenge period to adequately 
assess the take rate of the challenge for that given cohort. Sample sizes of 80 and 54 participants in the  
MVA-NP+M1 and placebo groups, respectively, will yield approximately 90% power to detect at least a 22% 
difference in vAUC at a two-sided, alpha=0.05 level. If enrolment is lower than anticipated, approximately  
two-thirds of the planned sample size will still yield at least 80% power to detect a 30% difference in vAUC 
(two-sided alpha = 0.05). 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
51 
10. ADVERSE EVENT REPORTING 
 DEFINITIONS 
Definition of Adverse Event 
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal 
(investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the 
treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal finding), 
symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) 
product, whether or not related to that medicinal (investigational or non-investigational) product. 
This includes any occurrence that is new in onset or aggravated in severity or frequency from the baseline 
condition, or abnormal result of diagnostic procedures, including clinical laboratory test abnormalities. 
Definition of Serious Adverse Event 
An SAE is any untoward medical occurrence that at any dose meets any of the following conditions: 
- 
results in death 
- 
is life-threatening, i.e., the participant was at risk of death at the time of the event (e.g., ventricular 
fibrillation and anaphylaxis). The term does not refer to an event which hypothetically might have caused 
death if it were more severe. 
- 
requires 
inpatient 
hospitalization 
or 
prolongation 
of 
existing 
inpatient 
hospitalization: 
Hospitalization refers to an overnight admission into hospital for the purpose of investigating and/or 
treating the AE. Hospitalization for an elective procedure, or routinely scheduled treatment for a pre-
existing condition that has not worsened, is not an SAE. 
- 
results in persistent or significant disability/incapacity, i.e., causing substantial disruption of the 
participant’s ability to conduct normal life 
- 
is a congenital anomaly/birth defect 
- 
is medically significant, i.e., may not be immediately life-threatening or result in death or hospitalization 
but may jeopardize the participant’s health or may require intervention to prevent one of the above 
outcomes. Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization or development of 
drug dependency or drug abuse. 
Definition of Unlisted (Unexpected) Adverse Event 
An AE is considered unlisted if the nature or severity is not consistent with the applicable product reference 
safety information in the Investigator Brochure.  
Definition of Events of Special Interest  
Adverse events of special interest (AESI) for this study are listed in Appendix 1. AESI should be recorded and 
reported using the same procedures as for SAEs. They should therefore be recorded over the duration of the 
study to which the participant is recruited and reported to the Sponsor according to the process in Section 10.7. 
 
 INTENSITY OF ADVERSE EVENTS 
Each AE must be rated on a 5-point scale of increasing intensity according to the Common Terminology Criteria 
for Adverse Events (CTCAE) version 4.0: 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
52 
Note: the semi-colon within the description of the grade indicates ‘or’. 
Grade 1: 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. 
Grade 2: 
Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities 
of daily life (preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.). 
Grade 3: 
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of 
hospitalization indicated, disabling; limiting self-care activities of daily life (bathing, dressing and undressing, 
feeding self, using the toilet, taking medications, and not bedridden). 
Grade 4: 
Life-threatening consequences; urgent intervention indicated. 
Grade 5: 
Death related to AE. 
 CAUSALITY ASSESSMENT 
Causality of each AE will be assessed according to the WHO-Uppsala Monitoring Centre (UMC) system for 
standardized case causality assessment. 
Note: all of the assessment criteria per causality should be reasonably complied to. 
Certain: 
- 
Event or laboratory test abnormality with plausible time relationship to study drug. 
- 
Cannot be explained by disease or other drugs.  
- 
Response to withdrawal plausible (pharmacologically, pathologically). 
- 
Event definitive immunologic or phenomenologically (i.e., an objective and specific medical disorder or 
a recognized pharmacological phenomenon). 
Probable/Likely 
- 
Event or laboratory test abnormality with reasonable time relationship to study drug administration  
- 
Unlikely to be attributable to disease or other drugs.  
Possible 
- 
Event or laboratory test abnormality with reasonable time relationship to study drug administration 
- 
Could also be explained by disease or other drugs. 
Unlikely 
- 
Event or laboratory test abnormality with a time to study drug administration that makes a relationship 
improbable (but not impossible) 
- 
Disease or other drugs provide plausible explanations. 
Not related 
- 
Implausibly related to study intervention 
 ACTION TAKEN REGARDING THE STUDY DRUGS 
The action taken towards the study drug must be described as follows: 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
53 
- 
Participant permanently discontinued from study 
- 
Unknown 
- 
Not applicable. 
 OUTCOME 
The outcome of each AE must be rated as follows: 
- 
Recovered/resolved 
- 
Recovering/resolving 
- 
Not recovered/not resolved 
- 
Recovered with sequelae/resolved with sequelae 
- 
Fatal 
- 
Unknown. 
 RECORDING OF ADVERSE EVENTS 
All (S)AEs occurring during the clinical investigation must be documented in the (e)source documents. 
Whenever possible, diagnoses should be given when signs and symptoms are due to a common aetiology (e.g., 
cough, runny nose, sneezing, sore throat, and head congestion should be reported as “upper respiratory 
infection”). Investigators must record their opinion concerning the relationship of the (S)AE to the study drug 
in the eSource.  All measures required for (S)AE management must be recorded in the source documents and 
reported according to Sponsor’s instructions. 
All AEs occurring at any time during the study (including the follow-up period) will be followed by the 
Investigator until satisfactory resolution (e.g., value back to baseline value) or stabilization or until final database 
lock. If necessary, in order to obtain additional information to ensure safety to the participant, additional blood 
and urine samples may be taken at the discretion of the Investigator. Certain long-term AEs related to therapy 
cannot be followed until resolution within the setting of this study. If additional follow up or treatment is deemed 
as needed, it is up to the Investigator to inform the participant and to ensure adequate medical care by the 
participants treating physician (GP or specialist). 
 REPORTING OF SERIOUS ADVERSE EVENTS 
All SAEs independent of the circumstances or suspected cause must be reported on a Serious Adverse Event 
Form by the Investigator to Vaccitech and SGS Life Sciences Medical Affairs within 24 h of their knowledge 
of the event. 
The SAE form should include a clearly written narrative describing signs, symptoms, and treatment of the event, 
diagnostic procedures, as well as any relevant laboratory data and any sequelae, in order to allow a complete 
medical assessment of the case and independent determination of the possible causality.  
Follow-up and outcomes should be reported for all participants who experience an SAE. 
It is critical that the information provided on the Serious Adverse Event Form matches the information recorded 
in the (e)source documents for the same event. 
Copies of additional laboratory tests, consultation reports, post-mortem reports, hospital case reports, autopsy 
reports, and other documents should be sent when requested and applicable. Follow-up reports relative to the 
participant’s subsequent course must be submitted to SGS Life Sciences Medical Affairs until the event has 
subsided or, in case of permanent impairment, until the condition stabilizes. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
54 
 PREGNANCY 
All initial reports of pregnancy in participants must be reported to Vaccitech and SGS Life Sciences by the 
Investigator within 24 h of his/her knowledge of the event using a Pregnancy Form. Any participant who 
becomes pregnant during the study must be promptly withdrawn from the study (Section 8). 
The Investigator will contact the participant at the expected time of delivery for follow-up. Abnormal pregnancy 
outcomes (e.g. spontaneous or induced abortion, stillbirth, neonatal death, congenital abnormality, birth defect) 
are considered SAEs and must be reported using the Serious Adverse Event Form. 
 REPORTING OF SERIOUS ADVERSE EVENTS TO COMPETENT AUTHORITIES/ETHICS 
COMMITTEES 
SGS Life Sciences Medical Affairs assumes responsibility for appropriate reporting of AEs to the regulatory 
authorities. SGS Life Sciences Medical Affairs will also report to the Investigator all SAEs that are unlisted 
(unexpected) and associated with the use of the drug. The Investigator (or SGS Life Sciences Medical Affairs 
where required) must report these events to the appropriate Independent Ethics Committee/Institutional Review 
Board (IEC/IRB) that approved the protocol, unless otherwise required and documented by the IEC/IRB. 
Adverse events reporting, including suspected unexpected serious adverse reactions (SUSARs), will be carried 
out in accordance with applicable local regulations. 
After termination of the clinical study (determined as LPLV), any unexpected safety issue that changes the risks 
benefit analysis and is likely to have an impact on the participants who have participated in the study, together 
with proposed actions, will be reported by the Sponsor/SGS Life Sciences Medical Affairs to the competent 
authority(ies) concerned as soon as possible. 
11. ETHICAL ASPECTS 
 STUDY-SPECIFIC DESIGN CONSIDERATIONS 
Potential participants will be fully informed of the nature of the study and of the risks and requirements of the 
study before any study-related assessment will be carried out. During the study, participants will be given any 
new information that may affect their decision to continue participation. They will be informed that their 
participation in the study is voluntary and that they may withdraw from the study at any time with no reason 
given and without penalty or loss of benefits to which they would otherwise be entitled. Only participants who 
are fully able to understand the risks, benefits, and potential AEs of the study, and who provide their consent 
voluntarily will be enrolled in the study. 
 REGULATORY ETHICS COMPLIANCE 
11.2.1 
Investigator Responsibilities 
The Investigator(s) should be qualified by education, training, and experience to assume responsibility for the 
proper conduct of the study, should meet all the qualifications specified by the applicable regulatory 
requirement(s), and should provide evidence of such qualifications through up-to-date curriculum vitae or other 
relevant documentation requested by the Sponsor, the IRB/IEC, or the regulatory authority(ies). 
The Investigator is responsible for ensuring that the clinical study is performed in accordance with the protocol, 
current International Council for Harmonization (ICH) guidelines on GCP, and applicable regulatory and 
country-specific requirements. 
Good Clinical Practice is an international ethical and scientific quality standard for designing, conducting, 
recording, and reporting studies that involve the participation of human participants. Compliance with this 
standard provides public assurance that the rights, safety, and well-being of study participants are protected, 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
55 
consistent with the principles originating from the Declaration of Helsinki (1964 and revisions), and that the 
clinical study data are credible. 
11.2.2 
Independent Ethics Committee or Institutional Review Board (IEC/IRB) 
An IRB/IEC should safeguard the rights, safety, and well-being of all study participants. Special attention should 
be paid to studies that may include vulnerable participants. 
Before the start of the study, the Investigator (or Sponsor where required) will provide the IEC/IRB with current 
and complete copies of the following documents: 
- 
final protocol and, if applicable, amendments 
- 
Sponsor-approved ICF (and any updates or any other written materials to be provided to the participants) 
- 
Sponsor-approved participant recruiting materials 
- 
Investigator Brochure (or equivalent information) and addenda 
- 
available safety information 
- 
information on compensation for study-related injuries or payment to participants for participation in the 
study, if applicable 
- 
Investigator’s current curriculum vitae or other documentation evidencing qualifications (unless not 
required, as documented by the IEC/IRB) 
- 
information regarding funding, name of the Sponsor, institutional affiliations, other potential conflicts of 
interest, and incentives for participants 
- 
any other documents that the IEC/IRB may require to fulfil its obligation. 
This study will be undertaken only after the IEC/IRB has given full written approval of the final protocol and 
amendments (if any), the ICF(s) and updates (if any), applicable recruiting materials, and any other written 
information to be provided to the participants, and the Sponsor has received a copy of this approval. This 
approval letter must be dated and must clearly identify the IEC/IRB and the documents being approved. 
During the study, the Investigator (or Sponsor where required) will send the following documents and updates 
to the IEC/IRB for its review and approval, where appropriate:  
- 
protocol amendments 
- 
revision(s) to the ICF and any other written materials to be provided to the participants 
- 
new or revised participant recruiting materials approved by the Sponsor 
- 
revisions to compensation for study-related injuries or payment to participants for participation in the 
study 
- 
Investigator’s Brochure addenda or new edition(s) 
- 
summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at least annually) 
- 
reports of AEs that are serious, unlisted, and associated with the Investigational Medicinal Product (IMP) 
- 
new information that may adversely affect the safety of the participants or the conduct of the study 
- 
deviations from or changes to the protocol to eliminate immediate hazards to the participants 
- 
report of death of any participants under the Investigator’s care 
- 
notification if a new Investigator is responsible for the study at the clinical site 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
56 
- 
Development Safety Update Report, Short-Term Study Specific Safety Summary and Line Listings, 
where applicable 
- 
any other requirements of the IEC/IRB. 
For all protocol amendments (excluding the ones that are purely administrative, with no consequences for 
participants, data or study conduct), the amendment and applicable ICF revisions must be submitted promptly 
to the IEC/IRB for review and approval before implementation of the change(s), except when necessary to 
eliminate immediate hazard to the study participants. If a deviation from or a change to the protocol was 
implemented to eliminate an immediate hazard to study participants, then the implemented deviation or change, 
the reasons for it, and, if appropriate, the protocol amendment should be submitted to the IEC/IRB as soon as 
possible. 
The Investigator (or Sponsor where required) will notify the IEC/IRB about the study completion within 90 days 
after the end of the study (defined as LPLV). 
11.2.3 
Informed Consent 
Each participant must give written consent according to local requirements after the nature of the study has been 
fully explained. The consent form must be signed before performance of any study-related activity. The consent 
form that is used must be approved by both the Sponsor and the reviewing IEC/IRB. The informed consent 
should be in accordance with the principles that originated in the Declaration of Helsinki, current ICH and GCP 
guidelines, applicable regulatory requirements, and Sponsor policy. 
Before enrolment in the study, the Investigator or an authorized member of the clinical staff must explain to 
potential participants the aims, methods, reasonably anticipated benefits, and potential hazards of the study, and 
any discomfort participation in the study may entail. Participants will be informed that their participation is 
voluntary and that they may refuse to participate or withdraw consent to participate at any time, without penalty 
or loss of benefits to which the participant was entitled. Finally, they will be told that the Investigator will 
maintain a participant identification register for the purposes of long-term follow-up if needed and that their 
records may be accessed by health authorities and authorized Sponsor staff without violating the confidentiality 
of the participant, to the extent permitted by the applicable law(s) or regulations. By signing the ICF the 
participant is authorizing such access and agrees to allow his or her study physician to recontact the participant 
for the purpose of obtaining consent for additional safety evaluations, if needed. 
The language about the study used in the oral and written information, including the ICF, should be non-technical 
and practical and should be understandable to the participant (or the participant’s legally acceptable 
representative). The participant will be given sufficient time to read the ICF and the opportunity to ask questions. 
After this explanation and before entry into the study, consent should be appropriately recorded by means of the 
participant's personally dated signature. After having obtained consent, a copy of the ICF must be given to the 
participant. 
If a participant (or legally acceptable representative) is unable to read or write, an impartial witness should be 
present during the entire informed consent discussion. After the written ICF and any other written information 
to be provided to the participants, is read and explained to the participant (or legally acceptable representative), 
and after the participant (or legally acceptable representative) has orally consented to the participant’s 
participation in the study and, if capable of doing so, has personally dated and signed the ICF, the witness should 
personally date and sign the consent form. By signing the ICF, the witness attests that the information in the ICF 
and any other written information was accurately explained to, and apparently understood by, the participant (or 
legally acceptable representative), and that informed consent was freely given by the participant (or legally 
acceptable representative). 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
57 
The Investigator or designee is to document the process followed for consent collection in the source file and 
confirm that a copy of the ICF was provided to the study participant. 
11.2.4 
Privacy of Personal Data 
The collection and processing of personal data from participants enrolled in the study will be limited to those 
data that are necessary to investigate the safety, quality, and utility of the IMP used in the study. 
These data must be collected and processed with adequate precautions to ensure confidentiality and compliance 
with applicable data privacy protection laws and regulations. Appropriate technical and organizational measures 
to protect the personal data against unauthorized disclosures or access, accidental or unlawful destruction, or 
accidental loss or alteration must be put in place. Sponsor personnel whose responsibilities require access to 
personal data need to agree to keep the identity of the study participants confidential. 
The informed consent obtained from the participants includes explicit consent for the processing of personal 
data and for the Investigator to allow direct access to participants’ original medical records for study-related 
monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also addresses the transfer of the 
data to other entities and to other countries. 
12. ADMINISTRATIVE REQUIREMENTS 
 PROTOCOL AMENDMENTS 
Neither the Investigator nor the Sponsor will modify this protocol without a formal amendment. All protocol 
amendments must be issued by the Sponsor and signed and dated by the Investigator. Protocol amendments must 
not be implemented without prior IEC/IRB approval nor when the relevant competent authority has raised any 
grounds for non-acceptance, except when necessary to eliminate immediate hazard to the participants, in which 
case an amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the Investigator and IEC/IRB must be provided to the Sponsor or his 
designee. When the change(s) involves only logistic or administrative aspects of the study, the IEC only needs 
to be notified. 
 PARTICIPANT IDENTIFICATION, ENROLMENT, AND SCREENING LOGS 
The Investigator agrees to complete a participant identification and enrolment log to permit easy identification 
of each participant during and after the study. This document will be reviewed by the site Monitor for 
completeness. 
The participant identification and enrolment log will be treated as confidential and will be filed by the 
Investigator in the study file. To ensure participant confidentiality, no copies will be made. All reports and 
communications related to the study will identify participants by assigned number only. 
The Investigator must also complete a participant screening/enrolment log which documents all participants who 
were seen to determine eligibility for inclusion in the study and those who have been successfully randomized 
in the study. This log is to be shared with the Sponsor on a regular basis to allow Sponsor oversight. 
 SOURCE DOCUMENTATION 
The LabPas system is an electronic data capturing and information management system that will also serve as 
an eSource system for this study. The system combines all aspects of source data capturing with process control 
and clinical study management. All clinical and laboratory data, except those that are paper-based, will be 
collected directly in LabPas. The Source Document Identification Overview will specify which information will 
be eSource and which will be paper-based. The monitor will check data at the monitoring visits to the CPU. The 
Investigator will ensure that the data collected are accurate, complete, and legible. Data will be monitored within 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
58 
LabPas by the study monitor who has only reading rights. Any changes required following monitoring will be 
made by site personnel or the Investigator and will be documented with a full audit trail within LabPas. 
At a minimum, source documentation must be available for the following data : participant identification, 
eligibility, and study identification; study discussion and date of informed consent, dates of visits, results of 
safety and efficacy parameters as required by the protocol, record of all AEs, follow-up of AEs, concomitant 
medication, study drug receipt/dispensing/return records, study drug administration information, laboratory, date 
of study completion, and reason for early discontinuation of study drugs or withdrawal from the study, if 
applicable. 
Direct access to (e)Source documentation (medical records) must be allowed for the purpose of verifying that 
the data. 
It is required that the author of an entry in the (e)Source documents be identifiable. 
Source data may be directly captured from devices, transferred from third parties (e.g., laboratory data), or 
entered manually into the eSource system in use at the CPU. In such case, the majority of the source data will 
only be available electronically. The remainder of the data, captured initially on paper, may be entered 
retrospectively into the eSource system.  
Following the ICH-GCP guidelines, direct access to (e)Source documentation (medical records) must be 
allowed. 
 CASE REPORT FORM COMPLETION 
All source data, except those that are paper-based, will be collected directly into the eSource system. Paper-
based source data will be manually transcribed to the eSource system. Only the data required for the clinical 
database will be transferred electronically from the eSource system to the clinical database.  
The study data will be directly entered into the eSource by study personnel and transmitted in a secure manner 
to the Sponsor.  
All eSource entries, corrections, and alterations must be made by the Investigator or other authorized study-site 
personnel. 
Worksheets may be used for the capture of some data to facilitate completion of the eSource. Any such worksheet 
will become part of the participant’s source documentation. All data related to the study must be recorded into 
the eSource. Data must be entered into the eSource in English. Designated site personnel must complete the 
eSource as soon as possible after a participant visit, and the forms should be available for review at the next 
scheduled monitoring visit. 
The Investigator must verify that all data entries on the eSource are accurate and correct. 
 MONITORING 
The monitoring of the study will be done under the responsibility of the Sponsor by SGS Life Sciences. 
The monitor will perform on-site monitoring visits as frequently as necessary but in accordance with the 
Monitoring Plan. The monitor will record the dates of the visits in a study site visit log that will be kept at the 
clinical site. The first post initiation visit will be made as soon as possible after enrolment has begun. At these 
visits, the monitor will compare the data captured in the eSource system for completeness and accuracy and 
perform data source verification to any data that has been captured as paper source or entered in the system later 
on. The nature and location of all source documents will be identified to ensure that all sources of original data 
required to complete the eSource system are known to the Sponsor and clinical staff and are accessible for 
verification by the site Monitor. If electronic records are maintained at the investigational site, the method of 
verification must be discussed with the clinical staff. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
59 
Direct access to (e)Source documentation (medical records) must be allowed at all times for the purpose of 
verifying that the data recorded in the eSource system are consistent with the paper Source data (if applicable). 
Findings from this review of captured data will be discussed with the clinical staff. During on-site monitoring 
visits (notified and agreed upfront with the clinical staff), the relevant clinical staff will be available, the 
(e)Source documentation will be accessible, and a suitable environment for review of study-related documents 
will be provided. The monitor will meet with the Investigator on a regular basis during the study to provide 
feedback on the study conduct. 
 DATA MANAGEMENT 
Data management of the study will be performed under the responsibility of the Sponsor by SGS Life Sciences.  
After the data entered in the eSource system are released by the Investigator, the data will be uploaded into the 
clinical database to perform cleaning activities. Computerized data cleaning checks will be used in addition to 
manual review, including listings review, to check for discrepancies and to ensure consistency and completeness 
of the data. Queries emerging during data cleaning will be generated by the clinical data manager in the eSource 
system. The Investigator or his designee will answer the queries and update the source data, if needed.  
The clinical database will be locked as soon as it is considered clean. Before the clinical database will be locked, 
the study eSource system will be locked by the clinical staff. Only authorized and well-documented updates to 
the study data are possible after database lock. The locked database is used in the final statistical analysis for 
study reporting. Measures will be undertaken to protect participant data handed over by the Investigator to the 
data management department and during inspections against disclosure to unauthorized third parties. Participant 
confidentiality will be maintained at all times.  
 DATA QUALITY ASSURANCE 
The accuracy and reliability of the study data will be assured by the selection of qualified Investigators and 
appropriate study sites, review of protocol procedures with the Investigator and associated personnel prior to the 
study, and by periodic monitoring visits by the Sponsor or designate. 
Written instructions will be provided for the collection, preparation, and shipment of blood samples.  
The Sponsor or his designee will review the eSource system for accuracy and completeness during (on-site) 
monitoring visits and after transmission to the Sponsor; any discrepancies will be resolved with the Investigator 
or designee, as appropriate. After upload of the data into the clinical study database, their accuracy verified using 
appropriate validation programs. 
In accordance with Good Clinical Research Practice Guidelines and Recommendations, the Sponsor will be 
entitled to audit the facilities used in the clinical and laboratory parts of the study, as well as to access all the 
data files pertaining to the study. Similar procedures may also be conducted by agents of any regulatory body, 
either as part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The Investigator should immediately notify the Sponsor if they have been contacted by 
a regulatory agency concerning an upcoming inspection. 
 ON-SITE AUDITS 
Representatives of the Sponsor’s clinical quality assurance department may visit the clinical site at any time 
during or after completion of the study to conduct an audit of the study in compliance with regulatory guidelines 
and company policy. These audits will require access to all study records, including source documents, for 
inspection. Participant privacy must, however, be respected. The Investigator and clinical staff are to be present 
and available for consultation during routinely scheduled site audit visits conducted by the Sponsor or his 
designee. 
Similar procedures may also be conducted by agents of any regulatory body, either as part of a national GCP 
compliance program or to review the results of this study in support of a regulatory submission. The Investigator 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
60 
should immediately notify the Sponsor if they have been contacted by a regulatory agency concerning an 
upcoming inspection. 
 STUDY TERMINATION 
The Sponsor has the right to terminate the study at any time. In case of an early termination of the study for 
safety reasons, or temporary halt by the Sponsor, the IEC/IRB should be notified within 15 calendar days and 
should be provided with a detailed written explanation for the termination/halt. 
An end-of-study declaration will be submitted to the regulatory authorities and IEC/IRB after the complete study 
has ended. This notification will be submitted within 90 days after the end of the study. 
 RECORD RETENTION 
In compliance with the ICH/GCP guidelines, the Investigator/Institution will maintain all eSource and all paper 
source documents that support the data collected from each participant, as well as all study documents as 
specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical Trial, and all study 
documents as specified by the applicable regulatory requirement(s). The Investigator/Institution will take 
measures to prevent accidental or premature destruction of these documents.  
Essential documents must be retained until at least 2 years after the last approval of a marketing application in 
an ICH region and until there are no pending or contemplated marketing applications in an ICH region or until 
at least 2 years have elapsed since the formal discontinuation of clinical development of the IMP. These 
documents will be retained for a longer period if required according to the applicable regulatory requirements 
or per agreement with the Sponsor. It is the responsibility of the Sponsor to inform the Investigator/Institution 
as to when these documents no longer need to be retained. 
If the responsible Investigator retires, relocates, or for any other reasons withdraws from his responsibility of 
keeping the study records, custody must be transferred to a person who will accept the responsibility. The 
Sponsor must be notified in writing of the name and address of the new custodian. Under no circumstance shall 
the Investigator relocate or dispose of any study documents without having obtained written approval from the 
Sponsor. 
If it becomes necessary for the Sponsor or the appropriate regulatory authority to review any documentation 
related to the study, the Investigator must permit access to such reports. 
 USE OF INFORMATION AND PUBLICATION 
All information, including but not limited to, information regarding MVA-NP+M1 or the Sponsor’s operations 
(e.g., patent application, formulas, manufacturing processes, basic scientific data, prior clinical data, formulation 
information) supplied by the Sponsor to the Investigator and not previously published, and any data generated 
as a result of this study are considered confidential and remain the sole property of the Sponsor. The Investigator 
agrees to maintain this information in confidence, to use this information only to accomplish this study, and not 
to use it for other purposes without the Sponsor’s prior written consent. 
The Investigator understands that the information generated in this clinical study will be used by the Sponsor in 
connection with the continued development of the study product, and thus may be disclosed as required to other 
clinical Investigators or regulatory agencies. To permit information derived from the clinical studies to be used, 
the Investigator is obliged to provide the Sponsor with all data obtained in the study. 
The results of the study will be reported in a Clinical Study Report generated under the responsibility of the 
Sponsor. Recruitment performance or specific expertise related to the nature and the key assessment parameters 
of the study will be used to determine a coordinating Investigator. 
Clinical narratives may be written for the following events (for example): 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
61 
- 
All deaths (irrespective of drug relationship) 
- 
All other SAEs during treatment with the study drugs 
- 
All discontinuations of the study drugs due to AEs (irrespective of drug relationship) 
- 
At the discretion of the team and after statistical analysis of the data, certain discontinuations not related 
to AEs or treatment failure, i.e., related to lost to follow-up or withdrawal of consent (irrespective of 
treatment group) 
- 
Any events of special interest explicitly requested by the regulatory agencies. 
The principal Investigator will sign off the final version of the Clinical Study Report. A summary of this final 
version will be provided to the Investigators, the applicable regulatory authorities, and the IECs/IRBs, if required 
by the applicable regulatory requirements, within 1 year after the end of the study (LPLV). 
The Sponsor shall have the right to publish study data and information without approval from the Investigator. 
If an Investigator wishes to publish information from the study, a copy of the manuscript must be provided to 
the Sponsor for review at least 60 days before submission for publication or presentation. Expedited reviews of 
30 days will be arranged for abstracts, poster presentations, or other materials. If requested by the Sponsor in 
writing, the Investigator will withhold such publication for up to an additional 60 days to allow for filing of a 
patent application. In the event that issues arise regarding scientific integrity or regulatory compliance, the 
Sponsor will review these issues with the Investigator. The Sponsor will not mandate modifications to scientific 
content and does not have the right to suppress information. Authorship of publications resulting from this study 
will be based on the guidelines on authorship, such as those described in the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, which state that the named authors must have made a significant 
contribution to the design of the study or analysis and interpretation of the data, provided critical review of the 
paper, and given final approval of the final version. 
 REGISTRATION OF CLINICAL STUDIES AND DISCLOSURE OF RESULTS 
The Sponsor will register the existence of a clinical study and disclose its results as required by law. 
 CONFIDENTIALITY 
All study documents are provided by the Sponsor to the Investigator and appointed clinical staff in confidence. 
None of this material may be disclosed to any party not directly involved in the study without the Sponsor’s 
written permission. 
The Investigator must assure that participants’ anonymity will be maintained. The Investigator will keep a 
separate list with at least the initials, the participants’ study numbers, names, addresses, and telephone numbers. 
The Investigator will maintain this for the longest period of time allowed by his/her own institution and, in any 
case, until further communication from the Sponsor. 
 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
62 
 
13. REFERENCES 
1. Investigator Brochure MVA-NP+M1, version 2.0, 2018. 
2. Literature references 
1. 
Lagace-Wiens, P.R., E. Rubinstein, and A. Gumel, Influenza epidemiology--past, present, and 
future. Crit Care Med, 2010. 38(4 Suppl): p. e1-9. 
2. 
Treanor, J., Influenza Viruses, Including Avian Influenza and Swine Influenza. Principles and 
Practice of Infectious Diseases. Mandell GL, Bennett JE, Dolin R (Eds). 2: p. 2060–2085. 
3. 
Who, Influenza fact sheet  
4. 
Molinari, N.A., et al., The annual impact of seasonal influenza in the US: measuring disease 
burden and costs. Vaccine, 2007. 25(27): p. 5086-96. 
5. 
Dawood, F.S., et al., Estimated global mortality associated with the first 12 months of 2009 
pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis, 2012. 12(9): 
p. 687-95. 
6. 
Babakir-Mina, M., et al., Influenza virus A (H5N1): a pandemic risk? New Microbiol, 2007. 
30(2): p. 65-78. 
7. 
Kilbourne, E.D., et al., The total influenza vaccine failure of 1947 revisited: major intrasubtypic 
antigenic change can explain failure of vaccine in a post-World War II epidemic. Proc Natl Acad 
Sci U S A, 2002. 99(16): p. 10748-52. 
8. 
Bardenheier, B.H., et al., Influenza vaccine supply, 2005-2006: did we come up short? BMC 
Health Serv Res, 2007. 7: p. 66. 
9. 
Hannoun, C., F. Megas, and J. Piercy, Immunogenicity and protective efficacy of influenza 
vaccination. Virus Res, 2004. 103(1-2): p. 133-8. 
10. 
Hayward, A.C., et al., Natural T Cell Mediated Protection Against Seasonal and Pandemic 
Influenza: Results of the Flu Watch Cohort Study. American Journal of Respiratory and Critical 
Care Medicine, 2015. 15; 191(12): p. 1422-31 
11. 
Sridhar, S., et al., Cellular immune correlates of protection against symptomatic pandemic 
influenza. Nat Med, 2013. 19(10): p. 1305-12. 
12. 
Lee, L.Y., et al., Memory T cells established by seasonal human influenza A infection cross-react 
with avian influenza A (H5N1) in healthy individuals. J Clin Invest, 2008. 118(10): p. 3478-90. 
13. 
Berthoud, T.K., et al., Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic 
influenza A vaccine, MVA-NP+M1. Clin Infect Dis, 2011. 52(1): p. 1-7. 
14. 
Hochstein-Mintzel, V., et al., [An attenuated strain of vaccinia virus (MVA). Successful 
intramuscular immunization against vaccinia and variola (author's transl)]. Zentralbl Bakteriol 
Orig A, 1975. 230(3): p. 283-97. 
15. 
Goepfert, P.A., et al., Phase 1 safety and immunogenicity testing of DNA and recombinant 
modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis, 2011. 
203(5): p. 610-9. 
16. 
Howles, S., et al., Vaccination with a modified vaccinia virus Ankara (MVA)-vectored HIV-1 
immunogen induces modest vector-specific T cell responses in human subjects. Vaccine, 2010. 
28(45): p. 7306-12. 
17. 
Scriba, T.J., et al., Modified vaccinia Ankara-expressing Ag85A, a novel tuberculosis vaccine, is 
safe in adolescents and children, and induces polyfunctional CD4+ T cells. Eur J Immunol, 2010. 
40(1): p. 279-90. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
63 
18. 
Swadling, L., et al., A human vaccine strategy based on chimpanzee adenoviral and MVA vectors 
that primes, boosts, and sustains functional HCV-specific T cell memory. Sci Transl Med, 2014. 
6(261): p. 261ra153. 
19. 
Dangoor, A., et al., Clinical and immunological responses in metastatic melanoma patients 
vaccinated with a high-dose poly-epitope vaccine. Cancer Immunol Immunother, 2010. 59(6): p. 
863-73. 
20. 
O'Hara, G.A., et al., Clinical assessment of a recombinant simian adenovirus ChAd63: a potent 
new vaccine vector. J Infect Dis, 2012. 205(5): p. 772-81. 
21. 
Antrobus, R.D., et al., A T cell-inducing influenza vaccine for the elderly: safety and 
immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS One, 2012. 7(10): p. 
e48322. 
22. 
Antrobus, R.D., et al., Coadministration of seasonal influenza vaccine and MVA-NP+M1 
simultaneously achieves potent humoral and cell-mediated responses. Mol Ther, 2014. 22(1): p. 
233-8. 
23. 
Lillie, P.J., et al., Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, 
MVA-NP+M1, in humans. Clin Infect Dis, 2012. 55(1): p. 19-25. 
24. 
Rothberg, M.B., S.D. Haessler, and R.B. Brown, Complications of viral influenza. Am J Med, 
2008. 121(4): p. 258-64. 
25. 
Akritidis, N., et al., Electrocardiographic abnormalities in patients with novel H1N1 influenza 
virus infection. Am J Cardiol, 2010. 106(10): p. 1517-9. 
26. 
Ison, M.G., et al., Cardiac findings during uncomplicated acute influenza in ambulatory adults. 
Clin Infect Dis, 2005. 40(3): p. 415-22. 
 
 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
CONFIDENTIAL 
64 
APPENDIX 1: ADVERSE EVENTS OF SPECIAL INTEREST 
Adverse events of special interest represent a subset of adverse events that include autoimmune diseases and 
other systemic disorders of interest which could potentially have an autoimmune aetiology. Adverse events of 
special interest are listed below. The Investigator should use clinical and scientific judgment in deciding whether 
other adverse events (i.e., events not listed here) could have an autoimmune origin and should therefore be 
reported as adverse events of special interest. 
Bell's Palsy 
Guillain Barre Syndrome 
Myocarditis 
Stevens-Johnson Syndrome 
 
APPENDIX 2: TOXICITY GRADING SCALE FOR HEALTHY ADULT AND 
ADOLESCENT VOLUNTEERS ENROLLED IN 
PREVENTIVE VACCINE CLINICAL TRIALS 
 
https://www.fda.gov/downloads/BiologicsBloodVaccines/ucm091977  
 
A. 
TABLES FOR CLINICAL ABNORMALITIES 
 
Local Reaction to 
Injectable Product 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Pain 
Does not interfere 
with activity 
Repeated use of non- 
narcotic pain reliever 
> 24 hours or 
interferes with 
activity 
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity 
Emergency room 
(ER) visit or 
hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
ER visit or 
hospitalization 
Erythema/Redness * 
2.5 – 5 cm 
5.1 – 10 cm 
> 10 cm 
Necrosis or 
exfoliative 
dermatitis 
Induration/Swelling ** 
2.5 – 5 cm and 
does not interfere 
with activity 
5.1 – 10 cm or 
interferes with 
activity 
> 10 cm or 
prevents daily 
activity 
Necrosis 
* 
In addition to grading the measured local reaction at the greatest single diameter, the measurement should be 
recorded as a continuous variable. 
** Induration/Swelling should be evaluated and graded using the functional scale as well as the actual measurement. 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
 
CONFIDENTIAL 
65 
 
Vital Signs * 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Fever (°C) ** 
(°F) ** 
38.0 – 38.4 
100.4 – 101.1 
38.5 – 38.9 
101.2 – 102.0 
39.0 – 40 
102.1 – 104 
> 40 
> 104 
Tachycardia - beats per 
minute 
101 – 115 
116 – 130 
> 130 
ER visit or 
hospitalization for 
arrhythmia 
Bradycardia - beats per 
minute*** 
50 – 54 
45 – 49 
< 45 
ER visit or 
hospitalization for 
arrhythmia 
Hypertension (systolic) - 
mm Hg 
141 – 150 
151 – 155 
> 155 
ER visit or 
hospitalization for 
malignant 
hypertension 
Hypertension (diastolic) - 
mm Hg 
91 – 95 
96 – 100 
> 100 
ER visit or 
hospitalization for 
malignant 
hypertension 
Hypotension (systolic) – 
mm Hg 
85 – 89 
80 – 84 
< 80 
ER visit or 
hospitalization for 
hypotensive shock 
Respiratory Rate – breaths 
per minute 
17 – 20 
21 – 25 
> 25 
Intubation 
* 
Participant should be at rest for all vital sign measurements. 
** Oral temperature; no recent hot or cold beverages or smoking. 
*** When resting heart rate is between 60 – 100 beats per minute. Use clinical judgement when 
characterizing bradycardia among some healthy participant populations, for example, 
conditioned athletes. 
 
Systemic (General) 
Mild (Grade 1) 
Moderate (Grade 2) Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Nausea/vomiting 
No interference 
with activity or 1 – 2 
episodes/24 hours 
Some interference 
with activity or > 2 
episodes/24 hours 
Prevents daily 
activity, requires 
outpatient IV 
hydration 
ER visit or 
hospitalization for 
hypotensive shock 
Diarrhea 
2 – 3 loose stools or 
< 400 gms/24 hours 
4 – 5 stools or 
400 – 800 gms/24 
hours 
6 or more watery 
stools or 
> 800gms/24 hours 
or requires 
outpatient IV 
hydration 
ER visit or 
hospitalization 
Headache 
No interference with 
activity 
Repeated use of non- 
narcotic pain 
reliever > 24 hours or 
some interference 
with activity 
Significant; any 
use of narcotic 
pain reliever or 
prevents daily 
activity 
ER visit or 
hospitalization 
Fatigue 
No interference with 
activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
ER visit or 
hospitalization 
Myalgia 
No interference with 
activity 
Some interference 
with activity 
Significant; 
prevents daily 
activity 
ER visit or 
hospitalization 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
 
CONFIDENTIAL 
66 
 
Systemic Illness 
Mild (Grade 1) 
(Moderate (Grade 2) Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Illness or clinical adverse 
event (as defined 
according to applicable 
regulations) 
No interference with 
activity 
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily 
activity and 
requires medical 
intervention 
ER visit or 
hospitalization 
 
 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
 
CONFIDENTIAL 
67 
B. 
TABLES FOR LABORATORY ABNORMALITIES 
 
The laboratory values provided in the tables below serve as guidelines and 
are dependent upon institutional normal parameters. Institutional normal 
reference ranges should be provided to demonstrate that they are 
appropriate. 
 
Serum * 
Mild (Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4)** 
Sodium – Hyponatremia mEq/L 
132 – 134 
130 – 131 
125 – 129 
< 125 
Sodium – Hypernatremia mEq/L 
144 – 145 
146 – 147 
148 – 150 
> 150 
Potassium – Hyperkalemia mEq/L 
5.1 – 5.2 
5.3 – 5.4 
5.5 – 5.6 
> 5.6 
Potassium – Hypokalemia mEq/L 
3.5 – 3.6 
3.3 – 3.4 
3.1 – 3.2 
< 3.1 
Glucose – Hypoglycemia mg/dL 
65 – 69 
55 – 64 
45 – 54 
< 45 
Glucose – Hyperglycemia 
Fasting – mg/dL 
Random – mg/dL 
 
100 – 110 
110 – 125 
 
111 – 125 
126 – 200 
 
>125 
>200 
Insulin 
requirements or 
hyperosmolar 
coma 
Blood Urea Nitrogen 
BUN mg/dL 
23 – 26 
27 – 31 
> 31 
Requires 
dialysis 
Creatinine – mg/dL 
1.5 – 1.7 
1.8 – 2.0 
2.1 – 2.5 
> 2.5 or requires 
dialysis 
Calcium – hypocalcemia mg/dL 
8.0 – 8.4 
7.5 – 7.9 
7.0 – 7.4 
< 7.0 
Calcium – hypercalcemia mg/dL 
10.5 – 11.0 
11.1 – 11.5 
11.6 – 12.0 
> 12.0 
Magnesium – hypomagnesemia mg/dL 
1.3 – 1.5 
1.1 – 1.2 
0.9 – 1.0 
< 0.9 
Phosphorous – hypophosphatemia 
mg/dL 
2.3 – 2.5 
2.0 – 2.2 
1.6 – 1.9 
< 1.6 
CPK – mg/dL 
1.25 – 1.5 x 
ULN*** 
1.6 – 3.0 x ULN 
3.1 –10 x ULN 
> 10 x ULN 
Albumin – Hypoalbuminemia g/dL 
2.8 – 3.1 
2.5 – 2.7 
< 2.5 
-- 
Total Protein – Hypoproteinemia g/dL 
5.5 – 6.0 
5.0 – 5.4 
< 5.0 
-- 
Alkaline phosphate – 
increase by factor 
1.1 – 2.0 x ULN 
2.1 – 3.0 x ULN 
3.1 – 10 x ULN 
> 10 x ULN 
Liver Function Tests –ALT, AST 
increase by factor 
1.1 – 2.5 x ULN 
2.6 – 5.0 x ULN 
5.1 – 10 x ULN 
> 10 x ULN 
Bilirubin – when accompanied 
by any increase in Liver Function Test 
increase by factor 
1.1 – 1.25 x ULN 
1.26 – 1.5 x ULN 
1.51 – 1.75 x ULN 
> 1.75 x ULN 
Bilirubin – when Liver Function Test 
is normal; increase by factor 
1.1 – 1.5 x ULN 
1.6 – 2.0 x ULN 
2.0 – 3.0 x ULN 
> 3.0 x ULN 
Cholesterol 
201 – 210 
211 – 225 
> 226 
--- 
Pancreatic enzymes – amylase, lipase 
1.1 – 1.5 x ULN 
1.6 – 2.0 x ULN 
2.1 – 5.0 x ULN 
> 5.0 x ULN 
*  
The laboratory values provided in the tables serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. 
**  
The clinical signs or symptoms associated with laboratory abnormalities might result in 
characterization of the laboratory abnormalities as Potentially Life Threatening (Grade 4). For 
example. a low sodium value that falls within a grade 3 parameter (125-129 mE/L) should be 
recorded as a grade 4 hyponatremia event if the participant had a new seizure associated with 
the low sodium value. 
*** 
ULN” is the upper limit of the normal range. 
 

VACCITECH LTD 
CLINICAL STUDY PROTOCOL – FLU010 
10-JUL-2019 (FINAL 5.0) 
 
CONFIDENTIAL 
68 
Hematology * 
Mild (Grade 1) 
Moderate 
(Grade 2) 
Severe (Grade 3) 
Potential
ly Life 
Threaten
ing 
(Grade 4) 
Hemoglobin (Female) - gm/dL 
11.0 – 12.0 
9.5 – 10.9 
8.0 – 9.4 
< 8.0 
Hemoglobin (Female) 
change from baseline value - gm/dL 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
Hemoglobin (Male) - gm/dL 
12.5 – 13.5 
10.5 – 12.4 
8.5 – 10.4 
< 8.5 
Hemoglobin (Male) 
change from baseline value – gm/dL 
Any decrease – 1.5 
1.6 – 2.0 
2.1 – 5.0 
> 5.0 
WBC Increase - cell/mm3 
10,800 – 15,000 
15,001 – 20,000 
20,001 – 25, 000 
> 25,000 
WBC Decrease - cell/mm3 
2,500 – 3,500 
1,500 – 2,499 
1,000 – 1,499 
< 1,000 
Lymphocytes Decrease - cell/mm3 
750 – 1,000 
500 – 749 
250 – 499 
< 250 
Neutrophils Decrease - cell/mm3 
1,500 – 2,000 
1,000 – 1,499 
500 – 999 
< 500 
Eosinophils - cell/mm3 
650 – 1500 
1501 - 5000 
> 5000 
Hypereosinop
hilic 
Platelets Decreased - cell/mm3 
125,000 – 140,000 
100,000 – 124,000 
25,000 – 99,000 
< 25,000 
PT – increase by factor 
(prothrombin time) 
1.0 – 1.10 x 
ULN** 
1.11 – 1.20 x ULN 1.21 – 1.25 x ULN 
> 1.25 ULN 
PTT – increase by factor 
(partial thromboplastin time) 
1.0 – 1.2 x ULN 
1.21 – 1.4 x ULN 
1.41 – 1.5 x ULN 
> 1.5 x ULN 
Fibrinogen increase - mg/dL 
400 – 500 
501 – 600 
> 600 
-- 
Fibrinogen decrease - mg/dL 
150 – 200 
125 – 149 
100 – 124 
< 100 or 
associated 
with gross 
bleeding or 
disseminated 
intravascular 
coagulation 
(DIC) 
* 
The laboratory values provided in the tables serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. 
** “ULN” is the upper limit of the normal range. 
 
Urine * 
Mild (Grade 1) 
Moderate 
(Grade 2) 
Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Protein 
Trace 
1+ 
2+ 
Hospitalization or 
dialysis 
Glucose 
Trace 
1+ 
2+ 
Hospitalization for 
hyperglycemia 
Blood (microscopic) – 
red blood cells per 
high power field (rbc/hpf) 
1 - 10 
11 – 50 
> 50 and/or gross 
blood 
Hospitalization or 
packed red blood 
cells (PRBC) 
transfusion 
* 
The laboratory values provided in the tables serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate.